Early Detection of Prostate Cancer (2023) Flashcards

Question

How does a strong family history of prostate cancer affect a person's risk, and how should this impact screening strategies?

Answer 1

A strong family history of prostate cancer is a significant risk factor for developing the disease. Studies have found an elevated risk of prostate cancer in individuals with a family history of the disease, particularly high-risk prostate cancers. For instance, patients with two or more first-degree relatives with prostate cancer have a four-fold relative risk compared to those without a family history. It is recommended that these patients A strong family history of prostate cancer is a significant risk factor for developing the disease. Studies have found an elevated risk of prostate cancer in individuals with a family history of the disease, particularly high-risk prostate cancers. For instance, patients with two or more first-degree relatives with prostate cancer have a four-fold relative risk compared to those without a family history. It is recommended that these patients be genotyped to determine if their family history is associated with a pathogenic variant, such as BRCA1/2, Lynch Syndrome, ATM, or CHEK2, or other germline DNA damage-repair mutations often found in patients with metastatic prostate cancer. In the absence of this information, it may be appropriate to screen these patients earlier and more frequently, much like those with detected germline pathogenic variants. However, given the uncertainties involved in the PSA screening setting, Shared Decision Making (SDM) is highly recommended. This allows the screening strategy to be tailored to the individual's specific risk profile and preferences, thereby balancing the benefits of early detection against the risks of overdiagnosis and overtreatment.

Answer 2

The document strongly recommends offering regular prostate cancer screening every 2 to 4 years for people aged 50 to 69 years. This is supported by two Randomized Controlled Trials (RCTs), the ERSPC and the Goteborg-1 trials, which showed that regular Prostate-Specific Antigen (PSA) screening in this age group reduces the risk of metastatic prostate cancer and prostate cancer mortality compared to no or opportunistic screening. The number needed to screen (NNS), which is the inverse of the absolute risk reduction in prostate cancer mortality, and the number needed to diagnose (NND), which represents additional cases diagnosed to prevent one death from prostate cancer, vary depending on the screening protocol (including screening ages) and follow-up time. The PLCO cancer screening trial did not show a statistically significant difference in prostate cancer mortality between the screened and control groups, but this was likely due to a high level of PSA testing in the control group. A modeling study reconciling the PLCO and ERSPC data suggested that PSA screening can reduce prostate cancer mortality by about 30% at 11 to 13 years. Several models have shown that PSA screening can result in fewer deaths from prostate cancer but also highlighted that the benefits of screening must be balanced against the potential reduction in quality-adjusted life years due to long-term side-effects from treatment. Given these complexities and uncertainties, Shared Decision Making (SDM) is highly recommended in the PSA screening setting.

Answer 3

B. ERSPC and Goteborg-1 Explanation: The ERSPC and the Goteborg-1 trials provided evidence that regular PSA screening every 2 to 4 years in patients aged 50 to 69 years reduces the risk of metastatic prostate cancer and prostate cancer mortality compared to no or opportunistic screening.

Answer 4

B. The control group had a high degree of PSA testing. Explanation: The PLCO trial's control group had a high degree of PSA testing (contamination) with more than 80% of patients receiving at least 1 PSA test during the trial. This likely impacted the trial's ability to demonstrate a significant difference in prostate cancer mortality between the screening and control groups.

Answer 5

The NNS and NND are crucial metrics in evaluating the effectiveness of prostate cancer screening. The NNS is the inverse of the absolute risk reduction in prostate cancer mortality, meaning it indicates how many patients need to be screened to prevent one death from prostate cancer. The NND represents the additional cases that need to be diagnosed to prevent one death from prostate cancer. These metrics vary depending on the screening protocol (including screening ages) and the duration of follow-up.

Answer 6

Shared Decision Making (SDM) is highly recommended in the Prostate-Specific Antigen (PSA) screening setting due to the complexity and uncertainty associated with prostate cancer screening. While screening can potentially detect cancer early and reduce mortality, it also carries risks such as false-positive results, overdiagnosis, and overtreatment. These may lead to unnecessary biopsies and treatments, which can cause significant side effects and impact the patient's quality of life. SDM involves the patient and clinician discussing the potential benefits, risks, and uncertainties of PSA screening to make an informed decision that aligns with the patient's values and preferences.

Answer 7

Regular screening in patients aged 70 years and older or in patients with less than a 10 to 15-year life expectancy may result in more harm than benefit.63 Regular screening is not recommended because these patients are more likely to die from causes other than prostate cancer.64,65 Even if these patients are diagnosed with prostate cancer, they are unlikely to benefit from early detection or curative treatment given their limited life expectancy. Evidence from observational studies suggests that PSA screening in patients aged ≥70 years results in considerable overdiagnosis and overtreatment.66,67 The high rate of overdiagnosis in these patients is likely due to the slower progression of prostate cancer in older adults.68-70 Overdiagnosis can lead to unnecessary invasive procedures, which have significant side effects, and overtreatment can result in a decrease in quality of life. Observational data also suggest that many patients with a limited life expectancy are inappropriately screened.71 A large U.S. study found that 41% of patients aged 75 years or older underwent PSA screening, and 29% of patients with a life expectancy of less than 10 years also underwent screening.72 Similarly, a study in Sweden found that 47% of men aged 70 years or older underwent PSA testing.73 These findings suggest that clinicians need to be mindful of the potential harms of PSA screening in these populations and incorporate this information into SDM with their patients. For patients who are currently being screened and fall into one of these categories (i.e., age ≥70 years or life expectancy <10-15 years), clinicians should discuss the potential benefits and harms of discontinuing screening.

Answer 8

The passage discusses the importance of patient-specific considerations in determining the frequency of Prostate-Specific Antigen (PSA) screening. Clinicians should consider variables such as patient preferences, age, PSA levels, prostate cancer risk, life expectancy, and overall health following a shared decision-making (SDM) process. Randomized trials have shown that screening patients aged 50 to 69 years every 1 to 4 years reduces prostate cancer mortality. Furthermore, various studies have suggested that the balance between the benefits and harms of screening can be adjusted through personalized risk-stratified screening strategies. For patients with PSA levels between 1 and 3 ng/mL aged 45 to 70 years, the re-screening interval can be between 1 to 4 years. However, for those with a PSA level of less than 1 ng/mL or below the age-specific median, the re-screening interval can be extended. The risks associated with PSA screening include anxiety, false positives, overdiagnosis, and biopsy side-effects. There's evidence suggesting that patients who are in their 60s and have a PSA level below 1 ng/mL have a very low long-term risk of metastatic cancer or prostate cancer mortality. This low risk could justify discontinuing screening or significantly lengthening the re-screening interval. For patients older than 70 years, the decision to continue screening should be based on their previous PSA levels, overall health, and life expectancy. Screening for patients with less than a ten-year estimated life expectancy is not likely to provide a benefit in terms of disease-specific or overall mortality. The risk of overdiagnosis increases with age. Life expectancy can be estimated using a number of tools, including risk calculators, social security life tables, and online calculators provided by insurance companies. Given the limitations in evidence supporting specific screening intervals and when to discontinue screening, the use of SDM is recommended to assist clinicians in tailoring the decision to each patient.

Answer 9

b) Every 1 to 4 years. The text suggests this as an appropriate screening interval for these individuals, as it represents a balance between detecting potential issues early and avoiding unnecessary harm from frequent testing.

Answer 10

c) Low. The text indicates that the risk is extremely low (0.5% and 0.2%, respectively) in a largely unscreened population.

