Genitourinary Malignancies - Board Review Summary
ORAL-BOARD INTAKE CHECKLIST
Prostate Consult Script
| Domain | What to ask / check | Why it matters |
|---|---|---|
| Fitness and goals | Age, life expectancy, comorbidities, anticoagulation, baseline performance, competing mortality, and patient preference for AS vs RT vs RP. | Low-risk disease may need no treatment; high-risk treatment intensity depends on biology, competing mortality, and tolerance. |
| Urinary / sexual baseline | AUA/IPSS, bother score, obstructive vs irritative symptoms, nocturia, incontinence, IIEF/sexual function, alpha-blocker use. | High IPSS affects SBRT and brachy candidacy and predicts GU toxicity; baseline erectile/urinary function drives counseling. |
| Anatomic flags | Prior TURP/HoLEP, median lobe, gland size, hip prostheses, inflammatory bowel disease, prior pelvic RT/surgery, rectal procedures. | Changes modality, margins, image guidance, brachy feasibility, and rectal/bladder risk. |
| Pre-RT housekeeping | Colonoscopy if due before pelvic RT, medication review, germline testing triggers, fertility discussion when appropriate, and dental/medical optimization when needed. | Avoids post-RT rectal instrumentation and catches inherited-risk or systemic-therapy implications. |
| ADT readiness | Cardiometabolic history, diabetes/lipids, mood/cognition, hot flashes, baseline testosterone when relevant, DEXA/calcium/vitamin D for longer-course ADT. | ADT toxicity is part of the RT plan, not an afterthought. |
Gynecomastia pearl: with nonsteroidal antiandrogen exposure, tamoxifen is usually the most effective prevention/treatment. Prophylactic low-dose electron RT to breast buds can reduce gynecomastia/breast pain, but it is less common and should be individualized.
PART I - PROSTATE: WORKUP, DEFINITIONS, AND RISK STRATIFICATION
Risk Groups and Treatment Frame
| Risk group | Core features | Practical treatment implication |
|---|---|---|
| Low risk | Generally cT1-T2a, GG1, PSA <10 | Active surveillance preferred. Definitive treatment only for strong preference, progression, or hidden adverse features. |
| Favorable intermediate risk | Single IR feature, GG1-2, and limited core burden | AS may be reasonable in selected low-volume GG2 with favorable MRI/genomics and no cribriform/intraductal disease. RT alone is often enough if treating. |
| Unfavorable intermediate risk | At least 2 IR features, any GG3, or ≥50% positive biopsy cores | Definitive RT + short-course ADT is the clean board answer. |
| High risk | cT3a, GG4-5, or PSA >20 | Definitive RT + long-course ADT. Consider pelvic RT and dose intensification selectively. |
| Very high risk | Examples include cT3b-T4, primary Gleason pattern 5, multiple high-risk features, or high-volume GG4-5 cores | Curative-intent RT + long-course ADT. Add systemic intensification for cN1 or STAMPEDE-like high-risk biology when appropriate. |
| cN1 M0 | Pelvic nodal disease without distant metastasis | Curative-intent EBRT + long-course ADT + abiraterone/prednisone is the major modern intensification answer. |
Do not over-anchor on labels: the important low-risk decision is whether a patient is safe for active surveillance. Favorable intermediate-risk surveillance should require favorable volume, MRI, pathology, and patient reliability.
Definitions to Memorize
Biochemical failure after definitive RT: nadir + 2 ng/mL (Phoenix definition).
After SBRT: true recurrence is more convincing when nadir + 2 occurs after 18 months, or if PSA at 18 months divided by PSA at 6 months is >~2.5.
Biochemical recurrence after RP: ≥0.2 ng/mL on 2 readings.
Surrogate endpoint pearl: MFS, not BCR or FFBF, is the validated surrogate for OS.
After SBRT: true recurrence is more convincing when nadir + 2 occurs after 18 months, or if PSA at 18 months divided by PSA at 6 months is >~2.5.
Biochemical recurrence after RP: ≥0.2 ng/mL on 2 readings.
Surrogate endpoint pearl: MFS, not BCR or FFBF, is the validated surrogate for OS.
Imaging, Genomics, and Germline Testing
- PSMA PET is a major staging tool in unfavorable intermediate-risk, high-risk, recurrent, and metastatic disease. It causes stage migration, so do not compare PSMA-era outcomes casually with older conventional-imaging trials.
- ProPSMA showed superior accuracy versus CT + bone scan in higher-risk staging.
- In salvage, PSMA PET yield is limited at very low PSA, especially <0.2. A negative scan should not block clinically indicated prostate-bed RT.
- Decipher is the most relevant RT-adjacent genomic classifier and is built into multiple NRG strategies.
- Germline testing is especially relevant for metastatic, regional, very high-risk, strong family-history, young-onset, Ashkenazi ancestry, intraductal/cribriform, or DNA-repair-suspicious disease.
ProtecT and Cribriform Disease
ProtecT remains the core counseling trial for localized prostate cancer. At 15 years, prostate-cancer mortality was low and similar across active monitoring, RT, and surgery, but metastases were more frequent with monitoring. About 50% of active-monitoring patients underwent treatment by 10 years.
Cribriform / intraductal pearl: cribriform or intraductal carcinoma should push away from surveillance. It is a pathology-based "do not monitor casually" feature, especially in GG2-3 disease.
