Prostate cancer Flashcards
(295 cards)
1
Q
What share of male cancer consists of prostate cancer?
A
20%
2
Q
What is the estimated mortality of prostate cancer out of all male cancers?
A
10%
3
Q
In autopsy studies, what race had the highest prevalence of prostate cancer?
A
US Black followed by US white and european followed by Asian
4
Q
What kind of molecule is Prostate Specific Antigen (PSA)?
A
Serine Protease
5
Q
When was PSA first used clinically?
and for what?
A
1986
post-treatment follow-up
6
Q
What is the risk of prostate cancer at PSA 4?
What is the risk of Gleason >7 at PSA 4?
A
26,9%
6,7%
7
Q
What was the conclusion of the PLCO Trial?
A
There is no evidence of mortality benefit for organized annual screening compared with opportunistic screening
8
Q
What was did the Göteborg Randomized Population-Based Screening Trial find?
A
42% lower PCa mortality in the organized screening vs the opportunistic testing arm
9
Q
To avoid 1 PCa death:
How many men have to be screened?
How many PCa’s have to be diagnosed?
A
139 screened
13 PCa found
10
Q
When does the USPTF (US Preventive Services Task Force) recommend individual (a man can choose for himself after information) screening of prostate cancer?
A
Men aged 55-69
11
Q
When does the EAU recommend PSA-testing?
A
After counselling the patient on potential risks and benefits
AND
good performance status and a life expectancy of >10-15 years
12
Q
How should an inital PSA-test be followed?
A
Offer an risk-adapted strategy (based on initial PSA level), with follow-up intervals of 2 years for those initially at risk:
- PSA >1 at 40 years of age
- PSA >2 at 60 years of age
Postpone follow-up to 8 years in those not at risk
13
Q
How does the EAU recommend that you avoid unnecessary biopisies for men with PSA 2-10 and normal digital rectal examination (DRE)?
A
use one of the following tools:
risk-calculator
imaging
additional serum or urine-based test
14
Q
Which risk calculator is superior when predicting clinicallly significant prostate cancer?
A
ERSPC-RC
15
Q
What is the risk of prostate cancer if PSA is < 2 but there is a suspect DRE (digital rectal examination)?
A
5-30%
16
Q
How reliable is TRUS (transrectal ultrasound) for detecting prostate cancer?
A
TRUS in not reliable in detecting prostate cancer.
Thus, there is no evidence that US-targeted biopises can replace systematic biopsies.
17
Q
How many biopsies should you take in a 30 cc prostate?
A
At least 8 systematic
18
Q
How many biopsies should you take in a prostate >30cc?
A
10-12
19
Q
What type of painrelief should be used when performing prostate biopsies?
A
a periprostatic block
20
Q
What are the top 4 complications of prostate biopsies?
A
Haematospermia 37,4%
Haematuria >1 day 14,5%
Rectal bleeding >2 days 2,2 %
Prostatitis 1%
21
Q
How common is fewer > 38,5 after prostate biopsies?
A
0,8%
22
Q
ISUP 1
A
Gleason 2-6
Low risk
23
Q
ISUP 2
A
Gleason (3+4) =7
Intermediate risk favourable
24
Q
ISUP 3
A
Gleason (4+3) =7
Intermediate risk unfavourable
25
ISUP 4
Gleason 8
| High risk
26
ISUP 5
Gleason 9
| High risk
27
What did the PROMIS trial find?
Sensivity of mpMRI for clinically significant PCa is almost double compared to TRUS-biopsy
27% of primary biopsy procedures could be avoided if mpMRI was used as a triage test
28
What did the PRECISION trial show?
That when using MRI-targeted biopsies you can find a greater share of clinically significant PCa
29
If an MRI is performed that show PI-RADS 3 or more, how should you aim the prostate biopsies?
Combine targeted and systematic biopsies
30
Risk stratification of PCa:
| what are the criterias for low risk?
PSA <10
Gleason <7 / ISUP1
cT1a-2a
31
Risk stratification of PCa:
| what are the criterias for intermediate risk?
PSA 10-20
Gleason 7 / ISUP2-3
cT2b
32
Risk stratification of PCa:
| what are the criterias for high risk?
PSA >20
Gleason >7 / ISUP4-5
cT2c
33
When should you perform a Bone Scan for patients with PCa?
Symptomatic patients regardless of PSA
Intermediate unfavourable risk cancer (Gleason 4+3)
High risk cancer (PSA >20)
Locally advanced cancer (T3 or worse)
34
When should you perform a mpMRI for patients with PCa?
Intermediate unfavourable risk cancer
High risk cancer
Locally advanced cancer
35
Risk stratification of PCa:
| what are the criterias for locally advanced PCa?
Any PSA
Any Gleason
cT3-4 or N+
36
When should you perform an abdominal CT for patients with PCa?
Intermediate unfavourable risk cancer and worse for N-staging
37
What is the sensisivity of an abdominal CT for detecting nodal invasion of PCa?
<40%
| MRI performance is similar
38
What is the sensivity and specificity for prostate cancer when using PSMA PET/CT?
sensitivity 50%
| specificity >90%
39
What is the gold standard for N-staging in prostate cancer?
surgery -lymph node dissection
40
When is surgery the best option for a patient with prostate cancer?
<65 years
| intermediate risk disease
41
How likely is it that a patient in monitoring will recieve active treatment within 10 years?
54,8%
42
Number needed to treat with radiotherapy to avoid:
clinical progression?
metastatic disease?
9
| 33
43
Number needed to treat with surgery to avoid:
clinical progression?
metastatic disease?
9
| 27
44
What is vital to inform patients of before chosing course of action after a prostate cancer diagnosis?
"No active treatment has shown superiority over any other active management options in terms of survival"
"all active treatments have side-effects"
45
Which side effect(s) is worse with surgery compared to radiation or active-monitoring?
Incontinence
| Impotence
46
How many men used incontinence protection after surgery for prostate cancer 6 years postop?
17%
47
How many men had erections firm enough for intercourse at the time of diagnosis of Prostate Cancer?
67%
48
How many men had erections firm enough for intercourse after prostatectomy vs radiotherapy for prostate cancer?
12% vs 22%
49
Number needed to harm with surgery vs radotherapy rather than active monitoring when it comes to urinary incontinence at 2 years:
Surgery 5
| Radiotherapy 143
50
When it comes to quality of life how does surgery, radiotherapy and active monitoring compare?
No significant differences
51
Should PLND (Pelvic lymph node dissection) be performed on patients with localized PCa?
No (strong recommendation)
52
Should PLND (Pelvic lymph node dissection) be performed on patients with intermediate risk PCa?
No (strong recommendation)
53
Should PLND (Pelvic lymph node dissection) be performed on patients with high risk PCa?
Yes (strong recommendation)
54
What is the difference between open, laprascopic or robot assisted radical prostatectomy in terms of functional and oncological results?
NONE
55
What is the difference between active surveillance and watchful waiting?
Active surveillance focuses on delaying therapy until the tumour becomes progressive and curative treatment can be offered
Watchful waiting focuses on minimising treatment-related toxicity and i palliative
56
What follow up should Active surveillance include?
Digital rectal examination
PSA
Repeated biopsies
57
What should the neoadjuvant ADT-duration be after radiotherapy?
(ADT = androgen deprivation therapy)
intermediate risk 6 months
| high risk 3 years
58
When is brachytherapy as monotherapy recommended?
```
Stage cT1b-T2a
Gleason 6 <50% of biopsy cores with cancer / Gleason 7 <33% of biopsy cores with cancer
PSA <10
<50cc prostate
IPSS< 12
Urinary flow >15mL/min
```
59
What anatomical sites should be included in extended pelvic lymph node dissection (ePLND)?
external iliac axis
obturator fossa
around the internal iliac artery
60
What is standard recommended radiotherapy dose in most European Centers for prostate cancer?
≥ 76-78 Gy in 37 fractions
61
What is the benefit of ADT (androgen deprivation therapy) in addition to radiotherapy?
20% added 10-year survival
20% added disease specific survival
No difference in cardiovascular mortality
62
When should you wait with ADT for patients with high risk prostate cancer that is unable to recieve local treatment?
PSA doubling time >12 months and
| PSA < 50
63
What are the possible different courses of action after surgery of a high risk N+ prostate cancer?
Offer adjuvant ADT
Offer adjuvant ADT + additional radiotherapy
Offer observation for patients efter eLND and < 2 nodes with microscopic involvement and PSA <0,1
64
What treatment should be offered for a geriatric patient who presents with metastasised prostatecancer and symptoms?
Castration:
1. bilateral orchiectomy
2. GnRH agonist with flare protection Bicalutamide
3. GnRH antagonist
For fit patients castration can be combined with docetaxel or abiraterone acetate
plus prednisolone or prostate radiotherapy
65
How quickly do you reach castration levels with antiandrogen (degarelix)?
By day 3
66
When should you treat prostate cancer patients with intermittent ADT?
Highly motivated asymptomatic patients who have a major PSA response after the induction period
67
What are the side effects of hormone therapy?
| 9
Loss of libido and sexual interest , erectile dysfunction, impotence
Fatigue
Hot flushes
Decline in intellectual capacity, emotional liability, depression
Decrease in muscular strength
Increase in (abdominal)fat apposition, diabetes, risk of CV events
Osteoporosis
Anaemia
68
How low is castrations lewel testosteron?
