Predicting the 5-Year Risk of Biochemical Relapse After Postprostatectomy Radiation Therapy in ≥PT2, pN0 Patients With a Comprehensive Tumor Control Probability Model

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

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9 Scopus citations

Abstract

Purpose To fit the individual biochemical recurrence-free survival (bRFS) data from patients treated with postprostatectomy radiation therapy (RT) with a comprehensive tumor control probability (TCP) model. Methods and Materials Considering 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 = 1 ng/mL (C), and the fraction of patients who relapse because of clonogens outside the treated volume (K), assumed to depend (linearly or exponentially) on pre-RT PSA and Gleason score (GS). Data from 894 node-negative, ≥pT2, pN0 hormone-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). Results The median follow-up time, pre-RT PSA, and dose were 72 months, 0.25 ng/mL, and 66.6 Gy (range 59.4-77.4 Gy), respectively. The best-fit values were 0.23 to 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 (area under the curve [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 <7 and ≥7, respectively. Conclusions Individual 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-node irradiation, systemic therapy, or both for specific subgroups (GS <7: PSA >0.8-1.0 ng/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.

Original languageEnglish (US)
Pages (from-to)333-340
Number of pages8
JournalInternational Journal of Radiation Oncology Biology Physics
Volume96
Issue number2
DOIs
StatePublished - Oct 1 2016

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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    Fiorino, C., Broggi, S., Fossati, N., Cozzarini, C., Goldner, G., Wiegel, T., Hinkelbein, W., Karnes, R. J., Boorjian, S. A., Haustermans, K., Joniau, S., Palorini, F., Shariat, S., Montorsi, F., Van Poppel, H., Di Muzio, N., Calandrino, R., & Briganti, A. (2016). Predicting the 5-Year Risk of Biochemical Relapse After Postprostatectomy Radiation Therapy in ≥PT2, pN0 Patients With a Comprehensive Tumor Control Probability Model. International Journal of Radiation Oncology Biology Physics, 96(2), 333-340. https://doi.org/10.1016/j.ijrobp.2016.06.014