Factors predicting progression to castrate‐resistant prostate cancer in patients with advanced prostate cancer receiving long‐term androgen‐deprivation therapy

Abstract

ObjectivesTo assess time to progression to castrate-resistant prostate cancer (CRPC) and factors influencing longer-term outcomes in patients receiving androgen-deprivation therapy (ADT) in an extension to the Triptocare study (NCT01020448). This is pertinent as the Triptocare study did not show that urinary prostate cancer antigen-3 (PCA3) score was a reliable marker of cancer stage in advanced prostate cancer and was not useful for assessing response 6 months after initiation of ADT with triptorelin 22.5 mg. Patients and MethodsAn international, multicentre, non-interventional, observational, longitudinal, prospective study involving patients from the Triptocare study. CRPC status of patients was collected for up to 3 years from ADT initiation. Patient treatment and assessments were at the investigator's discretion. Co-primary endpoints were rate of CRPC at 3 years after initiating ADT and the median time to CRPC. An exploratory endpoint was the association of Triptocare baseline variables (including TMPRSS2-ERG and PCA3 scores) and PCA3 score at Triptocare last value available with CRPC onset. ResultsOf the 325 patients in the Triptocare study safety population, 180 patients were enrolled in the Triptocare LT study (102 received continuous and 78 received intermittent ADT). CRPC rates at 3 years were 24/102 (23.5%) and 6/78 (7.7%) patients in the continuous and intermittent ADT groups, respectively. The median time to CRPC was not reached for either group. PCA3 score status at baseline was the only variable associated with a higher risk of progression to CRPC in both the intermittent and continuous ADT groups; compared with a baseline PCA3 score of ≥35, a PCA3 score below the level of quantification had a hazard ratio ( ConclusionIn men with locally advanced or metastatic prostate cancer, a PCA3 score of ≥35 at the time of initiating ADT may predict a lower risk of developing CRPC in the following 3 years.

Are all gonadotrophin‐releasing hormone agonists equivalent for the treatment of prostate cancer? A systematic review

“…Likewise, triptorelin 1-, 3-and 6-month formulations suppress testosterone to castration levels (≤50 ng/dL) in >90% of patients from day 29 after the first injection (reviewed in Ploussard and Mongiat-Artus [54], and Breul et al [55]), and this testosterone suppression is maintained over the long-term (33 months) [56]. Different formulations of goserelin are effective at controlling testosterone levels, an effect that has been shown to persist in the long term [18,57].…”

“…As with the efficacy data, the few comparative trials on safety and tolerability were short-term and had low patient numbers, making it difficult to detect AEs with a low frequency. In single-agent clinical trials of leuprorelin, triptorelin or goserelin, the AE profiles have been broadly similar [52,56,75]. Goserelin and leuprorelin were compared in combination with two anti-androgens (bicalutamide and flutamide) as part of exploratory analyses of data from a controlled trial [40].…”

“…A long-term follow-up study of men receiving leuprorelin 3-month formulation for up to 43 months reported hot flushes, decreased libido, erectile dysfunction, increase sweating, nocturia, and weight increase as AEs occurring with a frequency of ≥15%but those occurring after the initial 9-month treatment period were not reported separately [51]. In 180 patients receiving triptorelin for up to 3 years, ADT-related AEs reported after the first 9 months of treatment included gynaecomastia (three patients; 1.7%), increased weight (three; 1.7%), hot flushes (two; 1.1%), asthenia (one; 0.6%), and erectile dysfunction (one; 0.6%) [56]. During 9 months of treatment with triptorelin or leuprorelin, the increased weight was not significantly different between treatment groups [36].…”

“…The absence of direct comparative data prevents firm conclusions being made on the possible differential effects of the three GnRH agonists on PSA levels. A wealth of data from non-comparative trials have shown the ability of different long-acting formulations of leuprorelin, triptorelin, and goserelin to reduce and maintain PSA levels at ≤4 ng/mL for 1-7 years [23,52,54,56,63].…”

Tumor Burden and Intraosseous Metabolic Activity as Predictors of Bone Marrow Failure during Radioisotope Therapy in Metastasized Prostate Cancer Patients

“…Patients affected by castration-resistant prostate cancer (CRPC) present an extremely high incidence of skeletal metastases [ 1 ]. In recent years, numerous novel treatment modalities have been developed to treat metastasized CRPC [ 2 – 5 ]. Among these, radionuclide therapy with alpha-emitting Ra-223-Dichloride (Ra-223) has been recently approved [ 6 ].…”