<50 ng/dl
69
When should bone health agents (bisphosponates/denosumab) be used?
For men with risk of osteoporotic fractures
70
What are valid (cytostatic) options for treatment of HSMPC (hormone sensitive metastatic prostate cancer)?
Early
Docetaxel
Enzalutamid
Abiraterone
71
What is the current wiev of prostatectomy and radiation for low volume disease?
Radiation is proven beneficial
| Surgery is not yet proven
72
What are two ways a prostate cancer cell can become castration resistant?
1. mutation of the androgen receptor so they get a higher affinity and can be activated by non-steroidal ligands
2. by-pass pathways independent of the androgen receptor
73
Definition of castration-resistant PCa:
```
Testosteron <50 ng/dL or 1,7 nmol/L
and
biochemical progression
or
radiological progression
```
74
What kind of drug is Docetaxel?
Mitosis inhibitor
75
What is the second line treatment after Docetaxel?
Cabacitaxel
76
Where does Docetaxel have its effect?
In the cell membrane
77
What kind of drug is Enzelutamid?
It binds androgen within the cell and prohibits it to enter the cell nucleus
78
According to EAU what is the "correct" order to use antiprostate cancer drugs?
ADT (androgen deprivation therapy)
(Zoledronic acid or Denosumab to prevent SRE)
Abirateron or Enzelutamid
Docetaxel
Cabacitaxel
Radium-223
79
When is it wrong to use bone protective agents in prostate cancer?
In hormone sensitive bone metastatic PCa
80
What is importen to remember when prescribing Zoledronic acid or Denosumab?
Also offer calcium and vitamin-D
81
How should you act with a patient who has a spinal cord compression from metastasised PCa?
start immediate high-dose corticosteroids and assess for spinal surgery followed by irradiation
Offer radiation therapy alone if surgery is not appropriate
82
MOA:
Leuprolide
Goserelin
GnRH agonist
| Increase LH release
83
MOA:
Degarelix
Abarelix
GnRH Antagonist
84
MOA:
Abiraterone
Ketoconazole
Androgen Synthesis Inhibitors (Adrenal)
Ketoconazole: CYP 17, 11B hydroxylase
Abiraterone: CYP 17
85
MOA:
Bicalutamide
Flutamide
Nilutamide
1st Gen Anti-Androgen
| decreases binding at AR
86
MOA:
Enzalutamide
Apalutamide
Darolutamide
2nd Gen Anti-Androgen
| decreases binding at AR, decreases nuclear translocation and transcription
87
MOA:
Docetaxel
Cabazitaxel
Chemotherapy
| microtubule disruption
88
MOA:
| Mitoxantrone
Chemotherapy
| Topoisomerase II inhibition
89
MOA:
Olaparib
Rucaparib
PARP inhibitor
| BRCA 1/2 mutations, other HRR mutations
90
MOA:
| Sipuleucel-T
Immunotherapy
| Target cells displaying PAP-GMCSF
91
MOA:
| Pembrolizumab
Immunotherapy
| Anti-PD1
92
PLCO Trial
- RCT - Screening trial
- Prostate, lung, colorectal, ovarian screening = PLCO
- No difference in prostate cancer specific mortality with yearly PSA screening vs. no screening
- Criticism = contamination (there was a LOT of screening and even previous biopsy in the control arm as well)
93
MOA:
Denosumab
Zoledronic acid
Bone Protecting Agents
| Decrease osteoclast activity
94
MOA:
| Radium-223
Alpha particle creating double strand breaks in DNA
95
Treatment options:
| Low Risk Prostate Cancer
```
AS
Cryo
(HIFU)
RP (no LND)
XRT (prostate +/- SV)
Brachy monotherapy
```
96
Treatment options:
| Favorable Intermediate Risk Prostate Cancer
```
AS
Cryo
(HIFU)
RP (no LND)
XRT (prostate +/- SV +/- LN) +/- 4-6 months ADT
Brachy +/- XRT
```
97
Treatment options:
| Unfavorable Intermediate Risk Prostate Cancer
(AS)
RP + LND
XRT (prostate + SV + LN) + 4-6m ADT
Brachy + XRT +/- 4-6m ADT
98
Treatment options:
| High Risk Prostate Cancer
RP + LND
XRT (prostate + SV + LN) + 2-3y ADT
Brachy + XRT + 1-3y ADT
99
Treatment Options:
| N1M0 Prostate Cancer
```
WW
ADT immediately (alone; intermittent or continuous)
RP + LND + XRT + long term ADT
XRT (prostate + SV+ LN) + long term ADT
```
100
Definition:
| Low Volume Metastatic Burden in Prostate Cancer
No visceral mets
Any # nodal mets
Bone mets confined to vertebral bodies/pelvis
101
Definition:
| High Volume Metastatic Burden in Prostate Cancer
At least 1 visceral (non-nodal) met
| >= 4 bone mets with at least one bone met outside of vertebral column/pelvis
102
ERSPC Trial
ERSPC = European Randomized Study for the Screening of Prostate Cancer
- RCT, 162k men age 55-69, PSA checked every 4 years
- Primary outcome = prostate cancer specific mortality (1 death fewer per every 1,000 men screened)
103
Urine Biomarkers
PCA3
Select MDx
MiPS
104
Tissue Biomarkers
OncotypeDx
ConfirmMDx
Prolaris
Decipher
105
Serum Biomarkers
PHI
| 4K score
106
CAP/ProtecT trial
- 415k men randomized to one single PSA vs no PSA at 50-69 years
- 10 years follow up
1. More cancer in intervention arm
2. No difference in cancer mortality
3. No difference in survival
- -> Single PSA test not recommended for population screening
107
Important AEs
| Abiraterone
Glucocorticoid deficiency, increased mineralocorticoid production
Give with steroids
108
Important AEs:
| Enzalutamide
Seizures, falls, HTN, hallucination, CV, mental
109
AUA Guideline Statement for screening in men >70 in excellent health
- Higher threshold for biopsy (>10 ng/mL)
| - Stop screening if PSA <3ng/mL
110
Important AEs:
| Apalutamide
rash, hypothryoidism, falls/fractures, seizures, CV
111
Important AEs:
| Ketoconazole
Decreased androgen, glucocorticoid and mineralocorticoid synthesis
Hepatotoxicity, N/V
112
Important AEs:
| Docetaxel, Cabazitaxel
BM suppression, neutropenia
113
How do tumor look on multiparametric MRI?
T1/T2?
DWI?
DCE?
