Postop Radiation Slows PSA Rise in High-Risk Prostate Cancer (CME/CE)

Authors: MedPage Today

By Charles Bankhead, Staff Writer, MedPage Today
Published: October 18, 2012
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

Men with high-risk prostate cancer had a significantly lower risk of biochemical relapse when treated with adjuvant radiation therapy after radical prostatectomy, results of a large randomized trial showed.

After a median follow-up of almost 11 years, men who received radiotherapy after removal of the prostate had a biochemical progression rate of 39.4% compared with 61.8% in men randomized to a wait-and-see policy after surgery.

The reduced risk of biochemical progression did not translate into a survival benefit, as the two treatment groups did not differ with respect to progression-free survival (PFS), distant metastasis-free survival, or overall survival, as reported online in The Lancet.

The results suggested older age might have had a detrimental effect on radiotherapy's ability to improve clinical PFS.

"Our results suggest that postoperative irradiation significantly improves biochemical progression-free survival and local control and might improve clinical progression-free survival in patients younger than 70 years and those with positive surgical margins, although it might have a possible detrimental effect in patients aged 70 years or older," Michel Bolla, MD, of Centre Hospitalier Universitaire A Michallon in Grenoble, France, and co-authors wrote in conclusion.

For organ-confined prostate cancer, radical prostatectomy achieves good long-term local control. However, extracapsular extension or seminal vesicle invasion is associated with a risk of local failure as high as 50%, the authors noted in their introduction.

Higher Gleason score, higher baseline prostate-specific antigen (PSA) level, and positive surgical margins, along with seminal vesicle invasion, have proven to be independent predictors of biochemical (PSA) progression-free survival.

Three phase III clinical trials showed that local control in high-risk patients improved with postoperative irradiation of the surgical bed. Of those trials, the European Organization for Research and Treatment of Cancer (EORTC) 22911 improved PFS (PSA and clinical) after a median follow-up. Bolla and colleagues reported results from long-term follow-up in the trial.

EORTC 22911 involved patients recruited at 37 centers throughout Europe. Principal eligibility criteria included age 75 or younger, WHO performance status 0 or 1, and previously untreated stage cT0-3 cN0 M0 prostate cancer (pathologic stage pT2-3 N0) with at least one high-risk feature: extracapsular extension, positive surgical margins, or seminal vesicle invasion.

The analysis included 1,005 patients, all of whom underwent radical prostatectomy, followed by randomization to immediate radiation therapy or active surveillance and irradiation delayed until PSA or clinical relapse. Follow-up in both groups included PSA measurement (median of 10).

After a median follow-up of 10.6 years, 198 patients in the postoperative irradiation group had PSA recurrence compared with 311 in the wait-and-see group. The difference represented a 51% reduction in the hazard for recurrence in favor of postoperative irradiation (HR 0.49, P<0.0001).

The 10-year biochemical PFS was 60.6% in the radiotherapy group and 41.1% in the wait-and-see group and was unaffected by adjustment for baseline characteristics.

"By year 10, the cumulative proportion of patients who had started an active salvage treatment in the wait-and-see group was 47.5% compared with 21.8% in the postoperative irradiation group," the authors wrote.

The clinical PFS benefit observed at 5 years with postoperative irradiation had disappeared by 10 years (70.3% versus 64.8%, HR 0.81, P=0.0539). Postoperative irradiation significantly reduced the risk of locoregional recurrence (HR 0.45, P<0.0001) but not distant relapse (HR 0.99).

Overall survival also did not differ significantly between treatment groups. The 10-year survival was 76.9% in the irradiation group and 80.7% in the wait-and-see group. Prostate cancer-specific mortality also did not differ significantly between the groups (3.9% versus 5.4%).

The authors found significant treatment effect heterogeneity by age for PSA progression-free survival (P=0.0443), clinical PFS (P=0.0003), and overall survival (P=0.0008). Younger patients and those with clear surgical margins derived significant benefit from postoperative irradiation, but older patients and those with residual tumor cells did not.

The author of an associated commentary said the trial results do inform on the critical issue of who should get postoperative irradiation and who should not.

"Ultimately, the decision to treat needs multidisciplinary input," wrote Jason A. Efstathiou, MD, of Massachusetts General Hospital and Harvard Medical School. "When surgery has probably not cured a patient, prospective data still support postoperative radiation."

"The onus is on the uro-oncology team ... to discuss postoperative radiation with the patient, address optimal timing of initiation when it is used, and to provide justification when it is not."

The study was supported by the Ligue Nationale contre le Cancer in Grenoble, France, and the EORTC.

Neither the study authors nor Efstathiou had relevant disclosures.

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