“These results are exciting, because they suggest that more patients with very high-risk, non-metastatic prostate cancer may benefit from the addition of an androgen receptor inhibitor to radiation therapy and androgen deprivation,” Dr. Timothy Showalter, a radiation oncologist with UVA Health, tells SurvivorNet.

What Does ‘Very High-Risk’ Prostate Cancer Mean?

Doctors consider several factors when determining how likely prostate cancer is to grow, return, or spread. These include your prostate-specific antigen (PSA) blood test level, the cancer’s Gleason score or Grade Group, and how far the tumor has grown beyond the prostate. Cancer involving nearby lymph nodes may also require more intensive treatment.

Although these features can indicate a greater risk of recurrence, they do not mean that the cancer will inevitably spread. Treatment is often given with the goal of curing the disease.

What Is the DASL-HiCaP Trial Studying?

DASL-HiCaP is a phase 3 clinical trial investigating whether adding darolutamide to hormone therapy and radiation can help men with very high-risk prostate cancer live longer without their cancer spreading.

Hormone therapy, also called androgen-deprivation therapy (ADT), lowers testosterone levels or blocks its effects because prostate cancer cells often rely on testosterone to grow. For men with high-risk disease, hormone therapy is commonly given alongside radiation and may continue for 18 to 36 months. Some patients may also receive abiraterone, another medication that suppresses hormone production.

The DASL-HiCaP trial compares darolutamide with a placebo, with both groups receiving hormone therapy and radiation. Darolutamide blocks the effects of male hormones on prostate cancer cells. Researchers want to determine whether adding it provides further protection against the cancer returning or spreading.

What Has the Trial Found So Far?

After a median follow-up of approximately 3.8 years, an estimated 95% of men receiving darolutamide were alive without their cancer spreading at four years, compared with 88% of men receiving a placebo alongside hormone therapy and radiation. This represents a 7-percentage-point improvement in metastasis-free survival.

The results suggest that adding darolutamide may help reduce the risk of prostate cancer spreading to other parts of the body.

The trial also found an improvement in PSA progression-free survival, meaning patients receiving darolutamide were less likely to experience a worsening of their prostate-specific antigen (PSA) results. Four-year PSA progression-free survival was 91% with darolutamide compared to 83% with placebo.

However, the trial has not yet shown that adding darolutamide extends overall survival.

Overall survival was 97% in the darolutamide group and 95% in the placebo group, but the difference was not statistically significant. Longer follow-up will help researchers determine whether preventing or delaying cancer spread ultimately translates into longer lives.

“Although prior studies have demonstrated clinical benefits to adding other androgen receptor inhibitors for high-risk, localized prostate cancer, the DASL-HiCaP trial extends the eligible population to include high-grade tumors with relatively low PSA levels,” Dr. Showalter says.

What Side Effects Have Been Reported?

Adding darolutamide was associated with a higher overall rate of severe side effects.

Approximately 43% of patients receiving darolutamide experienced a grade 3 or higher adverse event, compared with 36% of those receiving placebo. These events can be medically significant, although not all were necessarily caused by darolutamide.

Fatigue was among the more common concerns. It occurred in about 64% of patients receiving darolutamide and 57% receiving placebo.

Hot flashes were also common in both groups, affecting approximately 66% and 64% of patients, respectively. These symptoms may partly reflect the effects of hormone therapy itself.

Some potentially concerning side effects were similar between the groups. Falls occurred in approximately 5% of patients receiving darolutamide and 6% receiving placebo, while reported fractures occurred in approximately 3% of each group. Cognitive symptoms were also reported at similar rates.

“Although darolutamide does not require a companion steroid, there is still a risk of fatigue and other adverse events, so the addition of this drug should be considered in a shared decision-making process between patients and doctors,” Dr. Showalter explains.

Overall, the findings suggest that many patients could continue treatment, but adding another medication may increase the burden of side effects, particularly fatigue.

Researchers will continue evaluating quality of life and longer-term safety to better understand how treatment affects patients’ daily lives.

What Do These Results Mean for Patients?

For men with very high-risk prostate cancer, the results offer encouraging evidence that adding darolutamide to hormone therapy and radiation may reduce the likelihood of cancer spreading. However, the decision to add another medication should take into account a patient’s cancer characteristics, existing health conditions, preferences, and tolerance for additional treatment.

“These results provide more treatment options for men with very high-risk prostate cancer who receive treatment with radiation therapy and long-term androgen deprivation, since it shows that adding darolutamide to standard treatment reduces the risk of metastasis or death,” Dr. Showalter says.

Darolutamide is not a replacement for radiation or hormone therapy in this trial; it was studied as an addition to both. The findings also do not establish whether darolutamide is better than abiraterone, another medication sometimes used to intensify treatment for high-risk prostate cancer.

Patients should discuss with their oncology team whether their cancer characteristics make treatment intensification appropriate, how long they would need additional medication, what side effects to expect, and whether the potential benefit fits their treatment goals.

Questions to Ask Your Doctor

• Does my PSA level, Grade Group, or tumor stage put me in the very high-risk category?
• Has my cancer spread to nearby lymph nodes, and how does that affect my treatment options?
• Would radiation and hormone therapy be sufficient for me, or might adding another medication be appropriate?
• If darolutamide is an option, how long would I need to take it?
• What side effects might affect my energy, concentration, sleep, or ability to work?
• How would the additional medication affect my out-of-pocket costs and insurance coverage?
• Are there clinical trials available that may be appropriate for my situation?

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