Answer 11

b) Not likely to provide a benefit. The text suggests that screening is not likely to provide a benefit in terms of disease-specific or overall mortality for these individuals.

Answer 12

A shared decision-making process is important when deciding to screen for prostate cancer because the balance between benefits and harms of screening can vary greatly among individuals based on a range of factors such as patient preferences, age, PSA levels, prostate cancer risk, life expectancy, and overall health. Shared decision-making helps to ensure that patients are fully informed and involved in the decision, and that the decision is tailored to their individual circumstances and preferences.

Answer 13

The re-screening intervals for prostate cancer might be personalized based on the patient's PSA levels and age. For instance, if a patient's PSA levels are between 1 and 3 ng/mL and they are between the ages of 45 and 70 years, the re-screening interval could be between 1 to 4 years. However, for those with a PSA level of less than 1 ng/mL or below the age-specific median, the re-screening interval can be extended.

Answer 14

Life expectancy significantly impacts the decision to continue prostate cancer screening. For patients with less than a ten-year estimated life expectancy, screening is not likely to provide a benefit in terms of disease-specific or overall mortality. Conversely, patients who are very healthy with an estimated life expectancy of at least ten years could benefit from ongoing screening every two to four years, as they are more likely to benefit from therapeutic interventions if indicated.

Answer 15

The risks of overdiagnosis and prostate cancer increase with age because the likelihood of developing slow-growing, non-aggressive forms of prostate cancer that may never cause symptoms or lead to death also increases with age. Therefore, screening older individuals might lead to overdiagnosis, where cancer is detected and treated unnecessarily, potentially causing more harm than benefit.

Answer 16

The document suggests that clinicians may use Digital Rectal Exam (DRE) along with Prostate-Specific Antigen (PSA) tests to establish the risk of clinically significant prostate cancer, but warns against using DRE as the sole screening method due to its low positive predictive value (PPV). The PROBASE trial highlighted that DRE was not effective for early detection. However, DRE can be beneficial when used in conjunction with PSA testing for patients with PSA ≥ 2 ng/mL, to determine the risk of clinically significant prostate cancer. The document also suggests that an abnormal DRE improves the PPV for any prostate cancer detection, particularly when combined with an elevated PSA level. Nevertheless, the utility of DRE becomes less impactful in subsequent screening rounds, and the difference in the risk of clinically significant prostate cancer between patients with suspicious versus non-suspicious DRE is modest.

Answer 17

b) Because it has a low positive predictive value (PPV) for detecting prostate cancer. Explanation: The document indicates that the PPV of DRE for detecting prostate cancer is low, which suggests that it is not an efficient sole screening method.

Answer 18

a) When the patient has a PSA level ≥ 2 ng/mL. Explanation: The document suggests that among patients with PSA ≥ 2 ng/mL, clinicians should strongly consider supplementary DRE to establish the risk of clinically significant prostate cancer.

Answer 19

According to the material, using DRE in conjunction with an elevated PSA level in prostate cancer screening improves the Positive Predictive Value (PPV) for any prostate cancer detection, particularly for higher-grade disease. In the ERSPC Rotterdam study, the PPV of a suspicious DRE along with an elevated PSA level ≥ 3 ng/mL to detect prostate cancer was 48% compared to 22% in patients with a normal DRE. Explanation: The use of DRE, therefore, can enhance the efficiency of prostate cancer screening by helping to identify higher-risk patients when used in tandem with PSA testing, particularly in those with elevated PSA levels.

Answer 20

The limitation of using DRE as a supplementary method in subsequent prostate cancer screening rounds is that the impact of an abnormal DRE on the Positive Predictive Value (PPV) for prostate cancer detection becomes attenuated. This means that the efficiency of DRE in detecting prostate cancer decreases in subsequent rounds. Explanation: While DRE can enhance the detection of prostate cancer when combined with PSA testing initially, its utility in improving detection rates diminishes in the later stages of repeated screening. Therefore, reliance on DRE for detection should be tempered in subsequent screenings.

Answer 21

Black ancestry, germline mutations, strong family history of breast/ovarian cancer, strong family history of prostate cancer OR indicated by risk calculator and SDM.

Answer 22

PCA3 is a gene that is over-expressed in more than 95% of prostate cancer cases. The PCA3 test, often used in conjunction with other diagnostic tools, measures the amount of PCA3 mRNA in urine after a Digital Rectal Examination (DRE). A higher PCA3 score is correlated with a greater likelihood of prostate cancer. The PCA3 test can be especially useful in deciding whether a biopsy is necessary for men with elevated PSA levels, as it is more specific to prostate cancer than a PSA test alone.

Answer 23

This is a urine test that measures the TMPRSS2:ERG gene fusion, which is present in approximately half of all localized prostate cancers. Similar to the PCA3 test, T2:ERG is a more specific indicator for prostate cancer than PSA alone. When T2:ERG and PCA3 tests are used together, the combined test is more accurate in diagnosing prostate cancer than either test alone.

Answer 24

The material suggests that PSA velocity should not be used as the sole indication for secondary biomarker, imaging, or biopsy when screening for prostate cancer. This recommendation is based on large-scale studies in Europe and the U.S. that showed no additional value of PSA velocity in predicting clinically significant prostate cancer when other factors such as patient's age, PSA, DRE, percent free PSA, family history of prostate cancer, and the presence of a previous biopsy are known. It's notable that very high PSA velocity is more closely associated with inflammation on biopsy than with cancer.

Answer 25

c) It should not be used. Explanation: The material recommends that PSA velocity should not be used as the sole indication for secondary biomarker, imaging, or biopsy when screening for prostate cancer. It doesn't add significant value in predicting clinically significant prostate cancer when other factors are considered.

Answer 26

c) Presence of inflammation on biopsy. Explanation: It is highlighted in the material that a very high PSA velocity is more closely associated with the presence of inflammation on biopsy rather than cancer, contrary to what one might initially expect.

Answer 27

Important factors in predicting the presence of clinically significant prostate cancer include the patient's age, PSA level, Digital Rectal Examination (DRE) results, percentage of free PSA, family history of prostate cancer, and the presence of a previous biopsy. These factors provide a more holistic view of the patient's risk and can help guide decisions regarding further testing or interventions.

Answer 28

Risk calculators, utilizing a combination of demographic factors, medical history, family history of prostate cancer, biomarkers, and imaging findings, are useful tools in the Shared Decision Making (SDM) process regarding prostate biopsy. These calculators have become increasingly accessible with the rise of Electronic Medical Records (EMR) and can facilitate real-time clinical conversations. The calculators offer estimates of cancer detection risk, but clinicians should understand that these estimates represent population averages and may have wide intervals for some subsets. Calculators may be based on historical data and may differ by subgroups. Clinicians should consider their experience and the specific characteristics of their patient population in addition to these estimates. Notable calculators include the Prostate Cancer Prevention Trial (PCPT) calculator, Chun calculator, ERSPC online tool, and the calculator by the Prostate Biopsy Collaborative Group (PBCG).

Answer 29

1. Prostate Cancer Prevention Trial (PCPT) calculator 2. Chun calculator 3. ERSPC Online tool 4. Prostate Biopsy Collaborative Group (PBCG)

Answer 30

a) Patient demographic factors, medical history, family history of prostate cancer, biomarkers, and imaging findings. Explanation: Contemporary risk evaluations for prostate cancer consider a combination of factors to provide a more accurate assessment of risk. These factors include patient demographic factors, medical history, family history of prostate cancer, biomarkers, and imaging findings.

