Editor's Note: The 2026 Annual Meeting of the Chinese Society of Clinical Oncology (CSCO) was held in Jinan, China. At the meeting, Professor Qiang Wei of the Department of Urology at West China Hospital, Sichuan University, presented a poster based on real-world data from the US Veterans Health Administration (VHA), focusing on patients with newly diagnosed metastatic castration-sensitive prostate cancer (mCSPC) who were older, frail, or had a high burden of comorbidities.This interview explores three key aspects of the study: its rationale, principal findings, and clinical implications. In a population that has historically been underrepresented in clinical trials, does adding an androgen receptor pathway inhibitor (ARPI) to androgen deprivation therapy (ADT) still confer a survival benefit? More specifically, what additional real-world evidence does the enzalutamide subgroup provide to inform clinical decision-making?
Oncology Frontier – UroStream: At this year’s CSCO annual meeting, you presented a real-world study involving patients with newly diagnosed mCSPC who were older, frail, or had a high burden of comorbidities. In clinical practice, concerns about treatment tolerability often mean that these patients do not receive adequate treatment intensification. Could you first explain the main clinical question addressed by this study?
Professor Qiang Wei: Prostate cancer is a typical age-related malignancy. Epidemiological data show that the median age at diagnosis is approximately 68 years, and more than 20% of patients are aged 75 years or older. Therefore, in real-world clinical practice, older adults are not a small or exceptional subgroup; they represent a substantial proportion of patients encountered in mCSPC management. In addition, advancing age is often accompanied by a greater burden of comorbidities, declining physical function, and frailty.
The treatment of mCSPC has entered an era of early treatment intensification, with multiple studies demonstrating survival benefits from combining ADT with an ARPI. However, older, frail, and highly comorbid patients have been relatively underrepresented in previous clinical trials.
Our study therefore focused on a highly practical clinical question: Can adding an ARPI to ADT still provide a survival benefit for patients with mCSPC who are older, in poorer physical condition, or burdened by multiple comorbidities? To address this question, we used real-world data from the US Veterans Health Administration and included patients with newly diagnosed mCSPC who met the criteria for older age, frailty, or a high comorbidity burden.
We analyzed two cohorts. The first comprised patients receiving ADT plus enzalutamide, while the second included patients with high-volume disease receiving any ARPI. The separate analysis of the enzalutamide subgroup is particularly noteworthy because it provides more direct real-world evidence to inform decisions about whether to use ADT plus enzalutamide in older, frail, or highly comorbid patients.
Oncology Frontier – UroStream: What were the key findings of the study? In particular, what survival outcomes deserve attention in the analyses of ADT plus enzalutamide and patients with high-volume disease?
Professor Qiang Wei: The study included 1,629 patients with newly diagnosed mCSPC, all of whom met at least one of the following criteria for older age, frailty, or a high comorbidity burden: age ≥75 years, a Veterans Affairs Frailty Index (VA-FI) score >0.2, or a Charlson Comorbidity Index (CCI) score ≥3. Among them, 272 received ADT plus enzalutamide, while 1,357 received ADT monotherapy.
Compared with ADT monotherapy, ADT plus enzalutamide was associated with a 30% reduction in the risk of death (adjusted hazard ratio [aHR] = 0.70, 95% confidence interval [CI]: 0.60–0.83; P < 0.001).
Median time to PSA progression or death was also prolonged from 11.5 months to 27.7 months (HR = 0.57, 95% CI: 0.47–0.70; P < 0.001), representing a 43% reduction in the risk of PSA progression or death in the ADT-plus-enzalutamide group.
An analysis of 1,541 patients with high-volume disease found that ADT plus an ARPI was likewise associated with a significant reduction in the risk of death (aHR = 0.73, 95% CI: 0.65–0.83; P < 0.001). Median time to PSA progression or death increased from 9.0 months to 15.2 months (HR = 0.57, 95% CI: 0.49–0.66; P < 0.001), corresponding to a 43% reduction in the risk of PSA progression or death with ADT plus an ARPI.
Taken together, these findings suggest that treatment intensification may provide meaningful overall survival (OS) benefits even in patients who are older, frail, or have a high burden of comorbidities. The enzalutamide subgroup provides valuable complementary real-world evidence supporting the use of ADT plus enzalutamide in this population. The findings also suggest that patients with high-volume disease may benefit from ARPI-based combination therapy.
Oncology Frontier – UroStream: Based on these real-world findings, what are the key clinical implications for using ADT plus enzalutamide in patients with mCSPC who are older, frail, or have a high burden of comorbidities?
Professor Qiang Wei: Advanced age, frailty, or a high burden of comorbidities does not automatically mean that treatment intensification is inappropriate. Clinical decisions should not be based on age alone. Instead, physicians should comprehensively assess the patient’s overall condition, degree of frailty, comorbidities, and tumor burden.
For patients who are assessed as suitable for treatment, we should make full use of the early treatment window in mCSPC and actively consider intensification with an ARPI on top of ADT, rather than defaulting to ADT monotherapy simply because a patient is older. In this study, ADT plus enzalutamide was significantly associated with longer OS, providing new real-world evidence supporting its use in older, frail, or highly comorbid patients.
Of course, the goals of treatment in older adults extend beyond prolonging survival; preserving functional status and quality of life is equally important. The key in clinical practice is therefore not simply to decide whether treatment should be intensified, but to conduct a systematic assessment to identify patients who are genuinely suitable for intensified therapy and achieve the best possible balance among efficacy, tolerability, quality of life, and patient preferences.
MAT-CN-XTD-2026-00145
Preparation date: September 19, 2026
For healthcare professionals only.
Professor Qiang Wei
