Radiation Ups Survival in Prostate Cancer, but Not Low Risk

Roxanne Nelson, BSN, RN

July 24, 2015

Dose-escalated external-beam radiation therapy (EBRT) appears to improve overall survival in men with intermediate- and high-risk prostate cancer, but not in those with low-risk disease, according to new data.

The findings were published online July 16 in JAMA Oncology.

In this retrospective analysis, researchers found that for men with low-risk disease, incremental increases in dose were not associated with a difference in survival.

But for patients with intermediate-risk disease, every incremental increase of about 2-Gy dose was associated with a 7.8% reduction in the hazard of death (hazard ratio [HR], 0.92; P < .001).

Similarly, in the high-risk group, with every approximate 2-Gy increase in the radiation dose, there was an associated 6.3% reduction in the hazard of death (HR, 0.94; P < .001).

"Our results add to the body of evidence questioning aggressive local treatment strategies in men with low-risk prostate cancer but supporting such treatment in men with greater disease severity," write the authors, led by Anusha Kalbasi, MD, a resident in the Department of Radiation Oncology, Hospital of the University of Pennsylvania, in Philadelphia.

"The conversation between physicians and patients with low-risk prostate cancer is and has been evolving," Dr Kalbasi told Medscape Medical News. "Our study adds to this conversation by suggesting that physicians should strongly consider disease risk when weighing the risks and benefits of dose-escalated EBRT."

True Impact on Survival?

Aggressive treatment strategies that do not have an impact on overall survival are controversial in low-risk prostate cancer, write Dr Kalbasi and colleagues, "where cancer-specific mortality is low and competing risks are high."

They note that although the results of several randomized clinical trials have found that dose-escalated EBRT showed improved biochemical and local control in prostate cancer, the evidence is scant as to whether dose escalation improves overall survival.

In an accompanying editorial, Phillip J. Gray, MD, and Anthony L. Zietman, MD, both from Massachusetts General Hospital in Boston, reiterate that to date, randomized clinical trials have not shown an improvement in overall survival with dose escalation, even in studies with 10 or more years of follow- up.

Thus, the significant survival benefit seen in the current article does seem to suggest a true relationship between dose and survival that appears to have been missed in previous randomized clinical trials.

"The authors' suggestion of a causal link, while plausible, must, however, be examined with the eye of scrutiny," they write. "The biggest concern is whether a true survival benefit from an enhanced local therapy can be present only 7 years after definitive treatment."

Dr Gray and Dr Zietman also note that the lack of a benefit seen in patients with low-risk disease "is hardly surprising," because the risk for cancer-specific mortality is already quite low.

"Indeed, mounting evidence suggests that for many, if not most, low-risk patients the most appropriate dose of radiation may in fact be 0 Gy," they write.

But for those with more aggressive disease, dying from prostate cancer is of considerable concern, and these are the patients who stand to derive the most benefit from intensification of therapy, the editorialists note.

That said, "care must be taken in its implementation," they emphasize, even though numerous studies, including the current study, appear to support dose-escalation delivered by varying techniques.

"Dose escalation beyond the currently accepted levels should be studied in the context of well-designed clinical trials capable of tracking not only patient outcomes but also effects on quality of life, a vital factor missing from nearly every large database," say Dr Gray and Dr Zietman.

"What dose can be safely delivered with external beam radiotherapy remains a moving target," they add.

Benefit in Higher-Risk Groups Only

In their study, Dr Kalbasi and colleagues compared the effectiveness of dose-escalated vs standard-dose EBRT for men who were diagnosed from 2004 to 2006, using the National Cancer Database.

Three cohorts were evaluated: those with low-risk (n = 12,229), intermediate-risk (n = 16,714), or high-risk (n = 13,538) prostate cancer.

Overall survival was compared between treatment groups, and in a secondary analysis, dose response for survival was evaluated.

Most of the patients in all three cohorts received dose-escalated EBRT (low-risk, 61.6%; intermediate-risk, 65.6%; and high-risk, 65.6%). The median follow-up for surviving patients was 85 to 86 months in all three groups.

Among low-risk patients, dose-escalated EBRT was associated with a decreased hazard of death in the unadjusted model (HR, 0.89; P = .02), but in adjusted models, the association was no longer significant (HR, 0.98; P = .54).

For men in both the intermediate- and high-risk cohorts, dose-escalated EBRT was associated with a statistically significant decreased hazard of death in all models (HR, 0.84; P < .001 for intermediate-risk; HR, 0.82; P < .001 for high-risk disease).

The study was supported by grants from the National Cancer Institute and the David and Leslie Clarke Fund. The authors and the editorialists have disclosed no relevant financial relationships.

JAMA Oncol. Published online July 16, 2015. Abstract, Editorial


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