[Moderately hypofractionated dose escalation radiotherapy for localized prostate cancer, ESHYPRO: Results of a retrospective single-centre series evaluating safety and efficacy]. / Escalade de dose en radiothérapie modérément hypofractionnée pour les cancers de la prostate localisés, ESHYPRO : résultats d'une série monocentrique rétrospective évaluant la toxicité et l'efficacité.

PURPOSE: Prostate cancer is the most frequent cancer among men and radiotherapy hypofractionation regimens have become standard treatments for the localized stages, but the absence of increased risk of acute and late genitourinary or gastrointestinal toxicity of the dose escalation still must be demonstrated. MATERIAL AND METHODS: The study population included all patients with localized prostatic adenocarcinoma treated at the institut Curie from February 2016 to March 2018 by external radiation delivered by a linear accelerator using an image-guided conformal intensity modulation technique at a total dose of 75Gy in 30 fractions of 2.5Gy in the planning target volume that included the prostate and the proximal seminal vesicles, and could be paired with a prophylactic lymph node radiotherapy at 46Gy in 23 fractions with simultaneous integrated boost. RESULTS: A total of 166 patients were included. Among them, 68.6% were unfavourable intermediate or (very) high risk. The median age and follow-up were 71.4years and 3.96years. One hundred and forty-nine patients received prophylactic lymph node radiotherapy (89.8%). One hundred and thirty-one patients received hormonotherapy (78.9%). Genito-urinary toxicity events of grades 2 or above during radiotherapy, at 6months, 1year and 5years were respectively 36.7%, 8.8%, 3.1% and 4.7%. Two patients had late grade 4 toxicity at 5years (1.6%). Grade 2 gastrointestinal toxicity events during radiotherapy, 6months, 1year and 5years were respectively 15.1%, 1.9%, 14.6% and 9.3%. Of these, eight patients had grade 3 toxicity (6.2%). There was no grade 4 toxicity. Analyses did not reveal any predictive factor for toxicity. The 5-year overall, progression-free, and specific survival rates were respectively 82.4%, 85.7%, and 93.3%. Serum prostate specific antigen concentration and cardiovascular risk factors were found to be predictive factors of deterioration in overall survival (P=0.0028 for both). CONCLUSION: External radiotherapy for localized prostatic cancer with our moderately hypofractionated dose escalation regimen is well tolerated. In the absence of increased late toxicity, the analysis of the modes of long-term relapses will be interesting to determine the benefit of this dose escalation on local and distant relapses.

Salvage low-dose-rate brachytherapy for locally recurrent prostate cancer after definitive irradiation.

Purpose: The optimal management of locally recurrent prostate cancer after definitive irradiation is still unclear but local salvage treatments are gaining interest. A retrospective, single-institution analysis of clinical outcomes and treatment-related toxicity after salvage I-125 low-dose-rate (LDR) brachytherapy (BT) for locally-recurrent prostate cancer was conducted in a Comprehensive Cancer Center. Patients and methods: A total of 94 patients treated with salvage LDR-BT between 2006 and 2021 were included. The target volume was either the whole-gland +/- a boost on the GTV, the hemigland, or only the GTV. The prescribed dose ranged from 90 to 145 Gy. Toxicity was graded by Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Results: Median follow-up was 34 months. Initial radiotherapy was external beam radiotherapy in 73 patients (78 %) with a median dose of 76 Gy and I-125 BT in 21 patients (22 %) with a prescribed dose of 145 Gy. Median PSA at salvage was 3.75 ng/ml with a median interval between first and salvage irradiation of 9.4 years. Salvage brachytherapy was associated with androgen deprivation therapy for 32 % of the patients. Only 4 % of the patients were castrate-resistant. Failure free survival was 82 % at 2 years and 66 % at 3 years. The only factors associated with failure-free survival on multivariate analysis were hormonosensitivity at relapse and European Association of Urology (EAU) prognostic group. Late grade 3 urinary and rectal toxicities occurred in 12 % and 1 % of the patients respectively.No significant difference in toxicity or efficacy was observed between the three implant volume groups. Conclusion: The efficacy and toxicity results are consistent with those in the LDR group of the MASTER meta-analysis. Salvage BT confirms to be an effective and safe option for locally recurrent prostate cancer. A focal approach could be interesting to reduce late severe toxicities, especially urinary.

[Does radiation therapy for prostate cancer increase the risk of second cancers?] / La radiothérapie du cancer de la prostate augmente-t-elle le risque de seconds cancers ?

PURPOSE: The increased risk of second cancer after prostate radiotherapy is a debated clinical concern. The objective of the study was to assess the risk of occurrence of second cancers after prostate radiation therapy based on the analysis the literature, and to identify potential factors explaining the discrepancies in results between studies. MATERIALS AND METHODS: A review of the literature was carried out, comparing the occurrence of second cancers in patients all presenting with prostate cancer, treated or not by radiation. RESULTS: This review included 30 studies reporting the occurrence of second cancers in 2,112,000 patients treated or monitored for localized prostate cancer, including 1,111,000 by external radiation therapy and 103,000 by brachytherapy. Regarding external radiation therapy, the average follow-up was 7.3years. The majority of studies (80%) involving external radiation therapy, compared to no external radiation therapy, showed an increased risk of second cancers with a hazard ratio ranging from 1.13 to 4.9, depending on the duration of the follow-up. The median time to the occurrence of these second cancers after external radiotherapy ranged from 4 to 6years. An increased risk of second rectal and bladder cancer was observed in 52% and 85% of the studies, respectively. Considering a censoring period of more than 10 years after irradiation, 57% and 100% of the studies found an increased risk of rectal and bladder cancer, without any impact in overall survival. Studies of brachytherapy did not show an increased risk of second cancer. However, these comparative studies, most often old and retrospective, had many methodological biases. CONCLUSION: Despite numerous methodological biases, prostate external radiation therapy appears associated with a moderate increase in the risk of second pelvic cancer, in particular bladder cancer, without impacting survival. Brachytherapy does not increase the risk of a second cancer.