Search

Background: Salvage radiotherapy (SRT) and androgen-deprivation therapy (ADT) are widely used in routine clinical practice to treat patients with prostate cancer who develop biochemical recurrence (BCR) after radical prostatectomy (RP). However, there is no standard-of-care consensus on optimal duration ADT. Investigators propose three distinct risk groups in patients with prostate cancer treated with SRT in order to better define the indications and duration of ADT combined with SRT., Study Design: The URONCOR 06-24 trial (ClinicalTrials.gov identifier NCT05781217) is a prospective, multicentre, randomised, open-label, phase III, clinical trial. The aim of the trial is to determine the impact of short-term (6 months) vs long-term (24 months) ADT in combination with SRT on distant metastasis-free survival (MFS) in patients with prostate cancer with BCR after RP (intermediate and high risk)., Endpoints: The primary endpoint is 5-year MFS rates in patients with prostate cancer treated with long- vs short-term ADT in combination with SRT. Secondary objectives are biochemical-relapse free interval, pelvic progression-free survival, time to start of systemic treatment, time to castration resistance, cancer-specific survival, overall survival, acute and late toxicity, and quality of life., Methods and Analysis: Total of 534 patients will be randomised 1:1 to ADT 6 months or ADT 24 months with a luteinizing hormone-releasing hormone analogue in combination with SRT, stratified by risk group and pathological lymph node status., Ethics and Dissemination: The study is conducted under the guiding principles of the World Medical Association Declaration of Helsinki. The results will be disseminated at research conferences and in peer-reviewed journals., Trial Registration Number: EudraCT number 2021-006975-41., (© 2024 BJU International.)

Radical prostatectomy (RP) is one of the primary treatment options for localised prostate cancer (PCa). Despite its curative intent, 1/3 of patients will experience biochemical recurrence (BCR) during follow-up. Experts have devoted efforts to associate the influence of each individual factor with the risk of BCR to select the optimal treatment for each patient. Optimal management must aim to find a balance between delaying the onset of metastatic disease and overtreating an indolent disease with treatments that can affect quality of life of the patients. Thus far, effective treatment options for men with BCR remain controversial in terms of ideal treatment timing (adjuvant vs. salvage), radiotherapy (RT) fields and doses, selection and duration of systemic therapy and potential synergies between treatments and their therapeutic sequencing. Next-generation imaging techniques, such as Prostate-Specific Membrane Antigen Positron Emission Tomography, are used for early detection of disease progression and exact site of recurrence or progression, thereby enhancing decision making for future disease management. In this review, we evaluate available evidence of controversial topics regarding BCR after RP and explore future directions, such as prognostic and/or predictive factors of response, genetic panels, second-generation hormone treatments, ultra-hypofractionated RT and ongoing clinical trials in this clinical scenario., Competing Interests: Given his role as Editorial Board member, Felipe Couñago had no involvement in the peer-review of this article and has no access to information regarding its peer-review., (© 2023 The Author(s).)

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., (© 2020 John Wiley & Sons Ltd.)

Background/objective: 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)., Patients and Methods: 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: minimum <20 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 Fine & Gray regression model for metastasis free survival (MFS), biochemical disease-free survival (bDFS) and time to TT recovery., Results: There were no statistically significant differences in 10-year bDFS, MFS, or OS between the <20 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., Conclusions: 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., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

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., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tcr.2019.06.49). The series “Radiotherapy for Breast Cancer in Advanced Age” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2020 Translational Cancer Research. All rights reserved.)

Background: 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., Methods and Materials: 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., Results: 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 radiotherapy <30 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., Conclusions: 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., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: To present data on the late toxicity endpoints of a randomized trial (DART 01/05) conducted to determine whether long-term androgen deprivation (LTAD) was superior to short-term AD (STAD) when combined with high-dose radiation therapy (HDRT) in patients with prostate cancer (PCa)., Patients and Methods: Between November 2005 and December 2010, 355 eligible men with cT1c-T3aN0M0 PCa and intermediate-risk and high-risk factors (2005 National Comprehensive Cancer Network criteria) were randomized to 4 months of AD combined with HDRT (median dose, 78 Gy) (STAD) or the same treatment followed by 24 months of AD (LTAD). Treatment-related complications were assessed using European Organization for Research and Treatment of Cancer-Radiation Therapy Oncology Group and Common Terminology Criteria for Adverse Events v3.0 scoring schemes. Multivariate analyses for late toxicity were done using the Fine-Gray method., Results: The 5-year incidence of grade ≥2 rectal and urinary toxicity was 11.1% and 8.2% for LTAD and 7.6% and 7.3% for STAD, respectively. Compared with STAD, LTAD was not significantly associated with a higher risk of late grade ≥2 rectal toxicity (hazard ratio [HR] 1.360, 95% confidence interval [CI] 0.660-2.790, P=.410) or urinary toxicity (HR 1.028, 95% CI 0.495-2.130, P=.940). The multivariate analysis showed that a baseline history of intestinal comorbidity (HR 3.510, 95% CI 1.560-7.930, P=.025) and the rectal volume receiving >60 Gy (Vr60) (HR 1.030, 95% CI 1.001-1.060, P=.043) were the only factors significantly correlated with the risk of late grade ≥2 rectal complications. A history of previous surgical prostate manipulations was significantly associated with a higher risk of grade ≥2 urinary complications (HR 2.427, 95% CI 1.051-5.600, P=.038). Long-term AD (HR 2.090; 95% CI 1.170-3.720, P=.012) and a history of myocardial infarction (HR 2.080; 95% CI 1.130-3.810, P=.018) were significantly correlated with a higher probability of cardiovascular events., Conclusion: Long-term AD did not significantly impact urinary or rectal radiation-induced toxicity, although it was associated with a higher risk of cardiovascular events. Longer follow-up is needed to measure the impact of AD on late morbidity and non-PCa mortality., (Copyright © 2016 Elsevier Inc. All rights reserved.)