Answer 31

b) Because they facilitate clinician-patient discussion of detection risk in real-time. Explanation: Web-based risk calculators have become increasingly important in clinical encounters because they are easily accessible and can be used to provide real-time risk estimates during clinical conversations. This helps in informing patients and facilitates the shared decision-making process.

Answer 32

Risk calculators for estimating the risk of prostate cancer have several limitations. These calculators provide estimates based on population averages, which means they might have wide intervals for certain subsets. These estimates might not always reflect the individual's exact risk. The calculators often rely on historical data, including screening and detection approaches that may be outdated due to advances in technology, such as the widespread adoption of prostate MRI. Calibration of risk calculators may also differ by subgroups, which means some calculators may not perform equally well for all population groups. Therefore, clinicians should not solely rely on these risk calculators and should incorporate their experience and understanding of their patient population in refining these risk estimates.

Answer 33

The PCPT risk calculator incorporates multiple elements including the patient's race, age, Prostate-Specific Antigen (PSA) levels, percent free PSA, family history of prostate cancer, Digital Rectal Exam (DRE) findings, results from prior biopsy, and urinary Prostate Cancer Antigen 3 (PCA3) levels. These combined factors provide a more comprehensive estimation of a patient's risk for developing prostate cancer.

Answer 34

The given material discusses when it may be appropriate to forgo near-term prostate biopsy based on low risk of clinically significant prostate cancer. Risk assessment tools such as online calculators or nomograms can incorporate various factors including PSA levels, family history, race/ethnicity, age, DRE, percent free PSA, and PSA density to estimate the risk. If both the clinician and the patient perceive the risk as low, it may be reasonable to skip a prostate biopsy following Shared Decision Making (SDM). However, it's crucial to inform patients about the potential risk of underdiagnosing significant prostate cancer and the need for future follow-up screening, if the biopsy or additional testing is forgone.

Answer 35

d) Dietary habits Explanation: While dietary habits might influence the overall risk of developing cancer, they are not typically part of the risk calculation model which includes PSA levels, family history of prostate cancer, race/ethnicity, age, DRE, percent free PSA, and PSA density.

Answer 36

c) When the risk for significant prostate cancer is considered low by both clinician and patient Explanation: A prostate biopsy might be forgone following shared decision making (SDM), if both the clinician and the patient perceive the risk for significant prostate cancer as low, despite some clinical features indicating a risk for prostate cancer (e.g., mildly elevated PSA).

Answer 37

Potential consequences of forgoing a prostate biopsy when the risk of clinically significant prostate cancer is perceived as low could include the risk of underdiagnosing a significant prostate cancer. This might occur if the risk estimation was incorrect or if the disease progresses unexpectedly. Therefore, patients should be informed of this potential risk and the need for regular follow-up screening. Explanation: While forgoing a biopsy can save the patient from unnecessary procedures and their associated side effects, it is essential to balance this with the potential risk of underdiagnosing a significant disease. Regular follow-up screenings can help monitor any changes in the patient's condition.

Answer 38

Clinicians can assess the risk of clinically significant prostate cancer using validated online calculators or nomograms. These tools incorporate multiple risk factors, such as PSA levels, family history of prostate cancer, race/ethnicity, age, digital rectal examination (DRE) results, percent free PSA, and PSA density. By integrating these factors, clinicians can estimate a patient's risk of prostate cancer and the risk of clinically significant prostate cancer. Explanation: These tools aim to provide a more nuanced assessment of a patient's risk by considering a broad range of factors rather than relying solely on individual risk factors. This can help in making informed decisions about whether to proceed with a biopsy or additional testing.

Answer 39

The material asserts the importance of informing patients about the potential findings of a prostate biopsy, which may reveal a cancer with a low mortality risk that could be safely monitored with Active Surveillance (AS) rather than treated immediately. A pre-biopsy conversation about such outcomes may increase patient acceptance of AS and lower rates of treatment. The material cites a study in which 44% of initial and 61% of repeat positive biopsies found Gleason Grade Group 1 (GG1) prostate cancer. AS is the preferred management for low-risk prostate cancer by the American Urological Association (AUA) and other international guidelines. Despite this, overtreatment is documented among patients with low-risk prostate cancer and a less than 10-year life expectancy. The primary intent of screening and surveillance is to identify higher-grade cancers for definitive treatment.

Answer 40

a) It may increase patient acceptance of Active Surveillance. Explanation: A pre-biopsy discussion can prepare patients for the potential outcome of identifying a low-risk prostate cancer. This might increase their acceptance of Active Surveillance, a management approach that involves regular monitoring rather than immediate treatment.

Answer 41

b) To identify higher-grade cancers that may prompt definitive treatment. Explanation: The main objective of screening and surveillance is to detect higher-grade cancers that could potentially require definitive treatment, such as surgery or radiation, rather than simply monitoring.

Answer 42

A pre-biopsy discussion can influence subsequent treatment decisions by preparing patients for potential outcomes, including the possibility of identifying a low-risk prostate cancer that could be safely monitored with Active Surveillance rather than treated immediately. This can potentially increase their acceptance of Active Surveillance and lower rates of overtreatment. Explanation: Having this discussion beforehand can help alleviate patient anxiety, give them a clearer understanding of the potential pathways ahead, and enable them to make informed decisions about their care. It can also set realistic expectations about the potential for overtreatment and unnecessary interventions, especially in low-risk prostate cancer.

Answer 43

Despite the preference of Active Surveillance for managing low-risk prostate cancer, a concern has been documented regarding overtreatment among patients with low-risk prostate cancer and less than a 10-year life expectancy. This suggests that some patients are receiving more aggressive treatment than necessary given their prognosis. Explanation: Overtreatment can lead to unnecessary side effects and compromise quality of life without significant benefits in terms of cancer control or survival. This highlights the importance of adherence to guidelines and shared decision-making to ensure that the chosen treatment pathway aligns with the patient's prognosis and preferences.

Answer 44

This section discusses the potential use of MRI prior to the initial biopsy to increase the detection of Gleason Grade Group 2 (GG2+) prostate cancer. The clinical value of multi-parametric MRI (mpMRI) has been demonstrated in studies, showing it can increase the likelihood of detecting clinically significant prostate cancer while lowering the detection of insignificant disease. However, results are inconsistent among biopsy-naïve patients. Some studies have shown mpMRI driven biopsy strategy can lead to higher detection of clinically significant prostate cancer and avoid the detection of insignificant disease, while others do not demonstrate a difference. A Cochrane review analyzed pooled data from 18 studies, finding a high sensitivity but low specificity for mpMRI in detecting GG2+ prostate cancer. Currently, obtaining an mpMRI in biopsy-naïve patients prior to their first biopsy could be considered reasonable, but is not a standard approach due to varying evidence. Shared decision-making (SDM) is highly recommended due to the uncertainty.

Answer 45

b) It helps to increase the detection of GG2+ prostate cancer. Explanation: mpMRI prior to initial biopsy has shown potential to increase the likelihood of detecting clinically significant prostate cancer, specifically GG2+ cancers, while also reducing the detection of clinically insignificant disease.

Answer 46

c) It found the sensitivity of a pre-biopsy MRI is high but the specificity is low for GG2+ prostate cancer. Explanation: The Cochrane review pooled data from 18 studies and found that the sensitivity of a pre-biopsy MRI is high (0.91), indicating that it is good at correctly identifying those with GG2+ prostate cancer. However, the specificity is low (0.37), which means it may incorrectly identify some individuals without GG2+ prostate cancer as having the disease.

