Bayer AG (XETRA: BAYN) has reported Phase 3 results showing that adding NUBEQA (darolutamide) to androgen deprivation therapy and radiation reduced the hazard of metastasis or death by 58% in patients with very high-risk localized or locally advanced prostate cancer, including selected patients receiving salvage radiotherapy after prostatectomy. Presented at the European Society for Medical Oncology Congress 2026 on October 24, the findings demonstrated four-year metastasis-free survival of 95% with darolutamide compared with 88% for placebo when both were administered alongside established treatment.
The results come from the investigator-initiated DASL-HiCaP trial, an international study conducted through academic clinical research collaborations involving 1,106 participants. The trial extends the evidence supporting darolutamide beyond its existing indications in non-metastatic castration-resistant and metastatic castration-sensitive prostate cancer. However, the new treatment setting remains investigational, and the interim analysis has not established a statistically significant improvement in overall survival.
The findings are clinically relevant because patients with very high-risk prostate cancer may experience metastatic progression despite receiving radiotherapy and long-term androgen deprivation therapy. Adding a potent androgen receptor inhibitor could provide more intensive suppression of androgen signalling during a period when treatment is intended to prevent or delay metastatic disease. The central question is whether the improvement in metastasis-free survival can justify two years of additional systemic treatment and eventually translate into longer overall survival.
What do the Phase 3 DASL-HiCaP results reveal about metastasis-free survival?
DASL-HiCaP is a randomised, placebo-controlled Phase 3 trial evaluating the addition of darolutamide to androgen deprivation therapy and locoregional radiation in patients with prostate cancer at very high risk of recurrence. The study enrolled 1,106 participants across Australia, New Zealand, Canada, the United States, Ireland and the United Kingdom, with equal randomisation to darolutamide or placebo. Both groups received hormone therapy and radiation according to the trial protocol.
Participants received darolutamide 600 milligrams twice daily or matching placebo for 96 weeks, alongside a luteinising hormone-releasing hormone analogue for the same period. Radiotherapy was directed to the prostate or prostate bed and relevant pelvic lymph nodes. The study included patients undergoing primary radiotherapy and selected patients receiving salvage treatment following previous radical prostatectomy.
The prespecified primary endpoint was metastasis-free survival assessed using conventional imaging. This endpoint measures the time until distant metastasis or death, providing a clinically consequential assessment of whether treatment delays cancer spread. The protocol included a planned interim analysis after approximately 87 metastasis-free survival events.
At a median follow-up of 3.8 years, the trial reported a metastasis-free survival hazard ratio of 0.42 for darolutamide compared with placebo. The 95% confidence interval ranged from 0.27 to 0.66, with a p-value of 0.0001. The result demonstrates a statistically significant reduction in the hazard of metastasis or death.
Four-year metastasis-free survival reached 95% in the darolutamide group and 88% in the placebo group. The seven-percentage-point absolute difference provides an important complement to the 58% relative hazard reduction. Because event rates were comparatively low, both measures are necessary to understand the size of the treatment effect.
Detailed congress reporting identified 27 metastasis-free survival events among 553 darolutamide-treated participants and 63 events among 553 placebo-treated participants. These counts provide further context for the magnitude of the observed difference, although the primary statistical analysis accounts for the timing of events rather than relying exclusively on their total number.
The result crossed the trial’s prespecified interim statistical boundary, supporting the conclusion that the primary endpoint was met. Continued follow-up will assess whether the separation between treatment groups persists and whether the benefit translates into improvements in longer-term survival.
Why does adding darolutamide to radiation and androgen deprivation therapy matter in high-risk prostate cancer?
Androgen signalling remains a central driver of prostate cancer growth and survival. Androgen deprivation therapy reduces the body’s production of testosterone or interferes with hormonal stimulation, forming an established component of treatment for patients at risk of recurrence or progression. However, suppressing circulating androgen levels does not necessarily eliminate all androgen receptor signalling within cancer cells.
Darolutamide is an oral androgen receptor inhibitor designed to block androgen binding and interfere with receptor-associated signalling. Adding it to conventional hormone therapy provides a strategy for more intensive suppression of the biological pathway supporting prostate cancer growth. The objective is to reduce the ability of residual malignant cells to survive and contribute to recurrence or metastasis.
