Outcome of Endometrial Cancer Stage IIIA with Adnexa or Serosal Involvement Only

Objective. The aim of this study is to look at possible differences in outcome between serosa and adnexal involvement stage IIIA endometrial carcinoma. Methods. 67 patients with stage IIIA endometrial carcinoma were included, 46 with adnexal involvement and 21 with serosa. A central histopathological review was performed. Results. The 7-year locoregional failure rate was (LRFR) 2.2% for adnexal involvement and 16.0% for involvement of the serosa (P = .0522). The 7-year distant metastasis-free survival was 72.7% for adnexal involvement and 58.7% for serosa (P = .3994). The 7-year disease-specific survival (DSS) was 71.8% for patients with adnexal involvement and 75.4% for patients with serosa. Conclusion. Endometrial carcinoma stage IIIA with involvement of the adnexa or serosa showed to have a comparable disease-specific survival. Locoregional control was worse for serosa involvement compared to adnexa

Short Androgen Suppression and Radiation Dose Escalation in Prostate Cancer:12-Year Results of EORTC Trial 22991 in Patients With Localized Intermediate-Risk Disease

The European Organisation for Research and Treatment of Cancer (EORTC) trial 22991 (NCT00021450) showed that 6 months of concomitant and adjuvant androgen suppression (AS) improves event- (EFS, Phoenix) and clinical disease-free survival (DFS) of intermediate- and high-risk localized prostatic carcinoma, treated by external-beam radiotherapy (EBRT) at 70-78 Gy. We report the long-term results in intermediate-risk patients treated with 74 or 78 Gy EBRT, as per current guidelines. Of 819 patients randomly assigned between EBRT or EBRT plus AS started on day 1 of EBRT, 481 entered with intermediate risk (International Union Against Cancer TNM 1997 cT1b-c or T2a with prostate-specific antigen (PSA) ≥ 10 ng/mL or Gleason ≤ 7 and PSA ≤ 20 ng/mL, N0M0) and had EBRT planned at 74 (342 patients, 71.1%) or 78 Gy (139 patients, 28.9%). We report the trial primary end point EFS, DFS, distant metastasis-free survival (DMFS), and overall survival (OS) by intention-to-treat stratified by EBRT dose at two-sided α = 5%. At a median follow-up of 12.2 years, 92 of 245 patients and 132 of 236 had EFS events in the EBRT plus AS and EBRT arm, respectively, mostly PSA relapse (48.7%) or death (45.1%). EBRT plus AS improved EFS and DFS (hazard ratio [HR] = 0.53; CI, 0.41 to 0.70; P < .001 and HR = 0.67; CI, 0.49 to 0.90; P = .008). At 10 years, DMFS was 79.3% (CI, 73.4 to 84.0) with EBRT plus AS and 72.7% (CI, 66.2 to 78.2) with EBRT (HR = 0.74; CI, 0.53 to 1.02; P = .065). With 140 deaths (EBRT plus AS: 64; EBRT: 76), 10-year OS was 80.0% (CI, 74.1 to 84.7) with EBRT plus AS and 74.3% (CI, 67.8 to 79.7) with EBRT, but not statistically significantly different (HR = 0.74; CI, 0.53 to 1.04; P = .082). Six months of concomitant and adjuvant AS statistically significantly improves EFS and DFS in intermediate-risk prostatic carcinoma, treated by irradiation at 74 or 78 Gy. The effects on OS and DMFS did not reach statistical significance

Patients' and clinicians' preferences in adjuvant treatment for high-risk endometrial cancer:Implications for shared decision making

Background. Decision making regarding adjuvant therapy for high-risk endometrial cancer is complex. The aim of this study was to determine patients' and clinicians' minimally desired survival benefit to choose chemoradiotherapy over radiotherapy alone. Moreover, influencing factors and importance of positive and negative treatment effects (i.e. attribute) were investigated. Methods. Patients with high-risk endometrial cancer treated with adjuvant pelvic radiotherapy with or without chemotherapy and multidisciplinary gynaecologic oncology clinicians completed a trade-off questionnaire based on PORTEC-3 trial data. Results. In total, 171 patients and 63 clinicians completed the questionnaire. Median minimally desired benefit to make chemoradiotherapy worthwhile was significantly higher for patients versus clinicians (10% vs 5%, p = 0.02). Both patients and clinicians rated survival benefit most important during decision making, followed by long-term symptoms. Older patients (OR 0.92 [95%CI 0.87 & ndash;0.97]; p = 0.003) with comorbidity (OR 0.34 [95% CI 0.12 & ndash;0.89]; p = 0.035) had lower preference for chemoradiotherapy, while patients with better numeracy skills (OR 1.2 [95%CI 1.05 & ndash;1.36], p = 0.011) and chemoradiotherapy history (OR 25.0 [95%CI 8.8 & ndash;91.7]; p < 0.001) had higher preference for chemoradiotherapy. & nbsp;Conclusions. There is a considerable difference in minimally desired survival benefit of chemoradiotherapy in high-risk endometrial cancer among and between patients and clinicians. Overall, endometrial cancer patients needed higher benefits than clinicians before preferring chemoradiotherapy. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/)

Clinical Behavior and Molecular Landscape of Stage I p53-Abnormal Low-Grade Endometrioid Endometrial Carcinomas

