In the realm of cancer research, it’s a rare gem when a study not only captures attention but also reshapes the very foundation of patient care. Imagine a breakthrough that’s currently unfolding, promising a game-changing impact on the lives of men facing recurrent prostate cancer after their first treatment. This isn’t your typical study—it’s a beacon of hope, rewriting the rules of the fight against cancer.
Coming back after treatment
The first sign that prostate cancer might be coming back is usually an increase in a substance called prostate-specific antigen (PSA) in the blood. After the prostate is removed through surgery, PSA levels are expected to drop to zero, and after radiation therapy, they should go down to very low levels. PSA is produced by prostate cancer cells, so if its levels go up again after the initial treatment, it suggests that new tumors might be forming in the body. This is called biochemical recurrence, indicating the presence of new tumors that are still too small to be seen on regular imaging scans.
When dealing with biochemical recurrence, doctors usually use hormonal therapies medicines that block the body from making testosterone, a hormone that fuels prostate cancer growth. However, recent findings from a big clinical trial suggest there’s a better and more promising way to handle it.
Exploring Research Approach and Findings
Throughout the EMBARK phase 3 clinical study, 1,068 male subjects were recruited, all displaying a doubling of their PSA levels within nine months post-initial treatment. The accelerated upsurge in PSA serves as a crucial indicator, signaling a heightened risk of swift cancer progression in men under observation.
Divided into three randomly assigned groups, the male participants experienced distinct treatments. The first group received leuprolide, a hormonal therapy administered through injections every 12 weeks. In the second group, a combination therapy was implemented, incorporating leuprolide alongside a daily oral dosage of enzalutamide—a drug engineered to prevent testosterone from binding to its cell receptor. The third group exclusively underwent daily treatment with enzalutamide.
Before this study, scientists found out that using enzalutamide helps slow down the growth of prostate cancer in men whose cancer has spread. Now, they’re thinking that if they use this drug earlier in the treatment, it might also help men who are facing a recurrence of the cancer at a biochemical level.
The hypothesis was confirmed with a five-year follow-up post-treatment. A higher percentage of men treated with enzalutamide (87.5% with combined therapy, 80% with enzalutamide alone) avoided cancer worsening compared to those exclusively on leuprolide (71.4%).
Enzalutamide treatment, whether alone or combined, surpassed leuprolide in preventing PSA increases. A significant majority—97.4% with combined therapy and 88.9% with enzalutamide alone—avoided PSA progression, compared to the 70% rate with leuprolide. Additionally, men with PSA levels below 0.2 ng/mL at 36 weeks could discontinue treatment. Notably, nearly 90% of those on enzalutamide opted for treatment cessation, experiencing periods of up to 20 months without intervention.
The administration of enzalutamide was well received, with the most frequent side effect being mild to moderate nipple pain and breast enlargement. A significant majority of individuals in each of the three groups are still alive, prompting ongoing scrutiny by EMBARK investigators to identify potential differences in long-term survival linked to the treatment.
Notations and remarks
In the light of EMBARK’s findings, Dr. Neal Shore, co-lead author of the study and director of the Carolina Urologic Research Center, passionately advocates for enzalutamide treatment to become the new gold standard for high-risk biochemical recurrence. Emphasizing a personalized approach, he suggests that the decision to combine enzalutamide with leuprolide is a crucial conversation for men to have with their doctors, ensuring a tailored and effective treatment plan.
A notable development since the launch of the EMBARK study is the advancement in detecting metastatic prostate cancer. Using specialized imaging scans, doctors can now identify tiny tumors previously unseen, thanks to elevated levels of prostate-membrane specific antigen (PSMA) in cancer cells. This breakthrough allows for direct treatment of these metastatic tumors with surgery or radiation, offering the potential for a cure.
Nonetheless, Dr. Stephen Freedland, a lead researcher in the EMBARK study and urologist at Cedars-Sinai Medical Center in Los Angeles and the Durham VA Medical Center in Durham, North Carolina, underscores the enduring relevance of the study’s findings. In instances where PSA continues to rise despite negative PSMA results, Dr. Freedland emphasizes that EMBARK unequivocally recommends the adoption of systemic treatment—specifically highlighting the effectiveness of enzalutamide, whether in combination with hormonal therapy or alone.
If PSMA findings show only a few metastatic tumors in what’s called oligometastatic prostate cancer, we can treat those tumors with surgery, radiation, or hormonal therapy. On the other hand, if PSMA reveals widespread metastatic cancer all over the body, we can’t use “metastasis-directed therapy” anymore. In such cases, Dr. Freedland recommends going for hormonal therapy, especially with enzalutamide, as it’s shown to be the best option for slowing down cancer progression according to the EMBARK study.
Examining a significant subset of individuals managing prostate cancer—specifically those contending with persistent cancer post-surgery or radiation therapy—this study reveals intriguing findings. Dr. Marc Garnick, a distinguished professor at Harvard Medical School, expresses surprise at the results and emphasizes a crucial discovery.
He commends the identification that individuals with low PSA values after 36 weeks of treatment might be able to discontinue therapy. Doctors Shore and Freed land highlight the research’s valuable contribution to understanding persistent cancer in a large patient group. Congratulations are due to the authors for their impactful and important contribution in this critical area.
