[ROQs] GU, Prostate Flashcards

Question

What were the findings of the STAMPEDE Trial as they relate to RT vs no RT?

Answer 1

- All patients: RT to prostate vs. no RT -- ↑ 3-yr FFS: 33% vs. 23% -- ↑ Median FFS: 17 mos vs. 13 mos -- 3-yr OS: Not different - Low met burden: RT to prostate vs. no RT -- ↑ 5-yr OS 65% vs. 53% -- ↑ Median OS 85.5 vs. 63.6 mos -- No change in severe toxicity -- 5% grade 3-4 during RT, 4% grade 3-4 after RT -- No difference in SBRT vs. hypofx - High Met burden: RT to prostate vs. no RT -- 3-yr OS 52-53%, not different -- 5-yr OS not different -- 3-yr FFS 15-16% not different - Nonregional nodal mets: RT to prostate vs. no RT -- 3-yr OS 80% vs. 73% -- 3-yr FFS 51% vs. 29% - Mets to regional nodes: RT to prostate plus WPRT vs. no RT -- 2-yr FFS 85% vs. 55% - Secondary Analysis -- Pts w/ ≤ 3 bone mets (CT AP, bone scan, NOT PET/CT) w/o visceral mets derive the most OS and FFS benefit ## Footnote - HORRAD trial found **NO** OS, or PSA RFS benefit to adding RT, even when stratified by <5, 5-15, > 15 metastases - STAR-CAP MA (HORRAD + STAMPEDE) showed OS benefit in <3 bone metastases (77% w/ RT, 70% w/o RT), but no overall benefit for all pts.

Answer 2

- 55 Gy in 20 fx QD (better FFS) - 36 Gy in 6 fx weekly

Answer 3

- ≤3 bone mets or nonregional LN metastasis →↑ OS and ↑FFS with RT to prostate -- ≥4 bone lesions or visceral metastases → **NO** OS or FFS benefit - ↑FFS with 55 Gy/20 fx over 36 Gy in weekly fractions. - regional N+ → ↑FFS benefit RT to prostate + WPRT - nonregional N+ → ↑FFS w/ RT to prostate only - locally advanced, N+, and M+ → ↑OS w/ docetaxel, both in low and high metastatic disease burden - HR non-metastatic prostate cancer → ↑MFS, ↑PCSS, ↑bFFS, and ↑PFS w/ Abiraterone

Answer 4

- ADT alone - ADT + Docetaxel (~18%), which is the current SOC - Results: ADT + Docetaxel vs. ADT Alone -- OS: 81 vs. 71 months, HR 0.78 (SS). -- Biochemical FFS: 37 vs. 20 months, HR 0.61 (SS). -- Rate of Gr ≥ 3-5 AEs: 52% vs. 32% (SS). -- Zoledronic acid demonstrated no improvement in any of the arms.

Answer 5

- HR **non**-metastatic prostate cancer, defined as LN+ or, if LN-, having ≥ 2 high-risk features like tumor stage T3 or T4, Gleason score of 8-10, or PSA ≥40 ng/mL. Arms: - Abiraterone acetate (1000 mg) + prednisolone (5 mg) daily x 2 years or until progression vs. - Abiraterone acetate plus prednisolone along with enzalutamide (160 mg) daily for 2 years or until progression. Key Findings: Abiraterone vs. ADT alone (SS). - Metastasis-Free Survival: HR of 0.53 (95% CI, 0.44-0.64) (SS) - Overall Survival (OS): HR of 0.60 (95% CI, 0.48-0.73) (SS) - Enzalutamide Addition: No benefit Conclusion: For patients with high-risk non-metastatic prostate cancer, the addition of abiraterone acetate to standard androgen-deprivation therapy markedly improves survival outcomes. However, clinicians should weigh these benefits against the increased risk of significant adverse

Answer 6

- **HR** PCA randomized to prostate-only RT (68/25) vs. 🏆 WPRT (50 Gy Pelvis + 68 Gy SIB to prostate±SV, all in 25 fx): -- 5-yr bPFS 81% vs. 95% -- 5-yr DMFS 89% vs. 96% -- 5-yr DFS 77% vs. 90% -- 5-yr pelvic recurrence 52% vs. 13% -- *5-yr OS: 91-92% (NS)* -- Late grade 2 GI toxicity 4.5% vs. 6.4% -- Late grade 3 GI toxicity 0 vs. 1.8% Memory Hook: **P**rosate **O**nly vs. **P**elvic → POP ## Footnote PO → Prostate only P-RT → Pelvic RT Footnote PO → Prostate only P-RT → Pelvic RT

Answer 7

- Time-to-onset: 15 days - Recovery of testosterone: 90 days

Answer 8

IR or HR PCa → 77 Gy/ 35 fx vs.→🏆 Above + SIB focal boost up to 95 Gy to MRI nodules (95 Gy achieved in 20% 2/2 OAR constraints) -- ↑ 5-yr bDFS 85% vs. 92% (SS) *-- DMFS and OS are not different -- Late grade ≥2 GU 23% vs. 28%, NS -- Late grade ≥3 GU 3.5% vs. 5.6%, NS -- Late grade ≥2 GI 12% vs. 13%, NS*

Answer 9

- adjuvant RT vs. 🏆 salvage RT at PSA failure for HR PCa pts (defined as two-consecutive PSA >0.1, or any PSA rising x3) -- 10-yr DM 7% vs. 10%, NS -- 10-yr PFS ~75%, NS -- No change in OS - RT Choices: 66 Gy/33 fx vs. 52.5 Gy/20 fx (per treating physician choice)

Answer 10

- Men who have undergone radical prostatectomy w/i 22 wks of enrollment - Post-op PSA of ≤ 0.2 ng/mL, and one or more of the following: (1) pT3/T4 disease (2) G 7-10 disease (3) Pre-op PSA ≥ 10 ng/mL (4) +margins

Answer 11

- I-121: 145 Gy - Pd-103: 125 Gy (2/2 shorter 1/2 life) - Cs-131: 115 Gy (2/2 shorter 1/2 life)

Answer 12

- I-121: 110 Gy - Pd-107: 100 Gy - Cs-131: 85 Gy MEMORY AID: Boost dose should be less than the source mass #

Answer 13

- 13.5 Gy x 2 fx - 10.5 Gy x 3 fx - 9.4 Gy x 4 fx (BID)

