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The optimal duration of androgen deprivation combined with high-dose radiotherapy in prostate cancer remains controversial. The DART 01/05 trial was designed to determine whether long-term androgen deprivation is superior to short-term androgen deprivation when combined with high-dose radiotherapy. The 5-year results showed that 2 years of adjuvant androgen deprivation combined with high-dose radiotherapy significantly improved biochemical control, metastasis, and overall survival, especially in patients with high-risk disease. In this report, we present the 10-year final results of the trial.This open-label, phase 3, randomised, controlled trial was done in ten hospitals in Spain. The eligibility criteria included patients aged 18 years or older with histologically confirmed T1c to T3, N0, and M0 adenocarcinoma of the prostate, according to the 2002 classification of the American Joint Committee on Cancer, with intermediate-risk and high-risk factors, prostate-specific antigen (PSA) less than 100 ng/mL, and a Karnofsky performance score of at least 70%. Patients were randomly assigned (1:1) to receive 4 months of neoadjuvant and concomitant short-term androgen deprivation (STAD) plus high-dose radiotherapy (minimum dose 76 Gy; median dose 78 Gy) or to receive the same treatment followed by 24 months of adjuvant long-term androgen deprivation (LTAD), via a randomisation scheduled generated by Statistical Analysis Software programme (version 9.1) and an interactive web response system. Patients assigned to the STAD group received 4 months of neoadjuvant and concomitant androgen deprivation (oral flutamide 750 mg per day or oral bicalutamide 50 mg per day) with subcutaneous goserelin (2 months before and 2 months combined with high-dose radiotherapy). Anti-androgen therapy was added during the first 2 months of treatment. Patients assigned to LTAD continued with goserelin every 3 months for another 24 months. The primary endpoint was biochemical disease-free survival at 5 years. For this 10-year study we analysed overall survival, metastasis-free survival, biochemical disease-free survival, and cause-specific survival. Analysis was by intention to treat. This trial is closed and is registered at ClinicalTrials.gov (NCT02175212) and in the EU Clinical Trials Register (EudraCT 2005-000417-36).Between Nov 7, 2005, and Dec 20, 2010, 355 patients were enrolled. One patient in the STAD group withdrew from the trial, hence 354 participants were randomly assigned to STAD (n=177) or LTAD (n=177). The median follow-up was 119·4 months (IQR 100·6-124·3). The 10-year biochemical disease-free survival for LTAD was 70·2% (95% CI 63·1-77·3) and for STAD was 62·3% (54·9-69·7; hazard ratio [HR] 0·84; 95% CI 0·50-1·43; p=0·52). At 10 years, overall survival was 78·4% (72·1-84·8) for LTAD and 73·3% (66·6-80·0) for STAD (HR 0·84; 95% CI 0·55-1·27; p=0·40), and metastasis-free survival was 76·0% (69·4-82·7) for LTAD and 70·9% (64·0-77·8) for STAD (HR 0·90; 95% CI, 0·37-2·19; p=0·81). For the subgroup of high-risk patients, the 10-year biochemical disease-free survival was 67·2% (57·2-77·2) for LTAD and 53·7% (43·3-64·1) for STAD (HR 0·90; 95% CI 0·49-1·64; p=0·73), the 10-year overall survival was 78·5% (69·6-87·3) for LTAD and 67·0% (57·3-76·7) for STAD (HR 0·58; 95% CI 0·33-1·01; p=0·054), and the 10-year metastasis-free survival was 76·6% (95% CI 67·6-85·6) for LTAD and 65·0% (55·1-74·8) for STAD (HR 0·89; 95% CI 0·33-2·43; p=0·82). Only 11 (3%) of 354 patients died from prostate cancer, all of them in the high-risk subgroup (five in the LTAD group and six in the STAD group). 76 (21%) patients died from other causes (mainly second malignancies in 31 [9%] and cardiovascular disease in 21 [6%]). No treatment-related deaths were observed.After an extended 10-year follow-up, we were unable to support the significant benefit of LTAD reported at 5 years. However, the magnitude of the benefit was clinically relevant in high-risk patients. Intermediate-risk patients treated with high-dose radiotherapy do not benefit from LTAD. A biological characterisation with the inclusion of genomic testing is needed in the decision-making process.Grupo de Investigación en Oncología Radioterápica and Sociedad Española de Oncología Radioterápica, the National Health Investigation Fund, and AstraZeneca.