- T1 + T2: Water content – tumors are water poor/dark on T2
- Diffusion‐weighted images (DWI): Water diffusion – tumors are dense/dark
- Dynamic contrast enhanced images (DCE): Contrast flow – vascularity, tumors are bright
114
Important AEs:
| Zoledronic Acid, Denosumab
Osteonecrosis of the jaw
115
PROMIS Trial
- 576 Men
• MRI, TRUS‐bx and Saturation transperineal bx
• Avoid 27% of the biopsies if negative MRI
• MRI guidance ‐ found 18% more cases of significant cancers
116
Important AEs:
| Olaparib
Anemia, fatigue, anorexia, diarrhea, cough, dyspnea, thrombocytopenia, AKI
117
Definition:
| Castration
Bilateral Orchiectomy
LHRH Agonist
GnRH Antagonist
Goal Testosterone <50 ng/dL
118
Definition:
| Biochemical Recurrence after RP
Undetectable PSA after surgery --> 2+ increases above threshold 0.2 ng/dL
119
PRECISION trial
- 500 men randomized to MRI vs. standard biopsy
Clinically Significant Cancer (GS ≥ 3+4): More found in MRI targeted group
Clinically Indolent Cancer: More found in standard biopsy group
28% in MRI group could avoid a biopsy
120
Definition:
| Biochemical Recurrence after RT
PSA increase by >= 2ng/mL above nadir
121
Treatment Options:
| M1 CSPC
```
ADT +
Abiraterone/prednisone
Docetaxel (high volume)
Apalutamide
Enzalutamide
EBRT (low volume)
```
122
Treatment Options:
| M1 CRPC
```
ADT+
Abiraterone/prednisone
Docetaxel
Enzalutamide
Radium 223
Mitoxantrone
Sipuleucel T
Pembrolizumab
```
123
Treatment Options:
| M0 CRPC
Ensure castrate levels of testosterone
If PSADT >10m (long): may be able to monitor
If PSADT <10m (short): Enzalutamide, apalutamide, darolutamide
124
AUA vs. NCCN Risk Stratification Table
125
Prostate Cancer Staging
126
SPCG-4 Trial
- Swedish trial, mostly healthy younger patients with intermediate or higher risk disease, followed for 23 years
- Surgery (RP) vs. watchful waiting
- Improved overall and disease specific survival in RP group compared to observation
127
PIVOT Trial
- Mixed risk disease, older sicker VA patients
- Underpowered*
- Surgery (RP) vs. watchful waiting
- No survival advantage in surgery group
- BUT surgery reduced the risk of metastases (p=0.0001) among men with Gleason score ≥ 7 tumors
128
CHAARTED Trial
M1 CSPC
ADT + Docetaxel
- 790 men with mHSPC randomized to ADT +/‐ docetaxel
- Improved OS (57.6 mo vs 44 mo)
- Improved PFS and rate of PSA <0.2
- Significant improvement in high‐volume disease
- At long term follow up, even greater OS benefit, especially in high volume disease
129
STAMPEDE Trial
M1 CSPC
ADT + Docetaxel
- Long term follow up
- Improved OS (43.1 mo vs 59.1 mo)
- No difference in low vs high volume disease
ADT + Abiraterone
-37% relative improvement in survival (HR 0.63) at 40 month follow up
ADT + Prostate EBRT
- 2061 men randomized to ADT v ADT plus EBRT to primary tumor
- Median OS 48m (EBRT) vs 46m (control)
- In all pts: HR 0.92, p 0.266
- In low met burden: HR 0.68, p 0.007
130
PROTECT Trial
- Mostly low risk disease
- Surgery (RP) vs. Radiation (RT) vs. Active Surveillance (AS)
- No differences in overall or disease specific survival between groups
‐ RP and RT were better than AS for Clinical progression (p<0.001) and Metastatic disease (p=0.004)
131
LATITUDE Trial
M1 CSPC
- 1199 patients receive ADT +/‐ abiraterone acetate + prednisone
- 50% symptomatic at baseline
- Needed 2of 3 high risk features (Gleason >=8, >=3 bone lesions, visceral mets)
- Improved OS and radiographic PFS
132
ENZAMET Trial
M1 CSPC
ADT + Enzalutamide
- Compared ADT + enzalutamide with standard of care (ADT+ bicalutamide, nilutamide, flutamide, docetaxel)
- Improved OS (HR 0.67)
- More AEs in enzalutamide group
133
TITAN Trial
M1 CSPC
ADT + Apalutamide
-HR 0.67
134
Adjuvant vs. salvage XRT after RP
```
Adjuvant
• pT3 pathology
• Positive margin
• No BCR
• Consider genomic testing
```
Salvage
• PSA recurrence
• Low pretreatment PSA and long PSADT better
• Give with ADT
135
Trials: Salvage RT + ADT
```
GETUG 16
• 743 Patients with PSA failure after RP
– PSA between 0.2 and 2 ng/mL
• RT vs RT plus 6 months ADT
• Improved progression free survival
```
RTOG 9601
• 760 Men with PSA failure after RP
• RT vs RT plus bicalutamide
• Improved overall survival
136
Biochemical Recurrence after Prostatectomy
- Undetectable PSA after surgery with a subsequent increases on
2 or more determinations above threshold of 0.2 ng/mL
137
Biochemical Recurrence after RT Treatment
– RTOG‐ASTRO Phoenix Consensus: PSA increase by > 2 ng/mL
above the nadir
– Consider earlier evaluation in candidates for salvage local
therapy (young, healthy)
138
Definition: CRPC
Testosterone <50 ng/dL AND
New radiographic or clinical mets on ADT OR
PSA greater than 2ng/mL and rising
139
SPARTAN Trial
M0 CRPC
PSADT <= 10m
ADT + Apalutamide (vs. ADT + placebo)
-Improved MFS (40.5 mo vs 16.2 mo)
140
PROSPER Trial
M0 CRPC
PSADT <= 10 mo
ADT + Enzalutamide (vs ADT + placebo)
-Improved MFS (36.6 mo vs 14.7 mo)
141
M1 CRPC ADT + Abiraterone Trials
• COU‐AA‐301 – ADT + Abiraterone
– Prior docetaxel
• COU‐AA‐302 – ADT + Abiraterone
– No prior docetaxel/chemotherapy naive
Addition of abiraterone: time to PSA progression and progression free survival both better in Abiraterone groups
142
M1 CRPC ADT + Enzalutamide Trials
AFFIRM – ADT + Enzalutamide
– Prior docetaxel
• PREVAIL – ADT + Enzalutamide
– No prior docetaxel/chemotherapy naive
Addition of enzalutamide better for overall survival
143
Chemotherapy Drugs for M1 CRPC
- Docetaxel (TAX 327, SWOG 9916): OS improved
- Cabazitaxel (TROPIC, FIRSTANA) - FDA approved after Docetaxel, OS improved
• Mitoxantrone (CALGB 9182)
– Currently limited role in mCRPC
144
ARAMIS Trial
M0 CRPC
PSADT <= 10 mo
ADT + Darolutamide (vs ADT + placebo)
-Improved MFS (40.4 mo vs 18.4 mo)
145
IMPACT Trial
M1 CRPC Immunotherapy with Sipuleucel-T
- Improved OS
- No difference in PFS
- No PSA decline
146
PROFOUND Trial
PARP Inhibitor: Olaparib
mCRPC
– Patient who progressed on enzalutamide or abiraterone
– >/= 1 homologous recomb. repair gene mutated
Improved PFS and OS
SE: anemia, fatigue, anorexia, diarrhea, cough, dyspnea, thrombocytopenia, AKI
147
TRITON2 Trial
PARP Inhibitor: Rucaparib
Phase 2 trial, mCRPC
>/=1 somatic or germline mutation
– Progressed on prior AR‐therapy and taxane
Most notable response rates (ORR/PSA) for BRCA1/BRCA2 mutations
• Accelerated FDA approval
148
What the RECOMMENDATION for PSA screening \< 40 yo?
GUIDELINE STATEMENT 1
Do NOT
Low prevalence of CaP, no evidence of screening benefit
149
For ages 40-54 what RECOMMENDATIONS for PSA for CaP screening?
GUIDELINE STATEMENT 2
Do NOT perform
\*not studied sufficiently in PLCO and ERSPC trials
_UNLESS_ shared decision making d/ higher risk:
1. AA race
2. Family hx of metastatic/lethal adenocarcinoma(prostate, male/female beast cancer, ovarian, pancreatic) spanning multiple generations, multiple first degree relatives at young ages
150
What does the panel RECOMMENDED for PSA screening for ages 55-69?
GUIDELINE STATEMENT 3
Shared decision making to proceed
Multiple approaches subsequent to PSA to determine need for second biopsy (no proof of utility as primary screening tests)
\*\*urine, serum biomarkers, imaging, risk calculators to help detect men harboring CaP
151
What does the panel offer and OPTION for PSA screening frequency?
GUIDELINE STATMENT 4
To reduce harms, interval q 2 years or more may be preferred over annually (can be individualized by baseline PSA)
Goteborg data→rescreening _every 4 years_ not likely to miss curable CaP among men PSA \< 1.0
152
What are the risks of prostate cancer screening?
1. Psychological
2. Hematuria
3. Hematochezia
4. Hematospermia
5. Dysuria
6. Retention
7. Pain
8. Infection
9. Over-diagnosis
10. Over treatment
11. Transient ED
153
Describe some elements included in SDM for PSA screening for CaP?
1. Putative mortality benefit of screening (overall 3% risk of dying)
2. Description of options after abnormal PSA
3. Likelihood of FP and FN (no screening test perfect, can be elevated for many reasons, PLCO trial annual screening no advantage over biannual in regards to mortality)
4. Description of subsequent tests needed
5. Harms of screening (additional procedures, hospitalizations, sepsis)
6. Information about prostate gland anatomy an function
7. CaP incident and mortality
8. Treatment options for early and late CaP
9. Complications of treatment options
154
Current AUA guidelines recommend which abx for prostate biopsy?
1 dose of either FQ _OR_ 1st/2nd Gen Cephalosporin +/- Aminoglycoside _OR_ 3rd Gen Cephalosporin
Aztreonam (if resistance)
Local antibiogram
Rectal swab can be considered (hx of resistance, travel, FQ in past 6 mo, healthcare worker)
155
List the grade groups for CaP:
1. Grade Group 1: Gleason 3+3
2. Grade Group 2: Gleason 3+4
3. Grade Group 3: Gleason 4+3
4. Grade Group 4: Gleason 8 (4+4, 3+5, 5+3)
5. Grade Group 5: Gleason 9-10 (4+5, 5+4, 5+5)
156
Prostate cancer T1 staging
T1a → \<5% of tissue removed, incidental during unrelated sx
T1b → \>5% of tissue removed, incidental during unrelated sx
**T1c → cancer found on biopsy, usually related to elevated PSA**
157
Prostate cancer T2 staging
T2 → prostate cancer completely inside gland
T2a → in only _\<_ 50% of one lobe
T2b → in \> 50% of one lobe
T2c → cancer in both lobes
158
Prostate cancer T3 staging
T3 → cancer broken through capsule
T3a → broken through capsule
T3b → spread to SV
159
Prostate cancer T4 staging
T4 → spread to other organs nearby (rectum, bladder, levator muscles, pelvic wall)
160
CaP Risk Stratification → Low Risk
161
CaP Risk Stratification → Intermediate Risk
162
CaP Risk Stratification → High Risk
163
At CaP diagnosis, it is a STRONG RECOMMENDATION to utilize SDM, incorporating these key elements:
GUIDELINE STATEMENT 1 (CLINICALLY LOCALIZED CAP)
1. Risk category
2. Patient values and preferences
3. Life expectancy
4. Pre-treatment General functional and GU sxs
5. Expected post-treatment functional status
6. Potential for salvage tx
164
EXPERTS suggest importance of counseling in regards to what factors at the time of CL CaP Dx?
