PMID- 27497691 OWN - NLM STAT- MEDLINE DCOM- 20170703 LR - 20171207 IS - 1879-355X (Electronic) IS - 0360-3016 (Linking) VI - 96 IP - 2 DP - 2016 Oct 1 TI - Predicting the 5-Year Risk of Biochemical Relapse After Postprostatectomy Radiation Therapy in >/=PT2, pN0 Patients With a Comprehensive Tumor Control Probability Model. PG - 333-340 LID - S0360-3016(16)30331-5 [pii] LID - 10.1016/j.ijrobp.2016.06.014 [doi] AB - 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 (alphaeff), 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 10(7) for alphaeff 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. CI - Copyright (c) 2016 Elsevier Inc. All rights reserved. FAU - Fiorino, Claudio AU - Fiorino C AD - Department of Medical Physics, San Raffaele Scientific Institute, Milan, Italy. Electronic address: fiorino.claudio@hsr.it. FAU - Broggi, Sara AU - Broggi S AD - Department of Medical Physics, San Raffaele Scientific Institute, Milan, Italy. FAU - Fossati, Nicola AU - Fossati N AD - Division of Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy. FAU - Cozzarini, Cesare AU - Cozzarini C AD - Department of Radiotherapy, IRCCS Ospedale San Raffaele, Milan, Italy. FAU - Goldner, Gregor AU - Goldner G AD - Klinik fur Radioonkologie, Medizinische Universitat Wien, Wien, Austria. FAU - Wiegel, Thomas AU - Wiegel T AD - Department of Radiation Oncology, University Hospital Ulm, Ulm, Germany. FAU - Hinkelbein, Wolfgang AU - Hinkelbein W AD - Department of Radiation Oncology, Charite Universitats Medizin, Campus Benjamin Franklin, Berlin, Germany. FAU - Karnes, R Jeffrey AU - Karnes RJ AD - Department of Urology, Mayo Clinic Rochester, Rochester, Minnesota. FAU - Boorjian, Stephen A AU - Boorjian SA AD - Department of Urology, Mayo Clinic Rochester, Rochester, Minnesota. FAU - Haustermans, Karin AU - Haustermans K AD - Department of Radiotherapy, University Hospitals Leuven, Leuven, Belgium. FAU - Joniau, Steven AU - Joniau S AD - Department of Urology, University Hospitals Leuven, Leuven, Belgium. FAU - Palorini, Federica AU - Palorini F AD - Department of Medical Physics, San Raffaele Scientific Institute, Milan, Italy. FAU - Shariat, Shahrokh AU - Shariat S AD - Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna General Hospital, Vienna, Austria. FAU - Montorsi, Francesco AU - Montorsi F AD - Division of Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy. FAU - Van Poppel, Hein AU - Van Poppel H AD - Department of Urology, University Hospitals Leuven, Leuven, Belgium. FAU - Di Muzio, Nadia AU - Di Muzio N AD - Department of Radiotherapy, IRCCS Ospedale San Raffaele, Milan, Italy. FAU - Calandrino, Riccardo AU - Calandrino R AD - Department of Medical Physics, San Raffaele Scientific Institute, Milan, Italy. FAU - Briganti, Alberto AU - Briganti A AD - Division of Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy. LA - eng PT - Journal Article DEP - 20160618 PL - United States TA - Int J Radiat Oncol Biol Phys JT - International journal of radiation oncology, biology, physics JID - 7603616 RN - 0 (Biomarkers, Tumor) RN - EC 3.4.21.77 (Prostate-Specific Antigen) SB - IM MH - Adult MH - Aged MH - Biomarkers, Tumor/blood MH - Disease-Free Survival MH - Female MH - Humans MH - Italy/epidemiology MH - Longitudinal Studies MH - Male MH - Middle Aged MH - *Models, Statistical MH - Neoplasm Recurrence, Local/blood/*epidemiology/*prevention & control MH - Neoplasm Staging MH - Prevalence MH - Prognosis MH - Proportional Hazards Models MH - Prostate-Specific Antigen/*blood MH - Prostatectomy MH - Prostatic Neoplasms/blood/*epidemiology/*therapy MH - Radiotherapy, Adjuvant MH - Radiotherapy, Conformal MH - Reproducibility of Results MH - Risk Assessment/methods MH - Sensitivity and Specificity EDAT- 2016/08/09 06:00 MHDA- 2017/07/04 06:00 CRDT- 2016/08/08 06:00 PHST- 2015/10/29 00:00 [received] PHST- 2016/05/23 00:00 [revised] PHST- 2016/06/10 00:00 [accepted] PHST- 2016/08/08 06:00 [entrez] PHST- 2016/08/09 06:00 [pubmed] PHST- 2017/07/04 06:00 [medline] AID - S0360-3016(16)30331-5 [pii] AID - 10.1016/j.ijrobp.2016.06.014 [doi] PST - ppublish SO - Int J Radiat Oncol Biol Phys. 2016 Oct 1;96(2):333-340. doi: 10.1016/j.ijrobp.2016.06.014. Epub 2016 Jun 18.