PART II - INTACT PROSTATE: AS, RT, RP, FRACTIONATION, AND TECHNIQUE
Localized Intact Prostate: Management Paradigm + Dose Anchors
| Scenario | Board-management answer | Dose / systemic anchor |
|---|---|---|
| Low risk | Active surveillance preferred. RT, RP, or brachytherapy only for progression, strong preference, or adverse feature reclassification. | No ADT. If treating: prostate-only EBRT 60 Gy / 20, SBRT 36.25-40 Gy / 5, or brachy monotherapy in selected anatomy. |
| Favorable intermediate risk | AS, RT, or RP depending on age, MRI/biopsy volume, cribriform/intraductal absence, genomics, and preference. RT alone is often enough. | No routine ADT. Prostate-only 60 Gy / 20 or SBRT 36.25 Gy / 5. Consider DIL boost only when imaging-defined and constraints permit. |
| Unfavorable intermediate risk | Definitive RT plus short-course ADT; pelvic nodes are selective rather than automatic. | Prostate 60 Gy / 20 or SBRT in selected patients; ADT 4-6 months. Avoid focal therapy outside trial. |
| High risk | Definitive RT plus long-course ADT. Dose escalation is best done by DIL boost or brachy boost in selected patients, not blind whole-gland escalation. | Prostate 60 Gy / 20 or conventional dose-escalated RT; ADT 18-36 months is the clean board answer. FLAME example: 77 Gy / 35 with DIL SIB to 95 Gy. |
| Very high risk / cN1 M0 | Curative-intent EBRT plus long-course ADT and systemic intensification, especially abiraterone for cN1 or STAMPEDE-like biology. | Modern 20-fx schema: prostate 60 Gy / 20, elective pelvis 44 Gy / 20, involved nodes up to 55 Gy / 20; add ADT + abiraterone/prednisone when appropriate. |
AS vs RT vs RP
ProtecT: no overall-survival difference among active monitoring, RT, and RP, but functional tradeoffs were different. Surgery produced the most durable incontinence and worse erectile dysfunction. RT caused more bowel bother, though the RT arm used older techniques without modern IMRT, IGRT, or spacers.
High-risk counseling pearl: low- and intermediate-risk disease are often more equivalent across modalities. In high-risk disease, RT plus systemic therapy may reduce metastatic risk more effectively than surgery alone, but local treatment should be individualized and multimodality therapy is often needed either way.
Conventional vs Moderate Hypofractionation
| Trial | Regimens | Main result | Board takeaway |
|---|---|---|---|
| RTOG 0415 | 73.8/41 vs 70/28 | Similar FFBF; more grade 2 GI with hypofractionation | Non-inferiority in low risk |
| PROFIT | 78/39 vs 60/20 | Same FFBF; late GI may be lower with 60/20 | Key regimen supporting moderate hypofractionation |
| CHHiP | 74/37 vs 60/20 vs 57/19 | 60/20 non-inferior to 74/37 | 60 Gy / 20 fx is the memorized standard |
| HYPRO | 78/39 vs 64.6/19 | Similar control, more grade 3 GU in hypofractionated arm | Not all hypofractionation is equal |
MARCAP HYDRA: isodose moderate hypofractionation, exemplified by 60 Gy / 20, is the current standard. Dose-escalated moderate hypofractionation does not clearly improve efficacy and increases GI toxicity.
Whole-gland dose principle: there is limited benefit to escalating the whole gland beyond about 80 Gy EQD2. The memorable equivalents are about 80 Gy at 2 Gy/fx, 60 Gy at 3 Gy/fx, or 37.5 Gy in 5 fx.
SBRT and Modern Platform Trials
| Trial | Comparison | Main message |
|---|---|---|
| PACE-A | SBRT vs RP | RP produced permanently worse incontinence and sexual function; SBRT caused more temporary bowel bother |
| PACE-B | 36.25 Gy / 5 vs conventional / moderate-hypo RT | Non-inferior efficacy; very low grade 3 toxicity; more cumulative grade 2+ GU with SBRT |
| PACE-C | 36.25 Gy / 5 vs 60 Gy / 20 with ADT | Similar early efficacy and overall toxicity; early GI signal slightly favored moderate hypofractionation |
| MIRAGE | MR-guided vs CT-guided SBRT | Tighter MR margins reduced toxicity |
| PartiQOL | Proton vs photon | No meaningful QOL or disease-control advantage for protons |
Spacer pearl: spacers reduce rectal dose and may reduce some acute grade 2 GI toxicity. Patient-reported QOL advantages are less consistent, and placement complications can occur. Do not place a spacer when posterior extracapsular extension makes the anatomy unsafe.
Focal Therapy, Brachytherapy, and LUTS
- Focal therapy is not a board-standard replacement for RT or RP. Recurrence is common and randomized comparative data are limited; use mainly in trial or highly selected counseling contexts.
- Brachytherapy remains a technically strong option in selected anatomy, especially as a boost for high-risk disease, but toxicity and urinary selection matter.
- ASCENDE-RT is the classic brachy-boost trial: better biochemical control, no OS gain, and much more grade 3 GU toxicity.
- HDR Monotherapy Fractionation: Multi-fraction HDR (e.g., 27 Gy / 2 fx) provides significantly better biochemical control and lower local failure rates at 8 years compared to single-fraction HDR (e.g., 19 Gy / 1 fx). Do not use 1-fraction HDR monotherapy outside of a clinical trial.
- IPSS ≥15-25 is a relative contraindication to prostate RT, and the threshold is lower for SBRT or brachytherapy. Evaluate UTI, medications, obstruction, and systemic causes before blaming RT for LUTS.
