title: Predicting the 5-Year Risk of Biochemical Relapse After Postprostatectomy Radiation Therapy in ≥PT2, pN0 Patients With a Comprehensive Tumor Control Probability Model.
abstract: 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.
  
  
  
  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).
  
  
  
  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 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.
  
  
  
  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.
authors: Department of Medical Physics, San Raffaele Scientific Institute, Milan, Italy. Electronic address: fiorino.claudio@hsr.it.
authors: Claudio
authors: C
authors: Fiorino
authors: Department of Medical Physics, San Raffaele Scientific Institute, Milan, Italy.
authors: Sara
authors: S
authors: Broggi
authors: Division of Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.
authors: Nicola
authors: N
authors: Fossati
authors: Department of Radiotherapy, IRCCS Ospedale San Raffaele, Milan, Italy.
authors: Cesare
authors: C
authors: Cozzarini
authors: Klinik für Radioonkologie, Medizinische Universität Wien, Wien, Austria.
authors: Gregor
authors: G
authors: Goldner
authors: Department of Radiation Oncology, University Hospital Ulm, Ulm, Germany.
authors: Thomas
authors: T
authors: Wiegel
authors: Department of Radiation Oncology, Charité Universitats Medizin, Campus Benjamin Franklin, Berlin, Germany.
authors: Wolfgang
authors: W
authors: Hinkelbein
authors: Department of Urology, Mayo Clinic Rochester, Rochester, Minnesota.
authors: R Jeffrey
authors: RJ
authors: Karnes
authors: Department of Urology, Mayo Clinic Rochester, Rochester, Minnesota.
authors: Stephen A
authors: SA
authors: Boorjian
authors: Department of Radiotherapy, University Hospitals Leuven, Leuven, Belgium.
authors: Karin
authors: K
authors: Haustermans
authors: Department of Urology, University Hospitals Leuven, Leuven, Belgium.
authors: Steven
authors: S
authors: Joniau
authors: Department of Medical Physics, San Raffaele Scientific Institute, Milan, Italy.
authors: Federica
authors: F
authors: Palorini
authors: Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna General Hospital, Vienna, Austria.
authors: Shahrokh
authors: S
authors: Shariat
authors: Division of Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.
authors: Francesco
authors: F
authors: Montorsi
authors: Department of Urology, University Hospitals Leuven, Leuven, Belgium.
authors: Hein
authors: H
authors: Van Poppel
authors: Department of Radiotherapy, IRCCS Ospedale San Raffaele, Milan, Italy.
authors: Nadia
authors: N
authors: Di Muzio
authors: Department of Medical Physics, San Raffaele Scientific Institute, Milan, Italy.
authors: Riccardo
authors: R
authors: Calandrino
authors: Division of Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.
authors: Alberto
authors: A
authors: Briganti
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000453:epidemiology* / Q000517:prevention & control*; D009367:Neoplasm Staging; D015995:Prevalence; D011379:Prognosis; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000097:blood / Q000453:epidemiology* / Q000628:therapy*; D018714:Radiotherapy, Adjuvant; D020266:Radiotherapy, Conformal; D015203:Reproducibility of Results; D018570:Risk Assessment / Q000379:methods; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D017430:Prostate-Specific Antigen