Conditional Survival Probabilities in Recurrent Prostate Cancer (PCa) Patients Receiving Radiation ± Antiandrogen Therapy: Secondary Analysis of a Randomized Clinical Trial

Abstract

<h3>Purpose/Objective(s)</h3> Salvage radiation therapy (SRT) and androgen-deprivation therapy (ADT) are routinely used in patients with elevated prostate-specific antigen (PSA) levels after radical prostatectomy (RP). Although overall survival (OS) and biochemical-failure (BF) following SRT are useful when counseling patients at the time of treatment, the utility of survival data from time of diagnosis diminishes over time. Conditional survival (CS) can provide more relevant estimates, especially given long-term PCa survivorship. The primary aim of this study was to analyze CS estimates for recurrent PCa patients undergoing SRT ± ADT. The secondary objective was to determine if factors prognostic of OS and BF at diagnosis remain relevant in survivorship. <h3>Materials/Methods</h3> We analyzed data from 760 post-RP patients enrolled in NRG/RTOG 9601 (1998–2003). Eligible patients included men who had undergone prior RP and had pT2/T3 disease without nodal involvement and detectable PSA levels of 0.2–4.0 ng/mL. Patients were randomly assigned to undergo SRT and receive either 24 mo of ADT or placebo. OS was calculated (Kaplan–Meier), cumulative incidence was used to estimate BF rates, and prognostic factors associated with OS and BF were analyzed by multivariable Cox proportional hazards modeling (MVA). <h3>Results</h3> Patients were followed for a median of 13 y. The 5- and 10-y OS estimates from diagnosis were 93% and 80%, respectively. At 1- (<i>n</i> = 755), 3- (<i>n</i> = 727), 5- (<i>n</i> = 680), 8- (<i>n</i> = 602), and 10-y (<i>n</i> = 543) survivorship, chances of surviving an additional 5 y were 92%, 89%, 86%, 80%, and 72%, respectively. On MVA at diagnosis, omission of ADT (HR 1.308, <i>P</i> = 0.0403), increasing age (HR 2.761, <i>P</i> < 0.0001), and Gleason score (GS) 8−10 (HR 1.054, <i>P</i> =0.01), were associated with all-cause mortality. For those who achieved survivorship at 5 y, only age (HR 2.973, <i>P</i> < 0.0001) and GS 8–10 (HR 1.801, <i>P</i> = 0.0063) were prognostic of mortality on MVA. The 5- and 10-y rates of BF from diagnosis were 36% and 52%, respectively. For patients who survived 1 (<i>n</i> = 725), 3 (<i>n</i> = 560), 5 (<i>n</i> = 435), 8 (<i>n</i> = 320), and 10 (<i>n</i> = 268) y without BF, chances of BF at an additional 5 y were 39%, 33%, 26%, 20%, and 20%, respectively. On MVA at time of SRT, omission of ADT (HR 2.139, <i>P</i> < 0.0001), GS 7 (HR 1.376, <i>P</i> = 0.0062), GS 8–10 (HR 1.717, <i>P</i> = 0.0005), and higher pretreatment PSA (HR 1.442, <i>P</i> = 0.0215), were associated with BF. For those who survived 5 y after treatment without failure, only omission of ADT (HR 1.407, <i>P</i> < 0.0384) was prognostic of BF. <h3>Conclusion</h3> Conditional risk of BF for patients treated with SRT remains elevated at levels similar to those at initial treatment for up to 3 y after SRT, after which BF rates decrease. ADT continues to confer a reduced risk for BF for long-term survivors. This data can be used to inform survivorship care planning and highlights the need for continued PSA surveillance after completion of treatment.