Radiotherapy addresses cancer within the treated anatomical region, while systemic hormone-directed therapy can influence disease processes beyond the radiation field. Combining local and systemic approaches is particularly relevant when patients have a substantial risk of microscopic disease outside the primary treatment area. A clinically effective intensified regimen may delay the emergence of detectable metastatic disease.
The DASL-HiCaP findings support the biological rationale for this combined approach. Patients receiving darolutamide experienced fewer metastasis-free survival events despite both study groups receiving established androgen deprivation therapy and radiotherapy. The result indicates that additional androgen receptor inhibition produced an incremental benefit within the trial population.
However, the findings do not establish that every patient receiving curative-intent radiotherapy would benefit equally from treatment intensification. The trial specifically enrolled patients with very high-risk disease characteristics, and its results should not automatically be extended to lower-risk populations. Patient selection will therefore be central to any future regulatory indication or treatment recommendation.
The distinction is also important because longer or more intensive hormone therapy can increase treatment burden. Even when a medicine delays progression, the expected benefit must be considered against adverse effects, comorbidities and the likelihood that an individual patient would otherwise experience recurrence.
What do the secondary endpoints reveal about prostate cancer progression?
The DASL-HiCaP study also reported favourable results for prostate-specific antigen progression-free survival, an endpoint measuring biochemical disease activity. Darolutamide was associated with a hazard ratio of 0.47, corresponding to a 53% lower hazard of PSA progression or death compared with placebo. The 95% confidence interval ranged from 0.33 to 0.67.
At four years, PSA progression-free survival was 91% with darolutamide and 83% with placebo. This eight-percentage-point difference supports the primary finding by showing that the intensified treatment strategy also delayed an important biochemical marker of disease activity. The result is consistent with the medicine’s androgen receptor-targeting mechanism.
PSA progression is relevant because rising PSA levels can indicate recurrent or persistent prostate cancer activity following treatment. However, biochemical progression is not interchangeable with distant metastasis, cancer-related mortality or overall survival. Some patients with biochemical recurrence may remain free of clinically detectable metastatic disease for extended periods.
The trial also evaluated time to subsequent hormonal treatment and the development of castration-resistant disease. Additional congress reporting indicated that these outcomes favoured darolutamide, supporting the possibility that treatment intensification delays later clinical management milestones. Their final importance will depend on the statistical analysis, follow-up and relationship with longer-term outcomes.
The consistency of the findings across metastasis-free survival and biochemical progression provides a more complete efficacy picture than either endpoint alone. Nevertheless, they remain measures of disease control and progression rather than direct evidence that patients live longer. A complete benefit-risk evaluation will need to account for both the prevention of metastatic events and the consequences of adding prolonged systemic therapy.
Has NUBEQA demonstrated an overall survival benefit in the DASL-HiCaP trial?
The interim analysis has not established a statistically significant improvement in overall survival. Bayer reported an overall survival hazard ratio of 0.88, with a 95% confidence interval ranging from 0.49 to 1.59. Four-year overall survival was 97% in the darolutamide group and 95% in the placebo group.
The wide confidence interval reflects uncertainty surrounding the estimated survival effect at this stage of follow-up. It includes values consistent with a potential benefit as well as values that do not exclude an unfavourable outcome. Consequently, the data cannot yet support a definitive claim that darolutamide extends overall survival in this setting.
Prostate cancer-specific survival also remains immature. The reported hazard ratio was 0.58, with a 95% confidence interval of 0.17 to 1.97, while the four-year prostate cancer-specific survival rate was approximately 99% in both groups. The low number of cancer-related deaths limits the precision of the available comparison.
The absence of a statistically significant survival finding does not invalidate the metastasis-free survival result. Metastasis-free survival is a clinically relevant endpoint, particularly in non-metastatic prostate cancer where patients may survive for prolonged periods after treatment. However, the distinction between delaying metastasis and extending life remains important when evaluating treatment value.
Longer follow-up will be necessary to determine whether the observed reduction in metastatic progression ultimately influences mortality. Subsequent treatments received after recurrence may also affect overall survival, making interpretation more complex as the study population moves through different lines of therapy.
The study’s continued follow-up will therefore be important for assessing whether the early benefit is sustained and whether additional outcome differences emerge over time. Until then, the most defensible conclusion is that darolutamide significantly improved metastasis-free survival without yet demonstrating an overall survival advantage in this population.