PART III - INTACT PROSTATE INTENSIFICATION: ADT, DOSE, PELVIS, AND NODES
Who Needs ADT?
| Risk group | Typical ADT approach | Board-style summary |
|---|---|---|
| Low risk | None | Active surveillance preferred |
| Favorable intermediate risk | Usually none | ADT benefit is not compelling in FIR |
| Unfavorable intermediate risk | 4-6 months | Best-supported short-course ADT group |
| High risk | 18-36 months on boards | ADT improves MFS and OS |
| Very high risk / cN1 | Long-course ADT + abiraterone in appropriate patients | Main modern intensification strategy |
RTOG 9408, EORTC 22991, and RTOG 0815 teach that short-course ADT in intermediate-risk disease improves biochemical, metastatic, and prostate-cancer-specific endpoints, but the benefit is strongest in unfavorable intermediate-risk disease.
MARCAP / SANDSTORM: concurrent + adjuvant ADT is better than prolonged neoadjuvant + concurrent ADT. This is a high-yield sequencing pearl.
High-Risk Dose Escalation
| Trial | Schema | Main result | Takeaway |
|---|---|---|---|
| ASCENDE-RT | EBRT boost vs LDR brachy boost after pelvic RT + ADT | Large bPFS gain, no OS gain, major increase in grade 3 GU | Brachy boost improves control but is toxic |
| FLAME | 77 Gy / 35 vs same + DIL SIB to 95 Gy | Improved bDFS without significant late GU/GI penalty | Best modern dose-escalation strategy |
| GETUG-18 | 70 Gy vs 80 Gy with 36 months ADT | OS signal favored 80 Gy, but toxicity and interpretation caveats remain | Important positive trial, not a reason for blind escalation in every patient |
Systemic Intensification Beyond ADT
| Trial | Intensification | Main result | Board takeaway |
|---|---|---|---|
| RTOG 0521 | Docetaxel added to RT + ADT | Early OS signal faded with longer follow-up | Do not routinely add docetaxel to all high-risk M0 men |
| STAMPEDE G/J | Abiraterone/prednisone with or without enzalutamide added to RT + ADT | Clear MFS and OS benefit with abiraterone; no added efficacy from enzalutamide, only more toxicity | Use abiraterone, not abiraterone + enzalutamide, in cN1 / very high-risk M0 |
Whole-Pelvis RT
| Trial | Main result | Interpretation |
|---|---|---|
| RTOG 9413 | Complicated 2 x 2 design; not cleanly definitive for modern pelvic RT | Historic but hard to apply literally |
| POP-RT | Improved bFFS and DMFS with WPRT; no OS difference | Best positive modern nodal-RT trial, but still debated |
| RTOG 0924 | Early reported: no DM or OS benefit for WPRT | Whole-pelvis RT is selective, not automatic |
| HOPE | Pelvic 25 Gy / 5 after HDR boost had similar QOL to conventional pelvic RT | Interesting hypofractionated pelvic strategy |
cN1 M0 answer: treat pelvic node-positive disease at diagnosis with curative intent using EBRT + ADT + abiraterone. A practical 20-fraction schema is prostate 60 Gy / 20, elective pelvic nodes 44 Gy / 20, and involved pelvic nodes up to 55 Gy / 20.
PART IV - POST-PROSTATECTOMY, SALVAGE, AND RADIORECURRENT DISEASE
Post-Prostatectomy / Salvage: Management Paradigm + Dose Anchors
| Scenario | Board-management answer | Dose / systemic anchor |
|---|---|---|
| Adverse pathology, PSA undetectable | Observation with early salvage is preferred for most. Reserve adjuvant RT for unusually high-risk shared-decision cases. | No routine adjuvant RT for the average patient with pT3/positive margin and undetectable PSA. |
| Early salvage PSA rise | Do not wait for high PSA; salvage earlier is better, and PSMA-negative imaging should not block prostate-bed RT when clinically indicated. | Prostate bed commonly 64-66 Gy; avoid routine escalation beyond about 66 Gy. |
| Salvage ADT decision | Pre-salvage PSA is prognostic and predictive. ADT benefit is small at very low PSA unless high-risk features are present. | Consider no ADT for PSA <0.5 and favorable features; consider 4-6 months ADT for higher-risk early salvage; higher PSA/later salvage supports stronger systemic discussion. |
| Pelvic nodes in salvage | Pelvic RT is an intensification strategy when nodal risk is meaningful; do not use pelvic RT alone as the intensification. | SPPORT-style treatment: prostate bed + pelvic nodes + short-course ADT; tailor to PSMA PET, pathology, PSA kinetics, and Decipher. |
| pN1 after RP | Usually consider prostate bed/pelvic RT + ADT when PSA is detectable or recurrence risk is high. Abiraterone/systemic intensification is a selected, multidisciplinary extrapolation rather than a simple one-size-fits-all rule. | Longer ADT and systemic intensification are most compelling with detectable PSA, multiple nodes, adverse pathology, high genomic risk, or PSMA-positive pelvic disease. |
| Biopsy-proven local recurrence after prior RT | Confirm local-only disease and urinary/rectal feasibility; salvage SBRT or brachytherapy are the strongest local RT options in selected patients. | Regimen is site/anatomy dependent; counsel carefully about urinary toxicity, fistula/rectal risk, and need for experienced salvage team. |
Adjuvant vs Early Salvage
ARTISTIC plus RAVES, RADICALS-RT, and GETUG-17 established that early salvage RT is favored over routine adjuvant RT for most men with adverse pathology after RP. Adjuvant RT improves biochemical control but increases overtreatment and toxicity, without a clear OS gain for the average patient.
Adjuvant RT: post-RP RT with undetectable PSA for adverse pathology.
Salvage RT: post-RP RT for rising PSA.
Early salvage: generally PSA <0.5.
Very early salvage: PSA 0.01-0.2.
Salvage RT: post-RP RT for rising PSA.
