Switching of GnRH Agent from Agonist to Antagonist in Patients with Castration-Resistant Prostate Cancer

Objectives: To evaluate the efficacy of alteration from gonadotropin-releasing hormone (GnRH) agonist to antagonist in patients with castration-resistant prostate cancer (CRPC). Methods: Fourteen patients with CRPC were switched from GnRH agonist to GnRH antagonist. CRPC was defined as 3 consecutive rises of PSA values under androgen deprivation therapy despite a testosterone level at the castration level. No patient underwent a change in oral anti-androgen agent or any additional therapy. Patients who showed increase of the PSA value within 10% or showed decrease in the PSA value compared to the baseline were defined as responders. We measured serum PSA, testosterone, follicular stimulating hormone (FSH), and leutenizing hormone (LH) at the time of alteration and 3 months after alteration. Results: The mean age at diagnosis was 74.8 ± 6.3 years with a mean initial PSA level of 537.3 ± 999.1 ng/mL. The mean age at alteration to GnRH antagonist was 81.4 years with a mean PSA level of 28.6 ng/mL. Two out of 14 patients (14%) were judged as responders based on PSA after alteration to GnRH antagonist, although they did not show any further reduction of the serum testosterone level (remain less than 0.03). Six patients showed further reduction of the serum FSH level after alteration;however, they showed no PSA response (from 46.4 ± 42.6 to 69.4 ± 70.3). Conclusions: The switch from GnRH agonist to GnRH antagonist affected 14% of the patients (2 out of 14 patients) with CRPC at 3 months based on PSA. Larger and longer-term studies are required to determine the efficacy of alteration to GnRH antagonist in patients with CRPC.

Depth of invasion to the bladder wall as a prognostic factor and its association with circulating cell-free DNA levels in patients with muscle-invasive bladder cancer

Background:Radical cystectomy(RC)is the standard surgical treatment for patients with muscle-invasive bladder cancer,but the prognosis is not favorable,and new prognostic factors need to be discovered.We investigated the potential of depth of invasion(DOI)as a prognostic factor in patients with muscle-invasive bladder cancer who underwent RC.Furthermore,we examined the association between preoperative levels of circulating cell-free DNA and DOI.Materials and methods:We retrospectively reviewed patients who underwent RC between January 2007 and December 2017;those who received neoadjuvant chemotherapy were excluded.Depth of invasion was measured using hematoxylin-eosin-stained RC specimens.Results:Of the 121 patients selected,41(33.9%)were eligible for analysis.The median follow-up period was 14 months and mean DOI was 17 mm(range,2-75 mm).Long DOI(>17 mm)was significantly associated with shorter progression-free survival(hazard ratio,14.5;95%confidence interval,3.9-53.97,p<0.0001)and cancer-specific survival(hazard ratio,18.97;95%confidence interval,4.04-88.99,p=0.0002)compared with short DOI.Multivariate analysis revealed that DOI was an independent risk factor for cancer-specific survival.The levels of circulating cell-free DNA were significantly higher in patients with a longer DOI than in those with short DOI(65 vs.20 ng/mL,respectively;p=0.028).Conclusions:Depth of invasion predicted with levels of circulating cell-free DNA and thus could be a useful prognostic factor.