Superior first-line prostate cancer treatment often not given due to ‘lack of awareness’
Key takeaways:
- Many men with metastatic hormone-sensitive prostate cancer have not received recommended first-line treatment.
- Physicians reported not giving recommended treatment based on guidelines and safety profile.
Many men with metastatic hormone-sensitive prostate cancer have not received recommended first-line therapies due to clinicians’ unfamiliarity with treatment guidelines and misinformation about toxicities.
Numerous organizations recommend androgen receptor pathway inhibitors (ARPIs) and/or chemotherapy in combination with androgen deprivation therapy (ADT) as initial treatment for men with metastatic hormone-sensitive prostate cancer.
However, a retrospective survey showed more than 50% of physicians who treated with only ADT did so because they thought that was what guidelines recommended and/or they had tolerability concerns.
“Every guideline worth any name — NCCN, American Urology Association, ASCO — endorse these treatments as standard of care with level-one evidence,” Neeraj Agarwal, MD, FASCO, professor of medicine and presidential endowed chair of cancer research at University of Utah’s Huntsman Cancer Institute, told Healio.
“If clinicians who are not prescribing these medications are saying they’re following the guidelines or they have concerns about tolerability, this means only one thing — they are not reading the literature. They are not aware of the guidelines. They probably have not looked into the guidelines for a long time.”
‘Significant improvement’ in OS
Men with metastatic hormone-sensitive prostate cancer had a median OS of less than 3 years about a decade ago, when ADT was the primary treatment option, Agarwal said.
Since then, docetaxel chemotherapy and ARPIs such as abiraterone (Zytiga, Janssen) enzalutamide (Xtandi; Astellas Pharma, Pfizer), apalutamide (Erleada, Janssen) and darolutamide (Nubeqa, Bayer) have been approved as first-line therapies.
“By moving these drugs upfront to newly diagnosed patients, we saw significant improvement in overall survival, which is around 50 to 60 months,” Agarwal said.
Multiple studies, conducted before or around when guidelines got updated, found men with metastatic hormone-sensitive prostate cancer did not receive first-line combination therapy, according to study background.
One investigation showed nearly 40% of patients in the U.S. did not receive ARPIs or chemotherapy with ADT in 2019 and 2020. Another trial found 47% of men around the world did not receive combination therapy between January and August 2020.
“Every single trial conducted in this setting has shown that quality of life was not impaired [with combination therapy],” Agarwal said. “In fact, it was maintained, and this quality of life was reported by the patients themselves.”
“The question was, ‘Why — despite level-one evidence — are patients not receiving these treatments?’” he added. Agarwal and colleagues evaluated data from the Adelphi Real World retrospective survey to investigate.
Physicians reviewed medical records and prospectively answered questions about men with metastatic hormone-sensitive prostate cancer they treated between July 2018 and January 2022.
In all, 107 physicians completed the survey. Participants included medical oncologists (60.7%) and urologists (39.3%), as well as physicians who worked in a community hospital (63.6%) or in an academic or cancer center (36.4%).
They provided responses about 617 patients (median age at first treatment, 68 years, interquartile range, 63-74; 58% white; 24.8% African American).
Reasons regarding treatment decisions served as the primary endpoint.
‘Striking’ results
Of patients treated, 69.7% did not receive combination therapy with ARPIs or chemotherapy.
Physicians who treated their patients with combination therapy primarily did so because of the safety profile (64.7%), guideline recommendations (61.5%) and superior quality of life (39.6%).
Physicians who chose not to treat with combination therapy reported safety (58.6%), guideline recommendations (53.5%) and quality of life (36.5%) as the top reasons for their choices, as well.
A significantly larger portion of physicians who treated with combination therapy reported they did so because of a patient’s high PSA levels than those who did not (39% vs. 18.4%; P < .001).
Conversely, significantly more physicians chose ADT alone because of ease of treatment (26.3% vs. 17.6%, P = .02).
Patient clinical characteristics that resulted in significantly higher rates of combination therapy included high PSA levels (P = .001) and high-volume disease (P = .001).
Physicians who wanted to lower PSA between 75% and 100% had a significantly higher likelihood of prescribing combination therapy than those who wanted to reduce PSA 0% to 49% (OR = 1.63; 95% CI, 1.04-2.56).
Physicians who selected treatment based on guideline recommendations had significantly higher odds of treating with combination therapy (OR = 3.46; 95% CI, 1.32-9.08).
Agarwal described the data as “striking.”
“Abiraterone was approved around 2018,” he said. “Apalutamide and enzalutamide were approved around the middle of 2019. Chemotherapy has been approved since 2014. These drugs were in place. They are approved.”
Researchers acknowledged study limitations, including the Adelphi Real World survey not being a “true random sample of physicians’ most recent eligible patients,” they wrote.
“Ultimately, the crux of the problem is lack of awareness,” Agarwal said.
Education pivotal to improvement
Agarwal emphasized the difficulty medical oncologists and urologists face keeping up with guideline recommendations.
“[Medical oncologists] are seeing multiple different cancer types in a given week,” he said. “It is extremely difficult to keep up with advancements in each cancer type. Urologists are surgeons who are mostly operating 2 or 3 days a week. They see patients in the clinic 1 or 2 days a week. Clinics are mostly run with the help of nurse practitioners and advanced practice clinicians. The combined workforces, for various reasons, are not able to keep up with the data.”
Implementation medicine begins with education.
“Educate patients directly,” Agarwal said. “If patients are educated, they will ask their doctors why they didn’t receive that treatment, which they thought should be offered.”
Clinicians need to stay up to date, as well.
Agarwal acknowledged difficulties some may face with lower budgets or limited availability, which may prevent travel to important meetings, but he also highlighted continuing medical education programs to stay informed.
Agarwal and colleagues have noticed improvement in combination therapy for men with metastatic hormone-sensitive prostate cancer.
They reported at ASCO Genitourinary Cancers Symposium in February 2025 that of patients in the Flatiron Health electronic health record database who received treatment since January 2023, 76.8% received combination therapy.
However, Agarwal noted that this population likely came from large academic institutions, cancer centers or large oncology practices.
“If Flatiron database is correct, it took 10 years from the approval of docetaxel chemotherapy to see ~80% patients receiving combination therapy in large practices,” he said. “We still don’t know what is going on in small town practices, and now we are going to have several new drugs being approved in this setting starting this year.
“Do we need another 10 years, or can we do something?”
References:
- Agarwal N, et al. JAMA Netw Open. 2024;doi:10.1001/jamanetworkopen.2024.48707.
- Swami U, et al. Abstract 95. Presented at: ASCO Genitourinary Cancers Symposium; Feb. 13-15, 2025; San Francisco.
For more information:
Neeraj Agarwal, MD, FASCO, can be reached at neeraj.agarwal@hci.utah.edu.
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