GUIDELINE STATEMENT 2
Modifiable Health-Related Risk Factors
Smoking
Obesity
(Also consider frailty)
165
Clinicians are RECOMMENDED to encourage patients to meet with whom at time of dx of CaP?
GUIDELINE STATEMENT 3
Different prostate cancer specialists
Urology
Radiation Oncology
Med Oncology
166
Effective SDM at time of CaP dx requires clinicians to inform patients of what to make proper treatment decisions?
GUIDELINE STATEMENT 4
Immediate and LT morbidity or side effects of proposed treatment decisions
Active surveillance: preserves QOL until Surgery/XRT necessary, declines in urinary, bowel, sexual function over time with age, anxiety
Sx: (immediate) bleeding, infection, pain, (longer term) ED, UI, stricture, bowel problems, death (\<0.1%)
XRT: (immediate) urinary irritation, bowel irrigation, GI effects (longer term) UI, ED, secondary cancer, radiation cystitis
167
Experts suggest clinicians SHOULD inform patients to participate in what additional measure at time of CaP?
GUIDELINE STATEMENT 5
Clinical trials (based on eligibility and access)
168
At time of dx for low risk or very low risk CL CAP, what imaging is RECOMMENDED?
GUIDELINE STATEMENT 6
Clinician should **NOT** perform CT A/P or Bone scans
(no evidence to support need for staging)
169
Clinicians should RECOMMEND which initial tx for very-low risk CL CaP?
GUIDELINE STATEMENT 7
Active Surveillance
(limited or no metastatic potential, major risk serial bx → at 3-5 year intervals after confirmatory bx)
Reminder:
1. PSA \<10
2. GG1 (Gl 6)
3. T1-T2a
4. \<34% biopsy cores positive
5. no core \>50% involved
6. PSA density \<0.15
170
Clinicians should RECOMMEND which initial tx for low risk CL CaP?
GUIDELINE STATEMENT 8
Active surveillance as preferable care option
(regardless of life expectancy)
\*\*Higher volume disease \>50% of cores positive or larger lesions on MRI, while still low risk, may benefit from tx
Reminder:
1. PSA \< 10
2. Grade Group 1
3. T1-T2a
171
Clinicians should RECOMMEND which initial tx for select low risk CL CaP?
GUIDELINE STATEMENT 9
Definitive tx RP or XRT
High probability of progression on AS (PIVOT, ProtecT→small reduction in progression)
Clinical Predictors:
PSA denisty \>0.15 (2x risk)
Obesity (3 x risk)
AA race
extensive Gl 6 on systematic cores
FHx of aggressive CaP or early mets
172
If a patient chooses RT for low-risk CL CAP, what is RECOMMENDATION regarding ADT?
GUIDELINE STATEMENT 10
NO ADT with RT
\*\*Exception → reducing size prostate for brachytherapy
173
If a patient is considering whole gland cryotherapy for low-risk CL CAP, what is RECOMMENDED counseling?
GUIDELINE STATEMENT 11
A/E are considerable: ED, UI, LUTs, bowel sxs, AUR, urethral sloughing
Survival benefit not shown when compared to AS
174
If a patient is considering focal therapy of HIFU for low-risk CL CAP, what is RECOMMENDED counseling?
GUIDELINE STATMENT 12
These intervention are NOT the standard of care
\*Fails to improve survival outcomes or provide comparable QOL, insufficient data to support
175
Clinicians should RECOMMEND which initial tx for low risk CL CaP with life expectancy _\<_ 5 years?
GUIDELINE STATEMENT 13
Watchful waiting/observation
Palliative, non-aggressive intent→no bx
176
What is EXPERT consensus for patients with low risk CL CaP considering AS in regards to tissue based genomic biomarkers ?
GUIDELINE STATEMENT 14
**_Have not_** shown a clear role in selection of candidates for AS
3 approved by FDA:
1. Genomic Classifier (GC)--22 marker based on RNA → high score on bx associated with increased risk of mets
2. Genomic Prostate Score (GPS)--12 cancer genes, 20 point increase associated with SS increase HG or non-organ confined dz
3. Cell Cycle Progression (CCP)--31 cell cycle genes--increased denotes HR disease
177
At time of dx for **UNFAVORABLE** intermediate risk CL CAP, what imaging is should be considered by EXPERT OPINION?
GUIDELINE STATMENT 15
CT A/P or MRI prostate or pelvis and Bone Scan (18F NaFl PET/CT or PMSA considered but not standard in US)
Baseline staging if 2 or more: palpable nodule on DRE (stage T2b/c), Gl 7, or PSA \>10
Reminder:
1. PSA 10-20 OR
2. GG 2-3 OR
3. T2b-c
1. Favorable GG1 (with PSA 10 - \<20) or GG2 (with PSA \<10)
2. **Unfavorable: GG2 (either PSA 10 - \<20) or T2b-c OR GG3 (PSA \< 20)**
178
At time of dx for intermediate risk CL CAP, what tx is RECOMMENDED?
GUIDELINE STATEMENT 16
RP or XRT+ADT
179
Patient with **FAVORABLE** intermediate risk CL CAP, what counseling is RECOMMENDED regarding RT and ADT?
GUIDELINE 17
Can be tx with RT alone, but less evidence than in combination with ADT
Unfavorable should especially be considered for ADT
Reminder:
1. PSA 10-20 OR
2. GG 2-3 OR
3. T2b-c
1. **Favorable GG1 (with PSA 10 - \<20) or GG2 (with PSA \<10)**
2. Unfavorable: GG2 (either PSA 10 - \<20) or T2b-c OR GG3 (PSA \< 20)
180
Patients with intermediate risk CL CAP, what other tx options can be considered besides RP or RT?
GUIDELINE 18, 19, 20, 21
MAY consider Cryosurgery (limited to 1 RCT) → _whole gland_ may be appropriate if contraindications to RP or RT
MAY offer AS → **favorable** int risk CL→ inform higher risk mets compared to definitive tx (benefit MRI + target bx)
Watchful waiting _\<_ 5 years life expectancy (no AS, no overall improvement in life expectancy with intervention)
HIFU → not the standard options because comparative evidence lacking
181
At time of dx for high risk CL CAP, what imaging is A CLINICAL PRINCIPAL?
GUIDELINE STATEMENT 22
CT/MRI and Bone Scan
Reminder:
1. PSA \>20 OR
2. GG 4-5 OR
3. _\>_T3
182
Clinicians should RECOMMEND which initial tx options for high risk CL CaP?
GUIDELINE STATEMENT 23
RP or RT + ADT
GUIDELINE STATMENT 24, 25, 26
should NOT recommend AS
Watchful waiting only if asx _\<_ 5 life expectancy
NO cryotherapy or HIFU (outside clinical trial)
NO primary ADT (unless limited life expectancy and local sxs)
183
In addition to treatment, what do EXPERTS suggest for high-risk CL CaP at time of dx?
GUIDELINE STATEMENT 27
consider referral for genetic counseling for patient and families
when high risk and strong fhx of specific cancers (breast, ovarian, pancreatic, GI tumors, lymphoma)
\*Germline DNA repair mutations
184
Describe AS CLINICAL PRICIPALS AND RECOMMENDATIONS:
GUIDELINE STATEMENT 28
CL CaP pts who elect AS should have accurate disease staging including _systematic bx with US or MRI_
(10-12 core with some targeted per DRE or MRI)
GUIDELINE STATEMENT 29
_Routine PSA and DRE_
optimal schedule not est, but ProtecT suggests q 3 mo x year 1, q3-6 subsequently
GUIDELINE STATEMENT 30
_Confirmatory bx within initial 2 years_ and surveillance bx thereafter (some protocols recommend repeat bx before committing to AS or w/in 6 mo)
GUIDELINE STATEMENT 31
Consider MP Prostate _MRI_ as part of AS (improve retention by reducing need for bx)
GUIDELINE STATEMENT 32
Tissue based _genomic markers have NOT shown_ clear role in AS and are not necessary for f/up
\*(ex. Prolaris, Oncotype Dx, Decipher Score)
GUIDELINE STATEMENT 33
Offer _definitive tx when develop adverse reclassification_ (growth, rises in psa, changes in density, upstaging)
\*PIVOT and ProtecT, 20% and 50% pts on AS received definitive tx by 10 years
185
What is RECOMMENDED that clinicians inform patient's about outcomes, preparation, and types of RP for CL CaP?
GUIDELINE STATEMENT 34
Younger or healthier men are more likely to experience cancer control from RP than older men
\*\<65 yo or \>10 year life expectancy
GUIDELINE STATEMENT 35
Open and RALP offer similar cancer control, continence, and sexual recovery
GUIDELINE STATEMENT 36
RALP or perineal techniques are associated with less blood loss than RRP
GUIDELINE STATEMENT 37
Nerve-spring is associated with better EF (50-95% erections)
GUIDELINE STATEMENT 38
NOT tx with neoadjuvant ADT or other systemic tx (outside clinical trial)
GUIDELINE STATEMENT 39
Older men experience higher rates of permanent ED and PPI compared to younger men
186
What do EXPERTS suggest for CL CaP undergoing RP in regards to PLND?
GUIDELINE STATEMENT 40
Consider for any
RECOMMENDED for unfavorable intermediate and high risk
Counsel for complications (i.e. lymphocele→ 0.4-16 % incidence, drain +/- sclerosis, occasional MIS marsupialization)
187
What is RECOMMENDED for adjuvant ADT after RP?