Early salvage: generally PSA <0.5.
Very early salvage: PSA 0.01-0.2.
Post-Op Dose, Fractionation, and Volume
Dose: no clear routine role for escalating the prostate bed beyond about 66 Gy.
Hypofractionation: NRG GU-003 supports moderate hypofractionated salvage RT from a 2-year QOL standpoint, but long-term late toxicity remains important.
Volume: PSMA PET failure analyses suggest some recurrences are posterior, inferior, and lateral to classic postop bed volumes, so do not draw the bed too narrowly.
Hypofractionation: NRG GU-003 supports moderate hypofractionated salvage RT from a 2-year QOL standpoint, but long-term late toxicity remains important.
Volume: PSMA PET failure analyses suggest some recurrences are posterior, inferior, and lateral to classic postop bed volumes, so do not draw the bed too narrowly.
Who Benefits from ADT in Salvage RT?
| Trial | Main result | Board takeaway |
|---|---|---|
| RTOG 9601 | Bicalutamide improved OS overall, but benefit was concentrated in higher pre-salvage PSA, especially >1.5 | At very low PSA, ADT benefit is small and may be offset by harm |
| GETUG-16 | 6 months LHRH improved BCR endpoints | Mostly an early-salvage / biochemical-benefit trial |
| SPPORT / RTOG 0534 | Most of the benefit came from adding ADT; no evidence supporting pelvic RT alone | If you intensify, do not forget the systemic part |
| POSEIDON | No meaningful OS benefit to adding hormone therapy when pre-PORT PSA was ≤0.5 | Very low PSA is the key "do less" group |
| RADICALS-HD | No OS benefit to adding short-course ADT; marginal MFS benefit, but no OS benefit, to long-course over short-course ADT | No compelling reason for routine prolonged hormone therapy postop |
Post-op synthesis: in early salvage disease with PSA roughly 0.1-0.5, ADT usually does not improve MFS or OS meaningfully. In later salvage, especially with higher PSA, adverse pathology, rapid PSADT, or high Decipher, the case for ADT is stronger.
High-Risk BCR and EMBARK
EMBARK: high-risk biochemical recurrence was PSA >2 after RT or >1 after RP, PSA doubling time ≤9 months, and testosterone >150 ng/dL in patients not suitable for salvage RT at enrollment. Enzalutamide + leuprolide improved MFS versus leuprolide alone. Board nuance: this does not mean systemic therapy should replace curative salvage RT when salvage RT is appropriate.
Radiorecurrent Local Failure After Prior RT
MASTER: among salvage local options after prior RT, SBRT and brachytherapy appear to have the best combination of control and toxicity in selected patients. This is retrospective evidence, but it is highly board-relevant.
PART V - METASTATIC PROSTATE: PRIMARY RT, MDT, mHSPC, AND mCRPC
Metastatic Prostate: Management Paradigm + Dose Anchors
| Scenario | Board-management answer | Dose / systemic anchor |
|---|---|---|
| De novo low-volume mHSPC | Systemic intensification plus RT to the primary is standard for appropriately fit patients. | Primary RT anchors: 55 Gy / 20 daily or 36 Gy / 6 weekly; systemic backbone ADT + ARPI. |
| De novo high-volume / visceral mHSPC | Primary RT does not clearly improve OS; use for symptoms, local control, or prevention of serious GU events in selected patients. | Systemic therapy drives survival; RT dose depends on palliative vs durable local-control intent. |
| Oligorecurrent HSPC | MDT/SBRT to all visible disease is a reasonable progression-delaying strategy in selected patients with limited lesions and good systemic options. | SBRT commonly 16-20 Gy x 1, 27-30 Gy / 3, or 30-40 Gy / 5 by site/OAR; PSMA PET improves lesion detection. |
| Oligoprogressive mCRPC | Consider SBRT when a few resistant clones progress while most disease remains controlled on a valuable systemic line. | Goal is delaying systemic switch; continue ADT and coordinate ARPI/chemo/radiopharmaceutical sequencing. |
| Symptomatic / polymetastatic disease | Palliative RT for pain, cord compression, fracture risk, hematuria/obstruction, or bulky local symptoms. | Common palliation: 8 Gy x 1, 20 Gy / 5, 30 Gy / 10; radiopharmaceuticals for appropriate bone/PSMA-positive mCRPC contexts. |
Low-Volume vs High-Volume Matters
CHAARTED / STAMPEDE high-volume means 4 or more bone metastases with at least one outside the vertebral bodies or pelvis, or visceral metastases, based on conventional imaging. PSMA PET complicates this because some "low-volume" patients by conventional criteria may have more PET-visible disease.
RT to the Primary in De Novo mHSPC
| Trial | Main result | Takeaway |
|---|---|---|
| STAMPEDE Arm H | OS benefit in low-volume metastatic disease | Primary RT is standard in de novo low-volume mHSPC |
| HORRAD | No OS benefit overall | Older negative study, especially in higher-volume disease |
| STOPCAP | Approximate 7% 3-year OS gain for men with <5 bone metastases | Memorize this number |
| PEACE-1 | RT to prostate improved rPFS and delayed serious GU events, but not OS in the abiraterone era | RT still matters, but its value includes local-event prevention |
Metastasis-Directed RT
STOMP, ORIOLE, and EXTEND support MDT as a progression-delaying strategy in oligometastatic prostate cancer. A highly testable, consistent endpoint across these trials is freedom from hormone therapy (ADT-free survival), as MDT safely delays the initiation or resumption of ADT. The WOLVERINE pooled analysis showed hazard ratios roughly 0.5-0.6 across key progression endpoints.
