SALT LAKE CITY — While most men with non-metastatic prostate cancer respond to androgen-deprivation therapy initially, many later experience rising prostate-specific antigen levels that indicate they have developed castration resistance.
Several options are now available to treat those who are found to have metastases. How to manage men with non-metastatic castration-resistant prostate cancer (nmCRPC) remains a matter of ongoing debate, however.
Patients with nmCRPC often have no symptoms, are frequently older and have multiple comorbidities. They may be taking multiple medications. On the one hand, in the absence of symptoms, adverse events associated with treatment could reduce their quality of life. On the other, some will progress to metastatic cancer, which could be prevented or forestalled by treatment with second-generation androgen receptor inhibitors such as apalutamide, enzalutamide, and darolutamide.
A team of researchers from the University of Utah led by Ahmad Sami Halwani, MD, studied the treatment patterns at the VA — which treats the largest number of men with nmCRPC in the country — to see what providers choose in a real-world setting. They conducted a retrospective observational study using patient information from the VA Clinical Cancer Registry and the VA Corporate Data Warehouse for 12,459 veterans diagnosed with prostate cancer who later developed nmCRPC from 2006 to 2020. They defined nmCRPC as evidence of rising PSA with at least two consecutive increases in PSA concentration and evidence of continued androgen deprivation as shown by serum testosterone level of 50 ng/dL or less and no evidence of metastases.1
Of the 7,659 patients who received first-line nmCRPC therapy, 72% received bicalutamide, 8% ketoconazole, 7% abiraterone, 6% enzalutamide, and 3% flutamide. The approval and subsequent use of abiraterone and enzalutamide starting in 2012 led to reduced use of bicalutamide in the first-line from 80% of patients in 2006 to 43% by 2020. Throughout the study period, ketoconazole remained the second most common first-line therapy and the most widely used second-and third-line therapy for nmCRPC. Thirty-one percent of the veterans who received any first-line therapy went on to receive a second-line treatment, and 32% of those receiving second-line therapy subsequently received a third-line drug.
While enzalutamide did drive down the use of bicalutamide, the researchers found that overall the adoption of newer androgen receptors including apalutamide, enzalutamide, and darolutamide was relatively slow, despite their “demonstrated improved metastasis-free survival and treatment-related quality of life.” Instead, providers continued to rely on older, first-generation anti-androgens in the first-line treatment of nmCRPC.
- Halwani AS, Patil V, Morreall D, Li C, Yong C, Appukkutan S, Partridge J, Jhaveri J, Rasmussen KM. Real-world treatment patterns among veterans with nonmetastatic castration-resistant prostate cancer (nmCRPC). J Clin Oncol 40, 2022 (suppl 16; abstr e17042)