GUIDELINE STATEMENT 41
unfavorable intermediate and high risk advised of r/b/a of adjuvant ADT when locally extensive CaP found during sx
188
What types of RT are RECOMMENDED for low risk CL CAP?
GUIDELINE STATEMENT 42
EBRT OR brachytherapy
189
What types of RT are RECOMMENDED for **favorable** intermediate risk CL CAP?
GUIDELINE STATEMENT 43
EBRT or brachytherapy ALONE or in combination +/- ADT
Reminder:
1. PSA 10-20 OR
2. GG 2-3 OR
3. T2b-c
1. **Favorable GG1 (with PSA 10 - \<20) or GG2 (with PSA \<10)**
2. Unfavorable: GG2 (either PSA 10 - \<20) or T2b-c OR GG3 (PSA \< 20)
190
What protocol of RT and tx are RECOMMENDED for high risk CL CAP? What are a/e?
GUIDELINE STATEMENT 44
24-36 mo of ADT in adjunct to EBRT alone or EBRT + brachytherapy
GUIDELINE STATEMENT 45
use of ADT with RT increases a/e on EF and systemic a/e (hot flashes, dec bone mineral density, gynecomastia, depression, fatigue, and weight gain)
191
What type of EBRT is RECOMMENDED for any risk category of CL CaP?
GUIDELINE STATEMENT 46
consider moderate hypofractionation (without nodal therapy)
GUIDELINE STATEMENT 48
Proton beam therapy offers no clinical advantage over other forms of therapy
192
For CL CaP patient with obstructive LUTS which is RECOMMENDED in regards to treatment?
GUIDELINE STATEMENT 47
Surgical approaches
Discourage with volume \>60 g
If RT for these patient or they have had previous large TURP, low dose brachytherapy should be discouraged
GUIDELINE 49
Brachytherapy has similar effects as EBRT with regard to EF and proctitis, BUT can exacerbate obstructive sxs
193
When is whole gland cryosurgery a possibility for treatment per EXPERT opinion? What should patients be informed in regards to this treatment and a/e?
GUIDELINE STATEMENT 50
Low- and intermediate risk CL CaP when RP or RT d/ comorbidities is not possible but \> 10 years life expectancy
(max recommended 60 g)
GUIDELINE STATEMENT 51
Cryosurgery has similar PFS as non-dose escalated EBRT + ADTin low- and intermediate-risk dz
Conclusive comparison of mortality lacking
GUIDELINE STATEMENT 52
TURP defects are relative contraindication d/t increased risk of urethral sloughing
GUIDELINE STATEMENT 53
Utilize a 3rd or higher generation, argon-based system (double freeze-thaw cycle)
GUIDELINE STATEMENT 54
Unclear +/- ADT improves cancer control, can reduce prostate size to facilitate tx
(\>40g, consider 3-6 mo of ADT)
GUIDELINE 55
ED is expected
GUIDELINE 56
A/E include UI, irritative, and obstructive urinary sxs (sloughing, fistula, bowel effects)
194
What should clinician inform patient with CL CaP considering focal therapy or HIFU?
GUIDELINE STATEMENT 57
these tx options lack evidence of efficacy
GUIDELINE STATEMENT 58
approved by FDA for destruction of prostate tissue, not explicitly for CaP
GUIDELINE STATEMENT 59
tumor location may influence oncologic outcome (apex avoided for morbidity risks cancer persistence)
GUIDELINE STATEMENT 60
CaP is often multifocal, focal therapy may not be curative and further tx needed
195
What should clinicians inform patients regarding long term secondary effects of RP, cryotherapy, and RT?
GUIDELINE STATEMENT 61
ED occurs, lacking ejaculate, preserved orgasm (no sexual dysfunction with observation)
GUIDELINE STATEMENT 62
Long term obstructive or irritative sxs for AS, RT whereas RP can relieve LUTs
GUIDELINE STATEMENT 63
Whole gland cryotherapy associated with worse sexual side effects and similar urinary/bowel a/e as RT
GUIDELINE STATEMENT 64
PPI occurs in most patients and persists long-term in small but significant subset (more than AS or RT)
GUIDELINE STATEMENT 65
Temporary proctitis s/p RT persists in some patient in LT (rare in AS or RP)
196
What is RECOMMENDED for follow up for CL CaP?
GUIDELINE STATEMENT 66
PSA (even though all PSA recurrences are not associated with mets or mortality)
RP _\<_ 0.02
RT + ADT nadir PSA \< 2 with T recovered (if ADT)
recommended for at least 10 years
197
What can be used to inform patients of individualized post-treatment prostate cancer recurrence?
GUIDELINE STATEMENT 67
Nomograms taking in to consideration:
tumor grade and stage
race
fhx
age
pathologic stage
etc
+/- genomic testing
198
What would you tell a patient are the benefits of PSA screening as expressed in the number of deaths averted per 1000 men from a key RCT? What study is this? What study refutes this?
ERSPC (European Randomized Study of Screening for Prostate Cancer): 1 death fewer per 1000
\*\*RRR of CSM 21% at median f/up of 11 years
PLCO (Prostate, Lung, Colorectal, and Ovarian): NO benefit
199
What are FP and FN in regards to CaP screening?
FP (false positive): elevated PSA with neg bx
FN (false neg): cancer present without elevation in PSA
200
Potential harms associated with PSA screening?
1. Over Diagnosis: ERSPC 66%, SEER 23-43%
2. Hematuria/hematospermia: ERSPC 20-50%
3. Fever: ERSPC 3.5-4.2%
4. Psychological
5. Sepsis: 4%
6. Pain (pain, fever, bleeding, infection, problems urinating 30%)
201
Discuss possible patient factors that may trigger prostate biopsy being performed?
1. PSA \> 3, ERSPC
2. Prostate volume
3. Inflammation (no benefit of abx in asx man)
4. Age (55-69)
202
What does the panel RECOMMEND for PSA screening \> 70 years old or any man with \< 10-15 year life expectancy?
GUIDELINE STATEMENT 5
NO screening
If so, increase threshold to PSA \> 10 (PIVOT study)
Discontinue if PSA \< 3
203
DDX of elevated PSA (asx)
BPH
UTI
Prostatits
Prostate cancer
204
Describe some key features of mpMRI prostate?
**Key Points**
Optimal scanning technique should utilize 3.0T surface coil; an endorectal coil may be necessary for older 1.5T scanners
T2→dark lesion concerning for cancer
DWI (diffusion weighted)→bright lesion corresponding T2 lesion
DCE (dynamic contrast enhanced imaging)→early enhancement with early washout corresponding to T2 lesion
ADC (apparent diffusion coefficient)→dark corresponding to T2 lesion
Identification and reporting of putative tumors uses anatomic and functional images.
The radiographic report should identify up to 4 suspicious lesions with each individual lesion reported and characterized using PI-RAD v2 criteria.
205
Stratified by PiRADS score, what is correlation to all tumor and Gl_\>_7 detection?
All tumor detection:
PI-RADSv2: 2→0-22%, 3→10-16%, 4→30-77% and 5→78-89%
Gleason _\>_7
PI-RADSv2: 2→5-6%, 3→0-14%, 4→21-78% and 5→75-100%
206
Can you use mp MRI in biopsy naïve patients?
Two randomized clinical trials (PROMIS, PIVOT, MRI-FIRST)have provided level 1 data to support use mpMRI prior to biopsy for ALL men
mpMRI-targeted prostate bx in naive patients detects more clinically significant CaP when combined with systematic biopsy (less clinically insignificant CaP, than systematic biopsy alone), but must combine systematic due to risk of missing some clinically significant cancer with targeted alone
207
How do FQ work? What are a/e?
Inhibit DNA gyrase
A/E include allergic reaction, tendonitis, and tendon rupture, exacerbation of muscle weakness in pts with MG
208
What is important for template of systematic biopsy?
Incorporation of templates that adequately sample apex, anterior apex, far-lateral region, including base and midgland (little benefit of TZ)
Size important
209
Describe risks of RP?
invasive, anesthesia, recovery and time off, limitation of activity post-op, risk death (\<0.1%), hemorrhage (\<5%), infection, positioning injury (fibular and ulnar nerves), injury to rectum (1%), bladder/bladder neck contracture (\<5%), damage to obturator nerves and iliac vessels
Risks of positive margins (up to 20%), need for adjuvant tx (RT +/- ADT)
210
What are risks of RT for CaP?
higher risk of bladder/bowel dysfunction→acutely (50%) → LT (5%) (brachy\>EBRT), no pathologic specimen, PSA is not a great marker, fatigue, impotence, incontinence (longer term)
211
Key element to account for when describing the start RP?
1. Pre-operative abx
1. (Ancef, Gent + Flagyl, Aztreonam +Flagyl, Gent+ Clinda, Aztreonam + Clinda)
2. Mechanical and Chemical DVT ppx
3. Positioning to pad pressure points (ulnar/fibular nerves)
4. RALP→supine arm tucking
5. Access Veress or Hasson (drop test, check opening pressure with gas, use visual obturator)
212
Describe standard steps of RALP?