Answer 47

The recommendation for using mpMRI prior to the initial biopsy is conditional because the evidence regarding its benefit is mixed. While some studies suggest that mpMRI can increase the detection of clinically significant prostate cancer and reduce the detection of insignificant disease, others do not demonstrate a significant difference. The data from studies on biopsy-naïve patients are particularly inconsistent. Thus, while mpMRI might be considered in these patients prior to their first biopsy, it cannot currently be considered the standard approach. Shared decision-making is recommended given these uncertainties. Explanation: Clinical recommendations should be based on robust and consistent evidence. In the case of using mpMRI prior to initial biopsy, the evidence is varied, with some studies showing benefits and others not. This mixed evidence base leads to a conditional recommendation, indicating that the decision should be tailored to individual patients and contexts.

Answer 48

The low specificity of mpMRI for GG2+ prostate cancer means that the method may incorrectly identify some individuals without the disease as having it. This could potentially lead to unnecessary biopsies or treatments, causing undue stress and side effects for patients, and additional costs for healthcare providers. It may also lead to patient anxiety due to a false-positive result. Explanation: Specificity refers to the ability of a test to correctly identify those without the disease. When specificity is low, the test may produce a significant number of false positives, potentially leading to unnecessary procedures or treatments. This underscores the importance of considering other factors and tests in the diagnostic process, and the importance of shared decision-making in the management of prostate cancer.

Answer 49

This section recommends that radiologists use the Prostate Imaging Reporting and Data System (PI-RADS) for reporting multi-parametric MRI (mpMRI) imaging, a standard that has been adopted widely since its initial development in 2012 and subsequent updates in 2015 and 2019. Studies have shown that PI-RADS score correlates with the likelihood of detecting any cancer and GG2+ cancer. However, the required evaluation criteria for PI-RADS can be subjective, leading to reader variability, especially among less experienced readers. Measures of interobserver agreement include weighted kappa and Conger kappa values for various studies. Factors such as patient selection, technical elements, biopsy methods, and pathologist expertise may influence performance differences between sites. Continued development of training criteria and further improvements to PI-RADS should increase accuracy and reader agreement. Clinicians should interpret PI-RADS scores in the context of known local experience and expertise.

Answer 50

: c) The reporting of mpMRI imaging. Explanation: PI-RADS was developed to standardize the reporting of mpMRI imaging for prostate cancer. It provides a structured system for lesion-based scoring and has been widely adopted since its introduction.

Answer 51

c) It has considerable reader variability. Explanation: While PI-RADS has become widely used and does correlate with the likelihood of detecting cancer, one of its limitations is reader variability. Because some evaluation criteria in PI-RADS are subjective, interpretations can vary, especially among less experienced readers.

Answer 52

Since its development in 2012, PI-RADS has undergone subsequent revisions in 2015 and 2019 to improve its usability and effectiveness in reporting prostate mpMRI findings. The benefits of PI-RADS include standardizing the reporting of mpMRI, and it has been shown to correlate with the likelihood of detecting any cancer and GG2+ cancer. However, PI-RADS has limitations, such as the subjectivity of some evaluation criteria, which can lead to reader variability, especially among less experienced readers. Inter-reader agreement, although improved with PI-RADS v2.1 compared to v2.0, and better with more experienced readers, remains a challenge.

Answer 53

Several factors can influence the performance differences in the use of PI-RADS across different sites. These include patient selection, technical factors like MRI manufacturer and field strength, the use of an endorectal coil, the method of prostate biopsy used for pathological correlation, as well as pathologist expertise and variability. Differences in reader experience and training also contribute to performance variations between sites.

Answer 54

This section suggests that for patients who have not yet had a biopsy and show a suspicious lesion on MRI, clinicians should perform targeted biopsies of the suspicious lesion, and may also opt for systematic template biopsy. Several studies have demonstrated a higher detection of clinically significant prostate cancer when both targeted and systematic biopsies are used. However, some research suggests that the systematic biopsy may increase detection of lower-grade (GG1) cancer. A study was conducted comparing targeted biopsy alone versus targeted plus systematic biopsies among patients with PI-RADS 3 to 5 findings on MRI. This study showed a reduction in detection of GG1 and GG2+ cancers in the target-only arm. The reduced detection of GG2+ cancers was not statistically significant but could be clinically significant. Shared decision-making is highly recommended given the uncertainty involved.

Answer 55

b) Clinicians should perform targeted biopsies and may also perform a systematic template biopsy. Explanation: The statement recommends that clinicians perform targeted biopsies of the suspicious lesion and may also perform a systematic template biopsy in biopsy-naïve patients with a suspicious lesion on MRI.

Answer 56

a) It can lead to over-detection of GG1 cancers. Explanation: One trade-off of adding systematic biopsies to the targeted biopsy approach is that more lower-grade (GG1) cancers are also likely to be diagnosed, which may lead to over-detection.

Answer 57

Targeted biopsies involve sampling specifically from areas identified as suspicious on MRI, while systematic template biopsies involve sampling tissue from multiple areas of the prostate, regardless of whether they appear suspicious on imaging. Using both methods in a biopsy-naïve patient with a suspicious lesion on MRI has been shown to improve the detection of clinically significant prostate cancer. However, the addition of systematic biopsies can lead to the over-detection of lower-grade (GG1) cancers. While one study suggested a slight reduction in detection of higher-grade (GG2+) cancers with targeted biopsies alone, this was not statistically significant and is subject to ongoing debate.

Answer 58

Clinicians should consider that while targeted biopsies alone or in combination with systematic biopsies can detect clinically significant prostate cancer, adding systematic biopsies can also lead to the over-detection of low-grade (GG1) cancers. Therefore, the decision should take into account patient preferences and clinical context, as well as the potential trade-offs involved. Shared decision-making is highly recommended given the uncertainties involved, and further research is needed to determine the best approach.

Answer 59

For patients with no suspicious findings on MRI but who are at elevated risk for GG2+ prostate cancer, this statement recommends a systematic biopsy. A systematic review of 42 studies found that the negative predictive value (NPV) of a "negative" MRI (defined as PI-RADS 1 to 2) to detect GG2+ prostate cancer among biopsy-naïve patients was 91%, meaning about 1 in 10 patients who have a negative MRI may have GG2+ cancer on biopsy. The NPV decreases to 87% if PI-RADS 3 is also considered negative. Risk calculation takes into account multiple factors, such as race, age, total PSA, PSA density, percent free PSA, and family history of prostate cancer. If systematic biopsy is omitted after shared decision making (SDM), patients should be informed of the risk of underdiagnosing clinically significant prostate cancer.

Answer 60

c) Proceed with a systematic biopsy. Explanation: The statement recommends a systematic biopsy for patients with no suspicious findings on MRI but who are at an elevated risk for GG2+ prostate cancer.

Answer 61

c) 91% Explanation: The NPV of a "negative" MRI (defined as PI-RADS 1 to 2) to detect GG2+ prostate cancer among biopsy-naïve patients is 91%. This means that about 1 in 10 patients who have a negative MRI may have GG2+ cancer on biopsy.

Answer 62

For patients with no suspicious findings on MRI but with an elevated risk for GG2+ prostate cancer, the recommended next step is a systematic biopsy. The negative predictive value of a "negative" MRI to detect GG2+ prostate cancer is 91% for PI-RADS 1 to 2 and decreases to 87% if PI-RADS 3 is also considered negative. This means that some patients with a "negative" MRI may still have GG2+ cancer on biopsy. If the decision is made to omit a systematic biopsy after shared decision making, it is important to inform patients of the risk of underdiagnosing clinically significant prostate cancer.

