Addition of hormone therapy to radiotherapy benefits men with localized prostate cancer
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The addition of androgen deprivation therapy to radiotherapy improved survival outcomes among patients with localized prostate cancer, according to study results published in The Lancet Oncology.
Additionally, prolonging the adjuvant component of ADT provided significant benefit — regardless of radiotherapy dose — among those with intermediate-risk and high-risk disease, researchers noted.
Rationale
“Prostate cancer is an extremely common cancer worldwide that has been studied in multiple randomized trials. Yet, to date there has been no prior effort to pool data from multiple global trials to quantify the benefits we see from common treatment intensification strategies,” Amar U. Kishan, MD, associate professor and vice-chair of clinical and translational research, and chief of the genitourinary oncology service for the department of radiation oncology at David Geffen School of Medicine at UCLA and UCLA Jonsson Comprehensive Cancer Center, told Healio.
“These benefits include the addition of ADT to radiotherapy, prolonging the duration of ADT that follows radiotherapy (adjuvant ADT prolongation), and extending the duration of ADT that may precede radiotherapy (neoadjuvant ADT extension),” Kishan added.
Methodology
Researchers used the Meta-Analysis of Randomized trials in Cancer of the Prostate Consortium (MARCAP) to obtain data on individual patients from randomized clinical trials.
“We founded the MARCAP consortium to allow us to pool data from trials to estimate the benefits of these treatments and also to pursue further lines of investigation that cannot be fully explored with a single clinical trial in isolation,” Kishan said.
The current meta-analysis included 10,853 men from 12 multicenter randomized clinical trials published between Jan. 1, 1962, and Dec. 30, 2020, that evaluated the use and/or prolongation of ADT among men undergoing definitive radiotherapy for localized prostate cancer. Studies also included data on distant metastases and survival and used ADT for a finite duration.
Metastasis-free survival served as the study’s primary outcome. Median follow-up was 11.4 years.
Key findings
Researchers observed improved metastasis-free survival with the addition of ADT to radiotherapy (HR = 0.83; 95% CI, 0.77-0.89), as well as with adjuvant ADT prolongation (HR = 0.84; 95% CI, 0.78-0.91).
However, the extension of neoadjuvant ADT did not improve metastasis-free survival (HR = 0.95; 95% CI, 0.83-1.09).
“Regardless of radiotherapy dose, patient age or prostate cancer risk group — as defined by the National Comprehensive Cancer Network classification — the addition of ADT to radiotherapy and prolonging adjuvant ADT improved all clinical endpoints, including OS,” Kishan said. “The number of men we would need to add ADT to, or prolong adjuvant ADT for, to avoid one man developing a metastasis is very low depending on the specific risk group and intervention. On the other hand, extending neoadjuvant ADT offered no benefit for any patient.”
Implications
These findings provide the strongest level of evidence so far to the magnitude of the benefit of ADT treatment intensification with radiotherapy for men with localized prostate cancer, Kishan said.
“The addition of ADT and prolonging the portion of ADT that follows radiotherapy was associated with improved metastasis-free survival in our study population. However, the magnitude of the benefit could vary, and shared decision-making with patients is recommended,” he added. “This is a very active area of research for us. The MARCAP consortium project was years in the making, and we are performing multiple pooled analyses as we speak to explore aspects such as radiotherapy dose escalation, sequencing of ADT and duration of ADT.”
For more information:
Amar U. Kishan, MD, can be reached at University of California, Los Angeles, 200 Medical Plaza Driveway, Suite B265, Los Angeles, CA 90095; email: aukishan@mednet.ucla.edu.
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