1. After positioning and access
2. Enter space of Retzius (drop bladder)
3. Isolate and ligate the DVC
4. Separate bladder and prostate
5. Athermal dissection of SV and Vas
6. Blunt and athermal dissection of posterior plane between rectum
7. Antegrade nerve sparing
8. Preservation of urethral length
9. Vesico-urethral anastomosis (test anastomosis)
10. PLND
213
Describe PLND with RALP?
* A **standard PLND** from the external iliac vein down to the internal iliac artery (including tissue within the obturator fossa), pelvic sidewall laterally, proximally up to the bifurcation of the common iliac artery, and distally to Cooper's ligament.
* **Definitions of extended and super extended lymph node dissection have been introduced. Their role is currently under investigation.**
* **Extended LND**: External iliac, obturator fossa, hypogastric/internal iliacs, common iliac below the point where the ureter crosses.
* **Super extended LND**: Above, plus pre-sacral lymph nodes and entire common iliac below the aortic bifurcation.
214
Ddx of bradycardia and hypotension during RALP? Next steps?
1. Cardiac events
2. Air embolus
3. Vagal response to pneumo
\*Check for injury if port in place
\*Desufflate to release intra-abdominal pressure
\*Auscultate for cogwheel murmur (air embolus)
215
What do you do if you lose control of DVC during RALP?
1. suction judiciously to keep up pneumo
2. turn pneumo to 20 mmHg (if pt can tolerate)
3. pack with sponge/raytec, lap → needle drivers → ligate, stitch
216
Describe intraoperative iatrogenic injuries during RALP and mgmt.?
1. Rectal injury
1. Sharp \< 1.5 cm → close primarily, leave drain, advance diet slowly
2. If RT/salvage → colorectal consult (diversion with colostomy)
3. Thermal injury → debride injury prior to closing
4. Large size → consider colostomy
2. Nerve transection
1. Intraoperative repair of obturator nerve (can ask for NSG-prob unavailable)
2. Robotic magnification or loupes, close perineural tissue in one later interrupted 6-0 Prolene non-absorbable monofilament (tension free)
3. Secondary hole (button hole) bladder
1. When dissecting posterior BN off prostate
2. Inspect BN for damage to UOs (can insert 5 Fr caths)
3. Leave drain, cystogram before foley removal
217
Post RALP patient severe pain and decreased UOP, next steps? DDx?
1. Examine patient, vitals, abdomen, JP output
2. Labs (CBC, BMP, Trop/CKMB, EKG, JP Cr)
3. Irrigate foley gently for clot
DDX:
1. Cardiac event
2. PE
3. Hemorrhage
4. Unrecognized bowel injury
5. Clogged Foley
218
Post RALP f/up ?
Removal of foley/staples
Kegels (help recovery continence)
+/-PDE5I (penile rehab)
Repeat PSA 1 mo
219
What are a/e for PDE5I?
All→ flushing, nasal congestion, priapism (theoretical)
Viagra→blue/green visual changes
Cialis→muscle aches
220
What are options for post RALP ED?
1. PDE5I
2. ICI (a/e priapism, pain, curvature/scarring)
3. VED (floppy, ecchymosis, pain)
4. IPP (if failure non-invasive)
221
If 39 yo M comes in for PSA due to fear, no FHX? What do you do?
Examine patient, VS
Review prostate screening guidelines (low prevalence, no benefit of screening)
222
Age adjusted PSA trends:
40-49 (don't screen): 0-2.5
50-59: 0-3.5
60-69: 0-4.5
70-79: 0-6.5
Not exhaustive, somewhat from old doctrine, but as a reference
223
Patient with cT2b CaP, PSA 7.8, and lower back pain, what should be considered as part of workup?
Bone Scan
224
What are treatment options for favorable intermediate risk CaP?
1. RP + PLND
2. EBRT + 4-6 mo ADT
3. EBRT + Brachy with 4-6 mo ADT
4. Brachy
225
What are potential problems when considering RP as tx option?
1. Advanced age
2. Previous intra-abdominal or pelvic surgery (trauma-i.e. GSW)
3. Post-prostatectomy sepsis (impact tissue planes)
226
What are definitions for BCR after RT?
ASTRO: 3 consecutive rises in PSA
Pheonix: Nadir + 2
227
A/E of ADT:
1. Body habitus changes→gynecomastia, testicular atrophy, loss of muscle mass, increase in fat
2. Elevation of lipids and cholesterol
3. Diabetes
4. CVD (+/-)
5. Anemia
6. Fatigue (common)
7. Osteoporosis
8. Sexual dysfunction→decreased libido, ED
9. Infertility
10. Hot flashes (common)
228
Define types of Biochemical recurrence (BCR)
rising PSA without metastatic disease
After initial therapy OR after _exhaustion of local treatment_ (i.e. salvage RT or salvage RALP/local ablative therapy)
RP: PSA 0.2 and confirmatory 0.2
RT: Pheonix → nadir + 2; Astro → 3 consecutive rises
229
Define metastatic hormone-sensitive prostate cancer
not yet treated with ADT or still responsive
absence of clinical progression, radiographic progression or rising PSA of _\>_2 above nadir
can occur as recurrence after initial local therapy or de novo mets→at time of initial dx
(distinction important when deciding systemic tx)
Also volume and site important
230
Define castrate resistant prostate cancer:
either metastatic→
non-metastatic→PET-CT (small volume better than CT/MRI/bone scans used in past)
patient on ADT
despite castrate levels of androgens (T\<50, \<20→post orchiectomy), the androgen receptors (AR) remain active and continues to drive CaP progression
PSADT at least 3 values measured _\>_ 4 weeks apart or continuous rising PSA (minimal value 2), or new radiographic or clinical progression
231
High volume metastatic CaP vs. low volume
CHAARTED study
visceral or bone mets _\>_ 4 mets
At least one outside vertebral column and pelvis
low volume is anything less
232
High risk metastatic CaP
LATITUDE study
poorer prognosis
Gl_\>_8, _\>_3 bone lesions, measurable visceral mets
233
In patients with suspicion of advanced prostate cancer and no histologic diagnosis, what is the next step based on CLINICAL PRINCIPLE?
GUIDELINE STATEMENT 1
Obtain tissue diagnosis from primary tumor or metastatic site (when feasible)
234
CLINICAL PRINCIPLE would dictate that clinicians discuss treatment options for advanced CaP based on:
GUIDELINE STATEMENT 2
life expectancy, comorbidities, preferences, tumor characteristics, and multidisciplinary approach (uro, med onc, palliative, RT)
235
When diagnosing advanced prostate cancer CLINICAL PRINCIPAL states clinicians should encourage what QOL and support measures?
GUIDELINE 3
1. Pain control, manage urinary sxs, a/e, and sexual sxs
2. Engagement in professional and community based advocacy groups
236
What SHOULD clinicians advise patients with BCR about risks and follow up studies?
GUIDELINE STATEMENT 4
risks of metastatic disease
serial PSA and clinical evaluation
consider radiographic assessment based on overall PSA and PSA kinetics
High risk s/p RP: GG4/5 (Gl _\>_ 8) or PSADT _\<_ 1 year
High risk s/p RT: GG4/5 (Gl _\>_ 8) or PSADT _\<_ 18 months
\*Pts that don't meet these criteria considered low risk
237
Clinicians SHOULD perform what in patients with BCR who are considered high risk for clinical metastasis?
GUIDELINE STATEMENT 5
Perform periodic staging imaging: cross sectional (CT/MRI) and bone scan
GUIDELINE STATEMENT 6
Conventional studies rarely detect mets PSA _\<_5
May utilize novel PET-CT (fluciclovine, choline, PMSA) as alternative (greater sensitivity)
Reminder:
High risk s/p RP: GG4/5 (Gl _\>_ 8) or PSADT _\<_ 1 year
High risk s/p RT: GG4/5 (Gl _\>_ 8) or PSADT _\<_ 18 months
\*Pts that don't meet these criteria considered low risk
238
In patients with BCR (after failure of local therapy) and no evidence of mets by _conventional_ imaging, clinicians SHOULD offer:
GUIDELINE STATEMENT 7
Observation vs. clinical trial
\*Jump to systemic therapy does not always yield better outcomes (balance with a/e and QOL)
GUIDELINE 8
ADT should not routinely be initiated
IF it is, **intermittent** (studies 8 mo treatment cycle) in lieu of continuous
239
In patients with mHSPC, clinicians SHOULD assess the extent of mets where and how?
GUIDELINE STATEMENT 9
bone, LN, visceral
Conventional imaging
Aggressive Cancer → D'Amico risk factors
cT3a or greater, GG 4/5, PSA \>20
CT/MRI (with consideration of chest) and bone scan
Rapid progression to met dz → high path or bx Gl score, short interval to BCR, short PSADT
PET holds great promise [PSMA, fluciclovine (PSA \>1)]
240
In newly dx mHSPC what stratification SHOULD clinicians perform? What also SHOULD be assessed to guide discussions of prognosis and further dz mgmt.?
GUIDELINE STATEMENT 10
High volume vs. Low volume
**High volume →** _\>_ 4 bone mets with at least one met outside spine/pelvis and/or presence of visceral mets
\*CHAARTED study shows OS benefit for high volume dz of chemohormonal tx
GUIDELINE STATEMENT 11
Assess for _symptoms_
\*bone pain with poorer 10-year survival
241
When initiating ADT in mHSPC, how SHOULD clinicians utilize PSA and imaging?
