Campbell Prostate Cancer + NCCN 2.2021 Flashcards
The American Brachytherapy Society guidelines suggest that prostate glands that are greater than ___ are technically more difficult to implant because of: ___ and ___;
___ can reduce prostate volumes by ___ % to optimize gland before brachytherapy
60cm
- increased frequency of pubic arch interference - large number of seeds required
Cytoreductive ADT
25% to 40%
Prostate volumes in excess of ___ may require ___ before RT to reduce volume of rectum or bladder exposed to radiation.
Neoadjuvant ADT for cytoreduction
Transurethral resection of the prostate (TURP) ____ (before or after?) external radiation, rather than after, may be advisable for men in, or at risk of, retention.
BEFORE radiation!
** post-treatment transurethral resection is performed, there may be a higher associated risk of incontinence (Polland et al., 2017), particularly after brachytherapy with up to 18% of men incontinent after TURP
Contraindications to RT for prostate cancer
Previous radical pelvic irradition
Previous pelvic surgery: potentially trap bowel within pelvic field
PResence of substantial or susceptible bowel (hernia ex.)
Poor tissue healing (chronic steroid therapy)
Risk strat:
Very low
• T1c AND
• Gleason score ≤6/grade group 1 AND
• PSA <10 ng/mL AND
• Fewer than 3 prostate biopsy fragments/cores
positive, ≤50% cancer in each fragment/core AND
• PSA density <0.15 ng/mL/g
Imaging: NOT indicated
Risk strat:
Low
- T1–T2a AND
- Gleason score ≤6/grade group 1 AND
- PSA <10 ng/mL
Imaging: NOT indicated
Risk strat:
Favorable intermediate
- T2b–T2c OR
- Gleason score 3+4=7/grade group 2 OR
- PSA 10–20 ng/mL AND
- Percentage of positive biopsy cores <50%
Imaging:
• Bone imaging: not recommended for staging
• Pelvic ± abdominal imaging: recommended if
nomogram predicts >10% probability of pelvic lymph node involvement
Risk Strat:
Unfavorable intermediate
• T2b–T2c OR
• Gleason score 3+4=7/grade group 2 or Gleason
score 4+3=7/grade group 3 OR
• PSA 10–20 ng/mL
Imaging:
- Bone imaging: recommended if T2 and PSA >10 ng/mL
- Pelvic ± abdominal imaging: recommended if nomogram predicts >10% probability of pelvic lymph
Risk strat:
High
• T3aOR
• Gleason score 8/grade group 4 or Gleason score
4 +5=9/grade group 5 OR
• PSA >20 ng/mL
Imaging:
• Bone imaging: recommended
• Pelvic ± abdominal imaging: recommended if
nomogram predicts >10% probability of pelvic lymph
Risk strat:
Very high
• T3b–T4 OR
• Primary Gleason pattern 5 OR
• >4 cores with Gleason score 8–10/grade group 4
or 5
Imaging:
• Bone imaging: recommended
• Pelvic ± abdominal imaging: recommended if
nomogram predicts >10% probability of pelvic lymph
Observation is most frequently employed in ___ .
General ffu consists of:
Men at low risk of prostate cancer death
Periodic PSA testing, clinical exam, use of imaging to monitor progression
SURVEILLANCE should be recommended as the best care option for ___ and preferable care option for ___ localized prostate cancer.
best for VERY LOW RISK
preferable for LOW RISK
Death in men on active surveillance, most commonly from ___
Cardiovascular disease
** Rarely from prostate cancer
Risk factors:
____ race found be associated withdverse pathologic outcomes such as positive surgical margins, upgrading, or upstaging.
African-American race
A history of ___ is significant and may reflect a germline disposition to prostate cancer.
A history of metastatic disease at a young age (<60) in a first-degree relative
Advising men to ____ is the single most cost-effective health intervention in the entire edifice of medical practice.
QUIT SMOKING!
Patients taking ___ in the SELECT trial had an increased risk of prostate cancer.