Answer 14

Adjuvant vs. salvage RT - 5-yr EFS: 88% vs. 89% (NS) -- Adjuvant RT does not improve EFS; No subgroup that benefitted from adjuvant RT - ↑ early and late GU tox - All three trials analyzed have failed to detect a benefit to adjuvant RT

Answer 15

- BCF for 79.2 Gy -- 5 yr: 35% -- 8 yr: 20% - BCF for 70.2 Gy -- 5 yr: 47% -- 8 yr: 35 % - OS not different

Answer 16

- Prostate: -- D90 > 100% -- V100 > 90% -- V150 < 50% - Rectum: -- RV100 < 1 cc -Urethra -- UV5 < 150% -- UV30 < 125% -- UV150 = 0%

Answer 17

- V100% > 95%-98% - D90>100% - Homogeneity -- V150% < 30-40% -- V200% < 20% - Rectum -- D2cc < reference prescription dose (145 Gy) -- D_max < 200 Gy - Prostatic urethra -- D10 < 150% of Rx -- D30 < 130% of Rx

Answer 18

- D90% >140 Gy (for I-125) - D90% > 125 Gy (for Pd-103 - V150% < 40% - V200% < 20% - Rectum -- V100% < 1cc (can be as high 2.5cc) - Urethra mean -- < 140% of prescription dose

Answer 19

- ↑ OS - ↑ tox

Answer 20

- 1-2 cm - Extend posteriorly to the edge of the obturator internus muscle - Taper obturator nodes when SVs appear - End when SVs join prostate

Answer 21

- IR PCa → 79.2 Gy vs. 79.2 Gy + 6 mos ADT -- 45 Gy + brachy boost also allowed (12%) -- 5-yr BCF 21% vs. 10% -- 5-yr DM 4% vs. 1% -- 5-yr PCM n=10 vs. 1 *-- 5-yr OS 79-84%, NS* -- No benefit in Gleason ≤ 6

Answer 22

Decipher - 0-0.45: low risk - 0.45-0.6: intermediate risk - 0.6-1.0 high risk

Answer 23

- PSA ≥ 0.7 (Feng et al., 2nday analysis of RTOG 9601) -- Improves MFS, DSS, and OS

Answer 24

PSA > 0.34 (RTOG 0534)

Answer 25

No pelvis only

Answer 26

Dose-escalated vs. CFRT in LR and IR PCa - 17% vs. 32% ## Footnote Compare w/ MDACC dose-escalation trial, which showed a biochem failure benefit in IR and HR PCa?

Answer 27

- LR and IR disease (4% had HR) → IM**P**T: 70.2 GyE vs. 79.3 GyE *w/o ADT* - Median FU 9 yrs: -- **Overall biochem failure: 32.3 vs. 16.7 GyE (SS)** -- **LR-only biochem failure: 28.2 vs. 7.1% (SS)** -- IR-only biochem failure: 42.1 vs. 30.4% (NS) -- **Pts started on salvage hormonal therapy: 11% vs. 6% (SS)** -- OS: 78.4% vs. 83.4% (NS) -- Tox: ~ (NS)

Answer 28

- Doses: 64-72 Gy - If PSA > 0.48, Dose ≥ may ↓ biochemical failure

Answer 29

5-yr RFS: 50-60%

Answer 30

- ↓ GI tox - Similar GU tox

Answer 31

- PSA doubling time < 3 years - Histologic upgrade on repeat bx - Unequivocal clinical progression (palpable nodule during surveillance confirmed histologically)

Answer 32

↓ by 20% w/ 5 mos of ARIs

Answer 33

↓ by ~30%

Answer 34

- HR and LN+ → RT 70 Gy (50 WPRT + 20 Gy boost) concurrent & adj ADT x 36 mos vs. RT alone -- 10-yr OS 58% vs. 40% (SS) -- 10-yr DFS 48% vs. 23% (SS) -- 10-yr CSS 90% vs. 70% (SS) -- 10-yr LRF: 6% vs. 24% (SS) -- 10-yr DMFS: 51% vs. 30% (SS) Note that this trial did not use the modern dose escalated doses (78 Gy)

Answer 35

- IR (70%) + others (LR/HR) PCa →70 Gy to prostate vs. 70 Gy + ADT for 6 months (2 months neoadj): -- 8-yr OS 74% vs. 61% (SS)

Answer 36

- LFTs - It can occasionally cause fulminant hepatic failure!

Answer 37

- GU: -- w/ RT, lower urinary sx get worse at 6 mos, but become comparable to AS and RP at 1 yr -- urinary incontinence gets hit the worst w/ RP, and never recovers to the levels of RT or AS - GI: -- w/ RT, bowel fx is consistently worse after RT when compared to AS or RP

Answer 38

- RP has worse sexual fx at all time points, and it never recovers to the RT or AS levels

Answer 39

No difference in the three arms

Answer 40

- ERSPC trial: q4 yrs - Sweden: q2 yrs - NCCN: -- PSA < 1 → q2-4 yrs -- PSA 1-3 → q1-2 yrs

Answer 41

- IR + HR localized PCa → adj. RT vs. salvage RT (RT options for both: 66 Gy in 33 fx or 52.5 Gy in 20 fx) - bPFS: 85% vs. 88% (NS) - urinary incontinence: worse w/ adj. RT

Answer 42

- 2 consecutive PSA rises and PSA > 0.1 ng/mL - 3 consecutive PSA rises regardless of whether the final reading was greater than 0.1 ng/mL

Answer 43

1. Calcium 1200 mg daily 2. Vitamin D3 800-1000 IU daily

Answer 44

- q3mos x 1 yr - q6mos afterwards

Answer 45

- Provided only on RP specimen WHEN - Tertiary component of the Gleason score is higher than the primary and secondary AND - Occupies <5% of the whole tumor

Answer 46

- Before first administration: -- ANC ≥ 1500 -- PIt ≥ 100k -- Hgb ≥ 10 - Subsequent administration: -- ANC ≥ 1000 -- Plt ≥ 50k

