The clinical course of metastatic castration-resistant prostate cancer (mCRPC) can vary considerably between patients. Beyond established prognostic factors, the potential impact of metastatic status at initial prostate cancer diagnosis, family history, and race remains incompletely understood.
The study, titled “Treatment and Outcomes of Patients With Metastatic Castration-resistant Prostate Cancer by Race, Initial Diagnosis, and Family History: Results From the TRUMPET Registry,” appears in the September 2026 issue of Clinical Genitourinary Cancer.
Authors: Lawrence Karsh, Clara Hwang, James Symanowski, Daniel Shevrin, Dina Elsouda, David Russell, James Spalding, Pavol Kral, Nader El-Chaar, and Neal Shore.
The TRUMPET Registry
TRUMPET was a prospective, observational, multicenter study that enrolled 1,028 patients from 147 institutions across the United States between March 2015 and September 2019. The final patient evaluation occurred in January 2021.
The current analyses were restricted to patients with metastatic, or M1, CRPC and included 832 patients, with a median age of 73 years and a median follow-up of 26.8 months. Three subgroup analyses were conducted according to metastatic status at initial prostate cancer diagnosis, family history of prostate cancer, and race.
The initial-diagnosis analysis included 453 patients: 199 who had de novo metastatic hormone-sensitive prostate cancer (mHSPC) at initial diagnosis and 254 who had nonmetastatic hormone-sensitive prostate cancer (nmHSPC) at initial diagnosis.
The family-history analysis included 831 patients, of whom 200 reported a family history of prostate cancer and 631 did not. The race analysis included 794 patients: 133 African American and 661 Caucasian patients.
Treatment patterns and health-related quality of life were primary endpoints, while secondary endpoints included overall survival, clinical progression-free survival, radiographic progression-free survival, PSA progression and response, skeletal-related events, opiate initiation, and healthcare resource utilization. Across the overall M1 CRPC population, median overall survival was 41.8 months (95% CI, 39.3–48.7).
Initial Diagnosis Was Associated With Overall Survival
Patients with nmHSPC at initial diagnosis had significantly longer overall survival than those initially diagnosed with de novo mHSPC. Median overall survival was 46.2 months versus 33.4 months, respectively. Patients with nmHSPC at initial diagnosis had a 32% lower adjusted risk of death compared with patients with de novo mHSPC at initial diagnosis (adjusted HR 0.68; 95% CI, 0.51–0.91).
The groups differed substantially in several baseline disease characteristics. Patients with de novo mHSPC were younger at enrollment and had higher PSA levels at prostate cancer diagnosis, higher Gleason scores, a shorter interval between initial diagnosis and registry enrollment, and a higher frequency of clinical N1 disease.
Importantly, when the Cox regression model was additionally adjusted for factors reflecting disease biology and aggressiveness, the overall survival difference disappeared. Overall survival was similar between the groups at 41.0 versus 39.0 months, with an adjusted HR of 0.96 (95% CI, 0.61–1.50).
The authors interpreted this sensitivity analysis as suggesting that the initially observed survival difference was driven by underlying disease characteristics. The risks of clinical, PSA, and radiographic progression, as well as opiate initiation and skeletal-related events, were similar between the initial-diagnosis groups.
Treatment patterns also highlighted limited treatment intensification during the hormone-sensitive phase. Among patients initially presenting with de novo mHSPC, only 23.5% had received docetaxel or abiraterone before developing mCRPC, including 21.6% who received docetaxel and 1.9% who received abiraterone.
Family History Was Also Associated With Survival
A second analysis examined outcomes according to self-reported family history of prostate cancer. Patients with a family history had significantly longer median overall survival than those without a family history: 53.2 months versus 39.6 months.
After adjustment for baseline and disease-related characteristics, patients with a family history had a 32% lower risk of death (adjusted HR 0.68; 95% CI, 0.51–0.90). In contrast, the risks of clinical progression, PSA progression, radiographic progression, opiate initiation, and skeletal-related events were similar between patients with and without a family history. PSA response was also similar between the groups.
Family history in TRUMPET was based on patient self-report, and genetic testing results were not collected. The authors emphasized that clinicians should not rely solely on family history to guide genomic testing decisions in mCRPC.
No Significant Differences in Clinical Outcomes by Race
The race analysis compared 133 African American patients with 661 Caucasian patients. African American patients were younger, had higher PSA levels at prostate cancer diagnosis, and had several differences in baseline disease characteristics and comorbidities compared with Caucasian patients. First-line treatment patterns also differed somewhat, with larger proportions of African American patients receiving androgen receptor pathway inhibitors and chemotherapy, while immunotherapy was more common among Caucasian patients.
Despite these baseline differences, the investigators found no statistically significant differences in any of the evaluated clinical outcomes between African American and Caucasian patients. Changes in health-related quality of life were also similar between the groups.
Differences were observed in healthcare resource utilization. A greater proportion of African American patients experienced prostate cancer-related hospitalizations and emergency room visits, whereas Caucasian patients had higher rates of visits to oncologists and urologists.
Health-Related Quality of Life Remained Similar Across Subgroups
Across all three analyses, changes in Functional Assessment of Cancer Therapy–Prostate and Brief Pain Inventory–Short Form scores were similar between the respective subgroups. Thus, while differences in overall survival emerged according to initial disease presentation and family history, corresponding differences in measured health-related quality of life were not identified.
Important Limitations
The authors highlighted several limitations when interpreting the findings. A substantial number of patients discontinued the study early or were lost to follow-up, creating the potential for selection bias. Because TRUMPET was observational, residual confounding also remained possible despite multivariable adjustment.
Family history was determined through patient self-report, creating the possibility of misclassification, and genetic testing was not conducted to evaluate genetic mutations that might influence prognosis.
The registry may also have included a higher proportion of patients treated with immunotherapy than would be expected in the broader mCRPC population because of its enrollment criteria.
Some treatment subgroups were small, limiting the ability to evaluate all outcomes across all groups, and the findings are limited in generalizability to the United States.
The study was also conducted before PSMA-PET was approved in the United States. In addition, because of the study period, the impact of more recently introduced mCRPC therapies, including PARP inhibitors and novel radioligands, could not be evaluated. The study was funded by Astellas Pharma Inc. and Pfizer Inc., the co-developers of enzalutamide.
Takeaway
The TRUMPET registry analysis suggests that initial diagnosis and prostate cancer family history may meaningfully impact survival and clinical outcomes in mCRPC.
Patients who initially presented with de novo mHSPC had a higher mortality risk than those initially diagnosed with nonmetastatic hormone-sensitive disease, although this difference was no longer apparent after adjustment for disease-biology factors. Patients reporting a family history of prostate cancer had a significantly lower adjusted risk of death than those without a family history.
In contrast, no statistically significant differences in clinical outcomes were identified between African American and Caucasian patients, and health-related quality-of-life changes were similar across all evaluated subgroups.
The authors concluded that initial diagnosis and prostate cancer family history may meaningfully influence survival and clinical outcomes in mCRPC, while emphasizing the need for dedicated prospective studies to further define the impact of these factors.
The full article is available in Clinical Genitourinary Cancer.