Patients with a particularly aggressive form of prostate cancer treated with extremely dose-escalated external beam radiotherapy (EBRT) plus androgen deprivation therapy (ADT) achieved better clinical outcomes than those treated with radical prostatectomy, a retrospective study indicated.
EBRT plus brachytherapy was associated with significantly lower prostate cancer–specific mortality than either EBRT alone (cause-specific hazard ratio 0.41, P=0.002) or radical prostatectomy (HR 0.38, P=0.001), with a better adjusted 5-year prostate cancer–specific mortality rate (3%) compared with EBRT alone (13%) or radical prostatectomy (12%), reported Amar U. Kishan, MD, of the University of California Los Angeles, and colleagues in .
EBRT plus brachytherapy also yielded better adjusted 5-year incidence rates of distant metastasis (8%) compared with EBRT alone or radical prostatectomy (24% each), with a significantly lower rate of distant metastasis compared with EBRT alone (propensity-score-adjusted cause-specific HR 0.30, P<0.001) or radical prostatectomy (HR 0.27, P<0.001).
"I would present extremely dose-escalated radiotherapy as an option to all patients I see," said Kishan in an email to 鶹ý. "The data, albeit retrospective, are compelling."
This cohort study included 1,809 patients with Gleason score 9-10 prostate cancer treated from 2000 to 2013 at 12 tertiary centers.
Patients were grouped into three cohorts based on the type of definitive therapy received: extreme dose escalation of external beam radiotherapy (EBRT) plus a brachytherapy boost (n=436; median age 67.5), EBRT alone (n=734; median age 67.7), or radical prostatectomy (n=639; median age, 61). Prostate cancer–specific mortality was the primary endpoint.
ADT is generally recommended among patients receiving EBRT, but may be contraindicated for medical reasons -- patients who did not receive ADT were not excluded.
Adjusted 7.5-year all-cause mortality rates were 10% with EBRT plus brachytherapy, 18% with EBRT alone, and 17% with radical prostatectomy. Within the first 7.5 years of follow-up, EBRT plus brachytherapy was associated with significantly lower all-cause mortality compared with EBRT alone (cause-specific HR 0.61, P=0.002) and radical prostatectomy (HR 0.66, P=0.03).
But these differences did not remain statistically significant beyond 7.5 years.
Use of EBRT plus brachytherapy declined over the years among the patients studied, mostly in favor of radical prostatectomy. From 2000 to 2005, 31% of patients received EBRT plus brachytherapy. This percentage dropped to 25% from 2006 to 2010 and to 15% from 2011 to 2013. During these same years, frequency of radical prostatectomy use rose from 24% to 53%.
"I would also stress that, should patients move forward with standard radiotherapy, they consider the importance of receiving at least high-dose radiation, along with a long duration of ADT," said Kishan, noting that outcomes were better in the subgroup that received ADT.
"For patients receiving radical prostatectomy, early postoperative radiotherapy (potentially with ADT at that point), may be superior to just radical prostatectomy," he said. "I think the important theme is that many patients with Gleason score 9-10 disease need a multimodality strategy that includes both intense local treatment and some form of systemic treatment."
Some of the limitations of the study include its retrospective nature, though a randomized trial in this population would likely not be feasible due to the relative rarity of the disease, according the authors -- only 7% to 10% of prostate cancer cases are Gleason score 9-10 on biopsy. Due to the aggressive nature of this disease, however, this comparative outcomes analysis was able to achieve statistical power within a contemporary treatment period.
Patient-reported outcomes or toxicity profiles by treatment type were not available for the researchers to analyze. In the , EBRT plus brachytherapy resulted in poorer urinary and physical function as reported by patients compared with EBRT alone.
"This is an important point," said Kishan. "Extremely dose-escalated radiotherapy may not be appropriate for patients with severe urinary symptoms, very large prostates or high-risk of bleeding that could make the brachytherapy procedure difficult."
Other limitations of the study were a short median follow-up time, not all centers providing data on the three treatment modalities, and only 41% of EBRT-treated patients receiving both radiotherapy doses of 70 Gy or greater and ADT for a duration of 2 years or longer -- suggesting a tolerance issue with the combination.
Disclosures
Kishan disclosed no relevant relationships with industry. Co-authors reported relationships with ViewRay, Soylent, Bayer, Astellas, Ferring, Dendreon, Blue Earth, GenomeDx, Augmenix, Janssen, Varian Systems, and Nanobiotix. One co-author was a Varian employee.
Primary Source
JAMA
Kishan AU, et al "Radical prostatectomy, external beam radiotherapy, or external beam radiotherapy with brachytherapy boost and disease progression and mortality in patients with Gleason score 9-10 prostate cancer" JAMA 2018; 319: 896-905.