The optimal prognostic value of testosterone following androgen deprivation therapy (ADT) is controversial. We studied the effect of serum testosterone levels on clinical outcome in localized prostate cancer (PCa) treated with ADT and high-dose radiotherapy (HRT).The DART01/05 trial randomized 355 men with intermediate and high-risk PCa to 4 months of ADT plus HRT (STADT, N = 178) or the same treatment followed by 24 months of ADT (LTADT, N = 177). This study included patients treated with LTADT who had at least 3 determinations of testosterone during ADT (N = 154). Patients were stratified into 3 subgroups by testosterone level: minimum20 ng/dL; median 20-49 ng/dL; and maximum ≥50 ng/dL. Kaplan-Meyer and Cox regression analysis were used for overall survival (OS) and FineGray regression model for metastasis free survival (MFS), biochemical disease-free survival (bDFS) and time to TT recovery.There were no statistically significant differences in 10-year bDFS, MFS, or OS between the20 ng/mL and 20-49 ng/dL subgroups. Multivariate analysis showed that a median testosterone ≥50 ng/dL was significantly associated with a decrease in bDFS (HR: 6.58, 95%CI 1.28-33.76, p = 0.03). Time to testosterone recovery after ADT did not correlate with bDFS, MFS, or OS and was not significantly associated with any of the testosterone subgroups.Our results do not support the concept that additional serum testosterone suppression below 20 ng/dL is associated with better outcomes than 20-49 ng/dL. Time to testosterone recovery after ADT and HRT did not impact clinical failure.

In the management of prostate cancer , few treatments have caused as much controversy as adjuvant radiotherapy (ART) after radical prostatectomy in high-risk patients In the present article, we assess the exclusion and inclusion criteria of the 6 randomised trials and 5-year biochemical relapse-free survival and overall survival rates in order to identify the patient subgroups most likely to benefit from ART. We also evaluate treatment-related toxicity and the indications for androgen deprivation therapy . The main aim of this analysis was to determine whether the available evidence, which previously appeared to support ART, now favours early salvage radiotherapy. If so, perhaps we can finally resolve the controversy surrounding the optimal timing of postoperative radiotherapy. Sin financiación 2.954 JCR (2021) Q3, 47/90 Urology & Nephrology 0.818 SJR (2021) Q1, 19/108 Urology No data IDR 2021 UEM

Medulloblastoma (MB) is a malignant embryonal tumor that develops especially in childhood, with overall survival (OS) at 5 years of up to 70%. The objective of this study is to analyze treatment delivery variables in a retrospective cohort and evaluate the impact of these treatment quality parameters on survival. From 2000 to 2018, 40 pediatric patients with medulloblastoma, treated according to current international protocols, were retrospectively analyzed. Treatment delivery quality indicators were analyzed including the extent of surgery, radiotherapy (RT) parameters, and chemotherapy variables, related with time and dose-intensity deviations. With a median follow-up of 74 months (range, 6-195), OS at 5 years was 74 ± 7%, 81 ± 8% for standard-risk, and 55 ± 16% for high-risk patients (p = 0.090). Disease-free survival at 5 years was not significantly affected by extent of surgery (p = 0.428) and RT-related variables such as surgery-RT interval (p = 0.776) neither RT duration (p = 0.172) or maintenance chemotherapy compliance (p = 0.634). Multivariate analysis identified risk groups predictive of worse DFS (p = 0.032) and leptomeningeal dissemination associated with inferior OS (p = 0.029).Conclusion: Treatment delivery optimization has improved survival rates of patients with MB. Despite this, in our study, we have not established a clear influence of the considered radiotherapy and chemotherapy treatment quality parameters on outcomes. What is Known: • Improvement in treatment modalities during the last decades has reached a 5-year OS of up to 70% in these patients. • Extent of resection and radiotherapy parameters such as interval between surgery-radiotherapy and radiotherapy duration has been described as probable survival prognostic factors. What is New: • Differences in medulloblastoma survival rates between prospective studies and retrospective series. • The impact on survival of the three main treatment variables, surgery, radiotherapy and chemotherapy, susceptible to improvement.