GUIDELINE STATEMENT 12
Baseline PSA, serial PSA at q3-6 mo. intervals after initiation of ADT
_consider_ periodic conventional imaging
\*PSA nadir (~6 -7 mo.) important in prognosis and risk stratification (PSA \< 4 and \< 0.2, important cutoffs regarding OS)
Imaging: esp. for poorly differentiated, ductal, neuroendocrine (often no PSA rise) → sxs → periodic imaging
242
In mHSPC, regardless of FHx or age, clinicians SHOULD offer the following:
GUIDELINE STATEMENT 13
genetic counseling and germline testing
GUIDELINE STATEMENT 14
ADT with either LHRH agonists or [antagonists or surgical castration]→avoid “testosterone flare”
GUIDELINE STATEMENT 15
Continued ADT in combo with androgen pathway directed tx (abiraterone + prednisone, apalutamide, enzalutamide) or chemotherapy
GUIDELINE STATEMENT 18
Do NOT offer androgen receptor pathway tx w/out ADT
243
What chemotherapy for mHSPC? What is pharmacologic MOA?
**Docetaxel** → potent inhibitor of microtubule assembly and disassembly
CHAARTED AND STAMPEDE TRIALS
Greater OS and longer median time to progression
\*A/E febrile neutropenia, lethargy, asthenia, GI effects
244
What androgen pathway agents are used for mHSPC? What is pharmacologic MOA?
1. Abiraterone Acetate (Zytiga)
→ non-steroidal irreversible inhibitor of **CYP17A1** (which catalyzes conversion of C21 progesterone precursors to C19 adrenal androgens, DHEA and androstenedione)
**ESSENTIALLY potent inhibition of gonadal and extragonadal androgen synthesis**
1000 mg daily (250 mg x 4 at once)
Significantly longer OS and median length of radiographic PFS
A/E → elevate liver enzymes (caution liver failure), mineralocorticoid-related HTN (20%) and hypokalemia (10%)
2. Apalutamide (Erleada)
→ non-steroidal anti androgen, acts as **AR inhibitor** that binds directly to t he ligand binding domain of AR (inhibits DNA binding)
240 mg daily
A/E: rash, seizure, GI, weight loss, arthralgia, fatigue, falls
3. Enzalutamide (Xtandi)
→ novel **AR signaling inhibitor, competitive** for androgen binding and inhibits translocation of AR, DNA binding, and co-activator recruitment
\*PFS significantly reduced + ADT (HR = 0.39)
160 mg daily
A/E: fatigue, seizures
245
In patients with mHSPC, low-volume mets clinicians MAY offer:
GUIDELINE STATEMENT 16
primary radiotherapy to prostate + ADT
246
When SHOULD clinicians offer first generation anti-androgens? What are they? What is pharmacologic MOA?
GUIDELINE STATEMENT 17
ONLY for blockage of testosterone flare
bicalutamide, flutamide, nilutamide
in combo with ADT for 2-4 weeks
MOA: **competes with androgen for AR**, blocking the action of androgens of adrenal and testicular origin
247
At what intervals should PSA and conventional imaging be used for nmCRPC?
GUIDELINE STATEMENT 19
PSA q3-6 mo. interval, and calculate PSADT at time of development of castrate resistance (PSADT _\<_ 10 mo. used to ID highest risk)
GUIDELINE STATEMENT 20
Assess for mets q6-12 mo.
\*Exact interval determined by PSADT, sxs, patient/MD preference (_\<_ 10 mo.), once on ART could extend intervals to 12 mo.
248
In patients with nmCRPC what denotes high risk of developing mets? What SHOULD patients be offered for tx?
GUIDELINE STATEMENT 21
Apalutamide, darolutamide, enzalutamide with continued ADT
high risk patients PSADT _\<_ 10 mo
(\*\*Lack of FDA approval of abiraterone + prednisone in men with nmCRPC--some data to support OS and PFS, but insufficient for approval)
249
In patients with nmCRPC AND low risk of developing mets? What SHOULD patients be offered for tx?
GUIDELINE STATEMENT 22
observation with continued ADT (PSADT \> 10 mo)
GUIDELINE STATEMENT 23
Do NOT offer systemic chemotherapy or immunotherapy (only clinical trial)
250
In patient with newly diagnosed mCRPC, what labs, imaging, and patient specific factors should be done/reviewed? What interval of imaging ongoing?
GUIDELINE STATEMENT 24
Baseline labs → PSA, testosterone, LDH, Hgb, ALP
Review CT/MRI and bone scan → location of mets (visceral highest risk)
Disease related sxs and performance status
\*Risk factors increased with elevated LDH, T \<20-50, higher PSA, shorter PSADT
GUIDELINE STATEMENT 25
Conventional (CT/MRI, bone scan) at least annually or interval determined by lack of response (BCR, sxs)
251
In pts with mCRPC what SHOULD be done to inform prognosis and counsel regarding familial risk and targeted tx?
GUIDELINE STATEMENT 26
Germline and somatic tumor genetic testing
→ ID DNA repair deficiency mutation and microsatellite instability status
252
In newly dx mCRPC clinician SHOULD offer the following tx and MAY offer which tx:
GUIDELINE STATEMENT 27
continued ADT + **abiraterone+ pred,** docetaxel, OR enzalutamide
GUIDELINE STATEMENT 28
MAY offer sipuleucel-T in asx or minimally sxs
→ immunotherapy (IMPACT trial RRR death 22%)
→ often does not show reduction PSA or radiologic dz
GUIDELINE STATEMENT 30
In sequencing agents, consider prior tx and new tx with alternate MOA
\*possibly abiraterone followed by enzalutamide (suggested in study)
253
What SHOULD clinicians offer to patients with **sxs of bony met**s from mCRPC AND without known visceral dz or LAN \>3 cm?
GUIDELINE STATEMENT 29
Radium-223
→ alpha emitting radiopharm capable of inducing ds DNA breakage in cancer cells with little damage to surrounding tissues
→ not usually associated with PSA decline, must assess for occult visceral dz (CT + CXR prior to cycle 4/6 months)
254
In mCRPC pts who received prior docetaxel +/- abiraterone + pred OR enzalutamide, clinician MAY offer:
GUIDELINE STATEMENT 31
Cabazitaxel
3 chemotherapies FDA approved:
docetaxel, mitoxantrone (no surv. benefit), and cabazitaxel
GUIDELINE STATEMENT 32
Cabazitaxel OVER other alternative androgen pathway directed tx as third line
255
In patients with deleterious or suspected deleterious germ-line or somatic homologous recombination repair gene-mutated mCRPC AND prior tx with enzalutamide OR abiraterone + pred and/or taxane chemotherapy, clinician SHOULD offer:
GUIDELINE STATEMENT 33
PARP inhibitor (Lynparza)
→ leverage defects in DNA repair → cell death
OR
Platinum base chemotherapy (Carboplatin) → (if cannot use/obtain PARP inhib.)
256
In patients with mismatch repair deficient or microsatellite instability high mCRPC, clinicians SHOULD offer:
GUIDELINE STATEMENT 34
Pembrolizumab (anti PD-1 → Ketruda)
257
In regards to bone health in advanced CaP, what SHOULD physicians discuss and recommend?
GUIDELINE STATEMENT 35
Discuss risk of osteoporosis associated with ADT, assess risk of fx
GUIDELINE STATEMENT 36
Preventative tx for fx: supplemental Ca, Vit D, smoking cessation, weight bearing exercise
GUIDELINE STATEMENT 37
High risk of fx → bisphosphonates or denosumab (Prolia) (dentist-jaw)AND referral to MD who manages osteoporosis (endo, ortho, PCP)
GUIDELINE STATEMENT 38
Should rx bone-protective (denosumab-Prolia or zolendronic acid-Reclast/Zometa) agent for mCRPC with bony mets to prevent SRE
258
Define adjuvant RT:
ART (adjuvant) is post RP with higher risk of recurrence because of adverse pathologic features prior to recurrence (i.e. undetectable PSA)
First PSA 2-3 mo
ART usually starts 4-6 mo (after return of acceptable urinary control)
259
Define salvage RT:
RT to prostatic bed and surrounding tissues, including LN, in patient with PSA recurrence after sx but no evidence of mets
260
Some outcomes to support ART:
SWOG, EORTC, ARO
Reduction in BCR
Locoregional recurrence
Hormone tx free survival
Clinical progression
Metastatic recurrence and OS (unclear benefit--1 of 3 studies suggest yes)
261
What are key NNT for the SWOG, EORTC, and ARO studies in relation to ART?
BCR 4.2 (combine SWOG and EORTC)
Local recurrence 9.8
Clinical Progression 13.8
\*\*based on NNT should be _offered_ to all patient at high risk of recurrence
262
Doses of RT for SRT and ART?
65 Gy in post RP setting
263
RT toxicity is measured how?
Rating system 0 - 5
0 → no change in function
3 → outpt tx
4 → inpt tx
5 → death
Common Toxicity Criteria Adverse Event
264
When counseling a patient for RP, what SHOULD they be counseled regarding the pathologic features and additional tx?
