medwireNews: Postprostatectomy adjuvant radiotherapy (ART) may offer greater benefit to patients with prostate cancer with adverse pathologic features than surveillance and early-salvage radiotherapy (ESRT), US study findings indicate.
Jason Efstathiou (Harvard Medical School, Boston, Massachusetts) and colleagues found that ART was associated with lower rates of biochemical recurrence and distant metastases after radiation, as well as improved overall survival (OS), compared with ESRT in their analysis of 1566 patients (median age 60 years) with margin-positive pathologic T2, or margin-positive or -negative pathologic T3 prostate adenocarcinoma.
Of the patients, who were treated at 10 US academic medical centers between 1987 and 2013, 371 men with prostate-specific antigen (PSA) levels of 0.1–0.5 ng/mL received ART at a median 4.4 months postsurgery, while 1195 men PSA levels below 0.1 ng/mL received ESRT at a median of 22.9 months postsurgery.
After propensity score matching to account for differences contributing to treatment allocation, median follow-up after surgery was 65.8 months with ART and 73.3 months with ESRT.
The researchers report that the 12-year actuarial postirradiation freedom from biochemical failure rate, defined as a PSA level rising to 0.2 ng/mL or higher, was significantly higher with ART than with ESRT, at 69% versus 43%.
The 12-year freedom from distant metastases rate was also significantly higher with ART than with ESRT (95 vs 85%), as was the OS rate (91 vs 79%).
In addition, multivariate analysis showed that receipt of ART and postoperative androgen deprivation therapy were associated with significantly reduced risks for biochemical failure after surgery and radiation, at subhazard ratios (SHRs) of 0.34 and 0.30, respectively.
By contrast, increasing Gleason score (SHR per unit increase=2.06), pathologic stage (T3b vs T2; SHR=1.87), and omitting nodal irradiation (SHR=2.27) were associated with significantly increased risks for biochemical failure.
To account for patients that would never have developed recurrence after surgery, Efstathiou and team performed a sensitivity analysis. This showed that the decreased risk for biochemical failure associated with ART only lost statistical significance when more than 56% in the ART cohort were assumed to have been cured by surgery alone.
The authors note that this threshold is greater than the estimated 12-year freedom from biochemical failure rate of 33% to 52% after radical prostatectomy alone, which they calculated using a contemporary dynamic nomogram.
Therefore “the difference in [freedom from biochemical failure] cannot be attributed to successful surgery alone,” they remark.
Writing in JAMA Oncology, Efstathiou et al point out that ART is currently used in less than 10% of high-risk patients.
“Our findings suggest that a greater proportion of such men may benefit from ART, especially those for whom the estimated risk of postprostatectomy recurrence is greater than 50%,” they write.
They conclude: “This study provides important insights into the use of postoperative RT for high-risk patients, but we acknowledge the need for randomized prospective evidence to guide best clinical practices.”
A number of trials to address this are underway.
By Laura Cowen
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