Roderick C N van den Bergh1, Niels J van Casteren2, Thomas van den Broeck3, Eve R Fordyce4, William K M Gietzmann5, Fiona Stewart4, Steven MacLennan4, Saeed Dabestani6, Joaquim Bellmunt7, Michel Bolla8, Erik Briers9, Philip Cornford10, Steven Joniau11, Malcolm D Mason12, Vsevolod Matveev13, Henk G van der Poel14, Theo H van der Kwast15, Olivier Rouvière16, Thomas Wiegel17, Thomas B Lam18, Nicolas Mottet19. 1. Department of Urology, University Medical Centre, Utrecht, The Netherlands. 2. Department of Urology, Ijsselland Hospital, Capelle aan de Ijssel, The Netherlands. 3. Department of Urology, University Hospitals, Leuven; Laboratory of Molecular Endocrinology, KU Leuven, Leuven, Belgium. 4. Academic Urology Unit, University of Aberdeen, Aberdeen, UK. 5. Department of Urology, Aberdeen Royal Infirmary, Aberdeen, UK. 6. Department of Urology, Skåne University Hospital, Malmö, Sweden. 7. Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. 8. Department of Radiation Oncology, Centre Hospitalier Universitaire Michallon, Grenoble, France. 9. Hasselt, Belgium. 10. Royal Liverpool and Broadgreen Hospitals NHS Trust, Liverpool, UK. 11. Department of Urology, University Hospitals Leuven, Leuven, Belgium. 12. Velindre Hospital, Cardiff, UK. 13. Department of Onco-Urology, Cancer Research Centre, Moscow, Russia. 14. Department of Urology, Netherlands Cancer Institute, Amsterdam, The Netherlands. 15. Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands. 16. Hospices Civils de Lyon, Radiology Department, Edouard Herriot Hospital, Lyon, France. 17. Department of Radiation Oncology, University Hospital Ulm, Ulm, Germany. 18. Academic Urology Unit, University of Aberdeen, Aberdeen, UK; Department of Urology, Aberdeen Royal Infirmary, Aberdeen, UK. 19. Department of Urology, North Hospital, CHU de Saint-Etienne, University of Jean-Monnet, Saint-Etienne, France. Electronic address: nicolas.mottet@chu-st-etienne.fr.
Abstract
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.
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.
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