The indication for salvage radiotherapy (RT) (SRT) in patients with biochemically-recurrent prostate cancer after surgery is based on prostate-specific antigen (PSA) levels at the time of biochemical recurrence. Although there are clear criteria (pT3-pT4 disease and/or positive margins) for the use of adjuvant radiotherapy, no specific clinical or tumour-related criteria have yet been defined for SRT. In retrospective series, 5-year biochemical progression-free survival (PFS) ranges from 35%-85%, depending on the PSA level at the start of RT. Two phase 3 trials have compared SRT with and without androgen deprivation therapy (ADT), finding that combined treatment (SRT+ADT) improves both PFS and overall survival. Similar to adjuvant RT, the indication for ADT is based on tumour-related factors such as PSA levels, tumour stage, and surgical margins. The number of patients referred to radiation oncology departments for SRT continues to rise. In the present article, we define the clinical, therapeutic, and tumour-related factors that we believe should be evaluated before prescribing SRT. In addition, we propose a decision algorithm to determine whether the patient is fit for SRT. This algorithm will help to identify patients in whom radiotherapy is likely to improve survival without significantly worsening quality of life.

There are few trials published on treatment in elderly women with low-risk breast cancer. Although the clinical behavior is like younger patients, there is a tendency to undertreat them, which may lead to an increase in the risk of local relapses and decrease their survival. The local recurrences omitting adjuvant treatment (tamoxifen or radiotherapy) after breast conserving surgery (BCS) even in low-risk patients is high, reaching up 20%, which is unacceptable. Although tamoxifen and radiotherapy seem to have a similar effect in reducing local recurrence with equal overall survival, the combination of both achieves the maximum benefit with local relapses of less than 2%. In recent years two studies have been published and were designed specifically for elderly patients. The CALGB 9343 and the PRIME II trials recommend omitting radiotherapy in patients with low-risk tumors treated with BCS and tamoxifen based on a similar survival, but with an increase in local relapses when radiotherapy is omitted, 10% at 10 years vs. 2%. There is no basis to ensure that a treatment with tamoxifen has less toxicity in this group of patients who are usually poly-treated, and it seems that treatment compliance is much lower than expected. The decrease in the number of sessions in external radiotherapy with hypofractionation and accelerate partial breast irradiation, especially intraoperative radiotherapy (IORT) with a single session, makes this recommendation very controversial. Elderly patients may benefit from radiation therapy after BCS.

Brachytherapy (BT) is widely used for salvage therapy in patients with biochemical failure (BF) after radiotherapy for prostate cancer (PCa). Although low-dose-rate (LDR) and high-dose-rate (HDR) BT are both used for salvage therapy, it is not clear whether there are any differences between these two approaches in terms of efficacy or toxicity in this setting. Therefore, we review the institutional experience of the members of the Urological Tumour Working Group (URONCOR) of the Spanish Society of Radiation Oncology (SEOR) to compare these two techniques.Between 2001 and 2016, 119 patients with biopsy-proven, locally-recurrent PCa underwent salvage BT (LDR, n = 44; HDR, n = 75) after primary radiotherapy. Relapse-free survival (RFS) and cause-specific survival (CSS) after salvage therapy were analyzed. Toxicity was assessed according to the RTOG scale.Median follow-up after salvage BT was 52 months. Overall, the 5-year prostate-specific antigen (PSA) RFS rate was 71% (95% CI, 65.9%-75.9%). No significant between-group differences in RFS were observed (p = 0.063). Five-year CSS for the LDR- and HDR-BT groups were 96.5% and 93%, respectively. Overall, 38 patients (32%) developed biochemical progression (Phoenix definition) after salvage BT: 14 patients (32%) in the LDR group and 24 (32.5%) in the HDR group. On the multivariate analysis, the following variables were significantly associated with progression, time to BF from primary radiotherapy30 months (p = 0.014); and post-salvage nadir PSA (p = 0.000). There were no significant between-group differences in toxicity. Overall, there were 13 cases of urethral stricture, 22 cases of urinary incontinence, and 13 cases of haematuria. Toxicity ≥grade 3 was observed in 23.5% of patients.These findings show that both HDR-BT and LDR-BT yield comparable efficacy and toxicity outcomes in patients undergoing salvage treatment for locally-recurrent prostate cancer after primary radiotherapy. Predictors of worse outcomes after salvage BT were post-salvage nadir PSA and time to BF from initial radiotherapy.