Answer 47

- IR and HR Pca → Random: RT alone, or RT + ADT x 3mo, or RT + ADT x - RT to Pros + SV (66 GY in 33 fx) - Median 10.6 yrs FU -- 10Y PSA Progression: 73.8% vs. 60.4% vs. 52.8% (SS for both) -- 10Y local progression: 28.2% vs. 15.7% vs. 13.3% (SS for both) -- 10Y EFS: 12.7% vs. 28.8% 3 vs. 36.0% 6 (SS for both) -- 10Y PCSM: 22.0% vs. 18.9% 3 mos vs. 11.4% (p-0.0002 for 6 months NADT vs. RT alone) -- 10Y all-cause mortality: 42.5% vs. 36.7% vs. 29.2% (p-0.0005 for 6 months NADT vs. RT alone) - Memory Hook: **AD**TROG

Answer 48

Population (RT → R for s/p **R**P) - pT3N0 or T2N0 w/ +margins, w/ PSA 0.2-4.0 after RP → RT 64.8 Gy to PF vs. RT + 24 mos bicalutamide (adj + conc) -- PSA failure is defined as >0.5 if PSA was 0, or >0.3 above nadir - RT 64.8 Gy to fossa vs. 🏆 RT + 24 mos bicalutamide (adj + conc) Outcomes: - **10-yr FFD: 46% vs. 30% (SS)** - BPFS improvement in GS<7, GS 7, and GS 8-10 - **12-yr DM: 14.% vs. 23.0%** - **12-yr PC death: 6% vs. 13%** - **12-yr OS : 76% vs. 71%** - No OS or DM benefit in PSA ≤0.6 (Dess 2020) -- But it did ↑ other cause mortality, including cardiac and neurologic - OS benefit in PSA <0.7 with a high Decipher score Toxicities: - Late grade 3-4 GI toxicity similar at 7% - Late grade 3-4 GU toxicity similar at 2.7 vs 1.6% - **Gynecomastia 70% vs. 11%** - Conclusions: Adding bicalutamide to RT improves FFP, OS, CSS, and DM. There was no OS benefit with bicalutamide in PSA ≤0.6

Answer 49

- Sup: SV or vas deferens, or 3 cm above pubic symphysis - Inf: Top of penile bulb or 1 cm below the vesico-urethral anastomosis - Above the pubic symphysis: -- Ant: 1-2 cm of posterior bladder wall -- Post: mesorectal fascia -- Lat: sacrorectogenitopubic fascia - Below the pubic symphysis: -- Ant: posterior to pubic symphysis -- Post: Anterior rectal wall -- Lat: medial levator ani -- Include retained seminal vesicles if involved

Answer 50

- HR or locally advanced pros ca patients -- No sig. Diff in tox for pros vs. pros + pelvis

Answer 51

- HR & LN- w/ at least 20% risk of LN involvement per Roach → WPRT vs. PORT -- PORT → 68 Gy in 25 fx, WPRT → 50 Gy in 25 fx + SIB to 68 Gy to pros ± SV - Median fu 68 months, 5 yr results: WPRT vs. PORT -- BFFS: 95 vs 81.2% (SS) -- DFS: 89.5 vs. 77.2% (SS) -- DMFS: 95% vs. 87.9% (SS) -- OS: 92.5% vs. 90.8 (NC) - Tox: WPRT vs. PORT -- ≥ Gr II late GU tox: 20% vs 8.9% (SS) -- All other NS MNEMONIC: **P**rostate **O**nly vs. **P**elvis + Prost → (POP)

Answer 52

- Post-EBRT brachy boost -- I-125 → 108-110 Gy -- Pd-103 → 90-100 Gy

Answer 53

- Post-EBRT brachy boost -- I-125 → 140-160 Gy -- Pd-103 → 110-125 Gy

Answer 54

PIRADS 5 lesion: - 80% → ≥ GS 7 - 17% → ≥ GS 8 - likely to have EPE

Answer 55

Fox Chase Cancer Center, Am J Clin Onc, 21 - Worse acute GU tox - Similar late GU tox

Answer 56

- 66% HR & 33% IR PCa -- Excluded: T3b, T4, PSA>40, prior TURP -- Randomization: 12 mos ADT + 46 Gy WPRT →LDR boost (115 Gy I-125) vs. EBRT boost (78 Gy total) - Outcomes: -- **15-yr bPFS 85% vs. 67% (SS)** -- 10-yr MFS 88% vs. 86%, (NS) -- 10-yr CSS 94% vs. 91%, (NS) -- 10-yr OS ~75% for both (NS)

Answer 57

- Tox: GU -- Prevalence of acute grade 3 GU toxicity 8.6% vs. 2.2% (NS) -- **5-yr cumulative Grade 3 GU toxicity 18% vs. 5% (SS)** -- **5-yr any pad usage 16% vs. 3% (SS)** -- **5-yr late catheterization 12% vs. 3% (SS)** - Tox: GI -- cumulative grade 3 GI toxicity: 8.1% vs. 3.2% (NS) -- prevalence grade 3 GI 1.0% vs. 2.2% (NS) - Tox: Erectile Fx: 45% vs. 37% (NS)

Answer 58

CRPC with ≥2 bone metastases, prior docetaxel allowed, Exclusion: visceral metastasis - 🏆 radium-223 monthly x 6 mos + SOM vs. placebo + best SOC (2:1 randomization) - Outcomes: -- Median OS 14.9 mos vs. 11.3 mos (SS) -- 30% reduction is risk of death (SS) -- Median time to bony event 15.6 vs. 9.8 mos (SS_ -- Median time to alk phos rise 7.4 vs. 3.8 mos (SS) -- PR of ≥30% reduction in alk phos 47% vs. 3% -- CR in alk phos 34% vs. 1% -- (total alk phos response rate 81%) -- Improved QOL with radium-223 -- Adverse effects in the radium-223 group were significantly lower than in the placebo arm - Alpharadin in Symptomatic Prostate Cancer Patients (ALSYMPCA)

Answer 59

- Preplan goals: - V100 > 95%-98%, D90>100% (Seattle Prostate Institute) -- Homogeneity: V150 < 30-40%, V200 < 20% (Seattle Prostate Institute) -- Rectum:V100 < 1cc (ABS), Max point <80% (Seattle Prostate Institute) -- Prostatic urethra: D5 < 150% of prescription dose, D30 < 125% of prescription dose (ABS), Urethra Max 100-125% (Seattle Prostate Institute) - Postplan goals: -- D90>140 Gy, V150 < 40%, V200 < 20% (Seattle Prostate Institute) -- Rectum: V100 < 1.3cc (ABS Guidelines) -- Urethra mean: < 140% of Rx dose

Answer 60

- mean dose to 95% of the bulb <50 Gy - D90 <50 Gy, - D70 <70 Gy. These constraints correlate to risks of severe ED of < 35%, <35%, and < 55%, respectively, per QUANTEC.

