Predicting The 5-Year Risk of Biochemical Relapse after Post-Prostatectomy Radiation Therapy In ≥pT2, pN0 Patients with A Comprehensive TCP Model

Publication date: Available online 18 June 2016
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Claudio Fiorino, Sara Broggi, Nicola Fossati, Cesare Cozzarini, Gregor Goldner, Thomas Wiegel, Wolfgang Hinkelbein, R. Jeffrey Karnes, Stephen A. Boorjian, Karin Haustermans, Steven Joniau, Federica Palorini, Shahrokh Shariat, Francesco Montorsi, Hein Van Poppel, Nadia Di Muzio, Riccardo Calandrino, Alberto Briganti
PurposeTo fit the individual biochemical-recurrence-free survival (bRFS) data of patients treated with post-prostatectomy radiation therapy (RT) with a comprehensive tumor control probability (TCP) model.Methods and MaterialsConsidering pre-RT prostate specific antigen (PSA) as a surrogate of the number of clonogens, bRFS may be expressed as a function of dose-per-fraction dependent radiosensitivity (αeff), the number of clonogens for pre-RT PSA=1ng/mL (C) and the fraction of patients that relapse due to clonogens outside the treated volume (K), assumed to depend (linearly or exponentially) on pre-RT PSA and Gleason score (GS). Data of 894 node-negative, ≥pT2,pN0 hormono-naive patients treated with adjuvant (n=331) or salvage (n=563) intent were available: 5-year bRFS data were fitted grouping patients according to GS (<7:392,=7:383,>7:119).ResultsMedian follow-up, pre-RT PSA and dose were 72 months, 0.25ng/mL and 66.6Gy (range:59.4-77.4Gy) respectively. Best-fit values were 0.23-0.26 Gy^-1 and 10⁷ for αeff and C for the model considering a linear dependence between K and PSA. Calibration plots showed good agreement between expected and observed incidences (slope:0.90-0.93) and moderately high discriminative power (AUC:0.68-0.69). Cross validation showed satisfactory results (average AUCs in the training/validation groups: 0.66-0.70). The resulting dose-effect curves strongly depend on pre-RT PSA and GS. bRFS rapidly decreases with PSA: the maximum obtainable bRFS (defined as 95% of the maximum) declined by about 2.7 and 4.5% for each increment of 0.1 ng/ml for GS< and ≥7 respectively.ConclusionsIndividual data were fitted by a TCP model and the resulting best-fit parameters were radiobiologically consistent. The model suggests that relapses frequently result from clonogens outside the irradiated volume, supporting the choice of lymph-nodal irradiation and/or systemic therapy for specific subgroups (GS<7:PSA>0.8-1.0ng/ml; GS≥7:PSA>0.3 ng/ml). Early RT should be preferred over delayed RT: the detrimental effect of PSA increase can never be fully compensated by increasing the dose, especially for patients with GS≥7.

Teaser

A comprehensive TCP model accurately fit the 5-year biochemical-relapse-free survival after post-prostatectomy radiotherapy of 894 ≥pT2, pN0 hormono-naive patients pooled from 5 large prospective data-bases. The model suggests that the optimal dose depends on pre-RT PSA/GS. Even when the optimal dose is delivered, the fraction of relapsing patients is never zero and dramatically increases with pre-RT PSA/GS, suggesting a potential benefit from pelvic-node irradiation and/or systemic therapy in selected groups (GS<7:PSA>0.8-1.0ng/ml; GS≥7:PSA>0.3 ng/ml).


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