Abstract
ObjectiveProstate cancer is the most common nonskin cancer and second most common cause of cancer mortality in older men in the United States (USA) and Western Europe. Androgen-deprivation therapy alone (ADT) remains the first line of treatment in most cases, for metastatic disease. We performed a systematic review and meta-analysis of all randomized controlled trials (RCT) that compared the efficacy and adverse events profile of a chemohormonal therapy (ADT ± docetaxel) for metastatic hormone-naive prostate cancer (mHNPC).MethodsSeveral databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The primary endpoint was overall survival. Data extracted from the studies were combined by using the hazard ratio (HR) or risk ratio (RR) with their corresponding 95% confidence intervals (95% CI).ResultsThe final analysis included 3 trials comprising 2,264 patients (mHNPC). Patients who received the chemohormonal therapy had a longer clinical progression-free survival interval (HR = 0.64; 95% CI: 0.55 to 0.75; p<0.00001), and no heterogeneity (Chi2 = 0.64; df = 1 [p = 0.42]; I2 = 0%). The biochemical progression-free survival (bPFS) also was higher in patients treated with ADT plus docetaxel (HR = 0.63; 95% CI: 0.57 to 0.69; p<0.00001), also with no heterogeneity noted (Chi2 = 0.48; df = 2 [p = 0.79]; I2 = 0%). Finally, the combination of ADT with docetaxel showed a superior overall survival (OS) compared with ADT alone (HR = 0.73; 95% CI: 0.64 to 0.84; p<0.0001), with moderate heterogeneity (Chi2 = 3.84; df = 2 [p = 0.15]; I2 = 48%). A random-effects model analysis was performed, and the results remained favorable to the use of ADT plus docetaxel (HR = 0.73; 95% CI: 0.60 to 0.89; p = 0.002). In the final combined analysis of the high-volume disease patients, the use of the combination therapy also favored an increased overall survival (HR = 0.67; 95% CI: 0.54 to 0.83; p = 0.0003). Regarding adverse events and severe toxicity (grade ≥3), the group receiving the combined therapy had higher rates of neutropenia, febrile neutropenia and fatigue.ConclusionThe combination of ADT with docetaxel improved the clinical progression-free survival, bPFS and OS of patients with mHNPC. A superior OS was seen especially for patients with metastatic and high-volume disease. This contemporary combination therapy may now be offered as a first-line treatment for selected patients.
Highlights
Prostate cancer is the most common nonskin cancer in older men in the United Kingdom (UK), United States (USA) and Western Europe [1]
Patients who received the chemohormonal therapy had a longer clinical progression-free survival interval (HR = 0.64; 95% confidence intervals (95% CI): 0.55 to 0.75; p
The biochemical progression-free survival was higher in patients treated with ADT plus docetaxel (HR = 0.63; 95% CI: 0.57 to 0.69; p
Summary
Prostate cancer is the most common nonskin cancer in older men in the United Kingdom (UK), United States (USA) and Western Europe [1]. It is often cured when diagnosed in a localized stage, and is responsive to various treatments even when advanced or metastatic. In patients with locally advanced, recurrent or metastatic tumors, the goals of therapy are to prolong survival and the progression-free interval, while maintaining a good quality of life (QOL) [1]. Since the 1940s, the primary therapy for men with metastatic prostate cancer has been ADT alone, to suppress the production of testosterone, either with surgical or chemical castration [4, 5]. Chemotherapy is typically initiated only after the patient no longer responds to ADT alone, when the disease enters a "castration resistant” state [5, 6]
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