Initial prostate cancer presentation, family history linked to survival in mCRPC

Patients with metastatic castration-resistant prostate cancer (mCRPC) who initially presented with nonmetastatic hormone-sensitive prostate cancer (HSPC) had longer overall survival (OS) than those initially diagnosed with de novo metastatic HSPC, according to a subgroup analysis of the prospective TRUMPET registry published in Clinical Genitourinary Cancer.¹

A separate analysis found that patients with a self-reported family history of prostate cancer also had longer OS, whereas no significant differences in clinical outcomes were observed between African American and Caucasian patients. According to the authors, these findings may help guide treatment decision-making for patients with mCRPC.

Registry analysis examines 3 patient subgroups

Investigators used data from TRUMPET (NCT02380274), a US-based prospective, observational multicenter registry designed to characterize treatment patterns, clinical outcomes, health-related quality of life (HRQoL), and health care resource utilization among patients with castration-resistant prostate cancer. The registry enrolled 1028 patients between March 2015 and September 2019 from 147 institutions across the US.

The current analysis was restricted to 832 patients with metastatic, or M1, CRPC. Median age was 73 years, and median follow-up was 26.8 months.

The median OS among patients with M1 CRPC was 41.8 months (95% CI, 39.3 to 48.7) after first-line treatment. Androgen receptor pathway inhibitors (ARPIs) were the most frequently used first-line therapies at CRPC diagnosis, although treatment patterns differed according to treating specialty.

Investigators performed 3 subgroup analyses: initial presentation with de novo metastatic HSPC vs nonmetastatic HSPC; self-reported family history of prostate cancer vs no family history; and African American vs Caucasian race. Time-to-event outcomes were evaluated using Kaplan-Meier methods and Cox proportional hazards models adjusted for clinically important baseline variables and selected factors with substantial between-group differences.

Initial diagnosis linked with survival outcomes

Among 453 patients included in the initial-diagnosis analysis, 199 had de novo metastatic HSPC at their initial prostate cancer diagnosis and 254 initially had nonmetastatic HSPC. Patients who initially had metastatic disease were younger at enrollment and had higher prostate-specific antigen (PSA) levels and Gleason scores at their original diagnosis, as well as a greater proportion of clinical N1 disease.

Median OS was 33.4 months for patients who initially had de novo metastatic HSPC compared with 46.2 months for those initially diagnosed with nonmetastatic HSPC. After adjustment, the nonmetastatic group had a 32% lower risk of death (adjusted HR, 0.68; 95% CI, 0.51 to 0.91). When the model was further adjusted for disease biology factors, OS was similar between the groups—39.0 vs 41.0 months, respectively (adjusted HR, 0.96; 95% CI, 0.61 to 1.50).

The authors noted, “These results suggest there may also be biologic differences between mCRPC that emerges from localized disease and mCRPC that progresses from de novo mHSPC which may impact survival outcomes. From a clinical standpoint, because mCRPC that progresses from de novo mHSPC represents a more biologically aggressive disease state, clinicians should consider more intensified treatment at the earliest opportunity for these patients.”

Family history associated with longer survival

The family-history analysis included 831 patients, including 200 who reported a family history of prostate cancer and 631 who did not. Median overall survival was 53.2 months among patients with a family history compared with 39.6 months among those without one. After adjustment, family history was associated with a 32% lower risk of death (adjusted HR, 0.68; 95% CI, 0.51 to 0.90).

The TRUMPET investigators proposed that earlier detection or greater disease awareness among men with a family history could contribute to the observed association.

No significant difference by race

The race analysis included 794 patients: 133 African American patients and 661 Caucasian patients. African American patients were younger at enrollment and had shorter intervals between initial diagnosis and registry enrollment, higher PSA levels at diagnosis, and a greater frequency of clinical M1 disease at initial diagnosis. They also had higher proportions of diabetes, hypertension, worse ECOG performance status, and high- or very-high-risk disease.

Despite these baseline differences, investigators did not identify statistically significant differences in the evaluated clinical outcomes between African American and Caucasian patients. Treatment patterns were broadly similar, although some differences in health care utilization were observed. Changes in patient-reported HRQoL, including Functional Assessment of Cancer Therapy–Prostate and Brief Pain Inventory–Short Form scores, were also similar across the evaluated subgroups.

Limitations and clinical implications

The primary limitation is the observational design. Although the investigators adjusted for multiple baseline characteristics, residual confounding remains possible, particularly because treatment selection and prognosis in prostate cancer are influenced by numerous factors that may not have been fully captured. The analysis also included substantial early discontinuation or loss to follow-up, raising the possibility of selection bias. Further, family history was self-reported and genetic testing was not performed to identify genetic mutations that may impact prognosis.

These considered, the authors concluded, “These findings may help to direct treatment decisions for patients with clinical characteristics that are associated with more aggressive disease. Future dedicated, prospective research should aim to expand on these findings and further elucidate how clinical outcomes are affected by each of these factors in the context of mCRPC.”

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