Some patients will have relapse of their prostate cancer after they undergo surgery or radiotherapy. When relapse occurs, it may first manifest as a rising PSA level, and imaging studies do not show that the cancer has spread elsewhere (metastasis). Patients may undergo radiotherapy (for patients who were first treated with surgery) or surgery (for patients who were first treated with radiotherapy) to treat the relapse. If these measures do not work, or patients are unsuitable for such aggressive treatment, patients may be started on hormonal therapy, especially those with rapidly rising PSA as they have increased risk of metastasis. Hormonal therapy would control the disease for some time but eventually, the cancer develops resistance to hormonal therapy.
At this stage, these patients are considered to have non-metastastic castrate resistant prostate cancer (M0 CRPC). It is estimated that 2 – 8% of patients with prostate cancer have M0 CRPC. Conventionally these patients are either monitored until they develop metastasis, whereupon 2nd line treatments are started, or they are put on clinical trials.
In Feb 2018, the FDA approved the drug apalutamide for use in patients with M0 CRPC, based on the results of the SPARTAN trial. Patients enrolled in this trial were deemed to have high risk for development of metastasis, based on PSA doubling time. Apalutamide was shown to significantly delay the time that patients were detected to develop metastasis (metastasis free survival); patients receiving apalutamide had median metastasis free survival of 40.5 months, compared to 16.2 months for those receiving placebo. The time that patients developed cancer symptoms requiring further anti-cancer treatment (progression free survival) was also significantly longer in patients who received apalutamide.
Apalutamide is the first medication approved for patients with non-metastatic castrate resistant prostate cancer. I believe apalutamide is not for all patients with M0 CRPC, but certainly patients with high risk of developing metastasis may consider it for treatment of their disease.