Role of Hormonal Treatment in Prostate Cancer Patients with Nonmetastatic Disease Recurrence After Local Curative Treatment: A Systematic Review

Context: The relative benefits and harms of hormonal treatment (HT) versus no or deferred HT in patients with nonmetastatic prostate cancer (PCa) relapse after primary curative therapy are controversial. Objective: To assess the effectiveness of HT for nonmetastatic PCa relapse, prognostic factors for treatment outcome, timing of treatment, and the most effective treatment strategy to provide guidance for clinical practice. Evidence acquisition: A systematic literature search was undertaken incorporating Medline, Embase, and the Cochrane Library (search ended March 2015). Studies were critically appraised for risk of bias. The outcomes included overall and cancer-specific survival, metastasis-free survival, symptom-free survival, progression to castrate resistance, adverse events, and quality of life. Evidence synthesis: Of 9687 articles identified, 27 studies were eligible for inclusion (2 RCTs, 8 nonrandomised comparative studies, and 17 case series). The results suggest that only a subgroup of patients, especially those with high-risk disease, may benefit from early HT. The main predictors for unfavourable outcomes were shorter PSA doubling time (<6–12 mo) and higher Gleason score (>7). Early HT may be warranted for patients with high-risk disease. An intermittent HT strategy appears feasible. Most studies had a moderate to high risks of bias. Conclusions: HT for PCa relapse after primary therapy with curative intent should be reserved for patients at highest risk of progression and with a long life expectancy. The potential benefits of starting HT should be judiciously balanced against the associated harms. Patient summary: This article summarises the evidence on the benefits and harms of hormonal treatment in prostate cancer (PCa) patients in whom the disease has recurred following earlier curative treatment. We found that only a select group of patients with aggressive PCa and a fast rising prostate-specific antigen may benefit from early hormonal treatment (HT), whereas in others HT may be more harmful than beneficial.