There have been few experiments on the treatment of elderly women with low-risk breast cancer. Although their clinical behaviour is similar to that of younger patients, there is a tendency to undertreat them, which may increase the risk of local relapses and reduce their survival. Even in low-risk patients, the rate of local recurrences after breast conserving surgery without adjuvant treatment (tamoxifen or radiotherapy) is high, approaching 20%, which is unacceptable. Despite the fact that tamoxifen and radiotherapy seem to have a similar impact in reducing local recurrence with similar overall survival, the combination of the two provides the best results with local relapses of less than 2%. Two studies that were designed specifically for elderly patients were published in recent years. Based on similar survival, these trials recommend omitting radiotherapy in patients with low-risk tumours treated with breast conserving surgery and tamoxifen, but with an increase in local relapses when radiotherapy is omitted, 10% at 10 years vs 2%. There is no evidence that tamoxifen treatment is less toxic in this group of patients who are typically poly-treated, and treatment compliance appears to be much lower than expected. This recommendation is highly contentious due to the reduction in the number of sessions in external radiotherapy with hypofractionation and the acceleration of partial breast irradiation, especially intraoperative radiotherapy with a single session. After breast conserving surgery, elderly patients may benefit from radiation therapy.

Este artículo se encuentra disponible en la página web de la revista en la siguiente URL: https://f6publishing.blob.core.windows.net/ba043069-cabc-42f8-9ff3-6304fb677393/WJCO-12-43.pdf The number of treatment options for metastatic hormone-sensitive prostate cancer has increased substantially in recent years. The classic treatment approach for these patients—androgen-deprivation therapy alone—is now considered suboptimal. Several randomized phase III clinical trials have demonstrated significant clinical benefits—including significantly better overall survival and quality of life—for treatments that combine androgen-deprivation therapy with docetaxel, abiraterone acetate, enzalutamide, apalutamide, and/or radiotherapy to the primary tumour. As a result, these approaches are now included in treatment guidelines and considered standard of care. However, the different treatment strategies have not been directly compared, and thus treatment selection remains at the discretion of the individual physician or, ideally, a multidisciplinary team. Given the range of available treatment approaches with varying toxicity profiles, treatment selection should be individualized based on the patient’s clinical characteristics and preferences, which implies active patient participation in the decision-making process. In the present document, we discuss the changing landscape of the management of patients with metastatic hormonesensitive prostate cancer in the context of several recently-published landmark randomized trials. In addition, we discuss several unresolved issues, including the optimal sequencing of systemic treatments and the incorporation of local treatment of the primary tumour and metastases.

