Therapy to Prevent PSA-Related Recurrence May Not Boost Prostate Cancer Survival

Rising prostate-specific antigen (PSA) levels indicate biochemical recurrence of prostate cancer.

Certain prostate cancer treatments used to reduce the risk of post-radiotherapy biochemical recurrence may not improve long-term overall survival, according to research published in the Journal of Clinical Oncology.

“Prostate cancer is fairly unique among cancers in that we have a good lab test (PSA) that tells us if there is cancer present or not,” study author Dr. Amar U. Kishan, an associate professor of radiation oncology at the David Geffen School of Medicine at UCLA and a researcher at the UCLA Health Jonsson Comprehensive Cancer Center, said in an interview with CURE®.

Biochemical recurrence, according to the National Institutes of Health, is the state of rising prostate-specific antigen (PSA) levels in patients who have been treated for prostate cancer.

“Specifically, a rising PSA after treatment above a certain threshold signifies that there is a recurrence. Because this is based off a lab test, rather than a scan result or a clinical symptom, this is called a ‘biochemical’ recurrence. Generally, this is diagnosed much earlier than a normal recurrence. This is part of the reason why prostate cancer survival is high even if it recurs — biochemical recurrences are caught very early, before the cancer has progressed enough to be visible on a scan or cause symptoms,” Kishan said.

Kishan and his team evaluated patient data from 11 randomized trial to determine if treatments that are administered with the goal of reducing biochemical recurrence after radiation have an outcome on overall survival, which is the time patients live before dying of any cause.

Notably, the post-radiotherapy treatments studied were dose escalation, androgen deprivation therapy (ADT), ADT prolongation and radiotherapy dose escalation. These therapies significantly improved the risk of biochemical recurrence, though when the researchers accounted for biochemical recurrence and non-cancer-related deaths, there was no association observed between the therapies and improved survival.

“What we show is that treatment intensification strategies that reduce the initial recurrence after radiation (the biochemical recurrence, based on PSA) do not necessarily prolong life. This has implications mostly for clinical trial design and for practitioners on what the bar should be to incorporate new treatments into practice,” Kishan said.

Kishan explained that it usually takes a long time for researchers to “read out” long-term studies on prostate cancer because people tend to live a long time with the disease and treatment intensification strategies are often adopted early, he said.

“We should be mindful of the current study's results when designing clinical trials and also when appraising evidence to support intensification strategies in the absence of evidence of survival or true surrogate endpoints being improved,” Kishan said. Of note, a surrogate marker or endpoint is a specific early outcome that should be able to reliably predict a long-term clinical outcome, such as disease recurrence or death.

While the research team analyzed overall survival, the study did not consider quality of life, which Kishan mentioned is extremely important for patients with prostate cancer.

“We only looked at whether biochemical recurrence was a surrogate for overall survival. While that ended up not being the case, I think we can see a clear gap in our understanding of the other half of the survivorship journey: quality of life,” he said. “It may very well be true that reducing recurrence improves quality of life, even it doesn't improve overall survival. Unfortunately, most trials have not been designed to detect that and therefore we can't conclude that. Ultimately, each patient must discuss with their doctor what their priorities and their family's priorities are when embarking on a course of treatment.”

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