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10-year results of Adjuvant Radiotherapy after Radical Prostatectomy in pT3N0 Prostate Cancer

Reviewer: Lara Bonner Millar, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: November 1, 2010

Authors: M. Bolla¹, H. Van Poppel², B. Tombal³, K. Vekemans⁴, L. Da Pozzo⁵, T. M. De Reijke⁶, A. Verbaeys⁷, J. F. Bosset⁸, R. Van Velthoven⁹, L. Collette¹⁰
Institution:
1 CHU de Grenoble - A Michallon, Grenoble, France
2 Leuven University Hospital - UZ Gasthuisberg, Leuven, Belgium
3 Cliniques Universitaires Saint Luc, Brussels, Belgium
4 Virga Jesse Hospital, Hasselt, Belgium
5 Istituto Scientifico H.S. Raffaele, Milano, Italy
6 Academisch Medisch Centrum, Amsterdam, Netherlands
7 Universitair Ziekenhuis Gent, Gent, Belgium
8 Hospitalier Regional de Besanc¸on-Hopital Jean Minjoz, Besancon, France
9 Institut Jules Bordet, Brussels, Belgium
10 EORTC Headquarters, Brussels, Belgium

Background

• PSA failure occurs in 15-40% of patients who undergo radical prostatectomy
• A finding of T3 disease (extracapsular extension, positive margins, or seminal vesicle involvement) after surgery is a high risk feature for local recurrence and biochemical failure
• Adjuvant radiation therapy has been demonstrated to reduce this risk in high-risk patients, and is recommended for patients with pT3 disease based on randomized evidence from the EORTC as well as other groups
• The EORTC previously reported the results of this study of RT vs observation for patients with pT3 disease after radical prostatectomy, and the 10 year results are presented here

Materials and Methods

• 1005 patients with pT3 prostate cancer, randomized between 1992 and 2001 to immediate 60 Gy external beam RT to the surgical bed vs a wait and see (WS) approach
• Patients were 75 years of age or younger and had WHO PS of 0-1
• 93% PS 0
• Median age 65 yrs
• RT started within 16 weeks of RP (patients required to be continent), with conventional (non-3D) technique , 50Gy/25 fx + 10Gy/5 fx boost with smaller margins.
• No Gleason scoring (used WHO grade)
• 43% had one pT3 risk factor, 43% had two risk factors, and 12% had all three risk factors.
• Primary endpoint: biochemical progression free survival (bPFS)
• Biochemical failure definition: increase of 0.2 from postop nadir measured on 3 occasions at least 2 weeks apart and dated from first day of rise.
• After biochemical or clinical failure, patients could receive salvage RT.

Results

• Median pre-op PSA was 12.4 and median post-op PSA was 0.2 ng/mL
• 69% had a post-op PSA? 0.2
• 10 yr bPFS was 60% for the XRT arm, vs 41% for WS (HR 0.49, SS)
• 10 yr clinical PFS was 70% vs 65% (P = 0.054)
• Local regional failure was decreased from 17 to 7% (p< 0.0001)
• Distant metastases did not differ: 10% XRT vs 11% WS
• Death due to prostate cancer did not differ: 5.4 % XRT vs 3 % WS (not sig)
• Overall survival did not differ: 77% XRT vs 81% WS
• At the time of failure, 58% of patients in the WS group did receive salvage RT and 22% got androgen deprivation therapy (ADT)
• Grade 3+ toxicity was 5.3% for XRT vs 2.5% for WS (p=0.052)
• On subset analysis, age ? 70 appeared to benefit less than younger patients.

Author's Conclusions

• Post-operative radiation improves local control and bPFS for pT3N0 patients after radical prostatectomy.
• Based on this study, post-operative radiation does not appear to improve overall survival or distant metastases free survival for this patient population.

Clinical Implications

• Patients with pT3N0 should be offered adjuvant radiation therapy given the improvement in bPFS and local control, with low grade 3+ toxicity using conventional methods, which may be even further decreased with the advances in treatment planning (IMRT, rectal balloon, fiducial placement)
• The impact of immediate adjuvant radiotherapy on overall survival may have been obscured by the fact that over half of the wait and see group also received radiation
• The SWOG 8794 trial did report an overall survival benefit for pT3 patients
• Could this be because of patients in the SWOG observation arm, only 1/3 got RT?
• Although further investigations are warranted, this study was well-designed, and provides strong data to support the use of adjuvant radiotherapy after radical prostatectomy for patients with T3 disease. Longer follow-up and further trials may eventually shed light on the impact of this treatment paradigm on overall survival.