Patient consuming >=140 micrograms/day of supplemental ___ had 2.6 times greater disease-specific mortality.
Vitamin E
Selenium
Lifestyle recommendations for active surveillance: ___
- Exercise regularly, and include vigorous activity if possible.
- Maintain a healthy weight.
- Stop smoking.
- Eat a vegetable- and grain-based diet; moderate red meat consump-
tion, especially processed meats; if eating meat, rely on fish and
skinless poultry. - Limit saturated fat intake.
- Take vitamin D, 1000 to 2000 IU/day, especially during periods
of reduced sunlight. - Consider a low-dose statin.
IMRT
Intensity-modulated radiation therapy
IMRT employs more complex, dynamic beam shapes wherein the intensity of radiation is varied across the beam (as opposed to uniform intensity across the beam in 3DCRT)
Low-dose-rate Brachytherapy
Permanent seed implantation: Delivers a dose over a number of weeks to months depending on the isotope chosen, hence the term low- dose-rate
125Iodine emits low-energy x-rays at 27 keV, with a half-life of 59.6 days.
103Palladium was introduced in 1986 because it has an energy spectrum similar to that of 125I, with 21-keV x-rays, but with a significantly shorter half-life of 17 days.
131Cesium, which emits x-rays at 30 keV (thereby offering dose characteristics similar to 125I)
High-dose-rate Brachytherapy
Delivers short but high doses of radiation using temporary catheters
Hollow catheters are placed through the perineum into the prostate using the same procedure as for LDR brachytherapy
iridium-192 (192Ir)
Advantages of HDR vs. LDR Brachytherapy:
The use of catheters allows for more ready inclusion of extracapsular
disease and seminal vesicles, if desired.
• There is greater opportunity for dose optimization by modifying
dwell times and positions of the source within the catheters.
• The use of high doses per fraction has a potential biologic dose advantage for prostate cancer if a low alpha/beta ratio exists.
• No need for personnel to handle the radioactive source during
treatment.
• The use of a single source for all patients using a multipurpose
facility makes HDR brachytherapy potentially more cost-effective.
Potential disadvantages for HDR versus LDR brachytherapy include: • There are potential treatment inaccuracies caused by catheter and organ/patient movement between imaging and time of source insertion (during treatment planning) or between fractions, interobserver contouring variabilities, and effects of edemaThe relatively high activity and energy of the 192Ir source requires
availability of a shielded room for treatment delivery.
• There are less favorable pathologic response results from avail- able post-treatment biopsy studies
Major acute toxicity of brachytherapy is ___
Obstructive and irritative uropathy
Low but non-negligible risk of need for temporary catheterization.
Relative contraindications to brachytherapy:
Large TURP defects, TURP within prior 3-6months
Factors assoc. with poor urinary outcomes or obstruction: Qmax < 10, IPSS >20, large median lobe
Prior pelvic RT
Connective tissue disease or IBD
Pubic arch interference
Lithotomy position
Rectal fistula or lack of TRUS access
The most important pathologic criteria predicting prognosis after radical prostatectomy are:
Gleason score Surgical margin status, Extracapsular extension Seminal vesicle invasion Lymph node involvement
Many men with clinical stage T3 disease have ____ and may not benefit from prostatectomy.
Select (low-volume disease) may benefit because local control may be achieved in most.
Regional spread
The presence of ___ increases progression from 7% to 18-35% at 5 years.
Focal or established extracapsular extension
Radical prostatectomy alone can result in disease-free survival in ___ despite clinically advanced disease.
At least one-half of men at 8 to 10 years
____ therapy before radical prostatectomy does NOT appear to improve DSS or OS.
Neoadjuvant androgen deprivation (NAD)
** For locally advanced tumors (specifically cT3), current data, both retrospective and prospective, do not support a significant benefit of NAD before surgery
The use of adjuvant RT is associated with ___.
Early use of ___ may be beneficial for advanced tumors at the time of biochemical recurrence in select patients.
