Beyond D'Amico risk classes for predicting recurrence after external beam radiotherapy for prostate cancer: the Candiolo classifier

Abstract

Background: The aim of this work is to develop an algorithm to predict recurrence in prostate cancer patients treated with radical radiotherapy, getting up to a prognostic power higher than traditional D'Amico risk classification.

Methods: Two thousand four hundred ninety-three men belonging to the EUREKA-2 retrospective multi-centric database on prostate cancer and treated with external-beam radiotherapy as primary treatment comprised the study population. A Cox regression time to PSA failure analysis was performed in univariate and multivariate settings, evaluating the predictive ability of age, pre-treatment PSA, clinical-radiological staging, Gleason score and percentage of positive cores at biopsy (%PC). The accuracy of this model was checked with bootstrapping statistics. Subgroups for all the variables' combinations were combined to classify patients into five different "Candiolo" risk-classes for biochemical Progression Free Survival (bPFS); thereafter, they were also applied to clinical PFS (cPFS), systemic PFS (sPFS) and Prostate Cancer Specific Survival (PCSS), and compared to D'Amico risk grouping performances.

Results: The Candiolo classifier splits patients in 5 risk-groups with the following 10-years bPFS, cPFS, sPFS and PCSS: for very-low-risk 90 %, 94 %, 100 % and 100 %; for low-risk 74 %, 88 %, 94 % and 98 %; for intermediate-risk 60 %, 82 %, 91 % and 92 %; for high-risk 43 %, 55 %, 80 % and 89 % and for very-high-risk 14 %, 38 %, 56 % and 70 %. Our classifier outperforms D'Amico risk classes for all the end-points evaluated, with concordance indexes of 71.5 %, 75.5 %, 80 % and 80.5 % versus 63 %, 65.5 %, 69.5 % and 69 %, respectively.

Conclusions: Our classification tool, combining five clinical and easily available parameters, seems to better stratify patients in predicting prostate cancer recurrence after radiotherapy compared to the traditional D'Amico risk classes.

Fig. 1

Candiolo nomogram. Points: bGS ≤ 6 0 pt, bGS = 3 + 4 35 pt, bGS = 4 + 3 48 pt, bGS = 8 76 pt, bGS = 9-10 106 pt; cT1 0 pt, cT2 17 pt, cT3-4 58 pt; PSA < 7 0 pt, PSA7-15 42 pt, PSA > 15 96 pt; %PC 1-20 % 0 pt, 21-50 % 29 pt, 51-80 % 50 pt, 81-100 % 81 pt; age ≥ 70 0 pt, age < 70 22 pt; very-low risk 0–56 pt, low risk 57–116 pt, intermediate risk 117–193 pt, high risk 194–262 pt, very-high risk 263–363 points

Fig. 2

bPFS (a-e), cPFS (b-f), sPFS (c-g) and PCSS (d-h) according to D’Amico classification (a-b-c-d) or to Candiolo classifier (e-f-g-h). Kaplan-Meier curves with overall and paired log-rank-test results, and Concordance Indexes in bold