For GS 9-10 Prostate Cancer, Best Treatment Results Seen With Combination Therapy

NEW YORK (Reuters Health) - The optimal treatment for prostate cancer with Gleason score (GS) 9-10 appears to be a combination of external beam radiotherapy (EBRT), brachytherapy (BT) and androgen deprivation therapy (ADT), according to a retrospective database study.

"I would like to underscore that these patients clearly have curable disease and should be offered curative-intent therapy instead of ADT alone,” said Dr. Amar U. Kishan from the University of California, Los Angeles.

“There is a lot of heterogeneity in terms of disease course, even in a collection of patients with aggressive disease, so improved tools to help us make more patient-specific prognostication will be imperative,” he told Reuters Health by email.

GS 9-10 prostate cancer, which comprises only 7% to 10% of cases, is especially aggressive. It remains unclear whether radical prostatectomy (RP) and radiotherapy offer equivalent outcomes for these patients.

Dr. Kishan and colleagues from 12 tertiary centers compared clinical outcomes of more than 1,800 patients with GS 9-10 prostate cancer after treatment with RP (n=639), EBRT with ADT (n=734), or EBRT+BT with ADT (n=436).

The median follow-up was 4.2 years after RP, 5.1 years after EBRT and 6.3 years after EBRT+BT, the team reports in JAMA on March 6.

Adjusted five-year prostate cancer-specific mortality rates were 12% after RP, 13% after EBRT, and 3% after EBRT+BT (P<0.001).

Similarly, rates of distant metastasis at five years were significantly lower after EBRT+BT (8%) than after RP (24%) or EBRT (24%), and distant metastasis occurred later in the EBRT+BT group.

Within the first 7.5 years of follow-up, EBRT+BT was associated with significantly longer overall survival compared with RP and EBRT.

Prostate cancer-specific mortality, all-cause mortality and distant metastasis rates did not differ significantly between patients treated with RP or EBRT.

“The optimal treatment for patients with Gleason score 9-10 prostate cancer may very well be a combination of intensified local therapy with upfront ADT (i.e., EBRT+BT+ADT),” Dr. Kishan said. “Patients receiving EBRT alone may not receive an intense-enough local therapy, whereas patients receiving RP may not receive enough upfront ADT.”

“Obviously, our standard for practice-changing evidence is a randomized controlled trial, and the data presented in the manuscript are retrospective,” he said. “However, I think a randomized trial in the setting of Gleason score 9-10 disease, let alone with three arms, is highly impractical. Thus, I believe these data are strong enough to suggest the following. First, patients with Gleason score 9-10 disease should at least be offered a course of radiotherapy with a brachytherapy boost, and medium-duration ADT (about 12 months).”

“Second,” Dr. Kishan said, “if patients are to undergo EBRT alone (without a brachytherapy boost), the EBRT should be dose-escalated to the order of 78 Gy, and ADT should be given for at least 24 months (this subset did better in our study). Third, if patients are to undergo RP, they should be counseled that they should be followed with close PSA surveillance, with early and judicious use of postoperative radiation, potentially with ADT. It should be clear that over 40% of RP patients without a strict postoperative RT protocol ended up receiving RT anyway.”


JAMA 2018.



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