Assessing the Role and Optimal Duration of Hormonal Treatment in Association with Salvage Radiation Therapy After Radical Prostatectomy

The addition of concomitant hormonal therapy (HT) to postoperative radiation therapy (RT) in patients affected by biochemical relapse (BCR) is still an open question and remains controversial. Evidence from randomized clinical trials (RCTs) suggests that the combination of HT with postoperative RT improves oncologic outcomes. However, use of androgen deprivation therapy (ADT) is associated with several side effects (cardiovascular morbidity, metabolic effects, non-metastatic bone fractures, sexual dysfunction, hot flushes, fatigue, and neurologic side effects) leading to a decreased quality of life. Therefore, the potential benefit of ADT should be weighed against the associated harms. Moreover, HT duration may have a differential effect according to the clinical and pathologic characteristics of patients.

Among several plausible risk factors, three were selected according to previously published predictive models that dealt with the risk of clinical recurrence (CR) after RT: pT stage pT3b, pathologic Gleason 8, and PSA level at SRT >0.5 ng/ml. These three risk factors might be useful to select those patients who might benefit the most from HT associated with postoperative RT. Patients were divided into three groups according to their number of risk factors (0 vs 1 vs 2).

We found that the association between CR-free survival and duration of concomitant HT differed significantly by the number of risk factors (0 vs 1, p = 0.001; 0 vs 2, p < 0.0001 on interaction test). Long-term ADT was highly beneficial for patients with two or more risk factors. Among these patients, CR risk was roughly halved going from 0 to 12 months, with a further 25% reduction in relative risk going from 12 to 18 months for HT duration. Similarly, for men harboring one single risk factor, CR rate was significantly lower among those treated with short-term HT (ie, ≤12 months), whereas a clear benefit of long-term HT (ie, >12 months) was not observed. Finally, the absolute risk of CR was shown to remain constant for patients without risk factors, regardless of HT duration.

In conclusion, three groups of patients were identified based on the number of risk factors. This classification aimed to select the optimal candidates for concomitant therapy and to determine the optimal ADT duration. Prospective RCT is still needed to validate these findings.

Authors:
Nicola Fossati, MD,^1& Daniele Robesti,^1& R. Jeffrey Karnes, MD,² Matteo Soligo,² Stephen A. Boorjian MD,² Alberto Bossi, MD,³ Gabriele Coraggio,³ Nadia Di Muzio, MD,⁴ Cesare Cozzarini, MD,⁴ Barbara Noris Chiorda⁴, Giorgio Gandaglia,¹ Simone Scarcella,¹ Detlef Bartkowiak⁵, Dirk Böhmer, MD, PhD,⁶ Shahrokh Shariat, MD,⁷ Gregor Goldner,⁸ Antonino Battaglia, MD, FEBU,⁹ Steven Joniau, MD, PhD,⁹ Karin Haustermans, MD, PhD,¹⁰ Gert De Meerleer, MD, PhD,¹⁰ Valérie Fonteyne, MD, PhD,¹¹ Piet Ost, MD, PhD,¹¹ Hein Van Poppel,⁹ Francesco Montorsi, MD,¹ Thomas Wiegel, MD,⁵ Alberto Briganti, MD¹

Author Affiliations:
1. Division of Oncology/Unit of Urology; URI; IRCCS Ospedale San Raffaele, Milan, Italy
2. Department of Urology, Mayo Clinic, Rochester, MN, USA
3. Department of Radiation Oncology, Gustave Roussy Institute, Villejuif, France
4. Department of Radiotherapy; IRCCS Ospedale San Raffaele, Milan, Italy
5. Department of Radiation Oncology, University Hospital Ulm, Ulm, Germany
6. Department of Radiation Oncology, Charité University Medicine Berlin, Germany
7. Department of Urology, Medical University of Vienna, Vienna, Austria
8. Department of Radiation Oncology, Medical University of Vienna, Vienna, Austria
9. University Hospitals Leuven, Department of Urology, Leuven, Belgium
10. University Hospitals Leuven, Department of Radiotherapy, Leuven, Belgium
11. Department of Radiotherapy, Ghent University Hospital, Ghent, Belgium
&. These authors contributed equally to the study

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