Answer 61

Abiraterone acetate is an oral drug that inhibits CYP17A1, reducing androgen synthesis from adrenal glands, testes, and tumor tissues. It is typically administered with low-dose prednisone to mitigate the side effects related to mineralocorticoid excess.

Answer 62

- ECE = 3/2PSA + 10(GS-3) - SVI = PSA + 10(GS-6) - LN = 2/3PSA + 10(GS-6)

Answer 63

- Time to DM post-RP: 10 yrs - Time to DM post-EBRT: 5 yrs - Time to death after development of DM: 5 yrs

Answer 64

* Shorter post-treatment PSA doubling time. * A higher initial clinical tumor stage. * A higher pre-treatment Gleason score. * A shorter interval from the end of radiotherapy to biochemical failure.

Answer 65

- Adjuvant: 64-66.6 - Salvage: 66.6-70 - Boost gross disease to definitive dose (~78)

Answer 66

- Modern High risk: T3-4, PSA>20, or GS>7 → superiority trial -- ADT 18 mos vs. 36 most, both starting 4 mos neoadj -- RT to 70 Gy with WPRT 44 Gy (4.5 Gy per week hypofractionation) - Outcomes -- 5-yr OS: 86% vs. 91% (NS) -- 10-yr OS: ~62% (NS) -- DM: ~3% (NS) -- 5-yr BCF: 84% vs. 88% (NS) -- **10-yr BCF: 69% vs. 75% (SS)** -- **5-yr DFS: 69% vs. 77% (SS)** -- 10-yr DFS: 39% vs. 45% (NS) -- 10-yr DSS: 92%( (NS) -- 5–yr DSS: 98% (NS) - **QOL favored 18 mos ADT** -- Testosterone recovery 2.1 vs. 4 yr (after completion of ADT --- With 18 mos ADT about 75% recover at about 5 years - Compeltion rates of ADT: 53% vs. 88% - 70 Gy RT dose might not have been optimal for prostate cancer

Answer 67

- Etiology: WPRT → acute radiation injury - Sx: abdominal pain and cramps - CT w/ contrast: thickened, edematous small bowel - Tx: temporary radiation break and bowel rest

Answer 68

- All around: 8 mm - Posteriorly: 5 mm

Answer 69

- pT1b-T3aN0M0: low risk 15%, int risk 73%, high risk 12% - Non-inferiority: 74 Gy/37 fx vs. 60 Gy/20 fx vs. 57 Gy/19 fx -- 5-yr BC 88% vs. 91% vs. 86% -- 10-yr BC 76% vs. 80% vs. 73% -- 10-yr OS 79% vs. 83% vs. 80% - Tox: -- **Acute ≥ Gr 2 bowel tox: 25% vs. 38% vs. 38% (SS)** -- Acute ≥ Gr 2 bladder tox: similar -- Late Gr ≥ 2 bowel tox: 13.7% vs. 11.9% vs. 11.3% (NS) -- Late Gr ≥ 2 bladder tox: 9.1% vs. 11.7%, vs. 6.6 % (NS) -- Pt reported sexual function improved in hypofx - Conclusions: 60 Gy was noninferior to 74 Gy; Cannot say 57 Gy is noninferior

Answer 70

- Intermediate risk prostate cancer; No ADT; Noninferiority - 78 Gy/39 fx vs. ✅ 60 Gy/20 fx; -- 5-yr BPFS 85% in both arms -- Similar late grade ≥3 GI or GU toxicity -- 10-yr data is lacking

Answer 71

- Low risk prostate cancer; non-inferiority - 73.8 Gy/41 fx vs. 70 Gy/28 fx Outcomes: - 5-yr DFS 85% vs. 86% - 12-yr DFS 56% vs. 62% - 12-yr BC 83% vs. 90% - Tox: No difference in patient-assessed QOL in EPIC GI, GU, sexual domains or Hopkins Symptom anxiety or depression **-- Late grade ≥2 GI 15.4% vs. 23.8%** -- Late grade ≥3 GI 3.2% vs. 4.4% **-- Late grade ≥2 GU 26.8% vs. 33.4%** -- Late grade ≥3 GU 3.4% vs. 4.4%"

Answer 72

-- GG5 → IIIC -- LN+ → IVA -- M1 → IVB

Answer 73

- Adjuvant ≤ 6 mos - Salvage > 6 mos

Answer 74

- 2 rises in PSA and PSA >0.1 or any PSA after 3 rises, s/p RP with nadir of ≤0.4. Current PSA ≤2 and no gross disease (45% had positive margins) s/p RP dose escalation trial (Prostate bed RT only. No WPRT allowed; No ADT in this trial) - 🏆 64 Gy/32 fxvs. 70 Gy/35 fx -- 6-yr bPFS 61-62%, not different -- No difference in PFS, OS, or time to ADT - Tox: -- Late grade 2 GU 21% vs. 26% -- Late grade 3 GU 8% vs. 4% -- **Late grade 2 GI 7% vs. 20%** -- Late grade 3 GI 4% vs. 2% - Conc: Salvage prostate RT to 70 Gy leads to no benefit in bPFS compared to 64 Gy, and results in worse GI toxicity

Answer 75

* PSA q6 mos -- NOTE: ProtecT used q 3 mos for 1-2 yrs * DRE q12 mos * Repeat bx q 12 mos * Repeat mpMRI q12 mos * MRI-US fusion bx improves detection of higher grade cancers * Transition to obs when life expectancy is < 10 yrs * Repeat molecular tumor analysis is discouraged

Answer 76

Vitamin E & Selenium

Answer 77

21% relative reduction in prostate cancer mortality

Answer 78

55 kBq/kg given q4 weeks for 6C

Answer 79

- Rise of ≥ 2 ng/mL above the nadir PSA is biochemical failure after EBRT, independent of androgen deprivation therapy. - Applies to both EBRT and brachytherapy. - Obtain a second PSA to r/o PSA bouce

Answer 80

≥ 3 consecutive elevations of posttreatment PSA ≥ Starting hormones after ≥ 1elevations in posttreatment PSA but before 3 consecutive elevations were documented

