Urology - Prostate cancer & abnormal PSA Flashcards Preview

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What are the risk factors for prostate cancer?

There are 3 important risk factors for prostate cancer:
1) Age
2) Ethnicity
3) Heredity - 1 in 10 cases is truly hereditary; if one first degree relative is diagnosed then the risk is doubled


How does prostate cancer present?

Prostate cancer is usually asymptomatic at presentation and is diagnosed by PSA screening.

Urinary symptoms (frequency, nocturia, hesitancy, poor flow) secondary to bladder outflow obstruction are usually due to benign prostate hyperplasia, unless there is extensive cancer within the prostate.

<1/5 of men present with symptoms of metastatic disease - e.g. bone pain, weight loss, malaise, spinal cord compression


What are the indications for prostate biopsy?

An abnormality on digital rectal exam (DRE) or an elevated age specific PSA are indications for postate biopsy.

DRE should be performed in all men who are concerned about prostate cancer, as most cancers are found in the peripheral zone of the prostate adjacent to the rectum.


How are prostate biopsies obtained?

Transrectal ultrasound (TRUS) guided biopsies are undertaken using local anaesthesia and antibiotic prophylaxis.

A TRUS probe is placed per rectum and 8-12 biopsies are taken from areas most likely to contain cancer. Areas that feel abnormal on TRUS are also taken for biopsy. Most prostate cancers are no visible on ultrasound, so TRUS biopsies can miss 10-20% of prostate cancers.

Men with suspicion of prostate cancer in whom TRUS biopsies are negative may be offered more extensive and systematic sampling using a template biopsy technique. This can pick up cancer in 40% of men who have had negative TRUS biopsies.


Which men should get PSA testing?

Current WHO guidelines for prostate cancer state that population based screening is not recommended. One argument against asymptomatic screening is that the number needed to treat to prevent one death from prostate cancer remains quite high.

Opportunistic screening with PSA is recommended once a man has been counselled about the advantages and disadvantages of the test.


What are the advantages of PSA testing?

- may lead to detection of cancer BEFORE symptoms develop
- may lead to detection of cancer at an early stage when it is more amenable to treatment
- repeat PSA tests are valuable in monitoring treatment response


What are the limitations of PSA testing?

- it is NOT a diagnosis (a biopsy is required)
- it is not tumour specific for prostate cancer
- PSA test may not be elevated in some cancers therefore providing false reassurance
- single PSA test will not distinguish aggressive tumours that are at an early stage


How is prostate cancer graded? What is the Gleason score?

Treatment options for prostate cancer depend on the PSA, grade (aggressiveness), and stage (extent) of the disease as well as the patients co-morbidities.

Prostate cancer is usually a multifocal disease. Individual foci of cancer seen in prostate biopsies or TURP chippings are given a grade, based on the glandular architecture from 1 to 5. The grades from the 2 largest foci are added to give an overall Gleason score - 2 being the least aggressive, 10 being the most. The Gleason score strongly predicts likelihood of death from prostate cancer.


How is prostate cancer staged?

Local stage is assessed by DRE and augmented by MRI scanning. In patients at risk of metastasis the pelvic lymph nodes are assessed using CT/MRI and the bones for scintigraphy.

The TNM classification system is the internationally recognised staging system.

Risk stratification scores amalgamate the PSA, Gleason and clinical stage into low, intermediate and high risk.


What is meant by the term localised disease? How does this affect treatment options?

Localised disease comprises:
1) men with impalpable prostate cancer and disease that is not visible with imaging (T1)
2) those with disease considered confined to the prostate on rectal examination and imaging (T2)
3) those confined to the prostate after pathological examination of a radical prostatectomy specimen (pT2)

Men with localized disease are potentially curable with radical therapy including radical prostatectomy, external beam radiotherapy, and brachytherapy. All have been approved for clinical use by NICE and are considered to have equal efficacy.

Prostate cancer is slow growing and so radical therapies normally only benefit men with a life expectancy exceeding 10 years. Up to half of these men will have diseases that will not affect their quality of life, so active surveillance may be more appropriate.


What men should receive active surveillance?

