Occasionally, a groundbreaking study emerges that fundamentally alters the approach to treating cancer patients. In the realm of prostate cancer recurrence post-initial treatment, such a paradigm shift is underway.
The typical indicator of recurrence is a surge in blood levels of prostate-specific antigen (PSA). Following prostate removal surgery or radiation therapy, PSA should ideally drop to zero or near zero. However, if PSA levels rise again, signaling a biochemical recurrence, it suggests the formation of new, small tumors not detectable through traditional imaging scans.
Conventional treatment for biochemical recurrence involves hormonal therapies, inhibiting testosterone production—the hormone fueling prostate cancer growth. However, findings from the EMBARK phase 3 clinical trial suggest a more effective approach.
The study enrolled 1,068 men with rapidly doubling PSA levels within nine months of initial treatment, indicating a high risk of swift cancer progression. Divided into three groups, one received leuprolide injections every 12 weeks, the second received leuprolide alongside daily oral enzalutamide (a drug redirecting testosterone), and the third received enzalutamide alone.
The results, spanning over five years post-treatment, unveiled promising outcomes. Men treated with enzalutamide, either alone or combined with leuprolide, demonstrated prolonged freedom from metastatic cancer compared to those receiving leuprolide only. Notably, 87.5% of those with combined treatment and 80% with enzalutamide alone avoided metastasis, while only 71.4% in the leuprolide group achieved the same.
Enzalutamide proved superior in preventing further PSA increases, with 97.4% of the combined therapy group and 88.9% of the enzalutamide-alone group avoiding PSA progression, contrasting with 70% in the leuprolide group. If PSA was below 0.2 ng per milliliter at 36 weeks, enzalutamide-treated men could discontinue treatment, with up to 90% going off for durations up to 20 months.
Notably, enzalutamide treatment was well-tolerated, with mild to moderate nipple pain and breast enlargement as the most common side effects. Ongoing follow-up will reveal potential treatment-related differences in survival over time.
Dr. Neal Shore, co-lead author of the study, suggests that enzalutamide treatment “should now be the standard of care for high-risk biochemical recurrence.” The decision to combine enzalutamide with leuprolide remains a discussion between patients and doctors.
While newer imaging methods like PSMA scans can detect metastatic prostate cancer, Dr. Stephen Freedland emphasizes that EMBARK’s findings still apply. If PSA continues to rise despite negative PSMA findings, systemic treatment with enzalutamide remains the optimal choice. For cases with a few metastatic tumors (oligometastatic prostate cancer), surgical or radiation treatments may suffice, while widespread metastatic cancer calls for hormonal therapy with enzalutamide.
The study addresses a significant portion of treated prostate cancer patients, providing a welcome and surprising contribution to the field. Dr. Marc Garnick applauds the study’s importance and the option for men to discontinue therapy based on low PSA values, marking a significant advancement in managing this patient population.
How do you feel about this promising new treatment? Leave your thoughts in the comments below.