Answer 81

Following EBRT, LDR, or HDT → a transient rise in PSA ~12-18 mos

Answer 82

Biochemical recurrence per AUA: Initial serum PSA ≥0.2 ng/mL f/b a confirmatory PSA level of >0.2 ng/mL

Answer 83

- A temporary increase in PSA levels followed by a subsequent decline to or below the previous nadir without additional treatment. -- ↑ ≥ 0.2 ng/mL above the nadir, followed by a decrease to the nadir or below

Answer 84

pT2-T4a (bladder neck only) with rising PSA of 0.2-2.0 - 66 Gy RT alone vs. 🏆 RT + 6 mos ADT - 46 Gy WPRT given if Partin score ≥10% before RP and no LND Outcomes: w/o ADT vs. w/ ADT - 5, 10-yr PFS: 62%/49% vs. 80%/64% - 10-yr DM: 31 vs. 25% - No change in OS - Grade 3 GU 8% vs. 7% Conclusion: ADT reduced DM but did not improve OS

Answer 85

- PSA ≥0.1 and <2.0, and T2-3N0/Nx, ± positive margin, Gleason ≤9 - Prostate bed (PB) RT 64.8-70.2 Gy vs. PBRT + 4-6 mos ADT vs. 🏆 WPRT + PBRT + 4-6 mos ADT -- PB: RT 64.8-70.2 Gy; WPRT: 45 Gy - Results: -- 5-yr FFP 71% vs. 81% vs. 87% (group 2 & 3 > group 1) -- 5-yr DM 9% vs. 6% vs. 5% (group 3 > group 1) -- 5-yr BF (PSA ≥0.4) 31% vs. 21% vs. 13% -- 5-yr BF (Phoenix) 20% vs. 14% vs. 8% (cumulative, group 3 & 2 > group 1) -- 5-yr castrate resistance 3% vs. 2% vs. 1% (cumulative, group 3 > groups 1 & 2) -- 5-yr regional failure 5% vs. 2% vs. 1% (cumulative, groups 3 & 2 > group 1) -- 5-yr OS 94-96%, not different -- Late grade 2+ toxicity (>3 mos) not different, except for worse BM toxicity with WPRT ** Takeaway: PSA > 0.35 benefits the most from the addition of WPRT to PBRT (See figure)** - Conclusion: The Addition of ADT and WPRT results in improved FFP compared to prostate bed RT alone without ADT. GI and GU toxicity are not worsened. Secondary endpoints of DM, BF, castrate resistance, and regional failure are also improved. - Memory hook: SPPORT trial provides support for WPRT in the adjuvant/salvage setting for prostate cancer

Answer 86

The bladder minus the prostate bed CTV should have the following constraints: * V65Gy < 50% * V40Gy < 70% RTOG SPPORT 0534

Answer 87

- Adjuvant trials → treated prostate only -- SWOG 8794: Ports included were to the prostatic fossa and periprostatic tissue only. -- EORTC 22911: Designated coverage of the prostate fossa up to the seminal vesicles to 50 Gy followed by a 10 Gy boost to the prostate fossa. -- German ARO 9602: Designated coverage from the seminal vesicles to the prostate apex to 60 Gy. - Salvage Trials → some allowed for pelvic RT based on certain criteria -- GETUG-AFU-16: Allowed for the pelvis to be irradiated in patients who did not undergo nodal assessment at the time of surgery or had a predicted nodal risk of 15% or greater. -- RTOG 9601: Did not allow for pelvic treatment as all patients underwent nodal assessment at the time of surgery. -- RTOG 0534/SPPORT: Randomized to prostate bed only, prostate bed + ADT, or prostate bed + ADT + pelvic lymph nodes. 5 year freedom from progression was highest (87.4%) in patients who received ADT and lymph node RT compared those receiving prostate bed+ADT (81.3%) or prostate bed RT alone (70.9%).

Answer 88

- No! -- Def: POP-RT → 5Y OS: 94-95% -- Ad/Salv: SPPORT → 5Y OS 94-96% - NCCN leaves treatment of the pelvis to the treating physician

Answer 89

Relative contraindications: * High IPSS (typically >20) * Prior pelvic radiotherapy * Transurethral resection defects * Large median lobes * Gland size >60cc at time of implant (note: gland size can be decreased with use of ADT) * Inflammatory bowel disease Absolute contraindications: * Limited life expectancy * Unacceptable operative risks * Distant metastases * Absence of rectum such that TRUS guidance is precluded * Large TURP defects, which preclude seed placement and acceptable radiation dosimetry * Ataxia telangiectasia

Answer 90

- ≥18 yrs w/ oligomet prostate cancer (≤ 5 mets) and treated with hormone therapy for ≥ 2 mos - PFS and eugonadal PFS were significantly improved with the use of metastasis-directed therapy (MDT) - Eugonaldal PFS: PFS in the presence of normal levels of test - Trial provides support for the use of RT to oligomers to afford ADT tx breaks to pts - MNEMONIC: External Beam Radiation to Eliminate Nominal Metastatic Disease (EXTEND) trial

Answer 91

- T1b-T3a, PSA<50 - neoadj ADT 3-6mos →64/32 vs. 74/37 Gy 3DCRT, concurrent ADT -- 5-yr bPFS, 60% vs. 71% (SS) -- 10-yr bPFS 43% vs. 55% (SS) -- Grade 3 GI tox: 10% vs. 6% (SS) -- Grade 3 GU tox: 4% vs. 2% (NS) -- Trend towards better clinical PFS, metastases-free survival, use of salvage HT.\- - Dose escalation improves bPFS and increases toxicity

Answer 92

- IR or HR PCa a/ risk of LN involvement >15% based on Roach - 1: 45 to the pros and sV f/b 34.2 to the pros and prox SV (total dose: 79.2) - 2: 45 Gy to pelvis, pros, SV f/b 34.2 Gy to the pros and prox SV (total dose: 79.2)

Answer 93

- Rectum V75<15%, V70<25%, V65<35%, V60<50% - Bladder V80<15%, V75<25%, V70<35%, V65<50% - Penile bulb mean <52.5 Gy [Identical to 0815. PREDICT-RT has more strict constraints]

Answer 94

PSMA: - Prostate - Sympathetic ganglia - Meningiomas - Adeno = Lacrimal glands

Answer 95

- PTV -- Limit D_max to 107% -- D98% ≥ R_x - Urethra: Limit D_max to 107% - Bladder + Bowel -- Limit D_max to 105% of R_x -- Limit D50% to 50% of R_x - Penile Bulb: Limit D_max to 100% for penile bulb - Femurs: Limit D_max to 55% for femurs

Answer 96

There is a bcPFS benefit for all IR disease, while a DMFS benefit can be seen only in unfavorable. PCSM was notably improved in men with GG3 (4+3) or ≥ 50% cores, but not in those with multiple intermediate risk factors. TL;DR - Even if this patient was UIR, some only recommend ST-ADT in GG3 or ≥ 50% cores, but not in those who are UIR due to multiple intermediate risk factors (e.g., PSA 10-20, T2b-T2c, and/or GG2), due to the PCSM benefit in these two subgroups.