Emerging concept: radioligand therapy before SBRT in oligorecurrent hormone-sensitive disease has shown a strong PFS and ADT-free-survival signal. This is exciting, but it is not yet a routine board-standard replacement for ADT/ARPI decision-making.
Systemic Therapy Landscape the Rad Onc Should Know
| Setting | Systemic anchor | RT implication |
|---|---|---|
| mHSPC | ADT + ARPI is standard for most; triplet therapy is considered for fit high-volume patients. | Primary RT still helps low-volume de novo disease; MDT is selected for oligometastatic/oligorecurrent disease. |
| High-risk BCR | Enzalutamide + leuprolide improves MFS in EMBARK-style patients. | Do not use systemic therapy to skip curative salvage RT when salvage RT is feasible and appropriate. |
| mCRPC with bone-predominant symptomatic disease | Ra-223 improves OS and delays skeletal events in appropriate patients without visceral metastases. | Coordinate focal palliative RT and radiopharmaceutical timing. |
| PSMA-positive mCRPC | Lu-PSMA improves OS after ARPI/taxane and is now also approved after ARPI when taxane delay is appropriate. | Know PSMA PET selection and marrow/renal/salivary toxicity issues. |
| Oligoprogressive mCRPC | ARTO and PCS-9 support MDT in selected patients on ARPI. | Goal is delaying systemic switch, not curing polymetastatic CRPC. |
Radiopharmaceutical Pearls (See Dedicated Page for Full Details)
| Agent / Trial | Mechanism & Board Hook |
|---|---|
| Lu-177-PSMA-617 (VISION, UpFrontPSMA) | Beta-emitter. UpFrontPSMA (mHSPC) highlighted the need for dual-tracer PET (PSMA + FDG). FDG-positive/PSMA-negative discordant disease indicates aggressive, potentially neuroendocrine variants that do not benefit from PSMA-RLT. Hematologic toxicity is cumulative but manageable. |
| Ac-225-PSMA (WARMTH Act) | Alpha-emitter (high LET, RBE ~4.2x higher than Lu-177). Highly effective, but dose-dependent xerostomia is the major limiting toxicity (nearing 100% after multiple cycles). |
| Tb-161-PSMA (VIOLET) | Dual beta and Auger electron emitter. Auger electrons deposit energy over ultra-short (nanometer) distances, making it uniquely effective for single cells and micrometastases with a superior therapeutic index. |
PART VI - BLADDER CANCER
Bladder Cancer: Management Paradigm + Dose Anchors
| Scenario | Board-management answer | Dose / systemic anchor |
|---|---|---|
| CIS / NMIBC | No routine curative RT; manage with TURBT, intravesical therapy, surveillance, and cystectomy for appropriate high-risk/refractory disease. | RT only for unusual palliation or nonstandard salvage contexts. |
| Ideal MIBC bladder preservation | Maximal TURBT followed by continuous-course chemoRT for unifocal cT2-T4a N0-1 disease with good bladder function and no extensive CIS/hydronephrosis. | Preferred anchor 55 Gy / 20 with radiosensitizer such as 5-FU/MMC, gemcitabine, or cisplatin-based therapy depending on fitness. |
| Less ideal but nonsurgical candidate | Bladder preservation may still be reasonable when cystectomy is unsafe, but counsel about lower complete response and salvage options if hydronephrosis, bulky disease, or incomplete TURBT. | Continuous-course bladder-only CRT is usually preferred; elective pelvic nodes are not routine in modern BC2001-style practice. |
| Post-cystectomy high-risk | Adjuvant pelvic/cystectomy-bed IMRT is an option for pT3-4, positive margins, node-positive disease, or low nodal yield where locoregional failure risk is high. | 50.4 Gy / 28 or about 50 Gy / 25; coordinate with diversion/stoma anatomy and systemic therapy. |
| Metastatic / bleeding palliation | RT for hematuria, pain, obstruction, or pelvic symptoms; systemic therapy controls distant disease. | Common palliation: 20 Gy / 5, 30 Gy / 10, or short hemostatic regimens by urgency. |
Staging and Candidate Selection
Where RT matters: CIS no RT; T1 essentially no routine curative RT; T2-T4a N0-1 can be considered for bladder preservation.
T stage: T2 invades muscle, T3 invades perivesical tissue, T4a invades prostate/uterus/vagina, T4b invades pelvic or abdominal wall.
Ideal TMT candidate: unifocal tumor, maximal TURBT, no extensive CIS, no significant hydronephrosis, good bladder function, and ability to undergo cystoscopic surveillance and salvage cystectomy if needed.
T stage: T2 invades muscle, T3 invades perivesical tissue, T4a invades prostate/uterus/vagina, T4b invades pelvic or abdominal wall.
Ideal TMT candidate: unifocal tumor, maximal TURBT, no extensive CIS, no significant hydronephrosis, good bladder function, and ability to undergo cystoscopic surveillance and salvage cystectomy if needed.
Why Bladder Preservation Matters
Modern multi-institutional data and randomized bladder-preservation trials support chemoRT as a mainstream option in selected MIBC. The practical logic is strong: survival can be similar to cystectomy in well-selected patients, cystectomy is morbid, long-term urinary/sexual/body-image QOL can be worse after diversion, and many patients are elderly or frail.