How do the results differ between primary radiotherapy and salvage treatment after prostatectomy?
DASL-HiCaP included patients receiving primary radiotherapy and those undergoing salvage treatment after previous prostatectomy. According to detailed reporting from the congress, approximately 935 participants were in the primary radiotherapy cohort and 171 in the salvage radiotherapy cohort. This distinction matters because the clinical circumstances and recurrence risks differ between patients treated for the first time and those receiving additional treatment after surgery.
Patients undergoing primary radiotherapy may have high-grade or locally advanced disease that makes recurrence more likely despite definitive local treatment. Those receiving salvage radiotherapy have previously undergone prostatectomy but require additional therapy because of persistent or recurrent disease indicators. Their prior treatment history can influence the remaining cancer burden and subsequent management options.
The reported metastasis-free survival benefit was observed across prespecified subgroups, including patients receiving primary or salvage radiotherapy. Detailed analyses also indicated favourable results among patients with and without pelvic nodal involvement. These findings suggest that the overall treatment effect was not confined to a single broad clinical category.
However, subgroup analyses have limitations, particularly when the number of participants or events is relatively small. The salvage radiotherapy cohort accounted for a minority of trial participants, meaning that its treatment effect is estimated with less precision than the overall result. A favourable subgroup result should not be interpreted as an independent confirmatory trial.
Patient-selection considerations may become particularly important if regulatory authorities review a proposed early-stage indication. The intended population would need to be defined using the characteristics and treatment approaches supported by the study, rather than extending the findings to all patients with biochemical recurrence.
The ability to identify patients at sufficiently high risk is also relevant to the treatment’s practical value. A large proportion of patients in both trial groups remained metastasis-free at four years, indicating that many participants had favourable outcomes during the observation period. Determining which individuals derive the greatest absolute benefit could help guide future treatment decisions.
What does the DASL-HiCaP safety profile indicate about two years of intensified hormonal therapy?
Bayer reported that the safety profile of darolutamide was consistent with previous clinical experience, with no new safety signal identified in the disclosed analysis. Nevertheless, adverse events were more frequent in some categories among participants receiving the investigational treatment. Any adverse event of Grade 3 or higher occurred in 43% of the darolutamide group and 36% of the placebo group.
Fatigue or asthenia of Grade 2 or higher was reported in 14% of darolutamide-treated participants compared with 10% receiving placebo. Hypertension occurred in 7% and 9%, respectively, while fractures were reported in 2% and 3%. Cardiac adverse events occurred in 3% of participants in each group.
These findings suggest that some adverse-event categories were broadly similar between treatment groups, although fatigue was more frequent with darolutamide. The overall increase in Grade 3 or higher adverse events indicates that treatment intensification was not without additional burden. A complete interpretation will require detailed information about event attribution, duration, treatment discontinuations and patient-reported quality of life.
The treatment regimen involved approximately two years of darolutamide or placebo alongside long-term androgen deprivation therapy. This duration is important because hormone-directed treatment can affect physical functioning, metabolic health and other aspects of quality of life over time. The consequences of combining therapies must be considered in patients who may otherwise remain free from metastatic disease for several years.
Darolutamide already carries established warnings relating to clinically important adverse reactions, including ischemic heart disease. These risks remain relevant when evaluating use in a population where the immediate objective is to prevent future progression rather than treat established metastatic disease.
Long-term tolerability may also affect treatment completion. The need to continue oral therapy twice daily over an extended period creates adherence considerations, particularly for patients receiving other medications or managing chronic medical conditions. The full trial results will need to clarify whether the observed efficacy benefit can be maintained with an acceptable treatment burden in routine practice.
How does DASL-HiCaP expand Bayer’s existing NUBEQA development programme?
NUBEQA is already approved in the United States for non-metastatic castration-resistant prostate cancer and metastatic castration-sensitive prostate cancer, including use in combination with docetaxel in the latter setting. Those indications are supported by previous clinical programmes demonstrating the treatment’s efficacy in different stages of prostate cancer. The DASL-HiCaP study investigates an earlier disease setting where patients have not yet developed detectable distant metastases.
The new evidence therefore extends the drug’s clinical development across another stage of the disease continuum. Rather than focusing on treatment following metastatic progression or castration resistance, the study evaluates whether additional androgen receptor inhibition can prevent or delay the development of metastatic disease. A successful regulatory expansion could broaden the group of patients eligible for darolutamide.
