Table of Contents
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Androgen Ablation Trials
RTOG 86-10
Eligibility
- Unfavorable prostate
- Bulky T2-T4 +/- regional LN
Treatment
- Arm I: Goserelin 2 month prior to and 2 months with RT
- Arm II: RT alone
Radiation
- Pelvic: 44-46 upto 50 Gy
- Boost 15-20 Gy to prostate
Results
- NED survival significant at 8-years 33% vs 21%
- G2-G6 seems to benefit the most with OS 70% vs 52% advantage at 8-yrs.
- Neoadjuvant hormonal therapy improves local control in bulky Geason 2-6 tumors treated by radiation
RTOG 85-31
Eligibility
- Unfavorable prostate
- Clinical T3
- T1 or T2 with pelvic or periaortic LN(+)
- pT3 (post-surgical) with margin(+) or SV(+)
- No metastatic disease
Treatment
- Arm I: Indefinite use of Gosereline starting after completion of XRT
- Arm II: XRT & Gosereline at relapse
Radiation
- Pelvic: 44-46 Gy
- Boost prostate to 65-70 Gy1.8 to 2.0 Gy fractions
Results
- bDFS at 5-yr 54% vs 33% in favor of LHRH-agonist.
- bDFS at 9-yr 10% vs 4% in favor of LHRH-agonist.
- OS significant.
- Long-term hormonal therapy with radiation shows better overall survival for Gleason 8-10 tumors (not all high-risk).
- Only 2% of the patients with positive LN had peri-aortic LN(+). Most LN(+) were in the pelvis below the common iliac.
RTOG 92-02
Eligibility
- T2c, T3, T4
Treatment
- Arm I: 4 months of Gosereline starting 2 months prior to XRT
- Arm II: 24 months of Gosereline starting 2 months prior to XRT
Radiation
- Pelvic: 44-46 Gy
- Boost prostate to 65-70 Gy1.8 to 2.0 Gy fractions
Results
- G 8-10: OS (81.0 vs 70.7, p = 0.044)
- All comers
- OS NS
- bNED 46 vs 21% p=0.001
- Freedom from Distant Met 89 vs 83% p=0.001
- Cause-specific survival 92 vs 87% p=0.07
EORTC (Bolla)
Eligibility
- Clinical T3 or T4 w/o regional LN
- T1 or T2, N0-NX, WHO histological grade 3.
Treatment
- Arm I: Goserelin with first day of RT for 3 years
- Arm II:RT alone
Radiation
- Pelvic: 50 Gy
- Boost prostate and seminal vesicle to 70 Gy
Results
- Significant OS at 5-yr 78% vs 62% in favor of LHRH-agonist.
- The only study showing a survival advantage for all high-risk patients.
D-Amico
Eligibility (Intermediate prostate)
- PSA > 10 (median PSA = 7.8)
- Gleason> 6 (51% had Gleason 7 or higher)
- or ECE (+)
- No regional LN
Radiation
- 3D prostate: 45 Gy in 1.8 Gy fx than
- 3D prostate to 70.35 in 2.0 Gy fx
Results
Groups | OS-5 |
---|---|
6 months of LHRH agonist + RT | 88% |
RT alone | 78% |
p-value | significant |
- Note: paper did not say when LHRH agonist started
- 6 months of AA significantly improves OS-5 for intermediate risk prostate cancer
Dose Escalation
Pollack (MDACC)[4]
Eligibility
- 301 patients with T1-3 N0
- Intermediate risk benefited
- Low-risk allowed
RT Treatment
- 4-field box to 46 Gy
- conformal boost to 78 Gy
- dosed to isocenter
Results
- for patients with PSA < 10 ng/mL bDFS was same at ~ 80%.
- for patients with PSA > 10 ng/mL bDFS was improved as seen in above table.
Groups | bDFS-6 |
---|---|
70 Gy | 43% |
78 Gy | 62% |
p-value | sig. |
- OS not significantly different.
Zietman (Mass Gen)[5]
Eligibility
- mostly low-risk
- only 25% of patients had Gleason 7 or higher
- 393 patients with T1b-T2b
- PSA < 15, median PSA = 6.3
RT Treatment
- conformal prostate and seminal vesicles to 50.4 Gy
- proton used for boost
- no Hormonal therapy used
Results
Groups | bDFS-5 |
---|---|
70.2 Gy | 60% |
79.2 Gy | 81% |
p-value | sig. |
- OS not significantly different.
Pelvic Radiation
Lymph Node Negative but at Risk
Eligibility (ROACH)
- 15% LN risk based on Partin or Roach
Results of Progression Free Survival at 4 years[6]
WP RT | PO RT | |
---|---|---|
neoadjuvant hormonl therapy | 59.6 | 44.3 |
adjuvant hormonal therapy | 48.9 | 49.8 |
- WP RT: whole pelvic RT
- PO RT: prostate only RT
- N & CHT: neoadjuvant hormonal therapy, began hormonal therapy 2 months before RT and continued to receive it during RT,
- AHT: Adjuvant hormonal therapy, began their drugs immediately following the completion of RT.