Continuous-Course CRT vs Split-Course CRT
| Paradigm | Field design | Takeaway |
|---|---|---|
| Continuous course | Bladder only, no routine elective pelvic nodes | Preferred modern approach; response assessment after completion |
| Split course / Shipley style | Bladder + pelvic nodes with planned interim cystoscopic reassessment | Historically important but less favored now |
Key Trials and Regimens
| Trial / regimen | RT | Chemo | Main message |
|---|---|---|---|
| BC2001 | 64 Gy / 32 or 55 Gy / 20 | MMC + 5-FU | CRT improved locoregional control vs RT alone |
| BC2001 reduced high-dose volume | 55 Gy / 20 SIB with 44 Gy / 20 to uninvolved bladder | MMC + 5-FU | Partial-bladder dose painting concept |
| RTOG / Michigan gemcitabine era | Daily RT or selected BID approaches | Gemcitabine or cisplatin/5-FU-based radiosensitization | Gemcitabine is a real radiosensitizer option |
BC2001 + BCON pooled analysis: 55 Gy / 20 had better invasive locoregional control than 64 Gy / 32. This is one of the clearest GU hypofractionation wins.
Post-Cystectomy RT
BART: adjuvant IMRT 50.4 Gy / 28 to cystectomy bed and pelvic nodes improves locoregional failure-free survival in high-risk MIBC with acceptable toxicity. This supports selective adjuvant RT for high-risk post-cystectomy patients, not blanket RT for everyone.
PART VII - RCC, SEMINOMA, PENILE, AND RARE GU QUICK HITS
RCC / Seminoma / Penile: Management Paradigm + Dose Anchors
| Entity / scenario | Board-management answer | Dose / planning anchor |
|---|---|---|
| Primary localized RCC, medically inoperable or nephron-sparing need | SBRT is a real definitive option, especially when surgery/ablation is unsafe or renal preservation is central. | 26 Gy x 1, 42 Gy / 3, or 40 Gy / 5-style regimens; use 4DCT/MRI fusion, motion management, and kidney/GI constraints. |
| Metastatic RCC | SBRT for oligometastatic/oligoprogressive disease, palliation, or consolidating resistant sites while systemic therapy continues. | Site-specific SBRT; RCC needs ablative BED when safe, not old low-dose conventional assumptions. |
| Stage I seminoma | Radical inguinal orchiectomy, then surveillance preferred for compliant patients; carboplatin is an alternative; RT is reserved for selected patients. | If RT: para-aortic 20 Gy / 10; avoid scrotal biopsy and use contralateral testis shielding. |
| Stage IIA/IIB seminoma | RT remains an option for low-volume nodal seminoma, but chemotherapy becomes increasingly favored as bulk rises. | IIA: dogleg/para-aortic-ipsilateral pelvis 20 Gy + boost to 30 Gy; IIB boost to 36 Gy. |
| Penile primary / nodes | Surgery is dominant; RT/CRT matters for organ preservation, positive margins, extranodal extension, bulky nodes, unresectable disease, or palliation. | Gross primary 65-70 Gy; ENE/gross nodal basin about 60 Gy; elective/adjuvant 45-60 Gy; include prepubic fat when high-risk anatomy warrants. |
Renal Cell Carcinoma
Old conventional RCC RT failed badly. Modern RCC RT is different: high dose per fraction, tight volumes, image guidance, motion management, and nephron-sparing intent in a disease where CKD drives competing mortality.
| Study | Main result | Takeaway |
|---|---|---|
| iROCK | Excellent outcomes in T1b-T2 RCC; single-fraction SBRT commonly 25-26 Gy x 1 | SBRT is not just for tiny tumors |
| Correa meta-analysis | Local control about 97%, grade 3+ toxicity about 1%, small impact on kidney function | Anchor SBRT numbers for primary RCC |
| FASTRACK II | Prospective phase II primary kidney SBRT with no local treatment failures reported during the study period | Strong prospective validation for medically inoperable primary RCC |
RCC SBRT planning: get renal function and albuminuria/proteinuria baseline, use contrast CT/MRI fusion when possible, assess motion with 4DCT, contour ITV, use PTV about 3-5 mm, watch bowel/duodenum/stomach, and match daily to kidney/tumor anatomy.
Seminoma
All patients: radical transinguinal orchiectomy with high ligation of the cord. Never scrotal biopsy.
AFP trap: AFP should not be elevated in pure seminoma. Elevated AFP means treat as NSGCT.
Stage I: surveillance preferred; alternatives are carboplatin or 20 Gy para-aortic RT.
Stage IIA: 20 Gy / 10 dogleg + boost to 30 Gy or chemotherapy.
Stage IIB: chemotherapy often preferred, but RT remains an option with boost to 36 Gy.
Stage IIC+: chemotherapy. NSGCT gets RT for palliation only.
AFP trap: AFP should not be elevated in pure seminoma. Elevated AFP means treat as NSGCT.
Stage I: surveillance preferred; alternatives are carboplatin or 20 Gy para-aortic RT.
Stage IIA: 20 Gy / 10 dogleg + boost to 30 Gy or chemotherapy.
Stage IIB: chemotherapy often preferred, but RT remains an option with boost to 36 Gy.
Stage IIC+: chemotherapy. NSGCT gets RT for palliation only.
Seminoma RT technique: AP-PA 3DCRT (modified dog-leg) only, no IMRT. IMRT increases the mean dose and low-dose bath to the kidneys, liver, and bowel, increasing the risk of second primary cancers. Per NCCN, total dose depends on node size: 30 Gy for 1-2 cm nodes (Stage IIA) and 36 Gy for 2-3 cm nodes (Stage IIB). Proton therapy using an AP-PA technique is also an acceptable alternative. Use contralateral testicular shielding when appropriate.
