Prostate Trials

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.
Bibliography
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2. Oliver RT, Mason MD, Mead GM, von der Maase H, Rustin GJ, Joffe JK, de Wit R, Aass N, Graham JD, Coleman R, Kirk SJ, Stenning SP; MRC TE19 collaborators and the EORTC 30982 collaborators. Radiotherapy versus single-dose carboplatin in adjuvant treatment of stage I seminoma: a randomised trial. Lancet. 2005 Jul 23-29;366(9482):293-300. PMID: 16039331
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