Study on the choice of medication time and with drawal time of intermittent endocrine therapy for prostate cancer

Objective To determine the best timing of discontinuance of intermittent endocrine therapy for prostate cancer (PCa). Methods From February 2012 to September 2014, 120 PCa patients confirmed by biopsy at the Department of Urology Surgery, Beijing Shijitan Hospital Affiliated to Capital Medical University, were included. They were divided into high-, moderate- and low-risk groups according to EAU Guidelines in 2015. All patients received intermittent endocrine therapy. When the serum level of prostate-specific antigen (PSA) dropped to 0.2 μg/L, the medication was not discontinued until 3 months later for the observation group; however, the medication was immediately discontinued after reaching the above-mentioned threshold for the control group. When the PSA level during the period of medication discontinuance increased to 4 μg/L, another course of intermittent endocrine therapy was administered until the occurrence of the failure event. The Cox proportional regression model was used to compare the difference between the two groups in the androgen-independent signs, progression of PCa and severe adverse events. Result After correction for multiple confounding factors, including severity grading before treatment, average duration of medication, average duration of medication discontinuance and the number of courses of therapy, it was found that the medication scheme adopted in the observation group was a protective factor against androgen-independent signs in the high-risk PCa patients (HR: 0.535, 95% CI: 0.458-0.612; P<0.001); it was also a protective factor against disease progression for the high- and moderate-risk patients (high-risk group, HR: 0.387, 95% CI: 0.297-0.477; P<0.001; moderate-risk group, HR: 0.697, 95% CI: 0.581-0.813; P<0.001). However, there was no significant difference in the incidence of severe adverse events among PCa patients treated by different medication schemes (HR: 1.003, 95% CI: 0.906-1.100; P=0.798). The medication scheme adopted in the observation group was an independent risk factor for severe adverse events in the low-risk PCa patients (HR: 1.489, 95% CI: 1.305-1.673; P<0.001). Conclusion As compared with the scheme of immediately discontinuing the medication after reaching the indicator threshold, maintenance medication for another 3 months was beneficial for the high- and moderate-risk PCa cases. The maintenance medication could reduce the androgen-independent signs and disease progression, without increasing the risk of severe adverse events. However, for the low-risk patients, there was no major difference between the two medication schemes, immediate discontinuance and maintenance medication for another 3 months. Instead, further medication may bring about a higher risk of severe adverse events. Key words: Prostate neoplasms; Intermittent endocrine therapy; Timing of medication discontinuance; Adverse events