Hypofractionated RT in the postoperative treatment of prostate cancer is “at a relatively early stage of evaluation,” Dr Morgan said.

“Hypofractionation in the postoperative setting is undoubtedly an appealing treatment strategy, with clear potential implications in terms of logistics and economies for the health care system,” Dr Zilli added. “Conflicting results have, however, been reported concerning long-term genitourinary late toxicity, limiting its current use in the real-world clinic.”

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The randomized phase 3 NRG-GU003 trial (ClinicalTrials.gov Identifier: NCT03274687) may answer key questions in coming years about adjuvant hypofractionation toxicity and effects on patient quality of life.

“Most of the studies completed to date were single-arm trials of moderately hypofractionated post-prostatectomy RT conducted in single institutions,” Dr Morgan said. But NRG-GU003 is comparing moderately hypofractionated with conventionally fractionated radiotherapy in the postoperative setting.

The available evidence on acute toxicity is limited and contradictory — and even less is known about late toxicities involving local non-target tissues, or the long-term effects of adjuvant hypofractionated radiotherapy.7-9

“The major concern for postoperative hypofractionation remains late genitourinary toxicity,” Dr Zilli said. “In contrast to the definitive setting, genitourinary toxicity in the postoperative setting may [involve] a mix of different factors ranging from radiation-induced damage and urothelial repopulation to surgery-related damage to the bladder neck and urethra.”

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Efficacy data are also immature. Little is known about survival outcomes, and even seemingly promising prostate-specific antigen changes, which are evidence of efficacy, should be interpreted with caution.

Findings from the SAKK 09/10 clinical trial (ClinicalTrials.gov Identifier: NCT01272050) may, according to Dr Zilli, provide a clearer picture about the role of dose escalation in the salvage setting.

“Biochemical control rates seem to be similar to standard fractionation,” he said. “Equivalence should, however, be prospectively confirmed. At the moment, even for standard fractionation, we lack clear evidence if dose escalation improves biochemical control and, eventually, survival outcomes.”


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