Answer 63

Clinicians can assess the risk of GG2+ prostate cancer in patients without suspicious findings on MRI by taking into account multiple factors. These factors include race, age, total PSA, PSA density, percent free PSA, and family history of prostate cancer. These can be used in available risk calculators to help assess the individual patient's risk. Even in the absence of suspicious findings on MRI, patients with elevated risk for GG2+ prostate cancer should proceed with a systematic biopsy to ensure that significant prostate cancer is not missed.

Answer 64

Clinicians can assess the risk of GG2+ prostate cancer in patients without suspicious findings on MRI by taking into account multiple factors. These factors include race, age, total PSA, PSA density, percent free PSA, and family history of prostate cancer. These can be used in available risk calculators to help assess the individual patient's risk. Even in the absence of suspicious findings on MRI, patients with elevated risk for GG2+ prostate cancer should proceed with a systematic biopsy to ensure that significant prostate cancer is not missed.

Answer 65

The statement suggests that clinicians may use adjunctive urine or serum markers for further risk stratification when deciding whether to proceed with biopsy. The aim is to enhance the specificity of the PSA test and prevent unnecessary biopsies, which carry risks such as overdiagnosis of GG1 prostate cancer. However, avoiding biopsies can also risk delayed diagnosis of clinically significant prostate cancer. Tests that only report the likelihood of any prostate cancer, instead of specifically GG2+ prostate cancer, may not effectively reduce overdiagnosis of low-grade prostate cancer. Biomarkers should not be used when the risk of GG2+ prostate cancer is extremely low or high, as their results would not influence further testing decisions. Widely available adjunctive tests include percent free PSA and PSA density, although it's debatable which newer biomarkers are the best. Secondary biomarkers can reduce the number of biopsies by 35% but would lead to non-detection of 9% of clinically significant prostate cancers. As always, shared decision making is highly recommended due to the uncertainty involved.

Answer 66

a) To enhance the specificity of the PSA test and prevent unnecessary biopsies. Explanation: The aim of using adjunctive urine or serum markers is to improve upon the poor specificity of PSA and to avoid the risks associated with unnecessary biopsies.

Answer 67

c) 35% Explanation: The use of secondary biomarkers could potentially reduce the number of biopsies by 35%.

Answer 68

Adjunctive urine or serum markers can help in further risk stratification when deciding whether to proceed with a prostate biopsy. These markers can improve the specificity of the PSA test and help avoid unnecessary biopsies, which carry risks such as overdiagnosis of low-grade GG1 prostate cancer. However, it's important to remember that avoiding biopsies can also risk delayed diagnosis of clinically significant prostate cancer. Using these markers can reduce the number of biopsies by about 35%, but may also result in non-detection of about 9% of clinically significant prostate cancers. Therefore, the use of shared decision making is highly recommended due to these uncertainties.

Answer 69

Adjunctive biomarkers are not recommended in situations where the risk of GG2+ prostate cancer is either extremely low or extremely high based on existing clinical and laboratory data. In these situations, the results of the adjunctive biomarkers would not influence the decision on whether to proceed with further testing, such as MRI or biopsy. For instance, in patients with a prostate nodule, a PSA level over 10 ng/mL, a strong family history of high-grade prostate cancer, or other significant risk factors, an adjunctive biomarker is unlikely to change the decision to proceed with a biopsy. On the other hand, for patients with a mildly elevated PSA, very low PSA density, no other risk factors, and a desire to avoid biopsy, ongoing screening is preferable to further testing.

Answer 70

The statement suggests that for patients with a PSA level higher than 50 ng/mL and no clinical evidence of inflammation, infection, or recent prostate-related medical procedures, the probability of high-grade prostate cancer could be as high as 98.5%. In cases where a biopsy might pose a significant risk (like anticoagulation, severe comorbidity, frailty) or delay urgent treatment (like spinal cord compromise from metastases), an immediate biopsy can be delayed or omitted. This extremely high risk of prostate cancer should be communicated with the patient, and shared decision making should be used to decide on whether to omit an immediate prostate biopsy. However, this does not rule out the possibility of proceeding with a biopsy or other prostate cancer evaluation if deemed clinically appropriate. It also doesn't remove the need for a biopsy at a later time. If an immediate biopsy is not performed, imaging to determine the extent of the disease or confirm metastasis could be beneficial.

Answer 71

d) 98.5% Explanation: For patients with a PSA level higher than 50 ng/mL and no clinical evidence of inflammation, infection, or recent prostate-related medical procedures, the likelihood of high-grade prostate cancer is estimated to be as high as 98.5%.

Answer 72

a) In cases where biopsy may pose a significant risk or delay urgent treatment. Explanation: The guideline suggests that in situations where a biopsy might be risky (like anticoagulation, severe comorbidity, frailty) or could delay urgent treatment (like spinal cord compromise from metastases), an immediate biopsy can be delayed or omitted.

Answer 73

If an immediate prostate biopsy is not performed, it is suggested to use imaging to determine the extent of the disease or confirm metastasis. This could be beneficial in understanding the severity and progression of the prostate cancer. Moreover, the omission or delay of an immediate biopsy does not rule out the possibility of proceeding with a biopsy or other prostate cancer evaluation later if deemed clinically appropriate.

Answer 74

The decision to omit an immediate prostate biopsy should be made using shared decision making. The patient should be thoroughly informed about the extremely high risk of prostate cancer in their case. After understanding the risks and benefits, the patient should play a part in making the decision on whether to omit an immediate prostate biopsy.

Answer 75

This series of statements recommends that clinicians should communicate with patients after a biopsy to review results, reassess the risk of undetected or future development of GG2+ disease, and jointly decide on the course of action, whether it be discontinuing screening, continuing screening, or performing further testing for early risk reassessment. Prostate cancer screening should not be discontinued based solely on a negative prostate biopsy, and a PSA threshold should not be the only determinant for a repeat biopsy after a negative result. If the decision is to continue screening after a negative biopsy, patients should be re-evaluated within the normal screening interval (two to four years) or sooner, depending on the risk of clinically significant prostate cancer and life expectancy. At the time of re-evaluation after a negative biopsy, a risk assessment tool that takes into account the protective effect of a prior negative biopsy should be used. Multiple factors should be considered in computing the risk of GG2+ disease, and the use of shared decision-making is highly recommended due to the inherent uncertainties involved.

Answer 76

b) Continue screening and re-evaluate the patient within the normal screening interval.

Answer 77

a) A risk assessment tool that considers the protective effect of a prior negative biopsy.

Answer 78

While a negative biopsy significantly lowers the probability of subsequently identifying GG2+ prostate cancer, this protective effect likely subsides over time. Patients with a prior negative biopsy remain at risk for undetected or subsequent development of GG2+ disease. Studies have shown that 5% to 25% of patients who undergo a subsequent biopsy in the short term are diagnosed with GG2+ disease. Furthermore, over a 20-year time horizon, the risk of prostate cancer mortality ranges from 1.4% to 5.2%. Thus, a negative biopsy alone should not be used to justify discontinuation of prostate cancer screening.

Answer 79

After a negative biopsy, clinicians should engage in shared decision making (SDM) with patients. This involves reviewing the biopsy results, reassessing the risk of undetected or future development of GG2+ disease, and deciding on the next course of action. This could include continuing screening, discontinuing screening, or performing further testing for early risk reassessment. This decision should consider multiple factors including age, Black ancestry, total PSA, percent free PSA, PSA density, abnormal DRE findings, presence of germline mutations, pathology findings on prior biopsy, results of available adjunctive testing, number of cores taken at initial biopsy, MRI findings, planned method of subsequent biopsy, and family history.