Penile Cancer
Penile cancer behaves conceptually more like vulvar or head-and-neck SCC than prostate adenocarcinoma. Surgery remains primary treatment, but RT matters for R1, LN+, ENE, and T3-4 cases and for organ preservation in selected patients. Prepubic fat is part of the high-risk CTV in modern contouring.
| Setting | Dose guidance | Board point |
|---|---|---|
| Gross penile disease | 65-70 Gy | Definitive organ-preservation or unresectable gross disease |
| Nodal basin with ENE | About 60 Gy | Boost high-risk groin/pelvic nodal basin |
| Adjuvant elective volume | 45-60 Gy | Adjuvant range depends on margin, nodal burden, and ENE |
| Palliation | 30 Gy / 10 | Bleeding, pain, wound burden, nodal symptoms |
Rare GU Quick Hits
| Entity | Board-review hook |
|---|---|
| Upper tract urothelial carcinoma | Surgery/systemic therapy dominate. RT is mainly postoperative for high-risk locoregional disease, definitive when surgery is not feasible, or palliative for bleeding/pain. |
| Urethral carcinoma | Management depends on sex, histology, and location. Distal disease is more surgical; proximal/locally advanced SCC can be treated with organ-preserving CRT, conceptually similar to anal/penile/vulvar SCC. |
| Paratesticular / spermatic cord sarcoma | Wide excision with high cord ligation; consider RT for close/positive margins, high grade, recurrent disease, or local-control concern. |
CROSS-CUTTING HIGH-YIELD POINTS
- Prostate consult setup: life expectancy, AUA/IPSS, IIEF, prior TURP/HoLEP, anticoagulation, hip prostheses, colonoscopy status, and ADT bone/cardiometabolic readiness all matter before choosing RT.
- MFS, not BCR or FFBF, is the validated surrogate for OS in prostate RT trials.
- Cribriform / intraductal prostate cancer should not be managed with casual surveillance.
- Prostate moderate hypofractionation standard: 60 Gy / 20.
- Whole-gland dose escalation beyond about 80 Gy EQD2 has limited value.
- FLAME is the cleanest positive dose-escalation trial because it boosts the DIL rather than the whole gland.
- ASCENDE-RT improves biochemical control but causes major GU toxicity and no OS gain.
- HDR Brachytherapy Monotherapy: 27 Gy / 2 fx is superior to 19 Gy / 1 fx, which has a high local failure rate.
- UIR prostate is the clearest intermediate-risk group that benefits from short-course ADT.
- Concurrent + adjuvant ADT is superior to prolonged neoadjuvant + concurrent sequencing.
- Very high-risk / cN1 prostate: RT + ADT + abiraterone is the major modern intensification answer.
- WPRT improves progression endpoints more consistently than OS and remains selective.
- Post-prostatectomy: early salvage beats routine adjuvant RT for most men.
- Post-op ADT benefit depends on PSA; it is strongest when salvage is later and PSA is higher.
- EMBARK applies to high-risk BCR patients not suitable for salvage RT; it does not erase the role of curative salvage RT.
- Low-volume de novo mHSPC: RT to the primary improves OS.
- Oligometastatic Prostate MDT: STOMP, ORIOLE, and EXTEND consistently show MDT improves freedom from hormone therapy.
- Radiopharmaceuticals: Dual-tracer PET (PSMA/FDG) identifies aggressive discordant disease. Ac-225 is an alpha-emitter limited by severe xerostomia. Tb-161 emits beta + Auger electrons (ideal for micrometastases).
- Lu-PSMA is now relevant both after ARPI/taxane and in selected pre-taxane mCRPC when taxane delay is appropriate.
- Bladder preservation is a mainstream standard for selected MIBC and is best delivered as continuous-course CRT.
- Ideal TMT bladder candidate: unifocal tumor, maximal TURBT, no extensive CIS, no significant hydronephrosis, and good baseline bladder function.
- Bladder hypofractionation winner: 55 Gy / 20.
- Primary RCC: SBRT is a real nephron-sparing treatment, not just palliative RT.
- Stage I seminoma: surveillance preferred; if irradiating, memorize 20 Gy para-aortic.
- Seminoma RT: Use AP-PA 3DCRT, not IMRT, to limit the low-dose bath to the kidneys/liver/bowel and reduce second cancer risk. NCCN doses: 30 Gy for 1-2 cm nodes, 36 Gy for 2-3 cm nodes.
- Seminoma trap: elevated AFP means do not treat as pure seminoma.
- Penile cancer: remember the high-risk CTV includes prepubic fat.
- Antiandrogen gynecomastia: tamoxifen is usually most effective; prophylactic breast-bud RT is an option but not routine.