GUIDELINE STATEMENT 1
Adverse pathologic features: + margins, SVI, EPE (recurrence \>60% @ 5 y)
Advised adjuvant therapy such as RT +/- ADT may be beneficial
265
Adverse pathologic findings on RP, patients SHOULD be advised that RT compared to RP alone reduces what?
GUIDELINE STATEMENT 2 and 3
should _inform_ and _offer_ due to reduction in:
BCR, local recurrence, and clinical progression
ART on subsequent mets and OS is less clear (⅓ RCT addressed this, ⅔ did not--were not designed for that)
reduction in salvage tx and associated toxicities
266
PSA recurrence after RP carries what risks? What SHOULD clinicians do to monitor?
GUIDELINE STATEMENT 4
higher risk of mets or death
regular PSA monitoring
early admit of salvage tx
[early rise of PSA → more rapid dev of mets \< 2 years, PSADT \<10 mo, mets w/in 5 years and died approx. 5 years (2-12)]
267
Definition of BCR after RP:
GUIDELINE STATEMENT 5
BCR → detectable or rising PSA after sx _\>_ 0.2 with second confirmatory _\>_ 0.2
Ultrasensitive assays ( _\>_ 0.07) → lack of data (but clinician knowledge and patient specific factors)
268
At PSA recurrence, what MAY be considered before tx:
GUIDELINE STATEMENT 6
A re-staging evaluation
(low yield bone scan PSA \<10)
MRI w/contrast (DCE) → highest and most consistent sens (\>70-80%) and spec for detection of local recurrence
LN recurrence → insufficient data, possibly PET
Bones → SPECT, DWE MRI, PET???
269
Pts with PSA or local recurrence after RP with no evidence of distant mets SHOULD be offered which txs and counseling:
GUIDELINE STATEMENT 7
SRT
(significant reduction in local recurrent and systemic progression)
GUIDELINE STATEMENT 8
effectiveness for SRT (for PSA recurrence) is greater when given at lower levels of PSA
→ ideally _\<_ 1
GUIDELINE STATEMENT 9
+ offer ADT
→ pts s/p RP PSA _\>_ 0.2 with no distant mets
270
Patients should be informed of what A/E and clinical benefits for RT:
GUIDELINE STATEMENT 10
Short and Long Term urinary, bowel, and sexual
Benefits of controlling dz recurrence
Urinary incontinence (mild worsening after ART/RP or new onset)
ED (few studies, likely worsened, additional salvage tx with ADT increase osteoporosis, CVD, other issues)
Secondary malignancy (little date, confounding i.e. smoking, real risk not known)
271
For EBRT what is moderate and conventional fractionation:
Moderate hypofractionation: 240-340 cGy per fraction
Conventionally fractionated 180-200 cGy per fraction
Ultrahypofactionated _\>_ 500 cGy per fraction
272
In men with low risk prostate cancer who decline AS, which RT SHOULD be _offered_?
GUIDELINES STATEMENT 1A
EBRT to prosate w/ or w/o SV
Offer moderate hypofractionation
273
In men with intermediate risk prostate cancer RT SHOULD be _offered_?
GUIDELINE STATEMENT 1B
EBRT to prosate w/ or w/o SV
Offer moderate hypofractionation
274
In men with high risk prostate cancer RT SHOULD be _offered_?
GUIDELINE STATEMENT 1C
Prostate, _not_ PLN
Offer moderate hypofractionation
275
Moderate hypofractionation should be offered to whom? What about f/up of studies?
GUIDELINE STATEMENT 1D
Offer regardless of patient age, comorbidity, anatomy, and urinary function
→ limited f/up beyond 5 years for most RCTs
276
What should men be counseled about regarding toxicities with moderate hypofractionation?
GUIDELINE STATEMENT 1E
small increased risk of acute GI toxicity
similar risk of acute and late GU and GI toxicity compared to conventional
277
What regimen of hypofractionated EBRT SHOULD be delivered? Is one recommended over another based on cancer or patient features?
GUIDELINE STATMENT 2A
6000 cGy delivered in 20 fractions of 300 cGy (4 weeks)
7000 cGy delivered in 28 fractions of 250 cGy
GUIDELINE STATEMENT 2B
One moderate hypofractionated regimen is not suggested over another for specific risk group
Efficacy of regimens does not appear to be impacted by age, comorbidity, anatomy, or urinary function
278
In men with CaP describe which men you can consider ultrahypofractionated RT?
GUIDELINE STATMENT 3A
Low-risk men who decline AS
GUIDELINE STATEMENT 3B
Intermediate-risk men (strong encouragement to participate in clinical trial or multi-institutional registry)
GUIDELINE STATEMENT 3C
High-risk men NO ultrahypofractionation outside of clinical trial or multi-institutional registry
279
What is ultrahypofractionated RT doses targeted to low and intermediate risk patients? What prostate size?
GUIDELINE STATEMENT 4A
3500 - 3625 cGy in 5 fractions of 700 - 725 cGy
Prostate volume \< 100 cc
GUIDELINE STATMENT 4B
5 fractions at doses of 3625 c Gy and above is not suggest outside trial or registry due to late toxicity
GUIDELINE STATEMET 4C
5 fraction using consecutive daily treatments is not suggested (late urinary and rectal toxicity)
280
For moderately- or ultra- hypofractionated tissue constraints used in clinical trials for RT compare in terms of toxicity and QOL?
GUIDELINE STATEMENT 5A
At least 2 low-dose volume constraint points for rectum and bladder should be used, one at high-dose end (near the total dose prescribed) and one in the mid-dose range (near the midpoint of the total dose)
GUIDELINE STATEMENT 5B
Use of normal tissue constraints differing from published studies is NOT recommended
281
What are other key features of RT with moderate hypofractionation or ultrahypofractionation?
GUIDELINE STATEMENT 6A
Not recommended for volume and margin definitions other than those published
GUIDELINE STATEMENT 7A
IGFR is universally recommended
GUIDELINE STATEMENT 8A
Non-modulated 3-D CRT techniques are not recommended
282
What are some worrisome features when considering RALP?
Advanced age
Hx of intra-abdominal and pelvic sx (collateral damage for adhesions etc.)
Post biopsy prostatitis/sepsis (impact tissue planes)
283
What should you do for a patient with hx of CaP, severe low back pain, weakness in LE, decreased rectal tone on DRE?
Concern mets and cauda equina syndrome
NSG consult
MRI
Possible urgent surgical decompression
284
What is the quickest way to medically castrate a CaP patient?
Ketoconazole and Prednisone → inhibits multiple cytochrome p450 enzymes, inhibits production of glucocorticoids and mineralocorticoids, castrate in 8 h
GnRH antagonists → block pituitary receptors, no flares, castrate in days (follow LFTs)
285
What are AUA recs for Abx ppx in patients with previous joint replacement? What is recommended?
Must meet **_both_** criteria below:
1. **Increased risk of hematogenous total joint infections**: 2 years after replacement, immunocompromised (inflammatory arteriopathies, drug induced, radiation), comorbidities (previous joint infections, malnourishment, hemophilia, HIV, DMII, cancer)
2. **Increased risk of bacteremia associated with urologic procedures**: stone manipulation, transmural incision into urinary tract, endoscopic procedure of upper tract, including bowel segments, _prostate biopsy_, high risk of colonization (indwelling or CIC, stent, retention, hx of recurrent UTI, diversion)
Tx:
single Quinolone dose, amp (2 g) + gent (1.5 mg/kg)
286
How does Bactrim (TMP/SMX) work?
inhibiting folate in bacterial cells → death
a/e nausea, vomiting, rash, diarrhea, Steven's Johnson, c. diff
287
How many men avoid treatment because of AS?
67%
288
What are predictors of positive response to SRT?
Radiation dose and modality
Slow PSADT (\< 10 mo)
Low pre-radiation PSA (optimally \<0.5)
Low Gleason score
289
Compare SRT to ART?
RFS → SRT: 47% ART: 52%
MFS → SRT: 69% ART: 70%
OS → SRT: 72% ART: 73%
\*Insufficient data, little long term difference
290
What are the theoretical mechanisms of RT + ADT synergistically?
1. Alter PSA kinetics in patients who eventually relapse
2. Systemic disease control (micromets might retain sensitivity to ADT)
291
Why can't you compare observational studies for ART and SRT?
1. Differences in failure definition, follow up duration, RT technique, use of ADT
2. SRT usually higher dose than ART
3. ART with more adverse pathology
4. ART studies include low risk patients w/ or /wo RT, so skews results
292
Patient presents with PSA 20, up from 2.3, 1 mo ago, with hx of RALP, pT3bN1M0? Labs? Imaging?
PSA, testosterone, LDH, Hgb, ALP
CT A/P, Bone Scan, F18 PET +/-
293
A/E of Abiraterone
Fluid retention
HTN
Hypokalemia
Liver dysfunction
(Monitor: PE (edema) BP, K+, LFTs → AST, ALT, bili q 2 weeks x 3 mo, then monthly)
294
The most common a/e of docetaxel?
infections, neutropenia, anemia, febrile neutropenia, hypersensitivity, thrombocytopenia, neuropathy, dysgeusia (taste), dyspnea, constipation, anorexia, nail disorders, fluid retention, asthenia, pain, nausea, diarrhea, vomiting, mucositis, alopecia, fingernail changes
295
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