- total of 4 months of total androgen deprivation was given in each arms.
Conclusion
- WP RT + N & CHT improves PFS compaired to the other three arms in patient with LN risk of > 15%.
Positive Pelvic LN
Eligibility for Gunar Zagars (MDA) Trial
- Any node positive prostate
- surgery stopped once LN(+) on frozen
Treatment
- 46 Gy to prostate
- 78 Gy to reduced prostate
- No pelvic nodes were treated
Results
Groups | # patients | OS-10 |
---|---|---|
I: Early AA | 183 | 67% |
II: AA + XRT | 72 | 80% |
Conclusion
- Give AA (forever!) for LN(+) patients
External Beam vs. Prostate Implant
Sathya (JCO 2005)
Eligibility
- 104 patients with T2-T3 N0 by Pelvic lymphadenoectomy
- PSA < 15
RT Treatment
- EBRT covered prostate and SV + 2 cm margin
- no CT planning
Results
Groups | bPFS-5 |
---|---|
66 Gy EBRT | 29% |
35 Gy Ir-192 + 40 EBRT | 61% |
p-value | sig. |
- OS not significantly different.
Post-operative RT Trials
EORTC 22911 (Bolla)
Eligibility
- Extra-capsular extension
- margins positive
- or Seminal vesicle invasion
- 1005 patients with pN0 M0
Radiation Treatment
- 50 Gy in 25 fx to surgical limits from the seminal vesicles to the apex with a margin to encompass sub-clinical disease in the periprostatic area.
- 10-Gy boost in 5 fractions circumscribing the previous landmarks of the prostate with a reduced security margin.
Results
Groups | bPFS | Local-regional Failure | OS |
---|---|---|---|
observation with salvage RT (50%) | 53% | 15% | 92% |
immediate post-op RT | 74% | 5% | 93% |
p-value | sig | not sig |
- post-op RT in patients with margin(+), SVI(+) or ECE(+) improves bPFS and LRF but not OS
SWOG 8794 (Swanson)
Eligibility (same as EORTC)
- Extra-capsular extension
- margins positive
- or Seminal vesicle invasion
- 473 patients with pN0 M0
Radiation Therapy Dose
- 6000-6400 cGy in 30-32 fractions
- to the isocenter.
- maximum dose < 5% of the prescribed dose
Radiation Therapy Field
- 9x9 or 10x10 field
- inferior: lower ischial tuberosities
- lateral: mid rectum to mid symphysis
- use indwelling bladder catheter or retrograde urethrography
- custom blocking to block rectum/bladder
Results
Groups | bDFS | DM-free Survival | OS |
---|---|---|---|
observation with salvage RT (32%) | 23% | 61% | 63% |
immediate post-op RT | 47% | 83% | 74% |
p-value | sig | trend | trend |
- post-op RT in patients with margin(+), SVI(+) or ECE(+) improves bPFS and LRF but not OS
Watchful Waiting
Scandinavian Prostatic Cancer Group Study (NEJM 2002, 2005)
Eligibility
- Randomized 695 patients
- T1b-T2
Results
- Worse Disease specific survival
Treatment | 10-DSM | 10-DM | 10-LP | 10-OS |
---|---|---|---|---|
Watchful Waiting | 14.4% | 25% | 44% | 68% |
Radical Prostatectomy | 8.6% | 15% | 19% | 73% |
p-value | 0.04 | .004 | < .001 | .04 |
Conclusions:
- Radical prostatectomy reduces
- disease-specific mortality (DSM)
- overall mortality
- risks of metastasis (DM)
- and local progression (LP)
Criticisms
- Pre-PSA-screen era
- 39% had Gleason 7 or higher
- 45% had PSA > 10.1 or higher
- 74.4% had T2 disease
- In other words these were more advance disease than the patients that would qualify for Watchful waiting or Active Surveillance.
Seminoma Trials
MRC (JCO 1999)[1]
Eligibility
- Stage I seminoma
Results
Field | Pelvic Recurrence | RFS | OS-3 | N/V land ower azospermia |
---|---|---|---|---|
Dog leg | 0% | 97% | 96% | 35% |
Para-aortic | 1.8% | 99% | 100% | 11% |
- Para-aortic equivant to dog-leg for stage I seminoma
MRC (ASCO 2004)[2]
Eligibility
- Stage I seminoma, exclude pT4
- 885 (RT) and 560 (carboplatin)
Treatment
- RT was initially randomized to 20 vs 30 Gy but once equivalence was estabilished the two arms were combined for analysis
- RT field: para-aortic
- Carboplatin dose = (7 x GRF + 25) mg
Results
Treatment | relative PA failure | Absolute PA failures | RFS-3 |
---|---|---|---|
Carboplatin x 1 cycle | 74% | 3.5% | 95.9% |
20-30 Gy RT | 9% | .3% | 94.8% |
p-value | .32 |
- PA = para-aortic
- non-inferiority of carboplatin x 1 but need to have longer than 4-year follow up.