224 - Natural History after Likely Cure vs. Recurrence vs. after ProsTate RadiOtheRapy (RAPTOR): A Pooled Analysis of More than 13000 Patients from 21 Randomized Controlled Trials

S. Roy¹, T. Romero², M. Roach III³, J. M. Michalski⁴, D. J. Joseph⁵, D. Dearnaley⁶, A. Tree⁷, L. Incrocci⁸, W. Heemsbergen⁹, M. Bolla¹⁰, A. Nabid¹¹, J. G. Armstrong¹², S. Malone¹³, E. M. Horwitz¹⁴, J. K. Wong¹⁵, S. Arcangeli¹⁶, G. Sanguineti¹⁷, A. Zapatero¹⁸, D. E. Spratt¹⁹, and A. U. Kishan²⁰; ¹Rush University Medical Centre, Chicago, IL, ²Department of Medicine, University of California, Los Angeles, Los Angeles, CA, ³University of California San Francisco, Department of Radiation Oncology, San Francisco, CA, ⁴Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, ⁵Radiation Oncology, Sir Charles Gairdner Hospital, Perth, Australia, ⁶The Institute of Cancer Research and Royal Marsden Hospital NHS Foundation Trust, London, United Kingdom, ⁷The Institute of Cancer Research, London, United Kingdom, ⁸Department of Radiotherapy, Erasmus Medical Center, Rotterdam, Netherlands, ⁹Erasmus Medical Centre, Rotterdam, Netherlands, ¹⁰Grenoble Alpes University, Centre Hospitalier Universitaire de Grenoble, Grenoble, France, ¹¹Centre hospitalier universitaire de Sherbrooke, Sherbrooke, QC, Canada, ¹²St Lukes Radiation Oncology Network, Dublin, Ireland, ¹³The Ottawa Hospital Cancer Center, Ottawa, ON, Canada, ¹⁴Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA, ¹⁵Fox Chase Cancer Center, Philadelphia, PA, ¹⁶University of Milan Bicocca - School of Medicine and Surgery, Milan, Italy, ¹⁷IRCCS Istituto Tumori Regina Elena, Rome, Italy, ¹⁸University Hospital La Princesa, Health Research Institute, Radiation Oncology, Madrid, Spain, Madrid, Spain, ¹⁹Case Western, Cleveland, OH, ²⁰Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA

Purpose/Objective(s): Conventionally, patients who do not experience a biochemical recurrence (BCR) within 5 years of radiotherapy (RT) for non-metastatic prostate cancer (PCa) are considered cured. However, the natural history of disease after this landmark time remains poorly understood. Similarly, the natural history following BCR within five years of RT remains unexplored. We performed a pooled analysis of men enrolled in 21 randomized controlled trials with long-term follow-up to determine incidence of subsequent cancer-specific events including distant metastasis (DM) and prostate cancer-specific mortality (PCSM) in both groups. Materials/

Methods: Individual patient data were obtained from the MARCAP consortium. Cumulative incidence of DM was estimated using competing risk methods considering any deaths as competing events. Competing risk regression (for DM and PCa-specific mortality [PCSM]) were applied to determine the association between treatment strategy ( e.g., escalating RT dose with or without androgen deprivation therapy) with DM and PCSM after adjustment for time to BCR, tumor stage, Gleason score, age at treatment, and baseline PSA. Time of randomization was used to define the intervals to events of interest.

Results: Overall, of the 13,468 eligible patients across 21 trials, 3,902 experienced a BCR event within 5 years (median follow-up 137 months, interquartile range [IQR] 135 – 139). Among patients who did not experience any BCR by 5 years (n=9,566), median follow-up was 129 (IQR, 128 – 130) months. The estimated 10-year cumulative incidence rates (95% CI) of DM and PCSM were 3.3% (2.9–3.7) and 1.2% (1.0–1.4), respectively. On competing risk regression, we did not find sufficient evidence to reject the null hypothesis of no association of upfront treatment with relative incidence of post-BCR DM and PCSM. Among patients who experienced a BCR within five years of RT, 10-year rates of DM and PCSM were 39.3% (37.7–40.8) 29.0% (27.5–30.5), respectively.

Conclusion: Among PCa patients treated with RT those who do not experience a BCR event by 5 years, the overall 10-year rates of DM and PCSM are approximately 3% and 1%, consistent with a curative state. However, for patients with BCR within 5 years, 10-year DM and PCSM rates approach 40% and 30%, consistent with aggressive disease. Further work will help refine the definition of “cure” following RT.