Cancer treatment can involve difficult trade-offs, and this can also be true of testosterone-blocking drugs used to treat prostate cancer. These drugs work in two other ways. Androgen deprivation therapy (ADT) shuts down the body's production of testosterone, a hormone that fuels the expansion of prostate cancer. A brand new class of medicine called androgen receptor signaling inhibitors (ARSIs) block testosterone by removing it from its cell receptor.
ADT can slow or control prostate cancer, and growing evidence suggests that adding ARSIs also improves survival when the disease is in advanced stages. This combination of treatments is named accelerated ADT. Researchers are actually also testing accelerated ADT for some men with early-stage prostate cancer.
However, all drugs that block testosterone have difficult negative effects, including metabolic changes that may harm cardiovascular health. In June, British researchers Reported that ADT and ARSIs given together increase cardiovascular risks; The authors concluded that men who intensify ADT must be counseled concerning the risks, and monitored for signs of heart problems before and after starting treatment.
Objectives and results of the study
These findings were derived from a scientific review of 24 clinical trials evaluating ADT and ARSI treatment for prostate cancer. Published between 2012 and 2024, the trials enrolled a complete of twenty-two,166 men aged 63 to 77 years. Their diagnoses ranged across the spectrum of prostate cancer, from non-metastatic cancer with aggressive features to metastatic prostate cancer now not responding to ADT itself.
The aim of the systematic review was to match ADT and accelerated ADT with respect to cardiac events, including hypertension, cardiac arrhythmia (abnormal heart beat), blood clots, or – within the worst case – heart attack or stroke.
The results showed that adding an ARTI to ADT almost doubled the chance of a cardiac event in all states of prostate cancer. The risks of severe “grade 3” events which will require hospitalization are between 7.8% and 15.6%. In particular, the administration of two ARSIs – abiraterone acetate and enzalutamide – increased the cardiovascular risk almost fourfold. Increasing evidence suggests that combining abiraterone acetate and enzalutamide worsens negative effects without improving prostate cancer survival. The use of this mixture is now widely discouraged by expert groups worldwide.
The authors emphasize that rapid treatment is more dangerous for men with pre-existing heart disease than for healthy men. together Editorialnotes Dr. Katelyn Atkins, a radiation oncologist at Cedars-Sinai Medical Center in Los Angeles, that heart problems is the second leading explanation for death in men with prostate cancer.
Candidates for conventional or accelerated ADT must be evaluated for atherosclerosis, fatty plaques within the coronary arteries that may accumulate asymptomatically, Dr. Atkins wrote. Fortunately, heart risk aspects are treatable by lowering blood pressure, eating a heart-healthy weight loss plan, exercising, and in some cases using cholesterol-lowering drugs called statins.
Expert Commentary
“More and more research shows that intensive therapy prolongs survival, and in some men it can even lead to a cure,” said Dr. David Crawford, chief of urologic oncology on the University of Colorado Anschutz Medical Campus who led the study. weren't included within the research. “We've learned time and time again from treating many cancers that it's not one drug followed by one other drug that produces the perfect results. Rather, it's finding the drugs to treat the cancer more effectively. has been
“Still, we need to focus on addressing the challenges of treating prostate cancer and preventing cardiovascular events and other side effects of ADT. As clinicians and in clinical studies, we've seen that men who lose weight maintain, exercise, build muscle, and maintain normal lipids and blood pressure much better than men who gain weight and have multiple cardiovascular risk factors.”
“Treatment intensification — that is, adding more and more drugs earlier in the management of prostate cancer — should be both encouraged and cautioned. The caution is for clinicians to consider and discuss preexisting risk factors.” and how you can modify them when making treatment decisions. The ARSI class of programs has greatly improved outcomes with the aim of achieving optimal outcomes while minimizing negative effects.”