Answer 97

MASTER MA (Otherwise, paucity of data) GU Tox for different therapies for radiorecurrent PCa: - RP: 21%. - SBRT: 2.6% - HDR: 9.6% - LDR: 9.1%

Answer 98

- VLR and LE < 20 yrs - LR and LE < 10 yrs

Answer 99

Only in RP specimens, when the third component with the Gleason component is higher, the primary and secondary, and occupies <5% of the tumor

Answer 100

Peripheral Zone - 68% Transitional Zone - 24% Central Zone - 8%

Answer 101

- 18F-DCFPyL - 68GA-PSMA-11

Answer 102

- pT2-T4a (bladder neck only) with rising PSA of 0.2-2.0 -- 66 Gy RT alone vs. 🏆 RT with 6 mos ADT -- 46 Gy WPRT given if Partin score ≥10% before RP and no LND - Outcomes: -- 5, 10-yr PFS 62%/49% vs. 80%/64% -- 10-yr DM 31% vs. 25% ADT -- No change in OS -- Grade 3 GU 8% vs. 7% - Conc: ADT reduced DM, but did not improve OS - On exploratory subanalysis, no apparent difference in any subgroup with all HRs crossing 1, but general trend favors ADT in all groups. There was better benefit in PSA >0.5 in initial publication"

Answer 103

- cT1-2 PCa → RP, EBRT < 72 Gy, EBRT ≥ 72 Gy, BCT, EBRT + BCT - EBRT < 72 Gy → inferior 5Y bRFS - All other arms were equal

Answer 104

% of total ADT benefit (for a mix of different risk prostate cancers) derived based on duration - By 6 mos: 56% of the benefit - By 1 yr: 85% of the benefit - By 2 yrs: 99% of the benefit Williams et al, IJORBP 2011

Answer 105

- Transitional zone - surrounds the urethra, hence LUTS symptoms w/ BPH

Answer 106

- PLCO: Prostate, Lung, Colorectal, Ovarian - PSA screening q6 yrs and DRE q4 yrs vs. usual care - No benefit to annual PSA screenings - High contamination rates: 80% of the screening arm was actually screened. 50% of the control arm was screened regardless

Answer 107

1. Low risk or favorable intermediate risk patients 2. Low-intermediate volume prostate, approximately < 60ml (must be smaller than template ~7x7) 3. No seminal vesicle invasion (Note: some experienced brachytherapists can implant the proximal seminal vesicles) 4. Low IPSS (<15) due to increased risk of late genitourinary toxicity 5. Able to undergo anesthesia

Answer 108

De novo metastatic castration-sensitive prostate cancer Arms: 2x2 factorial design - standard arm: ADT + docetaxel (before an amendment, ADT alone was also allowed) - standard + abiraterone - standard + 74 Gy/ 37 fx - 🏆 standard + abiraterone + 74 Gy Results (standard arm w/ and w/o abiraterone): - Low met burden & RT: -- 3-yr PFS: 3.0 SOC vs. 4.4 abi vs. 2.6 RT vs. 7.5 yrs RT+abi (significant for RT abi vs. abi, p=0.019) - Median OS 6.9 yrs no RT vs. 7.5 yrs RT, p=0.81 - Median OS 7.1 SOC vs. not reached RT+abi+SOC - Overall population -- Median PFS 2.2 yrs SOC vs. 4.5 abi -- Median CSS 5.8 yrs vs. not reached - ADT with docetaxel population -- Median PFS 2.0 yrs vs. 4.5 yrs -- Median OS in low met burden not reached -- Median OS high mets 3.5 vs. 5.1 yrs -- Median PFS low mets 2.7 yrs vs. not reached -- Median PFS high mets 1.6 yrs vs. 4.1 yrs -- Castrate resistance median 1.4 yrs vs. 3.2 yrs -- Median CSS 4.7 yrs vs. not reached Conclusions: - Adding abiraterone to ADT and docetaxel improves PFS and OS. - RT + abi improves PFS in low volume metastatic compared to abi alone. - OS seems to favor RT, especially when it is given with abiraterone.

Answer 109

- High risk PCa: -- GS 7-8, any T, PSA>20 -- GS 9-10, any T, any PSA -- All had PSA<150 - Randomization: 1:1 -- IMRT 72-75.6 Gy + 24 mos ADT (neoadj and adj) + **docetaxel x6 (adj)** -- IMRT 72-75.6 Gy + 24 mos ADT (neoadj and adj) +ADT **w/o CHT** - Outcomes: -- 4-yr OS 93% vs. 89% -- 6-yr DM 9% vs. 14% -- 6-yr DFS 65% vs. 55% -- 6-yr BC 79% vs. 75% -- 10-yr RMST difference 0.42, p=0.048 -- 10-yr DM 20% vs. 22%, p=0.29 -- 10-yr deaths n=62 vs. 50, p=0.16, HR crosses 1" - Conc: Chemo improves OS and DM at 4 years, but not different at 10 years

Answer 110

en-face e^- R_x to 85% IDL: - 12 Gy in 3 fx; 10-12 Gy in 1 fx - 10 cm diameter circle centered over the nipple - No bolus (skin is not a target) Alt. tamoxifen can be used for medical prophylaxis (Perdona et al. Lancer Onc 2005)

Answer 111

- Rec PCa - ≤3 oligometastatic lesions as seen on choline PET - Testosterone >50 - 🏆 SBRT or surgery to metastatic lesions (repeat SBRT allowed) - observation - Results: -- 3-yr ADT free survival 21 mos vs. 13 mos, p=0.11 - Conclusion: SBRT to all oligometastatic sites in prostate cancer improves ADT-free survival

