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Background This study aimed to evaluate the association of recurrent molecular alterations in prostate cancer, such as ERG rearrangements and phosphatase and tensin homolog gene (PTEN) deletions, with oncologic outcomes in patients with prostate cancer treated with brachytherapy. Methods Ninety-two men underwent I-125 brachytherapy with a 145 Gy delivered dose between 2000 and 2008. Pretreatment prostate biopsies were analyzed by immunohistochemistry (IHC) and FISH for ERG rearrangement and overexpression, PTEN deletion, and expression loss. Univariable and multivariable Cox-regression analyses evaluated association of ERG and PTEN status with biochemical recurrence (BCR). Results Within a median follow-up of 73 months, 11% of patients experienced BCR. Of 80 samples with both IHC and FISH performed for ERG, 46 (57.8%) demonstrated rearrangement by FISH and 45 (56.3%) by IHC. Of 77 samples with both IHC and FISH for PTEN, 14 (18.2%) had PTEN deletion by FISH and 22 (28.6%) by IHC. No significant associations were found between ERG, PTEN status, and clinicopathologic features. Patients with concurrent ERG rearrangement and PTEN deletion demonstrated significantly worse relapse-free survival rates compared with those with ERG or PTEN wild type (P < 0.01). In multivariable Cox regression analysis adjusted for the effects of standard clinicopathologic features, combined ERG rearranged and PTEN deletion was independently associated with BCR (HR = 2.6; P = 0.02). Conclusions Concurrent ERG rearrangement and PTEN loss was independently associated with time to BCR in patients undergoing brachytherapy. Future studies are needed to validate prostate cancer molecular subtyping for risk stratification. Impact Identifying patients in the ERG-rearranged/PTEN-deleted molecular subclass may improve treatment personalization.

OBJECTIVE:\ud Low-dose-rate brachytherapy (LDR-BT) in localized prostate cancer is available since 15 years in Italy. We realized the first national multicentre and multidisciplinary data collection to evaluate LDR-BT practice, given as monotherapy, and outcome in terms of biochemical failure.\ud METHODS:\ud Between May 1998 and December 2011, 2237 patients with early-stage prostate cancer from 11 Italian community and academic hospitals were treated with iodine-125 ((125)I) or palladium-103 LDR-BT as monotherapy and followed up for at least 2 years. (125)I seeds were implanted in 97.7% of the patients: the mean dose received by 90% of target volume was 145 Gy; the mean target volume receiving 100% of prescribed dose (V100) was 91.1%. Biochemical failure-free survival (BFFS), disease-specific survival (DSS) and overall survival (OS) were estimated using Kaplan-Meier method. Log-rank test and multivariable Cox regression were used to evaluate the relationship of covariates with outcomes.\ud RESULTS:\ud Median follow-up time was 65 months. 5- and 7-year DSS, OS and BFFS were 99 and 98%, 94 and 89%, and 92 and 88%, respectively. At multivariate analysis, the National Comprehensive Cancer Network score (p < 0.0001) and V100 (p = 0.09) were correlated with BFFS, with V100 effect significantly different between patients at low risk and those at intermediate/high risk (p = 0.04). Short follow-up and lack of toxicity data represent the main limitations for a global evaluation of LDR-BT.\ud CONCLUSION:\ud This first multicentre Italian report confirms LDR-BT as an excellent curative modality for low-/intermediate-risk prostate cancer.\ud ADVANCES IN KNOWLEDGE:\ud Multidisciplinary teams may help to select adequately patients to be treated with brachytherapy, with a direct impact on the implant quality and, possibly, on outcome

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The aim of this study was to develop a model exploiting artificial neural networks (ANNs) to correlate dosimetric and clinical variables with late rectal bleeding in prostate cancer patients undergoing radical radiotherapy and to compare the ANN results with those of a standard logistic regression (LR) analysis. 718 men included in the AIROPROS 0102 trial were analyzed. This multicenter protocol was characterized by the prospective evaluation of rectal toxicity, with a minimum follow-up of 36 months. Radiotherapy doses were between 70 and 80 Gy. Information was recorded for comorbidity, previous abdominal surgery, use of drugs and hormonal therapy. For each patient, a rectal dose-volume histogram (DVH) of the whole treatment was recorded and the equivalent uniform dose (EUD) evaluated as an effective descriptor of the whole DVH. Late rectal bleeding of grade ≥ 2 was considered to define positive events in this study (52 of 718 patients). The overall population was split into training and verification sets, both of which were involved in model instruction, and a test set, used to evaluate the predictive power of the model with independent data. Fourfold cross-validation was also used to provide realistic results for the full dataset. The LR was performed on the same data. Five variables were selected to predict late rectal bleeding: EUD, abdominal surgery, presence of hemorrhoids, use of anticoagulants and androgen deprivation. Following a receiver operating characteristic analysis of the independent test set, the areas under the curves (AUCs) were 0.704 and 0.655 for ANN and LR, respectively. When evaluated with cross-validation, the AUC was 0.714 for ANN and 0.636 for LR, which differed at a significance level of p = 0.03. When a practical discrimination threshold was selected, ANN could classify data with sensitivity and specificity both equal to 68.0%, whereas these values were 61.5% for LR. These data provide reasonable evidence that results obtained with ANNs are superior to those achieved with LR when predicting late radiotherapy-related rectal bleeding. The future introduction of patient-related personal characteristics, such as gene expression profiles, might improve the predictive power of statistical classifiers. More refined morphological aspects of the dose distribution, such as dose surface mapping, might also enhance the overall performance of ANN-based predictive models.

BackgroundTo assess the relationship between dosimetric parameters and the quality of life (QL) outcomes of patients with low-intermediate-risk localised prostate cancer (LPC) treated with low-dose-rate brachytherapy (LDR-BT).Materials and methodsWe evaluated the participants in two consecutive prospective studies of the QL of patients treated with LDR-BT for LPC. QL was evaluated by means of a patient-completed questionnaire assessing non functional [physical (PHY) and psychological (PSY) well-being, physical autonomy (POW), social relationships (REL)] and functional scales [urinary (URI), rectal (REC), and sexual (SEX) function]; a scale for erectile function (ERE) was included in the second study. Urethra (D10 ≤ 210 Gy) and rectal wall constraints (V100 ≤ 0.5 cc) were used for pre-planning dosimetry and were assessed with post planning computerized tomography one month later for each patient.ResultsQL was assessed in 251 LPC patients. Dosimetry did not influence the non-functional scales. As expected, a progressive impairment in sexual and erectile function was reported one month after LDR-BT, and became statistically significant after the third year. Rectal function significantly worsened after LDR-BT, but the differences progressively decreased after the 1-year assessment. Overall urinary function significantly worsened immediately after LDR-BT and then gradually improved over the next three years. Better outcomes were reported for V100 rectal wall volumes of ≤ 0.5 cc and D10 urethra values of ≤ 210 Gy.ConclusionsThe findings of this study show that dosimetric parameters influence only functional QL outcomes while non-functional outcomes are only marginally influenced.

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