Radiotherapy as salvage postoperative management of patients with adverse features

Thursday, 5 February 2009-  At the recent 6th ESOU Meeting held in Istanbul, Turkey, Asst. Prof. Dionysios Mitropoulos spoke on the rationale of using radiotherapy but only as a salvage option in the postoperative management of patients with adverse pathological features.

Noting that patients with adverse pathological features (i.e. extracapsular extension, seminal vesicle involvement, positive surgical margins, etc.) are thought to be at risk for failure after radical prostatectomy (RP), Mitropoulos said not all patients with prostate capsular invasion or seminal vesicle involvement will have disease recurrence.

"Moreover, data on elevated serum PSA levels after surgery are not mature enough to quantify an association with cancer-specific mortality," he added.

He said that a subset analysis of the EORTC 22911 trial showed that only patients with positive surgical margins would have prolonged biochemical disease-free survival with adjuvant radiotherapy (ART), while localisation of positive margins, Gleason score, seminal vesicle invasion and extracapsular extension had no statistically significant impact.

He also added that the SWOG 8794 and the German ARO/AUO trials also demonstrated a significant reduction of PSA relapse rates associated with ART. But a matched pair analysis of data from a pooled multi-institutional database comparing ART with salvage radiotherapy (SRT) showed that the five-year freedom from biochemical failure from surgery was marginally (p=0.049) significantly better for ART.

"The efficacy of any adjuvant radiotherapy has to be balanced against its side effects," Mitropoulos said. "Prospectively documented side effect rates in the EORTC trial were higher in the ART group (immediate and late grade 1-2 side effects). Retrospective analysis of the corresponding data in the SWOG trial revealed more side effects in patients undergoing ART (rectal, urethral stricture urinary incontinence)."

According to Mitropoulos, the impact of ART on quality of life is not yet known, while the aforementioned trials have not analysed ART’s impact on postsurgical erectile function recovery.

"However, the CaPSURE study has showed that the side effects of adjuvant therapy are not negligible, particularly for bowel function, continence and bladder function," Mitropoulos  said.

He said both EORTC and SWOG trials have not showed a significant benefit of ART for overall survival even though retrospective data support the notion that improved local control result in better outcomes in patients at high risk for relapse after surgery.

Moreover, Mitropoulos said trials showing benefit for ART are biased from the fact that certain patients in the ART arm may have no residual disease and thus, might never experience a biochemical failure.

"The hazard ratio (HR) close to 0.5 indicates that four patients need to be irradiated to prevent one PSA relapse to occur," he pointed out. "Differences in PSA-based endpoints mainly reflect different pathological features, that are, unfortunately, liable to inter-observer variation."



By Joel Vega

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