A range of BDFS (biochemical disease free survival) from 50% to 88% at 5 years
secondary therapy (RT or AD)
Men with seminal vesicle invasion who achieve a low PSA level (<0.3 ng/mL) after prostatectomy or have positive surgical margins may benefit more from ___.
men with more advanced disease never reaching an undetectable PSA level generally constitute a poor prognostic group likely harboring ___.
Adjuvant RT.
Unrecognized lymph node or distant disease.
Postradiation PSA “bounce”
NOT ALL MEN ARE DESTINED FOR BIOCHEMICAL
Varied definition: elevated PSA of 0.1 ng/mL to 0.5 ng/mL over the prebounce PSA with a subsequent decrease in PSA.
Occurred at a mean time of 9 months
Associated with an improvement in biochemical recurrence–free survival compared with those who did not have a bounce
Patients selected for salvage RP must have the ff: ___
Biopsy-proven radiorecurrent prostate cancer
At least 10 years of life expectancy
Lack of identifiable metastasis on imaging
PSA of less than 10 ng/mL
All current forms of hormonal therapy in PCA function by: ___
Reducing the ability of androgen to activate the AR
** by lowering androgen levels, decreasing conversion of testosterone to more potent DHT, or blocking androgen-AR binding
___ is overexpressed in 20-30% of CRPC metastases.
AR gene
** enhances response to low levels of endogenous androgens
AR mutations and splice variants:
___ predominant splice variant has been strongly associated with castration resistance and overall poor patient survival
AR-V7
GnRH agonists
Leuprolide
Goserelin
Triptorelin
SOA: Pituitary
MOA: Stimulates release of LH; feedback loop ultimately decreases LH production
Mainstay of therapy for metastatic disease; leads to increase in FSH; considerable side effects
GnRH antagonists
Degarelix
Abarelix
Cetrorelix
SOA: Pituitary
MOA: Binds to receptors and blocks release of GnRH
Prevents testosterone surge; leads to decrease in FSH; considerable side effects
Adrenal-targeting drugs
Ketoconazole Abiraterone Oreteronel (TAK-700)
Galeterone
SOA: Adrenal
MOA: Decreases androgen production from steroid precursors by blocking cytochrome P450 enzymes
Selective CYP17 inhibitors administered with low-dose prednisone; side effects can include hypertension, edema, and hypokalemia
1st generation AR antagonists
Flutamide Nilutamide Bicalutamide
SOA: Prostate, PCA
MOA: Nonsteroidal antiandrogen inhibits binding of testosterone and DHT to the AR
Monotherapy not indicated; associated with gynecomastia
2nd generation AR antagonists
Enzalutamide Apalutamide
SOA: Prostate, PCA
MOA: Blocks AR, minimizes nuclear translocation of AR, and diminishes AR-mediated transcription
Associated with falls, fatigue, and decreased appetite
5alpha-reductase inhibitors
Finasteride (type II isoenzyme inhibition)
Dutasteride (type I and II isoenzyme inhibition)
SOA: Prostate, PCA
MOA: Inhibits the conversion of testosterone to DHT
Commonly administered for BPH; not indicated for prostate cancer management
Four approaches for androgen blockade:
(1) surgical removal of the testicles (orchiectomy),
2) AR antagonism,
(3) inhibition of LHRH and/or LH, and
(4) inhibition of androgen synthesis
About one-quarter of men on ___ therapy note a delayed adaptation to darkness after exposure to bright illumination.
NIlutamide
** Effects reversible with cessation
Most common side effects of enzalutamide: ___
Fatigue, breast enlargement/tenderness, diarrhea, and hot flashes.
** Seizures were more common in men taking enzalutamide compared with placebo but occurred in less than 1%
Common side effects of apalutamide: ___
25% of men Experienced a rash, 12% experienced falls and fractures, and 8% had hypothyroidism
In a review of 24 trials involving more than 6600 patients, survival after therapy with ___ was equivalent to orchiectomy
An LHRH agonist
*** flare of LH and testosterone levels, resulting in a severe, life-threatening exacerbation of symptoms, almost exclusively occurring in men with metastases in the spine or weight-bearing regions
