Treatment with a short course of intensified hormonal therapy in combination with metastasis-directed stereotactic body radiation therapy (SBRT) may be safe and effective in patients with oligorecurrent and metastatic prostate cancer, according to a recent study published by Nikitas et al in European Urology.
Background
Nearly all patients diagnosed with metastatic hormone-sensitive prostate cancer are treated with androgen-deprivation therapy (ADT). However, hormonal therapy can cause significant side effects such as weight gain and loss of libido. As a result, many patients choose intermittent ADT, which involves periodically stopping and then resuming therapy to better manage treatment-related side effects. Although intermittent ADT may offer a better quality of life compared with continuous treatment, nearly all of the patients in this setting see their cancer return within 6 months.
Dual androgen receptor pathway inhibitors are a more potent but shorter course of hormonal therapy. A current strategy to prolong the use of hormonal therapy while controlling prostate-specific antigen levels is to leverage a combination of therapies like SBRT, which delivers highly focused and intense doses of radiation to the tumor and minimizes exposure to surrounding healthy tissues in short duration.
Study Methods and Results
In the single-arm phase II trial, researchers examined the safety and efficacy of adding metastasis-directed SBRT and dual androgen receptor pathway inhibitors to intermittent ADT in 28 patients with metastatic prostate cancer who had disease recurrence following radical prostatectomy. The researchers used prostate-specific membrane antigen positron-emission tomography/computed tomography scanning to identify patients with a limited burden of disease and who may benefit from the combination therapy.
The researchers found that 50% of the patients who received the combination therapy showed no signs of cancer and remained recurrence-free at 6 months following the treatment. Further, the patients with no prior hormonal therapy were less likely to experience cancer recurrence.
“In contrast, without this combined treatment approach, we would expect approximately 1% of patients to have no evidence of disease at the 6-month stage,” emphasized senior study author Amar Kishan, MD, Professor of Radiation Oncology at the David Geffen School of Medicine at the University of California, Los Angeles (UCLA).
Overall, the researchers found that the combination therapy was well tolerated; 93% of the patients completed the treatment regimen and only 21% of them experienced severe treatment-related side effects.
Conclusions
“We found that the majority of patients tolerated this treatment without significant side effects. This is important because we are always taking into account how our treatments affect patients’ short-term and long-term quality of life,” explained lead study author John Nikitas, MD, a radiation oncology resident at UCLA Health.
The researchers noted the study’s limitations included a small sample size from a single institution and the need for longer follow-up.
“These results suggest a substantial improvement and strongly suggest there can be a meaningful impact—namely, delaying the need for hormonal therapy and thus without the significant side effects of it—by attacking metastatic prostate cancer early,” Dr. Kishan highlighted. "This study marks a crucial step forward in managing recurrent metastatic prostate cancer. The combination of highly potent systemic therapy and targeted radiation has shown impressive results in maintaining low [prostate-specific antigen] levels after testosterone recovery, offering hope for improved outcomes in these patients, but further studies are still needed to determine the best regimen,” he concluded.
Disclosure: The research in this study was funded by Janssen Scientific Affairs. For full disclosures of the study authors, visit sciencedirect.com.
