Different outcomes among favourable and unfavourable intermediate-risk prostate cancer patients treated with hypofractionated radiotherapy and androgen deprivation therapy

Bracci et al. Radiation Oncology (2016) 11:78 DOI 10.1186/s13014-016-0656-0 RESEARCH Open Access Different outcomes among favourable and unfavourable intermediate-risk prostate cancer patients treated with hypofractionated radiotherapy and androgen deprivation therapy Stefano Bracci*, Mattia F. Osti, Linda Agolli, Luca Bertaccini, Vitaliana De Sanctis and Maurizio Valeriani Abstract Background: to evaluate the role of a risk stratification system in intermediate-risk prostate cancer (PCa) treated with hypofractionated radiotherapy (HyRT). Methods: 131 patients affected by intermediate-risk PCa were treated with HyRT at the total dose of 54,75 Gy in 15 fraction plus 9 months of androgen deprivation therapy (ADT). Patients were classified as favourable risk (FIR) if they had a single NCCN intermediate-risk factor (IRF), a Gleason score ≤3 + 4 = 7, and <50 % of biopsy cores containing cancer (PBCC). If these criteria were not met were classified as unfavourable risk (UIR). Univariate and multivariate analyses using Cox proportional hazards model were calculated for biochemical recurrence-free survival (bRFS), the risk of local recurrence and metastasis-free survival (MFS). Results: After a median follow-up of 56.7 months (range 9.8 to 93.7 months), 11 patients (8.4 %) died, of whom 2 (1.5 %) for PCa. In the univariate analysis, Gleason score, PPBCs, IRFs and PSA at first follow-up were prognostic factors for bRFS and LF while Gleason score, PPBCs and PSA at first follow-up were significant predictor for MFS. In the multivariate analysis only the PSA at first follow-up resulted a prognostic factor for bRFS and MFS. Patients with a value of PSA at first follow-up <0.7 ng/mL respect to those with PSA ≥0,7 ng/mL had a 5y-bRFS of 93.3 % vs. 57. 5 %, 5y-MFS of 99.0 % vs. 78.9 % and 5y-LF of 5.8 % vs. 38.3 %. Patients in the UIR PCa group with a PSA value <0. 7 ng/mL at first follow-up had significant better bRFS, LF and MFS. Conclusions: Risk factors currently not included in the guidelines are useful to stratify patients with intermediate-risk PCa in two groups of different prognosis even when HyRT is delivered. PSA at first follow-up is useful in UIR PCa to guide the overall length of ADT. Keywords: Intermediate-risk prostate cancer, Hypofractionated radiotherapy, Prognostic factors, 3D-CRT * Correspondence: Institute of Radiation Oncology, Sant’Andrea Hospital, Via di Grottarossa 1035-1039, 00189 Rome, Italy © 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Bracci et al. Radiation Oncology (2016) 11:78 Background Surgery and radiotherapy (RT) are the most commonly used treatments in the management of prostate cancer (PCa). Factor such as clinical stage, Gleason score and the value of PSA at diagnosis are usually used to categorize PCa in class of risk that are useful to guide therapy [1]. Conformal high dose RT delivered with conventional fractionation results in a significant biochemical control with acceptable toxicities and currently represents the standard therapy when RT is chosen as primary treatment [2–5]. However, hypofractionated RT (HyRT) that uses higher doses per fraction has been suggested as an attractive option. In fact, due to the slow proliferation rate of PCa cells that reflects in a lower α/β ratio than the surrounding healthy tissue, the use of doses higher than 2 Gy per fraction would give a therapeutic advantage in terms of reduced late damage and/or higher local control [6–8]. Unfortunately RT alone may not be sufficient for treating PCa and the addition of androgen deprivation therapy (ADT) in association to radiation is often a requisite. While ADT is not necessary in low-risk PCa as radiation alone provides high clinical response, short course ADT (i.e. for 4–6 months) and long course ADT (i.e. for 2–3 years) are usually needed to treat intermediate and high-risk PCa, respectively [9–14]. Differently from low and high-risk PCa, it has been suggested that intermediate-risk PCa has a particularly inhomogeneous behaviour with the consequence that the association of short course ADT to RT may results in an overtreatment or undertreatment of these patients [15]. Studies have found several predictors of outcome, currently not used to stratify PCa patients, that could be used for this purpose such as the number of intermediate-risk factors (IRFs), percentage of positive biopsy cores (PPBC), the primary Gleason pattern [16–20]. On this basis, recently a new classification for intermediate-risk PCa has been proposed that divide this category in favourable (FIR) and unfavourable intermediate-risk (UIR) [21]. The proposed risk stratification is of importance as it could have a clinical impact considering that FIR may beneficiate from RT alone as they behave as low-risk PCa while UIR from RT in association to ADT as they behave as intermediate or highrisk PCa [15, 21]. In this study we evaluated the impact of the proposed classification when HyRT is delivered, since this approach may be associated with hypothetical improved local control respect to conventional fractionated RT, in a population of patients with intermediate-risk prostate cancer treated with the same HyRT schedule + ADT. Moreover other variables that could be considered as potential predictors of response were investigated. Page 2 of 8 Methods Patients’ characteristics Between March 2007 and March 2014, 131 consecutive patients affected by intermediate risk prostate cancer were evaluated. The data were prospectively collected and retrospectively analysed after the approval of our Institutional Review Board (IRB) of Sant'Andrea Hospital. Written consent was obtained from all patients. All patients had histologically confirmed prostate cancer diagnosed with transrectal ultrasound (TRUS) guided biopsies. For all patients were obtained a complete history, physical examination with digital rectal examination, PSA level, total body computed tomography scan with iodine-based contrast and 99mTc bone scan. Local staging was assessed with TRUS or multiparametric magnetic resonance imaging (MRI) of the pelvis including diffusion-weighted imaging and dynamic contrast-enhanced study. According to the National Comprehensive Cancer Network (NCCN) guidelines, intermediate risk group includes patients with any clinical T2b–T2c prostate cancer or Gleason Score equal to 7 or pretreatment PSA value ranging from 10 to 20 ng/mL [1]. PCa were classified as F (...truncated)