Incidence of fatigue and low-dose corticosteroid use in prostate cancer patients receiving systemic treatment: a meta-analysis of randomized controlled trials.

Cancer-related fatigue (CRF) is a complex condition that is reported in > 50% of cancer patients. In men with castration-resistant prostate cancer (CRPC), CRF was reported in 12-21% of patients. Approved systemic therapy against CRPC is commonly administered in combination with androgen-deprivation treatment (ADT) and, in some cases, with daily, low-dose corticosteroids. Importantly, the use of low-dose corticosteroids is associated with multiple negative effects, including reduced muscle mass. On these grounds, we hypothesized that the chronic use of corticosteroids may increase the incidence of fatigue in patients with prostate cancer.

We reviewed all randomized trials published during the last 15 years conducted in patients with prostate cancer receiving systemic treatment and we performed a sub-group analysis to gather insights regarding the potential differences in the incidence of fatigue in patients receiving vs. not receiving daily corticosteroids as part of their systemic anti-neoplastic regimen.

Overall, 22,734 men enrolled in prospective randomized phase II and III trials were evaluable for fatigue. Estimated pooled incidence of grade 1-2 fatigue was 30.89% (95% CI = 25.34-36.74), while estimated pooled incidence of grade 3-4 fatigue was reported in 3.90% (95% CI = 2.91-5.02). Sub-group analysis showed that grade 3-4 fatigue was approximately double in patients who received daily corticosteroids as part of their anti-neoplastic treatment (5.58; 95% CI = 4.33-6.98) vs. those who did not (2.67%; 95% CI = 1.53-4.11).

Our findings highlight the need for ad hoc-designed prospective clinical trials to investigate whether the benefits associated with low-dose, daily corticosteroids outweigh the risks associated with corticosteroid-related adverse events such as fatigue.

World journal of urology. 2018 Dec 05 [Epub ahead of print]

Matteo Ferro, Giuseppe Di Lorenzo, Ottavio de Cobelli, Dario Bruzzese, Piero Pignataro, Marco Borghesi, Gennaro Musi, Mihai Dorin Vartolomei, Vincenzo Cosimato, Alessandro Serino, Vincenzo Ieluzzi, Daniela Terracciano, Rocco Damiano, Francesco Cantiello, Francesco Alessandro Mistretta, Matteo Muto, Giuseppe Lucarelli, Pietro De Placido, Carlo Buonerba

Division of Urology, European Institute of Oncology, Milan, Italy. ., Department of Clinical Medicine and Surgery, University Federico II of Naples, Naples, Italy., Division of Urology, European Institute of Oncology, Milan, Italy., Department of Public Health, Federico II University of Naples, Naples, Italy., Department of Molecular Medicine and Medical Biotechnology, University Federico II of Naples, Naples, Italy., Department of Urology, University of Bologna, Bologna, Italy., Division of Onco-hematology, University Hospital San Giovanni di Dio e Ruggi d'Aragona, Salerno, Italy., Second University of Naples, Naples, Italy., Department of Translational Medical Sciences, University of Naples "Federico II", Naples, Italy., Department of Urology, Magna Graecia University of Catanzaro, Catanzaro, Italy., University of Naples, Naples, Italy., Department of Emergency and Organ Transplantation, Urology, Andrology and Kidney Transplantation Unit, University of Bari, Bari, Italy.