ASCO GU 2018: Radiotherapy after Prostatectomy: Adjuvant vs Early Salvage
Increasing use of radical prostatectomy for locally advanced disease has made biochemical recurrence and identification of high risk pathologic features (pT3, positive margins, SV invasion, or LN+) more common. This may also be attributed to changes in PSA screening or increasing use of active surveillance. Adjuvant XRT has a theorized rationale to improve local persistence of disease (local control) to prevent metastatic spread. The mitotic death model has demonstrated improved biologic effectiveness with lower microscopic disease burden.
Radiotherapy outcomes in pre-salvage studies are improved with lower PSA levels. Two randomized trials (EORTC 22911 and ARO 96-02) have demonstrated a statistically significant improvement in biochemical recurrence in patients treated with adjuvant XRT with approximately 10-year median follow up. SWOG 8794 demonstrated an improvement in metastasis free and overall survival, as well. Modern radiotherapy techniques have improved toxicity with publications displaying patient reported GI/GU quality of life outcomes unchanged 2-4 years after postoperative XRT. Risk adapted models (ie. Stevenson or CAPRA-S nomograms) should be used to predict the probability of recurrence after radical prostatectomy. Similarly, genomic classifiers, such as the Decipher score, can be used to risk stratify patients who would benefit with adjuvant vs salvage therapy. Three clinical trials comparing adjuvant and salvage radiotherapy have either closed or are activity recruiting patients and include RADICALS, RAVES and GETUG. The primary outcomes include disease specific survival (RADICALS, GETUG) or biochemical recurrence (RAVES). In summary, adjuvant radiotherapy improves local control, decreases risk of metastasis and works best when PSA (marker for disease burden) is lowest. Three randomized trials, providing level 1 evidence, support its use with minimal toxicity for modern techniques. A risk adapted model selects patients whom are most likely to benefit.
Furthermore, Dr. Shipley argued in favor of early salvage radiotherapy, which by definition has a post prostatectomy PSA between 0.1-0.5 ng/ml. Completed randomized controlled trials are only available for adjuvant radiotherapy vs observation. All of which, mentioned above, showed a benefit from adjuvant therapy. However, in all of these trials there was no PSA progression in 30-40% of these patients followed for 10+ years after radical prostatectomy without any further treatment, despite adverse pathologic features. Memorial Sloan Kettering has developed a multi-institutional nomogram for salvage radiotherapy after prostatectomy. A proportion of patients free from progression has been correlated to the value of their postoperative PSA level before salvage radiotherapy.
Current ASTRO/AUA guidelines state that patients who are considering radical prostatectomy should be informed of the potential for adverse pathologic findings that may lead to recommendations for subsequent radiotherapy. PSA should be monitored after radical prostatectomy to trigger early salvage radiotherapy if indicated. In the UK, RADICALS-HD trial is looking to compare early salvage RT to adjuvant RT in the intermediate risk cohort following radical prostatectomy. In conclusion, retrospective reports with 10-year follow up comparing adjuvant and early salvage radiotherapy show an improvement with adjuvant for biochemical disease-free survival, but little difference in overall survival. National practice patterns suggest adjuvant therapy is not widely utilized and early salvage is better accepted by clinicians and patients.
Presented by:
Christopher L. Amling, MD, FACS, Oregon Health and Science University
William Shipley, MD, FACR, FASTRO, Massachusetts General Hospital, Harvard Medical School
Moderator: Paul L. Nguyen, MD
Written by: David B. Cahn, DO, MBS @dbcahn, Fox Chase Cancer Center, Philadelphia, PA at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA