By Megan Brooks
NEW YORK (Reuters Health) - Dose-intensified salvage radiotherapy is not superior to conventional dose salvage RT and is associated with increased late rectal toxicity in patients with biochemical recurrence of prostate cancer after prostatectomy, according to new findings.
"The results tell us more is not always better," Dr. Neeraj Agarwal of Huntsman Cancer Institute, in Salt Lake City, said in a statement from the American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium, where the research was presented.
"In this study of men with recurrence of prostate cancer after surgery, standard dose of radiation was as effective as the higher dose of radiation therapy in controlling the disease, and was less toxic," said Dr. Agarwal, who was not involved in the study.
Radical prostatectomy is the standard primary treatment for localized prostate cancer. However, up to 40% of patients will experience biochemical progression following surgery. For these patients, salvage radiation therapy to the prostate bed is the only available curative treatment option, study presenter Dr. Pirus Ghadjar, with Charité Hospital, Berlin, Germany, explained in his presentation.
"An important question is the optimal salvage radiation therapy dose. Retrospective comparisons have suggested that the biochemical progression-free survival is improved around 2.5% per grade dose intensification. But the results of well-conducted randomized trials are lacking until now," he said.
The Swiss Association for Clinical Cancer Research (SAKK) 09/10 trial was an open-label, multicenter, randomized superiority trial comparing dose-intensified (70 Gy in 35 fractions) versus conventional dose (64 Gy in 32 fractions) salvage radiation therapy to the breast prostate bed in 350 men with biochemical progression after radical prostatectomy.
Biochemical progression was defined as two consecutive prostate-specific antigen (PSA) rises with the final PSA > 0.1 ng/mL or three consecutive rises. The primary endpoint was freedom from biochemical progression, based on a PSA >= 0.4 ng/mL and rising or clinical progression.
At randomization, the median PSA level was 0.3 ng/mL. At the time of data cutoff (July 3, 2020), the median follow-up was 6.2 years and 138 biochemical progression events had occurred.
The estimated freedom from biochemical progression rate at six years was 62.3% in the conventional 64 Gy dose group and 61.3% in the dose-intensified 70 Gy.
After adjusting for stratification factors, there was no between-group difference in freedom from biochemical progression (hazard ratio, 1.14; log-rank P=0.44). The finding was consistent across subgroups.
There were also no significant differences regarding secondary efficacy endpoints of clinical progression-free survival, time to hormonal treatment, and overall survival.
Rates of late grade-2 and -3 genitourinary toxicity did not differ significantly between the two radiation dose groups, but late grade-2 and -3 gastrointestinal toxicity was more common with dose-intensified radiotherapy.
Discussant for the study Dr. Richard Valicenti of the University of California Davis School of Medicine said, "The results are in line with those from another phase-3 trial conducted at Peking University that showed dose escalation to 72 Gy had no improvement in four-year biochemical freedom from control compared with a 66 Gy regimen."
"These data from SAKK and the Peking University are in contrast to the outcomes of phase-3 trials for dose intensification for intact prostates. Unlike the SAKK and Peking University study, these trials had a radiographically identifiable target so it just might be the case that an intensified postoperative radiation dose is better to have a personalized target than not," Dr. Valicenti commented.
SOURCE: https://meetings.asco.org/gu/attend ASCO 2021 Genitourinary Cancers Symposium, presented February 11, 2021.