PSA decay during salvage radiotherapy for prostate cancer as a predictor of disease outcome – 5 year follow-up of a prospective observational study Adalsteinn Gunnlaugsson a,⇑ , Elisabeth Kjellén a , Ola Bratt b , Göran Ahlgren c , Vilberg Johannesson a , René Blom d , Per Nilsson a a Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, Lund University, 221 85 Lund, Sweden b Department of Urology, Sahlgrenska University Hospital, 41345 Gothenburg, Sweden c Department of Urology and Surgery, Skåne University Hospital, 221 85 Lund, Sweden d Department of Surgery, Halmstad Hospital, 302 33 Halmstad, Sweden article info Article history: Received 26 January 2020 Revised 25 May 2020 Accepted 25 May 2020 Available online 30 May 2020 Keywords: Prospective Observational trial Prostate cancer Salvage radiotherapy PSA decay-rate constant Predictive value abstract Background and purpose: Biochemical recurrence after prostatectomy is commonly treated with salvage radiotherapy (SRT). In this prospective observational study we investigated the PSA decay rate, deter- mined by predefined serial PSA measurements during SRT, as a predictor for treatment outcome. Materials and methods: Between 2013 and 2016, 214 patients were included in the study. The prescribed dose to the prostate bed was 70 Gy in 35 fractions (7 weeks) without hormonal treatment. PSA was mea- sured weekly during SRT. Assuming first order kinetics, a PSA decay-rate constant (k) was calculated for 196 eligible patients. The ability of k to predict disease progression was compared with known clinical prediction parameters using Cox regression, logistic regression and ROC analyses. Disease progression was defined as continuously rising PSA after SRT, PSA increase by 0.2 ng/ml above nadir after SRT, hor- monal treatment or clinical progression. Results: After a median follow up of 4.7 years the estimated failure-free survival at 5 years was 56%. The PSA decay-rate constant (k) was found to be the strongest predictor of disease progression in both uni- and multivariable analyses. Conclusion: The addition of k to established clinical variables significantly improves the possibility to pre- dict treatment outcome after SRT and could be used to personalize future therapies. Ó 2020 The Authors. Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/). 1. Introduction A successful surgical treatment for localized prostate cancer (PC) should result in an undetectable prostate-specific antigen (PSA) value. Still, around 20–40% of the patients experience a bio- chemical recurrence (BCR) [1], usually defined as a second confir- matory PSA measurement above 0.2 ng/mL [2]. The treatment of choice for BCR is salvage radiotherapy (SRT) [3,4], commonly 66–70 Gy in 33–35 fractions to the prostate bed [5–7]. Recent evidence from randomized studies shows that the outcome can be improved with irradiation of pelvic lymph nodes [8] and hormonal therapy [9,10]. About half of the patients treated with SRT are in complete bio- chemical remission 3–5 years after treatment [11]. SRT failure can either occur locally (due to a target miss, radiation resistant cancer or insufficient dose), or because of nodal or distant metastases. Multiple pre-treatment clinical factors can predict outcome of SRT [1,12–17]. These predictive factors are e.g. included in a nomo- gram developed by Stephenson et al. [18] which calculates the probability to stay free from disease progression six years after SRT. This information can be used for selecting patients for SRT. Previous retrospective studies have shown an association between PSA change during SRT and long term outcome [19,20]. The identification of robust parameters based on each patient’s instant response to treatment, rather than using pre-treatment fac- tors only, can be used to more effectively identify a group of patients with high risk of recurrence that are more likely to benefit from treatment escalation. This so called ”enrichment” strategy is https://doi.org/10.1016/j.ctro.2020.05.008 2405-6308/Ó 2020 The Authors. Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). ⇑ Corresponding author. E-mail address: adalsteinn.gunnlaugsson@skane.se (A. Gunnlaugsson). Clinical and Translational Radiation Oncology 24 (2020) 23–28 Contents lists available at ScienceDirect Clinical and Translational Radiation Oncology journal homepage: www.elsevier.com/locate/ctro