Answer 80

This statement emphasizes that clinicians should not automatically perform biomarker testing after a negative initial biopsy in patients with low probability for harboring GG2+ prostate cancer. While biomarkers may enhance the ability to identify patients at risk for high-grade disease, these tests generally provide the probability of disease or high-grade disease. In patients with a negative biopsy and low probability for GG2+ disease, it is unlikely that additional biomarker tests will provide any significant new information. For instance, a low PSAD (≤ 0.10 ng/mL2) at the time of initial prostate biopsy is associated with a low likelihood of harboring GG2+ disease, including in the setting of negative or equivocal mpMRI. Thus, reflex biomarker testing should not be done without prior consideration of the utility of the test or how the information gathered will affect the decision to undergo a repeat biopsy.

Answer 81

b) The utility of the test and how the information will impact the decision to undergo a repeat biopsy.

Answer 82

Biomarker tests are generally used to identify patients at risk for high-grade disease by providing the probability of disease or high-grade disease. However, in patients with a low probability for GG2+ disease who have had a negative biopsy, these tests are unlikely to provide any significant new information. For instance, a low PSAD (≤ 0.10 ng/mL2) at the time of initial prostate biopsy is associated with a low likelihood of harboring GG2+ disease, even in cases of negative or equivocal mpMRI. Thus, a biomarker test in this scenario is unlikely to provide additional clinically actionable information. Therefore, clinicians should not reflexively conduct biomarker tests without first considering their utility and how the information gathered will impact the decision to undergo a repeat biopsy.

Answer 83

After a negative biopsy, clinicians may use blood, urine, or tissue-based biomarkers for further risk stratification in patients if the results are likely to influence the decision about a repeat biopsy or otherwise significantly change the patient's management. These tests provide additional information for risk stratification in patients who previously had a negative biopsy and there's an ongoing suspicion for GG2+ prostate cancer. Several biomarkers have been developed and reported with varying performance characteristics. They generally present a percentage risk of biopsy-detectable disease, and the decision to proceed with a biopsy considering the performance metrics of the test is left to the clinician and patient. The use of these tests in conjunction with mpMRI in prostate cancer early detection paradigms hasn't been thoroughly studied yet. Understanding what information or data each test provides and considering whether additional information will impact management decisions before ordering a test is crucial.

Answer 84

b) If the results are likely to influence the decision regarding a repeat biopsy or otherwise substantively change the patient's management.

Answer 85

Before ordering biomarker tests after a negative biopsy, clinicians need to consider whether the results from these tests are likely to influence the decision regarding a repeat biopsy or otherwise significantly alter the patient's management. These tests should be used for further risk stratification in patients with an ongoing suspicion for GG2+ prostate cancer following a negative biopsy. Clinicians should understand what information or data each test provides and assess whether this additional information will impact management decisions. The use of shared decision-making is highly recommended given the uncertainty involved.

Answer 86

For patients with focal (one core) high-grade prostatic intraepithelial neoplasia (HGPIN) on biopsy, clinicians are not recommended to perform immediate repeat biopsy. While early studies, which used less than 12-core systematic sampling, reported a high risk of undetected prostate cancer, contemporary research indicates a 20% to 30% risk of any cancer detection (not just high-grade) in subsequent biopsies. This is the same risk as that following an initial benign biopsy. Additionally, even when repeat biopsy is conducted, the risk of GG2+ carcinoma is relatively low (around 10%). Thus, for patients with a diagnosis of focal HGPIN on initial biopsy, immediate repeat biopsy is not suggested. Nevertheless, routine follow-up, which may include mpMRI and/or additional biomarkers, is recommended. Patients with a diagnosis of HGPIN in the setting of other biopsy cores showing invasive prostate cancer should be managed according to the definitive carcinoma component.

Answer 87

d) No, routine follow up is warranted, which may include mpMRI and/or additional biomarkers.

Answer 88

Patients with a diagnosis of focal (one core) HGPIN on biopsy should not undergo an immediate repeat biopsy. This recommendation is based on contemporary studies indicating a 20% to 30% risk of any cancer detection (not just high-grade) in subsequent biopsies, which is similar to the risk following an initial benign biopsy. Instead, routine follow-up is warranted, which may include mpMRI and/or additional biomarkers. If HGPIN is found alongside other biopsy cores showing invasive prostate cancer, patients should be managed in accordance with the definitive carcinoma component.

Answer 89

For patients with multifocal high-grade prostatic intraepithelial neoplasia (HGPIN), clinicians may conduct additional risk evaluation, guided by prostate-specific antigen (PSA)/digital rectal examination (DRE) and multiparametric magnetic resonance imaging (mpMRI) findings. Few studies have focused on multifocal HGPIN (i.e., HGPIN in more than 2 cores), but older reports suggest a higher risk of cancer detection (around 30% to 45%) compared to isolated HGPIN. However, these studies didn't use repeat biopsy with mpMRI guidance or specify the detection of clinically significant prostate cancer. More recent data show that in approximately 25% of patients with previous multifocal HGPIN, serum PSA and/or DRE normalize after a non-cancer bearing prostate biopsy. The risk of detecting GG2+ in repeat biopsies of patients with multifocal HGPIN is around 30%, which is not higher than in those without this finding. Therefore, a recommendation to repeat a prostate biopsy after HGPIN should be based on PSA and DRE evolution, and mpMRI findings. A repeat prostate biopsy should not be recommended solely because of a previous diagnosis of HGPIN, even if multifocal. The use of shared decision making (SDM) is highly recommended due to the uncertainty involved.

Answer 90

c) PSA/DRE and mpMRI findings.

Answer 91

The decision to perform a repeat prostate biopsy in patients with a previous diagnosis of multifocal HGPIN should be based on the evolution of PSA and DRE results, as well as mpMRI findings. It's not recommended to repeat the biopsy solely based on a previous diagnosis of HGPIN, even if multifocal. In situations where persistent prostate cancer suspicion is present, the risk of detecting clinically significant prostate cancer in repeat biopsies is independent of the previous finding of HGPIN. Therefore, the use of shared decision making is highly recommended due to the uncertainty involved.

Answer 92

For patients with atypical small acinar proliferation (ASAP) or atypical intraductal proliferation (AIP), additional testing is advised. ASAP, which refers to a small focus or foci of atypical glands suspicious but not definitive for carcinoma, is associated with a 30% to 50% risk of prostate cancer detection on repeat biopsy, with about 10% to 20% of these being GG2+. Thus, following an ASAP diagnosis, clinicians should consider additional testing such as repeat systematic needle biopsy, possibly in conjunction with mpMRI and/or targeted biopsy, and PSA as well as urine or serum biomarkers. AIP refers to lesions that exhibit more architectural complexity and/or cytologic atypia than HGPIN but lack definitive criteria for intraductal carcinoma (IDC-P). A diagnosis of AIP, like IDC-P, is often seen alongside GG2+ cancer, but uncommonly, it may appear as the sole finding on biopsy or in association with GG1 cancer only. Given these associations, a diagnosis of AIP as either the sole finding or together with GG1 cancer only warrants additional testing, including early repeat systematic needle biopsy or mpMRI with or without targeted biopsy. Patients with ASAP or AIP alongside other biopsy cores showing invasive prostate cancer should be managed according to the definitive carcinoma component. Shared decision making (SDM) is highly recommended due to the uncertainty involved.

Answer 93

d) 30% to 50%.