Answer 112

- T1c-T2 and N1, or T2c-T4 and N0-N1, PSA ≤40 -- Modern high risk, node positive, and some int risk - Randomization: -- 6 mos ADT with RT to 70 Gy (50 Gy WPRT + 20 Gy boost) then +30 months ADT (36 mos total) -- vs. 6 mos ADT with RT only - Results: LT-ADT vs. ST-ADT -- 5-yr mortality: 15% vs. 19% -- 5-yr OS: 58% vs. 81% - MEMORY: EORTC trials used ADT for 36 mos

Answer 113

Many regimens, but this is acceptable: - PSA: 0.35 - 0.6 → ADT 6 mos - PSA: > 0.6 → ADT 24 mos

Answer 114

- 5-year FFBF by different pre-SRT PSAs: -- 0.01-0.2 → 71% -- 0.21-0.50 → 63% -- 0.51-1.0 → 54% -- 1.01-2.0 → 43% -- >2.0 → 37% - 10-year DM incidence by different pre-SRT PSAs: -- 0.01-0.2 → 9% -- 0.21-0.50 → 15% -- 0.51-1.0 →19% -- 1.01-2.0 → 20% -- 2.0 → 37% - Conc: Salvage RT at PSA < 0.2 → ↑ FFBF and ↓ DM

Answer 115

No (McGuffin et al. PRO 18) - trial used simethicone 80 mg BID

Answer 116

3500-3625 cGy in 5 fx

Answer 117

- Meta-analysis of M1 patients in STAMPEDE and HORRAD trial -- 🏆 RT to prostate + ADT vs. ADT alone Results: - In all M+, RT improved BF and FFS -- ~10% benefit at 3 yrs -- BF: 25% vs. 36% - If <5 bone mets: RT improves 3-yr OS -- 3-yr OS: 77% vs. 70% Conc: - RT to the primary prostate tumor in ≤5 bone mets improves OS

Answer 118

New dx metastatic prostate cancer w/ primary bone involvement - SOC ADT ± prostate radiation (either 70 Gy in 35 fx or 57.76 Gy in 19 fx, delivered 3 times a week) - Number of osseus metastases was stratified per protocol by < 5, 5-15, and > 15. - Results: Median FU 47 mos, no sig. diff -- OS: 45 vs 43 mos (NS) -- PSA RFS: NS -- Subset analyses (unclear if pre-specified or post-hoc) did not identify any subgroup that benefited from prostate radiation - The results of this trial are discordant with the STAMPEDE data

Answer 119

- For Prostate Only RT: -- Concurrent f/b adjuvant preferred over neoadjuvant/concurrent -- Improves MFS (8% benefit at 10 yrs) - for WPRT, sequencing does not matter

Answer 120

No, due to an increase in the rate of death

Answer 121

PSAV can be used to prevent unnecessary and potentially morbid repeat biopsies in younger men (<50 YO)

Answer 122

- Gleason score 8-10 - Pre-radiation PSA level >2.0 - PSA doubling time ≤10 mos - -margins - -SVI

Answer 123

- Men w/ pT3NOM0 s/p RP → 60-64 Gy of adj. RT or obs Results: - adj. RT improved metastatic-free survival and OS (SS) - HRQOL sub-study -- adj. RT led to worse bowel and urinary function, although bowel function differences disappeared over the 5-yr period. -- No difference for erectile dysfunction. -- Global HRQOL was initially worse for the RT group but improved over time and was better at the end of the period than the global HRQOL reported for the surgery alone (SS) → Treatment failures worsen QOL

Answer 124

- Bone - Muscle - Bowels - Bladder

Answer 125

- GS 8-10 or T3-4, N0-1(HR and LN+) -- RT 70 Gy (50 WPRT + 20 Gy boost) concurrent & adj ADT x 36 mos vs. RT alone - Results: -- 5-yr OS 78% vs. 62% -- 5-yr DFS 74% vs. 40% -- 5-yr CSS 94% vs. 78% -- **10-yr OS 58% vs. 40%** -- **10-yr LRF 6% vs. 24%** -- **10-yr DFS 48% vs. 23%** -- **10-yr DM-free survival 51% vs. 30%** -- **10-yr PCM 10% vs. 30%** -- **10-yr CSS 90% vs. 70%** -- **At 10 years, no change in CV mortality** Conc: LT ADT added to RT improves OS, DFS, PCM, and LRF in high-risk and node-positive prostate cancer w/o an increase in CV toxicity -- MNEMONIC: 228**63** → 36 most ADT trial

Answer 126

- Modern high risk, some intermediate -- 4 mos NCADT + 65-70 Gy RT (with 44-50 Gy WPRT) alone vs. w/ 24 mos adj ADT (28 mos total) Results: - Long-term ADT improved 10-yr DFS (22% vs. 13%), LR, DM, BF, and CSS. - For modern int risk, no diff in 10-yr OS (61% STAD vs. 65%), DSS, or PSAF - No difference in all-cause mortality between ST and LT ADT -- On subanalysis, OS advantage seen in GS 8-10: 45% vs. 32% Tox: - Late GI Grade 3+ toxicity increased: 2.6% vs. 1.2% (SS) Conc: - LT ADT improves LR, DM, BF, and CSS. OS is improved in GS 8-10. - Most of these patients were high-risk.

Answer 127

- 66% HR and 34% IR --EBRT to 66-74 Gy was initiated at month 5 of AS -- Zoledronic acid was started concurrently with AS. - Results -- Median FU 10.4 years, 6-mos AS vs. 18-m AS: -- **Prostate cancer-specific mortality: 13.3% vs. 9.7% (SS)** -- All-cause mortality: 32.3% vs. 28.0% (NS) -- **Distant progression: 27.5% vs. 20.7% (SS)** -- **Local progression: 7.9% vs. 4.9% (SS)** -- **PSA relapse: 45.9% vs. 34.0% (SS)** - Conc: -- Similar to RTOG 9202, RADAR improved all clinical endpoints except OS w/ use of long-term ADT. -- Zolendronic acid, once thought to reverse AS-induced decreased bone density and have anti-tumor activity against castration-sensitive PCa did not have any oncologic effects.