Patients with low risk of prostate cancer may benefit from active surveillance. This involves close monitoring and PSA checks. This aims to reduce treatment related morbidity associated with radical therapies, whilst still allowing the patient to receive treatment while the disease is still curable. Typically, 1/3 of patients progress to radical treatment.


What is a radical prostatectomy (RA)?

RA involves the surgical removal of the whole prostate and may be undertaken through an open, laparoscopic or robotic approach. The outcome for each approach is broadly similar, though recovery time is faster using a minimally invasive approach.


What should happen to the PSA post RA?

The PSA should fall to unrecordable levels after RA, but patients still require PSA monitoring for at least 5 years to ensure no evidence of recurrence (this applies to all radical therapies).

In men found to have high risk disease once the prostate has undergone pathological examination, or if the PSA starts to rise again after surgery, second line treatment with adjuvent or salvage radiotherapy may be required.


What are the complications of RA?

Erectile dysfunction and incontinence are the biggest complications. Bowel symptoms and retention are less common or severe.


What is EBRT? What do patients normally receive alongside this?

EBRT stands for external beam radiotherapy and is another example of radical treatment for PC. EBRT offers men with clinically localised prostate cancer an alternative to surgery with similar cancer outcome, but differing side effects.

Radiotherapy treatment often includes a period of 3 months of androgen deprivation therapy (ADT) using a leutinising hormone releasing hormone (LHRH) agonist prior to radiotherapy. This sensitizes the tumour to radiotherapy and allows the prostate to shrink, enabling smaller volumes to be treated and so reducing the amount of normal tissue that gets irradiated.


What are the complications of EBRT?

Bowel symptoms and frequency and urgency are the two biggest complications of EBRT. Others include:
- erectile dysfunction
- retention (minor)
- incontinence (minor)


What is brachytherapy?

Brachytherapy involves the insertion of a radioactive source directly into the prostate, allowing a high dose of radiation to be delivered over a short distance around the source, sparing normal tissue.

2 types are used - i) iodine 125 seeds as a permanent low dose rate implant in the treatment of localized prostate cancer and ii) Iridium 192 as a temporary, high dose implant used in conjunction with external beam radiotherapy for higher risk and locally advanced disease


What is the pathology of prostate cancer?

Prostatic tumours are often multicentric and located in the periphery of the epithelium. They are adenocarcinomas arising from glandular epithelium.

Gleason scoring is used to grade differentiation. The most common, and second most common pattern are graded 1-5; the sum of these gives the Gleason score.

Staging of prostate cancer is done by PSA, Gleason and TNM.


Where does prostate cancer spread?

The cancer can spread directly into the remainder of the gland and seminal vesicles. It can also spread via lymphatics to iliac and para-aortic nodes. Haematogneous spread to bone (usually producing osteosclerotic lesions), liver and lung also occurs.


How is localised prostate cancer managed?

Localised prostate cancer implies stages I-III and management is dependent on whether the patient is low, medium or high risk.

Low risk patients (PSA <10 + Gleason <6 + T1-T2a) - active surveillance or radical treatment (= radical prostatectomy, radiotherapy (this can either be EBRT or brachytherapy))

Intermediate risk patients (PSA 10-20 + Gleason 7 + T2b-T2c) - radical treatment

High risk patients (PSA >20 + Gleason 8-10 + T3-T4) - radical treatment (EBRT + androgen deprivation therapy OR RP + adjuvant RT)


How is metastatic prostate cancer managed?

Management of metastatic prostate cancer consists of palliative radiotherapy or palliative hormonal therapy.

Primary hormonal treatment can be androgen deprivation therapy; orchidectomy +/- GnRH agonist (e.g. goserelin) - may be a tumour "flare" for the first 2 weeks of Rx with GnRH, which is controlled by simultaneous administration of antiandrogens (e.g. cyporterone acetate); oestrogens not used very often because of cardiovascular side effects.

Secondary hormonal treatment involves androgens; cytochrome P450 inhibitors and corticosteroids.

If the tumour is found to be hormone resistant then miotoxanone or docetaxel + steroid and immunotherapy can be tried.

Painful boney mets are treated with local EBRT or bone targeted radio-isotopes (e.g. strontium)