Answer 94

After a diagnosis of ASAP or AIP, additional testing should be considered. For ASAP, this may include a repeat systematic needle biopsy with consideration of mpMRI and/or targeted biopsy, and PSA as well as urine or serum biomarkers. For AIP, additional testing may include an early repeat systematic needle biopsy or mpMRI with or without a targeted biopsy. If ASAP or AIP is found along with other biopsy cores showing invasive prostate cancer, patients should be managed according to the definitive carcinoma component. In all cases, shared decision making is highly recommended due to the inherent uncertainty involved.

Answer 95

For patients who are set to undergo repeat biopsy and have not previously had a prostate MRI, clinicians are strongly recommended to obtain a prostate MRI before the biopsy. The MRI serves to identify suspicious lesions that might have been missed in a prior biopsy, particularly when there is ongoing concern for GG2+ prostate cancer. Among patients with a prior negative systematic biopsy, MRI will identify a suspicious target in 36% to 90% of patients. A biopsy directed at the identified target will be positive in 37% to 66% of patients and positive for GG2+ cancer in 21% to 60% of patients. In those with a prior biopsy showing only GG1 disease, MRI will reveal a suspicious target in 33% to 51% of patients, and a biopsy directed at the target will test positive for GG2+ disease in 49% to 90% of patients. Due to these high rates of suspicious target identification and PPV for GG2+ disease in the repeat biopsy setting, an mpMRI is recommended if no prior imaging has been performed.

Answer 96

d) 49% to 90%.

Answer 97

A prostate MRI prior to a repeat biopsy is recommended in order to identify suspicious lesions that might have been missed during the first biopsy. This is particularly important when there is ongoing concern for GG2+ prostate cancer. MRI often identifies suspicious targets, and biopsies directed at these targets have a substantial positive predictive value for GG2+ disease, both in patients with a prior negative systematic biopsy and those with a prior biopsy showing only GG1 disease.

Answer 98

In patients who have indications for a repeat biopsy but do not present a suspicious lesion on an MRI, clinicians may opt to proceed with a systematic biopsy. This is a conditional recommendation based on the fact that repeat biopsy detects fewer and potentially less lethal cancers after an initial negative biopsy. Medicare data shows that 38% of patients with an initial negative prostate biopsy undergo a repeat biopsy within 5 years, with the percentage of positive biopsies falling from 34% to 25%. However, there are patients who may require repeat biopsy. Indicators of a likely clinically significant prostate cancer after a negative biopsy and MRI may include a PSA density > 0.15 ng/mL, a PHI density value > 0.44, or a PSA velocity of 0.27 ng/mL/year or more. Despite MRI being an important factor in deciding a repeat biopsy, it's notable that MRI misses 13% of all cancers according to a meta-analysis of 29 studies with 8,503 participants. Therefore, if a patient has sufficient risk of GG2+ cancer despite a negative prostate MRI, clinicians may still decide to proceed with systematic biopsy.

Answer 99

Clinicians might proceed with a systematic biopsy despite a negative prostate MRI if a patient has a high risk of GG2+ cancer. This is because MRI may miss a significant proportion of cancers. Factors that may indicate a high risk of clinically significant prostate cancer after a negative biopsy and a negative MRI include a PSA density > 0.15 ng/mL, a PHI density value > 0.44, or a PSA velocity of 0.27 ng/mL/year or more. Therefore, these factors can justify the decision to proceed with systematic biopsy despite a negative MRI.

Answer 100

PHI, or Prostate Health Index, is a mathematical formula that combines three different blood tests that measure different forms of Prostate Specific Antigen (PSA) - Total PSA, Free PSA, and [-2]proPSA. This index can help to better understand what elevated PSA levels might mean and the probability of finding prostate cancer on biopsy. When we refer to PHI density, it's an adaptation of the PHI to account for the size of the prostate, similar to PSA density. It's calculated by dividing the PHI value by the volume of the prostate gland (usually measured through transrectal ultrasound or MRI). A higher PHI density can be associated with a greater likelihood of having prostate cancer and, in particular, clinically significant disease. Thus, it can help in the decision-making process around the need for a prostate biopsy.

Answer 101

For patients who are scheduled for repeat biopsy and present a suspicious lesion on MRI, clinicians should carry out targeted biopsies of the suspicious lesion. They may also consider performing a systematic template biopsy. However, this decision should be based on an integrated evaluation of multiple factors. While a combined biopsy approach incorporating both systematic and targeted cores can optimize cancer yield, it also entails obtaining a larger number of cores. This can potentially increase patient discomfort and other biopsy-associated complications. Furthermore, the incremental yield of off-target biopsy samples may be influenced by the sampling error associated with software image registration during targeted biopsy. Therefore, decisions regarding systematic sampling in addition to target sampling should be based on MRI factors (such as quality and confidence in target presence) and clinical factors (such as PSA, technique of initial biopsy, and time since prior systematic biopsy).

Answer 102

d) An integrated evaluation of MRI factors such as quality and confidence in target presence, and clinical factors such as PSA, technique of initial biopsy, and time since prior systematic biopsy.

Answer 103

While a combined biopsy approach involving both systematic and targeted cores can optimize the yield of cancer detection, it also entails obtaining a larger number of cores. This can potentially increase patient discomfort and other biopsy-associated complications, such as infection, bleeding, and urinary problems. Furthermore, the apparent additional yield of off-target biopsy samples may be influenced by the sampling error associated with software image registration during targeted biopsy.

Answer 104

During fusion biopsy, clinicians may use software registration of mpMRI and ultrasound images when it's available. This approach, while providing better cancer detection rates in one Randomized Control Trial (RCT), has been shown to yield similar rates in multiple other studies when compared to cognitive registration. Software registration facilitates the fusion of multiple MRI and ultrasound images in different planes, creating a comprehensive view of the target lesion. This can be particularly beneficial for smaller MRI lesions. However, there are potential drawbacks to implementing software-based fusion biopsy programs, including technical issues, operator errors, and challenges with unusual anatomy. Therefore, in some cases, cognitive fusion techniques may be useful to augment software-based approaches to minimize the risk of misregistration. For clinicians using cognitive fusion technique exclusively, advanced training in MRI interpretation is recommended to optimize cancer detection.

Answer 105

b) It can provide a more comprehensive view of the target lesion.

Answer 106

The advantages of implementing a software-based fusion biopsy program include the ability to fuse multiple MRI and ultrasound images in different planes, creating a composite image that provides a more comprehensive view of the target lesion. This approach can be especially beneficial when dealing with small MRI lesions. However, there are several potential drawbacks as well. These include technical issues like software bugs and system crashes, operator error, and difficulties arising from unusual anatomy such as large prostates or previous transurethral resections of the prostate. Therefore, in certain cases, cognitive fusion techniques may be necessary to augment software-based approaches to minimize the risk of misregistration. Furthermore, for clinicians adopting cognitive fusion technique exclusively, advanced training in MRI interpretation is advised to optimize cancer detection.

Answer 107

Clinicians are recommended to obtain at least two needle biopsy cores per target in patients with suspicious prostate lesion(s) on MRI. The optimal number of biopsy cores may vary based on several factors including patient characteristics, target characteristics, and biopsy approach/technique. Generally, a higher number of biopsy cores per target improves the cancer detection rate, but could potentially lead to increased complication rates and time. However, the incremental value in cancer detection diminishes after obtaining more than three cores per target. Therefore, obtaining at least two needle cores per target provides the most reproducible and accurate cancer detection rate. For risk group stratification, all cores from the same MRI target should be considered as a single core.

