Fewer than half of patients with metastatic castration-resistant prostate cancer (mCRPC) advance to second-line therapy, with attrition rising steeply across subsequent treatment lines, according to a study published June 29 in JAMA Network Open.
The finding is from a retrospective cohort study of 5,096 patients with mCRPC who initiated first-line therapy between January 2021 and June 2025, with androgen receptor pathway inhibitors the most common treatments in first and second lines, noted co-first authors Gabriel Hooper, MD, and Yeonjung Jo, PhD, of the University of Utah in Salt Lake City, and colleagues.
“These findings underscore the growing complexity of mCRPC care, highlight critical gaps in access and sequencing that may limit the clinical impact of therapeutic innovation, and have direct implications for health policy and the design of future clinical trials,” the group wrote.
The mCRPC treatment landscape has expanded substantially over the past two decades, with multiple drug classes now available including androgen receptor pathway inhibitors (ARPIs), taxanes, poly(ADP-ribose) polymerase inhibitors (PARPIs), and the radioligand therapy lutetium-177 prostate-specific membrane antigen-617 (Pluvicto), the researchers explained. Yet large contemporary studies characterizing real-world treatment patterns and attrition rates are sparse, they noted.
To bridge the gap, the group culled data from the Flatiron Health Research Database, an electronic health record–derived dataset covering approximately 280 US centers, primarily community oncology practices. They identified patients with mCRPC initiating first-line therapy from 2021 to 2025. Treatment patterns were tracked across up to five lines of therapy and categorized by drug class. Attrition was defined as the percentage of patients who did not receive the next line of therapy, including those who died, declined further treatment, did not require additional therapy within the study period, or were lost to follow-up.
Of 5,096 patients who received first-line therapy, just 2,731 (53.6%) received second-line treatment and 1,334 (26.2%) received third-line treatment. Only 588 patients (11.5%) reached fourth-line therapy and 226 (4.4%) reached fifth-line therapy.
ARPIs were the most common first-line treatment (79.3%) and remained the most common second-line treatment (41.1%). Taxanes were the second most common first-line treatment (12.5%), and the most common third-line treatment (36.4%). The use of Pluvicto increased progressively from 2.2% of patients in the first-line setting to 31.4% by fifth-line initiation. PARPI use was limited throughout and peaked at 7.4% in third-line treatment, the researchers reported.
“Attrition in mCRPC occurs for multiple reasons, including patient preference, toxicity, disease progression, financial burden, patient frailty, or death from cancer or other causes,” the group wrote.
However, they noted that genetic testing in mCRPC patients to identify those with homologous recombination repair gene mutations could enable earlier use of PARPIs, for instance.
“Further research is needed to better understand the contributors to attrition in mCRPC, and improved strategies to improve access are critical, as delivering the most effective first-line treatment is essential to ensure patients benefit before they are lost to attrition,” the researchers concluded.
The full study is available here.