‘Well, I’m doomed’: How this cancer treatment can help men live longer

An Australian-led clinical trial has demonstrated that adding the hormone-blocking drug darolutamide to standard treatments significantly reduces the risk of cancer recurrence in men with very high-risk prostate cancer. Researchers reporting on the global Phase 3 study stated that the addition of the medication resulted in a 58 percent reduction in the likelihood of the disease relapsing and spreading to other organs or tissues over a four-year period. These findings have prompted calls to alter the standard of care for such patients, with the potential to save thousands of lives. The trial, identified as DASL-HiCaP, involved 1,106 participants who all suffered from very aggressive prostate cancer or had CT scans showing the disease had spread to pelvic lymph nodes. Each participant had previously undergone either a radical prostatectomy or primary radiation therapy. The median age of the cohort was 71. All individuals in the study received androgen deprivation therapy, commonly known as ADT, along with radiation treatments. The group was split evenly, with half receiving darolutamide and the other half taking a placebo. Data presented after four years indicated that 95 percent of the men in the darolutamide group had not developed metastatic prostate cancer, compared to 88 percent in the placebo group. Mortality rates associated specifically with prostate cancer were lower in the treatment arm, with five percent of participants dying from the disease versus 14 percent in the placebo group. Deaths resulting from other causes showed no difference between the two groups. Additionally, both trial arms reported similar profiles regarding side effects. Professor Christopher Sweeney, co-chair of the trial and director of the South Australian ImmunoGenomics Cancer Institute at the University of Adelaide, described the outcome as a very strong treatment effect that substantially decreased relapses. He noted that while combining testosterone suppression with radiation lowers relapse rates, some men still experience breakthrough disease. Sweeney added that the ultimate result is more men living longer and dying without prostate cancer. Darolutamide, marketed as Nubeqa, functions as an androgen receptor pathway inhibitor. It works by binding to androgen receptors within prostate cancer cells, thereby preventing testosterone or similar hormones from attaching and stimulating cell growth. Sweeney explained that the drug acts like a broken key, blocking residual hormones from activating the receptors. Currently, the medication is available and subsidized under Australia’s Pharmaceutical Benefits Scheme only for treating metastatic prostate cancer or cases that do not respond to testosterone suppression. However, the initial analysis suggests that thousands of additional men could benefit from its use in earlier stages. In 2025, more than 28,800 cases of prostate cancer were diagnosed in Australia, with an estimated 38 percent involving high-risk, very high-risk, or advanced disease annually. One patient involved in the trial, Howard Smith, shared his personal experience. Smith was in his late 60s when his prostate-specific antigen level rose sharply from 23 to 35 over five months. A subsequent biopsy confirmed his cancer was aggressive. Upon learning the cancer had spread to nearby glands, Smith recalled feeling doomed. His urologist warned him that this specific cancer was the one likely to kill him. Smith opted for radiation therapy instead of immediate surgery. Given his high-risk status, his radiation oncologist deemed him an ideal candidate for the trial. Because the trial was double-blind, Smith does not know whether he received the active drug or the placebo, as investigators continue to monitor participants to evaluate long-term survival. Now 71, Smith has remained cancer-free for two years, with a PSA level of 0.01. He described his situation as turning out exceptionally well, stating that he feels very lucky to have entered treatment just in time. Professor Henry Woo, director of uro-oncology at Chris O’Brien Lifehouse, characterized the trial results as quite profound. The research team emphasized that the data supports changing current medical practices for men facing aggressive forms of the disease. The study highlights the efficacy of combining existing therapies with targeted hormonal inhibitors to improve outcomes for a vulnerable demographic. As tracking continues, the focus remains on confirming long-term survival benefits and expanding access to the medication for eligible patients beyond the current subsidy restrictions. The findings provide concrete evidence for integrating darolutamide into broader treatment protocols for high-risk non-metastatic prostate cancer.