Answer 108

The optimal number of biopsy cores per MRI target can vary based on several factors. These include patient characteristics like age, PSA levels, and whether the patient is biopsy naïve or has had a prior biopsy. Target characteristics such as size, location, and PIRADS classification can also influence the optimal number of cores, as well as the biopsy approach/technique, including whether software or cognitive fusion is used and whether the biopsy is transrectal or transperineal. Generally, obtaining a higher number of biopsy cores per target can improve the cancer detection rate, but it could potentially lead to increased complication rates and time. The incremental value in cancer detection decreases after obtaining more than three cores per target. Therefore, obtaining at least two needle cores per target provides the most reproducible and accurate cancer detection rate. In addition, for the purposes of risk group stratification, all cores from the same MRI target should be considered as a single core.

Answer 109

When performing a biopsy on patients with a suspicion for GG2+ prostate cancer, clinicians may use either a transrectal or transperineal biopsy route. Cancer detection rates are not significantly different between the two approaches. Some evidence suggests transperineal biopsy may detect anterior and apical cancers at a higher rate, but prospective, randomized data are lacking. There is also some suggestion that the transperineal approach may have a lower risk of infection. Transperineal biopsies may be particularly useful for patients who have had infectious complications with a prior biopsy, are at higher risk for biopsy-related infection, or have anterior lesions less accessible transrectally. Conversely, a transrectal approach may be appropriate under certain circumstances, such as patient preference or clinician training. Using transperineal biopsy to mitigate rising rates of sepsis and antibiotic resistance is a reasonable approach gaining traction. However, the use of adjunctive measures can also reduce sepsis risk for a transrectal biopsy approach.

Answer 110

d) All of the above

Answer 111

Both transrectal and transperineal biopsy routes have their advantages and disadvantages. Cancer detection rates are generally similar between the two approaches. Some data suggest that transperineal biopsy may detect anterior and apical cancers at a higher rate, though definitive, prospective data are lacking. The transperineal approach also appears to carry a lower risk of infection, making it potentially advantageous for patients who have had infectious complications with a prior biopsy, are at higher risk for biopsy-related infection, or have anterior lesions less accessible transrectally. However, the use of transperineal biopsy is not yet widely adopted due to clinician training/experience and the lack of appropriate equipment for this approach in some settings. On the other hand, the transrectal approach might be more suitable in certain situations, such as patient preference or comfort, inability to be placed into the lithotomy position, or clinician experience. Additionally, sepsis risks associated with the transrectal approach can be reduced through adjunctive measures like rectal swab cultures and augmented antibiotic approaches.

Answer 112

d) All of the above

Answer 113

There are several areas that need further investigation in the field of prostate cancer screening and diagnosis. Shared decision-making regarding screening, the frequency of screening, and when to proceed to secondary testing or biopsy is critically important and requires more emphasis, particularly in explaining potential harms of screening. Decision aids that cater to different languages and levels of health literacy are needed. Populations at higher risk of prostate cancer, such as those with a family history of prostate cancer, Black ancestry, genetic risk, or elevated baseline PSA may benefit from more intensive screening, warranting further investigation. The effectiveness of various biomarkers and how they can complement or supplement each other is another area that requires research. Differences in the use of transperineal versus transrectal biopsy and the impact of prophylactic antibiotics during the transperineal approach also need investigation. The role of MRI imaging, particularly in cases where targeted biopsy did not detect cancer or only detected GG1 disease, is an area of interest, including the potential use of artificial intelligence in evolving MRI protocols. Further, the preferences and potential psychological consequences of prostate cancer screening in non-binary patients or transgender women also need exploration.

Answer 114

The Panel recommends against PSA screening in men under age 40 years.

Answer 115

The prevalence of prostate cancer in men under age 40 years is extremely low, about 0.1%.

Answer 116

No, there are no data available to estimate the benefit of prostate cancer screening in men under age 40 years as none of the prospective randomized studies evaluating the benefits of PSA-based screening included men under age 40 years.

Answer 117

The harms of PSA screening in men under age 40 years include the side effects of diagnostic biopsies and perhaps subsequent treatment.

Answer 118

Screening is discouraged for men under age 40 years due to the relatively low prevalence of clinically detectable prostate cancer in this age group, the absence of any evidence demonstrating benefits of screening, and the known harms of screening.

Answer 119

No, the panel does not recommend routine screening for men between the ages of 40 to 54 years who are at average risk.

Answer 120

There is no high-quality evidence to support the benefits of PSA screening in men under the age of 55 years. The two large randomized clinical trials did not include men under the age of 55 years, so they do not inform the decision.

Answer 121

The panel's recommendation is based on the relatively low benefits and high harms of screening in this population. The harms of screening in this age group are at least equal to the benefits, if not higher.

Answer 122

Yes, there may be subgroups of men who are at higher risk, such as African American men and those with a family history of metastatic or lethal adenocarcinomas. For such men, decisions regarding prostate cancer screening should be individualized.

Answer 123

No, the panel's recommendation does not imply that there is absolutely no benefit to screening this age group. It just means that the significant harms associated with screening likely outweigh the benefits.

Answer 124

The Panel recommends shared decision-making for men ages 55 to 69 years that are considering PSA screening, and proceeding based on men’s values and preferences.

Answer 125

There is moderate evidence for the benefit of PSA screening in this age group, which includes a relative risk reduction of 21% in prostate cancer-specific death according to the ERSPC study at a median follow-up of 11 years.

Answer 126

The shared decision-making process should consider the man’s individual life expectancy, baseline mortality risk from other co-morbid conditions, individual risk for prostate cancer given their race/ethnicity and family history, and the degree to which screening might influence their overall life expectancy and chance of experiencing morbidity from prostate cancer or its treatment.

Answer 127

Novel markers, imaging, and/or risk calculators can be considered for prostate biopsy decisions in men with a suspicious PSA level to inform biopsy decisions.

Answer 128

The guideline statement for screening interval in men who have decided on screening through shared decision-making is that a routine screening interval of two years or more may be preferred over annual screening.

Answer 129

The evidence for the preference of a two-year screening interval is mostly based on modeling studies and some evidence from randomized trials. Modeling studies have projected that screening men every two years preserves the majority of lives saved compared to annual screening while reducing the number of tests, false positive tests, and overdiagnosis.

Answer 130

The ERSPC trial suggests that a two-year screening interval significantly reduced the incidence of advanced disease compared to annual screening.

Answer 131

The PLCO trial suggests that there is little benefit from screening more frequently than every two years as prostate cancer mortality rates were similar in the two groups through 13 years of follow-up.

Answer 132

Martin et al. found that while there was a higher proportion of men diagnosed with prostate cancer in the intervention group (screened group), there was no significant difference in prostate cancer mortality after a median follow-up of 10 years between the intervention group and the control group

Answer 133

The Panel does not recommend routine PSA screening in men over age 70 years or any man with less than a 10 to 15 year life expectancy.

Answer 134

The rationale for this recommendation is based on the absence of evidence of a screening benefit in this population with clear evidence of harms. Men over age 70 years have a higher competing mortality compared to younger men, and no compelling evidence of a treatment benefit, especially in men with a limited life expectancy below 10 to 15 years.

Answer 135

The likelihood of overdiagnosis increases as men age and is particularly high for older men with low-risk disease. Modeling studies of overdiagnosis in the US population have estimated that among men aged 70 to 79 years, half or more of cases detected by PSA screening with PSA less than 10 and Gleason score 6 or below are overdiagnosed. Among men over age 80 years, three-fourths or more of cases detected by PSA screening with PSA less than 10 and Gleason score 6 or below are overdiagnosed.

Early Detection of Prostate Cancer (2023) Flashcards

(167 cards)