Nodular lymphocytic predominance Hodgkin lymphoma (NLPHL) is a very uncommon subtype of Hodgkin lymphoma (HL), representing approximately 5% of all HL cases, with an incidence of 0.3/100,000 cases per year and with unique characteristics which distinguish it from classic Hodgkin lymphoma. Given its low frequency, there is a lack of prospective randomized studies to inform practice, the accumulated experience of academic groups being the main source of relevant information for the management of these patients. Eighty-five patients recruited by the Spanish Lymphoma Group (GOTEL) from 12 different hospitals were retrospectively analyzed to describe their sociodemographic and clinical characteristics. The median follow-up was 16 years, with a 10-year overall survive of 92.9% and 81.2% at 20 years. Five patients developed a second malignancy. No transformation to a more aggressive lymphoma was detected. A total of 31% tumor relapses was found: 77% in a single location; most of them at a supra-diaphragmatic level. Patients received different first-line treatments, and progression was observed in 3/4 (75%) of the patients who did not receive any type of treatment, 6/23 (26%) who received both chemotherapy (CH) and radiotherapy (RT), 12/43 (27%) who received RT and 7/15 (47%) that received only CH treatment. The mean time to relapse was 3 years and 47% presented relapses beyond 5 years (higher probability in stage IV p < 0.001). This is one of the longest follow-up series of NLPHL published, confirming its excellent prognosis, and that treatments may be adapted to reduce toxicity. Causes of death in these patients are varied, and the minority due to a primary malignancy relapses.

Nomograms were established to predict biochemical recurrence (BCR) after radiotherapy (RT) with a low weight of the characteristic variables of RT and androgen deprivation therapy (ADT). Our aim is to provide a new stratified tool for predicting BCR at 4 and 7 years in patients treated using RT with radical intent. A retrospective, nonrandomized analysis was performed on 5044 prostate cancer (PCa) patients with median age 70 years, who received RT—with or without ADT—between November 1992 and May 2007. Median follow-up was 5.5 years. BCR was defined as a rise in serum prostate-specific antigen (PSA) of 2 ng/ml over the post-treatment PSA nadir. Univariate association between predictor variables and BCR was assessed by the log-rank test, and three linked nomograms were created for multivariate prognosis of BCR-free survival. Each nomogram corresponds to a category of the Gleason score—either 6,7, or 8–10—and all of them were created from a single proportional hazards regression model stratified also by months of ADT (0, 1–6, 7–12, 13–24, 25–36, 36–60). The performance of this model was analyzed by calibration, discrimination, and clinical utility. Initial PSA, clinical stage, and RT dose were significant variables (p

The aim of this study was to analyze long-term outcomes and prognostic factors associated with survival in patients with locoregional oligo-recurrent (LROR) pelvic malignancies treated in a multimodal protocol. Patients with an histologic diagnosis of LROR pelvic cancer (rectal 50 %, gynecological 50 %) with absence of distant metastases, undergoing surgery with radical intent and intraoperative radiotherapy (median dose 12.5 Gy) were considered eligible for participation in this study. Additionally, 48 % received external beam radiotherapy (EBRT) (median dose 50 Gy). From 1995 to 2012, a total of 143 patients from a single institution were analyzed. With a median follow-up time of 48 months (range 2–189), 5-year locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) were 53, 44, and 46 %, respectively. On multivariate analysis, no EBRT treatment to the locoregional (p ≤ 0.001), R1 margin status (p = 0.03), time interval from primary tumor diagnosis to LROR

[This corrects the article DOI: 10.1016/j.rpor.2015.04.003.].

Purpose: To report treatment outcomes in a cohort of extreme-risk prostate cancer patients and identify a subgroup of patients with worse prognosis. Materials and methods: Extreme-risk prostate cancer patients were defined as patients with at least one extreme-risk factor: stage cT3b–cT4, Gleason score 9–10 or PSA > 50 ng/ml; or patients with 2 or more high-risk factors: stage cT2c–cT3a, Gleason 8 and PSA > 20 ng/ml. Overall survival (OS), cause-specific survival (CSS), clinical-free survival (CFS), and biochemical non-evidence of disease (bNED) survival are the four outcomes of interest in a population of 1341 patients. Results: With a median follow-up of 71.5 months, 5- and 10-year bNED survival, CFS, CSS and OS for the entire cohort were 77.1 % and 57.0, 89.2 and 78.9 %, 97.4 and 93.6 %, and 92.0 and 71.3 %, respectively. On multivariate analysis, PSA and clinical stage were associated with bNED survival. PSA and Gleason score predicted for CFS, whereas only Gleason score predicted for OS. When a simplified model was performed using the “number of risk factors” variable, this model provided the best distinction between patients with ≥2 extreme-risk factors and patients with 2 high-risk factors, showing a hazard ratio (HR) of 1.737 (p = 0.0003) for bNED survival, HR 1.743 (p = 0.0448) for OS and an HR of 3.963 (p = 0.0039) for the CSS endpoint. Conclusions: Patients presenting at diagnosis with two extreme-risk criteria have almost fourfold higher risk for prostate cancer mortality. Such patients should be considered for more aggressive multimodal treatments.

