"When treating more-aggressive prostate cancer with radiation, we have ample evidence that adding hormonal therapy (ADT) to the mix improves treatment outcomes," senior author Dr. Amar U. Kishan of the University of California, Los Angeles, told Reuters Health by email. "There is a persistent belief that, now that we have technologies that allow a safe delivery of higher doses of radiation, the benefit of adding ADT is less. The study provides evidence that simply increasing radiation dose does not remove the need for adding ADT."
Dr. Kishan and his colleagues reviewed phase-3 clinical trials that analyzed various forms of RT for localized prostate cancer. They performed a meta-regression of 40 individual trials with more than 21,000 patients and compared the rates and cumulative proportions of five-year overall survival, prostate-cancer-specific mortality (PCSM), and distant metastasis for each treatment arm of every trial.
As reported in Prostate Cancer and Prostatic Diseases, the researchers found that radiation-dose escalation in either the absence or presence of short-term ADT (STADT) of eight months or less did not significantly improve any five-year outcomes.
By contrast, adding long-term ADT (LTADT) of 18 months or more to low-dose (74 Gy or lower) RT improved five-year PCSM (odds ratio, 0.34; P<0.001) and distant metastasis (OR, 0.35; P<0.001) over low-dose RT alone.
Adding STADT improved five-year PCSM over low-dose RT alone (OR, 0.55; P<0.001) as well. Overall survival was numerically but generally not significantly increased with the addition of ADT.
"The findings caution against the routine omission of ADT in men receiving high-dose radiation, which applies mainly to patients with unfavorable intermediate- and high-risk prostate cancer," Dr. Kishan said.
"A major limitation of this meta-analysis is the lack of individual patient data from each of the trials we evaluated, as well as the small number of trials that evaluated the impact of short-duration ADT along with high-dose radiotherapy," Dr. Kishan acknowledged. "A major strength is that we rigorously evaluated 40 randomized trials."
Two experts who were not involved in the study welcomed its results.
"The authors should be commended for their work in amalgamating such a large pool of studies," Dr. Chad Tang, a radiation oncologist at the University of Texas MD Anderson Cancer Center, in Houston, told Reuters Health by email. "This paper generates a useful meta-analysis of the existing data. By doing so, it provides additional evidence that RT dose escalation does not improve many important patient outcomes."
"However," he noted, "it is unlikely that many practitioners will move away from dose-escalated regimens, given the relative ease of administration and the reduction in radiation toxicities achieved with modern innovations, including intensity-modulated radiation therapy (IMRT), SpaceOAR (space organ at risk), and improved image-guided radiation therapy (IGRT), which were not employed in the analyzed dose-escalation trials."
"Regardless," Dr. Tang added, "this paper represents an important piece of work that will provide reference for future trial development."
Dr. Swapnil P. Rajurkar, an assistant clinical professor in the Department of Medical Oncology and Therapeutics Research at City of Hope in Upland, California, was not surprised by the findings.
"Randomized trials in patients with high-risk localized prostate cancer have shown improvement in disease-free survival and overall survival with RT plus long-term ADT versus RT alone," Dr. Rajurkar said by email. "However, these benefits should be balanced with consideration of the side effects of long-term ADT, including sexual dysfunction, fatigue, reduced muscle strength, and vasomotor symptoms."
Dr. Kishan said he and his team "are working on performing an individual-patient-data analysis that will allow us to evaluate early disease outcomes and more thoroughly evaluate the relative benefit of each strategy."
The study did not receive commercial funding. The authors and independent experts state that they have no conflicts of interest.
SOURCE: https://bit.ly/3tKRDfd Prostate Cancer and Prostatic Diseases, online August 16, 2021.
By Lorraine L. Janeczko
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