CONSOLIDATED DOSE TABLE
| Setting | Dose / regimen | Comment |
|---|---|---|
| Localized prostate moderate hypofractionation | 60 Gy / 20 fx | Modern default standard |
| Localized prostate SBRT | 36.25 Gy / 5 fx | PACE-style regimen |
| DIL boost (FLAME) | 77 Gy / 35 with SIB to 95 Gy | Improved bDFS without major late-toxicity penalty |
| HDR Brachytherapy Monotherapy | 27 Gy / 2 fx | Superior biochemical control compared to 1-fraction (19 Gy) regimens, which have unacceptably high local failure. |
| Definitive primary RT in low-volume mHSPC | 55 Gy / 20 or 36 Gy / 6 weekly | STAMPEDE Arm H-style prostate RT anchors |
| Post-prostatectomy prostate bed | 64-66 Gy | Typical salvage/adjuvant bed range; avoid routine escalation beyond ~66 Gy |
| cN1 prostate | 60 Gy / 20 | Prostate dose in modern 20-fx schema |
| cN1 elective pelvic nodes | 44 Gy / 20 | Elective nodal dose |
| cN1 involved nodes | Up to 55 Gy / 20 | Boosted nodal disease |
| Oligopelvis nodal recurrence | 54 Gy / 30 with SIB to 66.6 Gy | OLIGOPELVIS-style regimen |
| Metastatic prostate palliation | 8 Gy x 1, 20 Gy / 5, or 30 Gy / 10 | Symptom control / bone pain / local pelvic symptoms |
| Bladder conventional | 64 Gy / 32 | Classic BC2001 schedule |
| Bladder hypofractionation | 55 Gy / 20 | Preferred modern regimen |
| Bladder reduced high-dose-volume RT | 55 Gy / 20 SIB + 44 Gy / 20 | Partial bladder dose painting |
| Adjuvant post-cystectomy RT | 50.4 Gy / 28 | BART-style regimen |
| Bladder palliation | 20 Gy / 5 or 30 Gy / 10 | Hematuria, pain, obstruction, or pelvic symptoms |
| Primary RCC SBRT | 26 Gy x 1 | Common single-fraction regimen; FASTRACK II for smaller tumors |
| Primary RCC SBRT | 42 Gy / 3 | Common larger-tumor prospective regimen |
| Primary RCC SBRT | 40 Gy / 5 | Useful when GI proximity favors fractionation |
| Stage I seminoma | 20 Gy / 10 | Para-aortic RT |
| Stage IIA seminoma | 20 Gy / 10 + boost to 30 Gy | Dogleg/PA + GTV boost |
| Stage IIB seminoma | 20 Gy + boost to 36 Gy | Selected patients only; chemo often preferred |
| Gross penile disease | 65-70 Gy | Definitive organ-preservation or unresectable gross disease |
| Penile nodal basin with ENE | ~60 Gy | Boosted nodal basin |
| Penile elective adjuvant RT | 45-60 Gy | Adjuvant range |
| Penile palliation | 30 Gy / 10 | Palliative course |
KEY LANDMARK TRIALS (memorize)
| Trial | Disease | One-line takeaway |
|---|---|---|
| ProtecT | Localized prostate | No OS difference among monitoring, RT, and RP; monitoring has more metastases |
| ProtecT cribriform analyses | Localized prostate pathology | Cribriform / intraductal disease is not safe to monitor casually |
| CHHiP / PROFIT | Localized prostate | Moderate hypofractionation is non-inferior to conventional RT |
| HYDRA-MARCAP | Localized prostate fractionation | Isodose moderate hypofractionation such as 60/20 is modern standard |
| PACE-B / C | Localized prostate SBRT | SBRT is an accepted standard option with low severe-toxicity rates |
| RTOG 9408 | Intermediate-risk prostate | Short-course ADT improves outcomes, especially in UIR |
| FLAME | High-risk prostate dose escalation | DIL boost improves biochemical control without major late-toxicity penalty |
| ASCENDE-RT | High-risk prostate boost | Brachy boost improves biochemical control but at major GU-toxicity cost |
| STAMPEDE G/J | Very high-risk / cN1 prostate | Abiraterone added to RT + ADT improves MFS and OS |
| POP-RT | Whole-pelvis RT in intact prostate | Improves progression endpoints, not OS |
| RTOG 0924 | Whole-pelvis RT in intact prostate | Early reported: no DM or OS benefit for routine WPRT |
| ARTISTIC | Post-prostatectomy timing | Early salvage RT is favored over routine adjuvant RT |
| RTOG 9601 | Salvage RT +/- ADT | ADT benefit is concentrated in later salvage / higher PSA |
| GETUG-16 | Early salvage RT +/- ADT | Improves biochemical control, not clearly OS |
| SPPORT / RTOG 0534 | Salvage RT intensification | Main postoperative benefit comes from ADT, not pelvic RT alone |
| EMBARK | High-risk BCR | Enzalutamide + leuprolide improves MFS in patients not suitable for salvage RT |
| STAMPEDE Arm H | De novo low-volume mHSPC | RT to the primary improves OS |
| STOPCAP | Primary RT in metastatic prostate | Memorize the roughly 7% 3-year OS gain for men with <5 bone mets |
| PEACE-1 | mHSPC primary RT + abiraterone era | Improves rPFS and delays GU progression, not OS |
| WOLVERINE | Oligometastatic prostate MDT | Pooled modern trials support SBRT as a real progression-delaying strategy |
| UpFrontPSMA | mHSPC | Sequential Lu-PSMA + docetaxel improves PSA response; highlights utility of dual-tracer (PSMA/FDG) PET. |
| WARMTH Act | mCRPC (Ac-225-PSMA) | Largest Ac-225-PSMA study; highly effective but limited by prevalent dose-dependent xerostomia. |
| VIOLET | mCRPC (Tb-161-PSMA) | Establishes safety/efficacy of Tb-161, a novel beta + Auger electron emitter. |
| ALSYMPCA / VISION / PSMAfore | mCRPC radiopharmaceuticals | Ra-223 and Lu-PSMA are core radiation-adjacent systemic therapies |
| BC2001 | MIBC bladder preservation | ChemoRT improves locoregional control versus RT alone |
| BCON / Choudhury pooled analysis | Bladder fractionation | 55 Gy / 20 outperforms 64 Gy / 32 for local control |
| BART | Post-cystectomy high-risk MIBC | Adjuvant IMRT improves LRFS with acceptable toxicity |
| iROCK | Primary RCC SBRT | Strong multi-institutional data for localized RCC, including larger tumors |
| FASTRACK II | Primary RCC SBRT | Prospective phase II validation for medically inoperable primary RCC |
| Correa meta-analysis | Primary RCC SBRT | Local control about 97% with grade 3+ toxicity about 1% |