The medicine was jointly developed by Bayer and Orion Corporation, reflecting a longstanding pharmaceutical development collaboration. Its existing indications provide an established clinical and commercial foundation, but the high-risk localized prostate cancer setting remains a separate area requiring appropriate evidence and authorisation.
The wider treatment landscape includes other androgen receptor pathway inhibitors and intensified hormonal regimens. Some are supported by trials in high-risk non-metastatic or locally advanced disease, creating a competitive environment in which darolutamide’s efficacy, tolerability and patient-selection characteristics will be important. Comparisons across separate trials must account for differences in disease risk, radiation approaches, hormonal treatment duration and endpoint definitions.
For Bayer, the opportunity is to extend the medicine’s use into an earlier treatment period, potentially increasing its clinical reach. However, any commercial benefit will depend on regulatory decisions, the authorised indication, reimbursement and adoption by multidisciplinary prostate cancer teams.
The findings should not be presented as proof that darolutamide is superior to other androgen receptor pathway inhibitors in this setting. DASL-HiCaP compared darolutamide with placebo on top of established treatment, not directly with another active intensification regimen.
What regulatory and clinical evidence will be needed before NUBEQA can enter this earlier prostate cancer setting?
The positive metastasis-free survival result provides a potential basis for regulatory discussions, but Bayer has not announced a new United States approval for the DASL-HiCaP treatment setting. The company’s existing NUBEQA indications do not automatically authorise the regimen evaluated in this trial. Any future application would need to establish the proposed patient population, dosing schedule and clinical benefit-risk profile.
Regulators may examine the complete metastasis-free survival data, the prespecified statistical analysis and the maturity of secondary endpoints. The trial’s inclusion of both primary and salvage radiotherapy populations will require careful consideration when defining the supported indication. Safety data collected during and after the two-year treatment period will also contribute to the assessment.
The investigator-initiated nature of the trial is relevant to the evidence package because the study was conducted through an international academic collaboration. Bayer supported the research, but the trial’s scientific organisation involved groups including the Australian and New Zealand Urogenital and Prostate Cancer Trials Group, the University of Sydney and the Canadian Cancer Trials Group. The results provide evidence generated through a large, multinational research programme rather than a small exploratory company study.
Clinical implementation would require coordination between medical oncologists, radiation oncologists and urologists. Treatment selection would need to consider recurrence risk, baseline health, existing hormone therapy and the suitability of adding prolonged androgen receptor inhibition. These decisions would depend on the final approved indication and supporting clinical guidance.
Reimbursement will also be relevant because treatment involves nearly two years of additional oral therapy for patients who may have a relatively low short-term probability of metastatic progression. Payers may evaluate the absolute reduction in metastatic events, adverse-event burden and longer-term survival evidence when assessing value. The seven-percentage-point four-year metastasis-free survival difference provides an important starting point for that analysis.
What will determine whether darolutamide changes treatment for high-risk prostate cancer?
The DASL-HiCaP findings establish that adding darolutamide to androgen deprivation therapy and radiation significantly improved metastasis-free survival in a large population with very high-risk prostate cancer. The 58% relative hazard reduction is supported by a seven-percentage-point absolute improvement in four-year metastasis-free survival and favourable secondary disease-progression measurements. These findings strengthen the rationale for evaluating intensified androgen receptor inhibition before distant metastatic disease develops.
The principal remaining clinical uncertainty concerns long-term survival. Overall survival and prostate cancer-specific survival have not yet demonstrated statistically significant differences, and continued follow-up will be necessary to determine whether the metastasis-free survival advantage translates into additional benefits. The treatment’s long duration also requires careful evaluation of cumulative toxicity and quality of life.
For Bayer, the results provide a possible route to expanding NUBEQA into an earlier prostate cancer treatment setting. Whether that opportunity becomes a new approved indication will depend on the regulator’s assessment of the full evidence package and the extent to which the benefits justify treatment intensification.
The strongest immediate conclusion is that darolutamide can delay metastatic progression when added to established radiation and hormonal therapy in the selected high-risk population studied. Its longer-term role will be determined by the durability of that benefit, the eventual survival results and the ability to identify patients for whom the additional treatment burden is justified.
