Updated findings from the phase 3 trial demonstrate sustained survival benefits with enzalutamide plus androgen deprivation therapy, offering important insights for treatment planning and long-term patient management.

As treatment options for metastatic hormone-sensitive prostate cancer (mHSPC) continue to expand, long-term survival data are becoming increasingly important in evaluating the durability of treatment benefit and guiding clinical decisions.

Although androgen deprivation therapy (ADT) remains a foundational component of treatment, the addition of androgen receptor pathway inhibitors has reshaped the management of metastatic disease. Longer follow-up from pivotal clinical trials is now helping clarify how these strategies influence survival over time.

A five-year analysis of the phase 3 ARCHES trial, published in European Urology in 2026, provides further evidence supporting the long-term benefit of enzalutamide in combination with ADT for patients with mHSPC.

Five-Year Findings Reinforce a Sustained Survival Benefit
ARCHES was a randomized, double-blind, placebo-controlled phase 3 trial involving 1150 patients with mHSPC. Participants received either enzalutamide at 160 mg daily plus ADT or placebo plus ADT.

Earlier findings demonstrated improvements in radiographic progression-free survival and overall survival with enzalutamide-based treatment. The updated analysis evaluated outcomes after a median follow-up of 61.4 months, providing a longer-term perspective on treatment efficacy and safety.

At five years, the estimated overall survival probability was 66% among patients assigned to enzalutamide plus ADT, compared with 53% among those assigned to placebo plus ADT. The hazard ratio for death was 0.70 (95% CI, 0.58-0.85), corresponding to a 30% relative reduction in the risk of death. Median overall survival had not been reached in either group.

These results provide additional evidence that treatment intensification with enzalutamide can deliver a sustained survival benefit in mHSPC. However, because this was a post hoc analysis without statistical alpha protection, the reported P value was nominal and should be interpreted cautiously.

Exploring Outcomes Across Patient Subgroups
The updated analysis also examined survival among patients with different baseline disease characteristics, including metastatic disease volume.

Among patients with high-volume disease, investigators reported an exploratory difference of approximately 36 months in median overall survival favoring those initially assigned to enzalutamide.

Although this finding is notable, subgroup analyses should be interpreted with caution. The study was not designed to establish definitive differences in treatment benefit between individual patient subgroups.

Treatment crossover also represents an important consideration. Following the primary analysis, ARCHES was unblinded, allowing eligible patients originally assigned to placebo plus ADT to receive enzalutamide through an open-label extension. Subsequent therapies may also have influenced longer-term outcomes.

Despite these complexities, the findings add to the evidence supporting androgen receptor pathway inhibition as a component of treatment for appropriate patients with mHSPC.

Long-Term Treatment Requires Ongoing Clinical Assessment
As more patients live longer with metastatic prostate cancer, treatment decisions increasingly involve considerations beyond initial disease control.

The five-year ARCHES analysis did not identify new safety signals, offering additional reassurance regarding the longer-term safety profile observed in the trial.

Nevertheless, sustained treatment with enzalutamide and ADT requires continued attention to adverse effects, comorbidities, and functional health.

Fatigue, falls, cognitive changes, hypertension, metabolic complications, and changes in bone health are among the considerations that may influence long-term treatment tolerability and patient well-being.

Medical oncologists, urologists, advanced practice providers, oncology nurses, and pharmacists all contribute to evaluating treatment response, identifying adverse effects, and supporting appropriate medication management.

Regular assessment of prostate-specific antigen levels, symptoms, and disease status remains important, with imaging decisions informed by the broader clinical picture rather than biochemical findings alone.

Supportive care services, including rehabilitation, nutrition, psychosocial support, and palliative care when appropriate, may also help address the physical and emotional consequences of prolonged treatment.

These considerations are particularly relevant as the growing number of available therapies creates more opportunities to individualize treatment according to disease characteristics, comorbidities, patient preferences, and anticipated toxicity.

What the Findings Mean for Clinical Practice
The updated ARCHES results contribute to a growing body of evidence supporting treatment intensification in metastatic hormone-sensitive prostate cancer.

For clinicians, the five-year survival findings offer additional information for discussing prognosis and expected treatment benefits with patients considering enzalutamide plus ADT.

The results also reinforce the importance of maintaining a long-term approach to care.

Treatment effectiveness must be considered alongside tolerability, medication adherence, management of concurrent health conditions, and the patient’s ability to maintain daily functioning.

For multidisciplinary care teams, this means integrating evidence-based systemic therapy with ongoing assessment and supportive interventions tailored to individual patient needs.

Five years of follow-up from ARCHES provides further perspective on the survival outcomes associated with enzalutamide plus ADT in mHSPC.

While the post hoc nature of the analysis and treatment crossover warrant careful interpretation, the findings support the durability of benefit observed in earlier trial reports.

As prostate cancer treatment continues to evolve, longer-term evidence will remain essential to informing clinical decisions, refining expectations, and helping care teams balance improved survival with the realities of living with metastatic disease.

Ultimately, the significance of these findings extends beyond the survival estimates themselves. They underscore the importance of pairing effective systemic treatment with comprehensive, multidisciplinary care throughout the course of advanced prostate cancer.

Source
Armstrong AJ, Petrylak DP, Shore ND, et al. ARCHES 5-year survival with enzalutamide plus androgen-deprivation therapy in metastatic hormone-sensitive prostate cancer patients. Eur Urol. 2026;89:396-403.