Answer 128

1. I-125 = 60 days 2. Cs-131 = 10 days 3. Pd-103 = 17 days 4. 1-131 = 8 days 5. Ir-192 = 74 days

Answer 129

- Improved late GI tox - Similar GU tox Wortel et al, IJROBP 16

Answer 130

Central Zone

Answer 131

- ERSPC: PSA q4 yrs (q2 years in patients in Sweden) - NCCN guidelines (Prostate Cancer Early Detection, 1.2022) recommend tailoring the screening interval to PSA level: -- If < 1 → repeat q 2-4 yrs -- If 1-3 → repeat more frequently (every 1-2 years) - USPTF: individualized screening based on benefits vs. harms -- Less frequent screening, q 2-4 yrs, is reasonable

Answer 132

Biochem control rates w/o daily image guidance: - < 4 cm → 75% **- ≥ 6 cm → 35%!**

Answer 133

CSS benefit for: - ≤ 2 LNs + Gleason 7-10 with pT3b/pT4 or +margins (HR = 0.3) - 3-4 +LNs regardless of other factors **- No CSS benefit in ≥ 5 LNs**

Answer 134

As of NCCN 2023, PSMA/PET can be ordered without any inidiatlal CT or bone scan.

Answer 135

- T_1/2 x 3 mos -- Pd 103 → 2 mos -- I 125 → 6 mos

Answer 136

- Compared bowel QOL at 24 mos for IMRT vs. IMPT for LR/IR Prostate Cancer - Detected no change

Answer 137

- Efficacy and tox: Hypofractionated versus conventional radiotherapy post-prostatectomy - 62.5 Gy in 25 fx vs. 66.6 Gy in 37 fx - Eq 2 yr biochemical failure rates and short and long term GU tox - ↑ acute GI tox w/ Hypofx, but this disappears by 6 mos

Answer 138

- Failure by PSA levels: -- PSA 0.01-0.2 - 71% -- PSA 0.21-0.5 - 63% -- PSA 0.51-1.0 - 54% -- PSA 1.01-2.0 - 43% -- PSA > 2.0 - 37% - Higher values indicate an increased risk of biochemical failure: -- ADT (no vs. yes) HR 1.85 (1.53 to 2.25) -- GS 9-10 v ≤6 HR 2.43 (1.93 to 3.06)| -- EPE (yes vs. no) HR 1.32 (1.14 to 1.53) -- **Positive margin (yes vs. no) HR 0.71 (0.63 to 0.81)** -- Seminal vesicle inv (yes vs. no) HR 1.35 (1.14 to 1.60) -- Pre-SRT PSA (per ng/mL) HR 1.88 (1.71 to 2.07) -- **SRT Dose ≥66 Gy vs < 66 Gy HR 0.81 (0.71 to 0.91)** -- PSADT ≤ 6 mos vs. - Per the 2022 update: -- PSA DT (< 6 mos vs. ≥ 6 mos) HR Notably, +margins and higher RT doses are a/w lower risk of biochemical failure! All others are at an increased risk of biochemical failure

Answer 139

- Abi inhibits androgenic steroid synthesis beyond the castrate state by inhibiting adrenal (and possibly intratumoral) steroid synthesis. Upstream steroid precursors can accumulate if given without glucocorticoids. -- Excess upstream mineralocorticoids → HTN, hypokalemia -- Giving steroids with abi can decrease this effect

Answer 140

- RT regimen: 50.4 Gy / 28 fx IM**R**T f/b 28.8 GyE (DE) or 9.8 Gy (Non-DE) IM**P**T Median FU: 8.9 yrs: DE vs. non-DE - Overall Survival: 78.4% vs. 83.4% (NS) - **Biochemical Failure: 16.7% vs. 32.3%** - Biochemocal failure by NCCN risk grouping: -- LR: 7.1% vs. 28.2% (SS) -- IR: 30.4% vs. 42.1% (SS) - # requiring salvage ADT: 6% vs. 11% Toxicity: DE vs. non-DE - Acute GI tox ≥ G3: !% vs. 0% - Acute GU tox ≥ G3: 2% vs. 2% - Acute GU tox ≥ G2: 62% vs. 54% Why should you care about a proton trial? DE w/o ADT improves biochemical failure in LR and IR risk groups - These risk groupings had less representation in the other DE trials!

Answer 141

- LR and IR only; Gleason 4+3=7 excluded -- 92% were IR. 70% were UIR - Noninferiority: 78 Gy/39 fx or 62 Gy/20 fx to prostate vs. 🏆 SBRT 36.25 Gy/5 fx to PTV, 40 Gy to CTV SIB to prostate - QD or QOD; No ADT or SpaceOAR; FIducials not required - Primary endpoint: noninferiority of BPFS - Results: -- **5-yr BPFS 94.6% vs. 95.8%** -- **5-yr DM 1% both arms** - Tox: CTCAE -- Acute G2+ GI 12% vs. 10% (NS) -- 5-yr Late GI G ≥2, 10.2% vs. 10.7% (NS) -- Acute G2+ GU 27% vs. 23% (NS) -- **5-yr Late GU G ≥2, 18% vs. 27% (SS)** -- 5-yr G ≥2 ED 29.1% vs. 26.4% (NS) -- 5-yr G3 3 ED 6.1% vs. 4.4% (NS) -- No grade 4 ED - Conc: -- SBRT is noninferior to conventional fractionation in BPFS. -- There is a slightly increased risk of GU adverse events with five-fraction radiation.

Answer 142

- Transient rise in PSA of at least 0.2 ng/mL - Good prognostic marker, indicating a ↓ risk for biochem relapse - It happens 15 mos post-tx

Answer 143

All are SS: - Age at dx (continuous): HR 0.97; p < 0.001 - Gleason 7: HR 0.55; p = 0.002 - Gleason 8-10: HR 0.41; p = 0.002 - Prostate volume (continuous): HR 1.00; p = 0.892 - Neoadjuvant ADT: HR 1.24; p = 0.290

Answer 144

- Test <50 ng/dL (1.73 nmol/L)

Answer 145

- Castration level test - Biochemical or radiographic progression of disease

Answer 146

- HR PCa - 1st deg relative w/ HR PCa

Answer 147

- No! -- RT + ET have a demonstrated 10% 10-yr OS benefit vs. ET alone - SPCG-7/SGUO-3 Windmark et al, Lancet '09: -- 10-year overall mortality: 39.4% ADT alone vs. 29.6% RT+ADT (SS) -- 10-year cancer-specific mortality: 23.9% ADT alone vs. 11.9% RT+ADT (SS) -- 10-year PSA recurrence: 74.7% ADT alone vs. 25.9% RT+ADT (p<0.001)