Summary Background The optimum duration of androgen deprivation combined with high-dose radiotherapy in prostate cancer remains undefined. We aimed to determine whether long-term androgen deprivation was superior to short-term androgen deprivation when combined with high-dose radiotherapy. Methods In this open-label, multicentre, phase 3 randomised controlled trial, patients were recruited from ten university hospitals throughout Spain. Eligible patients had clinical stage T1c–T3b N0M0 prostate adenocarcinoma with intermediate-risk and high-risk factors according to 2005 National Comprehensive Cancer Network criteria. Patients were randomly assigned (1:1) using a computer-generated randomisation schedule to receive either 4 months of androgen deprivation combined with three-dimensional conformal radiotherapy at a minimum dose of 76 Gy (range 76–82 Gy; short-term androgen deprivation group) or the same treatment followed by 24 months of adjuvant androgen deprivation (long-term androgen deprivation group), stratified by prostate cancer risk group (intermediate risk vs high risk) and participating centre. Patients assigned to the short-term androgen deprivation group received 4 months of neoadjuvant and concomitant androgen deprivation with subcutaneous goserelin (2 months before and 2 months combined with high-dose radiotherapy). Anti-androgen therapy (flutamide 750 mg per day or bicalutamide 50 mg per day) was added during the first 2 months of treatment. Patients assigned to long-term suppression continued with the same luteinising hormone-releasing hormone analogue every 3 months for another 24 months. The primary endpoint was biochemical disease-free survival. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT02175212. Findings Between Nov 7, 2005, and Dec 20, 2010, 178 patients were randomly assigned to receive short-term androgen deprivation and 177 to receive long-term androgen deprivation. After a median follow-up of 63 months (IQR 50–82), 5-year biochemical disease-free survival was significantly better among patients receiving long-term androgen deprivation than among those receiving short-term treatment (90% [95% CI 87–92] vs 81% [78–85]; hazard ratio [HR] 1·88 [95% CI 1·12–3·15]; p=0·01). 5-year overall survival (95% [95% CI 93–97] vs 86% [83–89]; HR 2·48 [95% CI 1·31–4·68]; p=0·009) and 5-year metastasis-free survival (94% [95% CI 92–96] vs 83% [80–86]; HR 2·31 [95% CI 1·23–3·85]; p=0·01) were also significantly better in the long-term androgen deprivation group than in the short-term androgen deprivation group. The effect of long-term androgen deprivation on biochemical disease-free survival, metastasis-free survival, and overall survival was more evident in patients with high-risk disease than in those with low-risk disease. Grade 3 late rectal toxicity was noted in three (2%) of 177 patients in the long-term androgen deprivation group and two (1%) of 178 in the short-term androgen deprivation group; grade 3–4 late urinary toxicity was noted in five (3%) patients in each group. No deaths related to treatment were reported. Interpretation Compared with short-term androgen deprivation, 2 years of adjuvant androgen deprivation combined with high-dose radiotherapy improved biochemical control and overall survival in patients with prostate cancer, particularly those with high-risk disease, with no increase in late radiation toxicity. Longer follow-up is needed to determine whether men with intermediate-risk disease benefit from more than 4 months of androgen deprivation. Funding Spanish National Health Investigation Fund, AstraZeneca.