The TRUMPET Registry: Initial Presentation and Family History Determine Survival in mCRPC

KEY FINDINGS

• Initial presentation is decisive: Median overall survival was 33.4 months in patients whose initial diagnosis was de novo metastatic mHSPC and 46.2 months in those with non-metastatic HSPC (adjusted HR 0.68; 95% CI 0.51-0.91).
• The difference may be biological in origin: When the model was further adjusted for disease biology variables, the difference disappeared (39.0 versus 41.0 months; HR 0.96; 95% CI 0.61-1.50).
• Family history is paradoxically protective: Median overall survival was 53.2 months in those reporting a family history and 39.6 months in those who did not (adjusted HR 0.68; 95% CI 0.51-0.90).
• Ethnicity is not an independent determinant: Despite a markedly disadvantaged baseline profile, no significant difference in clinical outcomes was found between African American and Caucasian patients.
• The overall picture: Median overall survival after first-line treatment in the M1 CRPC cohort was 41.8 months (95% CI 39.3-48.7); the most frequent first-line option was ARPIs.

Background and Study Design

Metastatic castration-resistant prostate cancer (mCRPC) is a critical stage in the natural history of the disease at which treatment options begin to narrow progressively. Over the past decade, the sequential use of ARPIs, taxane-based chemotherapy, PARP inhibitors and PSMA-targeted radioligand therapies has markedly prolonged survival. Which clinical parameters determine prognosis in this heterogeneous patient group, however, is still not fully clear.

TRUMPET (NCT02380274) is a prospective, observational, multicentre registry that enrolled 1,028 patients with castration-resistant prostate cancer from 147 centres in the United States between March 2015 and September 2019. The current analysis published in Clinical Genitourinary Cancer is limited to the 832 patients in this cohort with metastatic (M1) CRPC; median age was 73 and median follow-up 26.8 months.

The investigators performed three separate subgroup analyses:

• Comparison of de novo metastatic mHSPC with non-metastatic HSPC at initial diagnosis
• Comparison of the presence versus absence of a self-reported family history of prostate cancer
• Comparison of African American with Caucasian patients

Time-dependent outcomes were assessed by the Kaplan-Meier method; Cox proportional hazards models were adjusted for clinically important baseline variables.

1. Initial Presentation and Survival

Of the 453 patients included in the initial-diagnosis analysis, 199 had de novo metastatic mHSPC at the time of their first prostate cancer diagnosis and 254 had non-metastatic HSPC. The group with metastatic disease at baseline was younger at the time of registration; their PSA levels and Gleason scores at initial diagnosis were higher and the rate of clinical N1 disease was greater.

Median overall survival was 33.4 months in the de novo metastatic group and 46.2 months in the group with a non-metastatic presentation. After adjustment, the risk of death was 32% lower in the non-metastatic group. When the model was further adjusted for disease biology factors, the difference between the groups disappeared - a finding indicating that the observed survival difference can largely be explained by the underlying tumour biology.

The authors emphasise that mCRPC progressing from de novo mHSPC represents a more aggressive disease state and that more intensive treatment should be considered at the earliest possible opportunity in these patients.

2. Family History of Prostate Cancer

831 patients were included in the family history analysis; 200 reported a family history of prostate cancer while 631 did not. Median overall survival was 53.2 months in the group with a family history and 39.6 months in those without; after adjustment, family history was associated with a 32% lower risk of death.

The TRUMPET investigators propose explaining this at first sight unexpected finding by earlier diagnosis and greater disease awareness in men with a family history. These men typically enter regular PSA follow-up at an earlier age and are therefore monitored more closely at every stage of their disease journey.

3. Ethnicity Analysis

794 patients were included in the race analysis: 133 African American and 661 Caucasian patients. African American patients were younger at registration, had a shorter interval between initial diagnosis and registration, higher PSA levels at diagnosis and a greater frequency of clinical M1 disease at initial diagnosis. They also had higher rates of diabetes and hypertension, a worse ECOG performance status and a greater proportion of high/very high risk disease.

Despite these marked baseline disadvantages, no statistically significant difference was found between the two groups in the clinical outcomes assessed. Patient-reported quality of life changes, including FACT-P and BPI-SF scores, were also similar across all subgroups.

Summary of Results

Methodological Limitations

The most important constraint of the analysis is its observational design. Although adjustment was made for many baseline characteristics, the possibility of residual confounding remains. A substantial rate of early treatment discontinuation or loss to follow-up in the cohort increases the risk of selection bias. In addition, family history relied on patient report, and genetic testing was not performed to identify germline mutations (BRCA1/2, ATM, MMR gene defects) that could affect prognosis.

Note: These findings are associative; they do not establish causality. Registry data are hypothesis-generating, and it is not appropriate to base treatment decisions on these data alone.

Implications for Clinical Practice

1. Revaluing the history in risk classification

This analysis brings back to the agenda, as parameters of proven prognostic value, two fundamental clinical data points beginning to be overshadowed by advanced imaging and molecular testing: the way the disease first presents and family history. Both can be obtained at the first clinic visit with no additional cost.

2. Early treatment intensification in de novo metastatic disease

The finding that mCRPC progressing from a de novo metastatic presentation exhibits more aggressive biological behaviour supports the approach of planning triplet therapy (ADT plus ARPI plus docetaxel) in the hormone-sensitive stage in these patients, followed by sequential therapies in the mCRPC stage without delay.

3. The importance of germline genetic testing

The longer survival observed in patients with a family history may reflect the advantage of regular follow-up in this group. However, the same group is also a priority target population for PARP inhibitor candidacy. Germline and somatic genetic testing in every mCRPC patient with a family history should be part of the standard approach, in line with the EAU and NCCN guidelines.

4. The power of equitable care

The fact that African American patients reached similar outcomes despite markedly disadvantaged baseline profiles suggests that equal access to treatment can close outcome gaps. This is an important observation that the organisation of health services systemically may be as decisive as biological risk.

5. From the standpoint of patient communication

Patients with a family history often carry the concern that "the genetic burden will worsen the prognosis". These data give clinicians the opportunity to soften that concern on a scientific basis and to show the patient the concrete survival return of regular follow-up.

Conclusion

This subgroup analysis of the TRUMPET registry shows that prognosis in metastatic castration-resistant prostate cancer is shaped not only by the current choice of treatment but also by the way the disease first presented and by the patient's family background. mCRPC progressing from de novo metastatic disease carries a more aggressive phenotype and calls for early treatment intensification; family history, most probably through earlier diagnosis and closer follow-up, is associated with a median survival advantage of 13.6 months.

Perhaps the most noteworthy finding is that outcomes in African American patients with markedly disadvantaged clinical profiles were similar to those in Caucasian patients - a strong indication that standardised and accessible oncological care can compensate for biological disadvantage. The constraints of the observational design should be borne in mind, and the findings should be confirmed in prospective studies.

References

• Karsh L, Hwang C, Symanowski J, et al. Treatment and outcomes of patients with metastatic castration-resistant prostate cancer by race, initial diagnosis, and family history: Results from the TRUMPET registry. Clin Genitourin Cancer. 2026;24(6):102615. doi:10.1016/j.clgc.2026.102615
• Clarke H. Initial prostate cancer presentation, family history linked to survival in mCRPC. Urology Times, 27 August 2026.
• ClinicalTrials.gov. TRUMPET: Registry of Patients With Castration-Resistant Prostate Cancer (NCT02380274).
• Urologic Oncology. Characteristics, treatment patterns, and outcomes of African American versus Caucasian patients with mCRPC: post hoc analysis of TRUMPET registry.