For men with advanced prostate cancer, androgen deprivation therapy helps control the disease for a period of time—but this treatment also causes troublesome side effects. To limit the side effects, many men opt for intermittent rather than continuous therapy. But: What do these patients gain in terms of quality of life…and what do they lose in terms of how long they live?
A new study provides answers that could dramatically alter doctors’ treatment recommendations and patients’ decisions about how to fight their prostate cancer. Here’s why…
ON AGAIN, OFF AGAIN?
Background: Male hormones (androgens) fuel the growth of most types of prostate cancer. The point of androgen deprivation therapy is to coax advanced prostate cancer into shrinking by using drugs that either block androgens from being used by the body or that stop the production of androgens altogether. The side effects include hot flashes, decreased libido, thinning bones and increased risk for cardiovascular problems. Men who are wary of or unable to tolerate these side effects often choose to take the drugs only when their cancer shows signs of increased activity…and to halt the therapy when cancer activity wanes.
Researchers wanted to gauge the pros and cons of this intermittent approach as compared with the standard continuous therapy. The study included 1,535 men with newly diagnosed, advanced prostate cancer that had spread outside of the prostate gland. Prior to treatment, the men had their baseline prostate-specific antigen (PSA) levels measured. PSA is a protein produced by the prostate gland, with higher levels generally correlating to higher prostate cancer risk and/or increased prostate cancer activity.
All the participants underwent seven months of androgen deprivation therapy. Then, those whose PSA had declined to a score of four or less were randomly assigned to one of two groups (this point was called the “time of randomization”). Half of the men were placed in the continuous-therapy group, so their treatment continued nonstop. The other half were assigned to the intermittent-therapy group, so their treatment was halted at the time of randomization—but whenever a patient’s PSA rose back up to his baseline level or to 20 (whichever was lower), that patient resumed his androgen deprivation therapy. For members of the intermittent group, this on-again, off-again treatment continued based on individual PSA scores.
The patients were followed for up to 10 years. Men in the intermittent group ended up receiving treatment about 47% of the time during the study period. Also, at various times during the study, all the men answered questions about their quality of life in five areas—erectile function, libido, vitality, physical functioning and mental health.
Over the course of the study, 928 of the original 1,535 participants died, most from their prostate cancer. Among those in the continuous-therapy group, 58% died…while among those in the intermittent group, 63% died. The group that received continuous therapy had a median survival period of 5.8 years from the time of the randomization, while the group that received intermittent therapy had a median survival period of 5.1 years. That difference in survival time is not huge—but it’s certainly something that patients would want to be aware of.
And what about those tough-to-tolerate side effects of androgen deprivation therapy? Men in the intermittent group did experience modest, temporary improvements in some aspects of quality of life when they put the therapy on pause after that initial seven-month course of treatment. For instance, three months later, they reported fewer erectile problems and better mental health. However, by nine months and again 15 months later, the quality-of-life improvements they reported were so minor that the researchers deemed them “not statistically significant.” Meanwhile, the rates of serious physical side effects (such as cardiovascular events) were similar in both groups—30.4% of the intermittent group and 32.7% of the continuous group.
What this means: The totality of the data from this study and another smaller clinical trial indicate that intermittent therapy is not as promising as once thought. For men with advanced prostate cancer, the benefits in terms of reduced side effects from intermittent androgen deprivation therapy are modest, given the potential for improved longevity with continuous treatment. Patients will want to discuss the pros and cons of each therapy schedule with their doctors in light of this new information—and some may find the drugs’ side effects easier to tolerate over time once they consider the likely advantages in terms of time gained.