PURPOSE: The clinical significance of the p53-abnormal (p53abn) molecular subtype in stage I low-grade endometrioid endometrial carcinoma (EEC) is debated. We aimed to review pathologic and molecular characteristics, and outcomes of stage I low-grade p53abn EEC in a large international cohort. EXPERIMENTAL DESIGN: Previously diagnosed stage I p53abn EC (POLE-wild-type, mismatch repair-proficient) low-grade EEC from Canadian retrospective cohorts and PORTEC-1&2 trials were included. Pathology review was performed by six expert gynecologic pathologists blinded to p53 status. IHC profiling, next-generation sequencing, and shallow whole-genome sequencing was performed. Kaplan-Meier method was used for survival analysis. RESULTS: We identified 55 stage I p53abn low-grade EEC among 3,387 cases (2.5%). On pathology review, 17 cases (31%) were not diagnosed as low-grade EEC by any pathologists, whereas 26 cases (47%) were diagnosed as low-grade EEC by at least three pathologists. The IHC and molecular profile of the latter cases were consistent with low-grade EEC morphology (ER/PR positivity, patchy p16 expression, PIK3CA and PTEN mutations) but they also showed features of p53abn EC (TP53 mutations, many copy-number alterations). These cases had a clinically relevant risk of disease recurrence (5-year recurrence-free survival 77%), with pelvic and/or distant recurrences observed in 12% of the patients. CONCLUSIONS: A subset of p53abn EC is morphologically low-grade EEC and exhibit genomic instability. Even for stage I disease, p53abn low-grade EEC are at substantial risk of disease recurrence. These findings highlight the clinical relevance of universal p53-testing, even in low-grade EEC, to identify women at increased risk of recurrence

PORTEC-4a: International randomized trial of molecular profile-based adjuvant treatment for women with high-intermediate risk endometrial cancer

Background Vaginal brachytherapy is currently recommended as adjuvant treatment in patients with highintermediate risk endometrial cancer to maximize local control and has only mild side effects and no or limited impact on quality of life. However, there is still considerable overtreatment and also some undertreatment, which may be reduced by tailoring adjuvant treatment to the patients’ risk of recurrence based on molecular tumor characteristics. Primary objectives To compare the rates of vaginal recurrence in women with high-intermediate risk endometrial cancer, treated after surgery with molecularintegrated risk profile-based recommendations for either observation, vaginal brachytherapy or external pelvic beam radiotherapy or with standard adjuvant vaginal brachytherapy Study hypothesis Adjuvant treatment based on a molecular-integrated risk profile provides similar local control and recurrence-free survival as current standard adjuvant brachytherapy in patients with high-intermediate risk endometrial cancer, while sparing many patients the morbidity of adjuvant t

Long-term results of the Dutch randomized prostate cancer trial: Impact of dose-escalation on local, biochemical, clinical failure, and survival

Purpose: Nowadays, advanced irradiation techniques make it possible to escalate safely the dose in prostate cancer. We studied the effect of a higher dose on tumor control in a randomized trial with a median follow-up of 110 months. Patients and methods: Patients with T1b-T4NO prostate cancer (n = 664) were randomized between 78 Gy and 68 Gy. Primary endpoint was biochemical and/or clinical failure (BCF) according to the American Society for Therapeutic Radiology and Oncology (ASTRO) guidelines (3 consecutive rises), and to Phoenix (nadir plus 2 mu g/L). Secondary endpoints were clinical failure (CF), local failure (LF), prostate cancer death (PCD), and overall survival (OS). Explorative subgroup analyses were performed. Results: BCF rate (HR = 0.8; 20% less events) and LF rate (HR = 0.5; 50% less events) were significantly lower in the 78 Gy arm (p < 0.05). CF, PCD and OS were similar in both arms. A significant heterogeneity of treatment effect was found for PSA cutoffs between 7 and 10 mu g/L. Conclusion: We observed significantly less BCF and LF in the high-dose arm. This suggests improvement of the therapeutic ratio. However, we observed similar rates of CF and PCD at the current update. More follow-up is needed to investigate which patients benefit in terms of prolonged OS. (C) 2013 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 110 (2014) 104-10

Less gastrointestinal toxicity after adjuvant radiotherapy on a small pelvic field compared to a standard pelvic field in patients with endometrial carcinoma

Objective: Radiotherapy is associated with short-term and long-term morbidity. This study compared toxicity rates among patients with endometrial carcinoma (EC) treated with adjuvant external beam radiation therapy (EBRT) on a small pelvic field (SmPF) in comparison with a standard pelvic field (StPF) or an extended field (EF). Methods: Patients with EC preoperatively diagnosed with high-grade histological disease (grade 3 endometrioid, papillary serous, clear cell, and mixed tumor type) or cervical involvement were treated with total abdominal hysterectomy, bilateral salpingo-oophorectomy, and lymphadenectomy in the University Medical Center Groningen between 1999 and 2008. Patients who received adjuvant EBRT were included in this study. External beam radiation therapy on SmPF (includes only the central pelvis and proximal vagina) was applied in case of negative lymph nodes after adequate lymphadenectomy (>= 10 lymph nodes removed at the bilateral obturator and external iliac nodal stations). In case of positive pelvic lymph nodes or inadequate lymphadenectomy, EBRT on StPF was given. External beam radiation therapy on EF was applied in case of common iliac and/or para-aortic lymph node metastases. Retrospectively, using the Common Terminology Criteria for Adverse Events v3.0, acute toxicity was scored during radiotherapy, whereas late toxicity was scored, from 3 months onward after treatment. Results: Toxicity could be evaluated in 75 patients treated with SmPF (n = 33), StPF (n = 28), and EF EBRT (n = 14). Most patients with late adverse events had also reported toxicity during radiotherapy (71%). The most common late adverse events were gastrointestinal tract related, more frequently present in the StPF group (60.7%) compared to SmPF (33.3%; P = 0.032). In particular, nausea and anorexia were more frequent in the StPF group (32.1%) compared to the SmPF group (3.0%; P = 0.004), as well as ileus (14.3% vs 0%, P = 0.039, respectively). Conclusions: Treatment with adjuvant EBRT on SmPF results in less gastrointestinal late adverse events compared to treatment with EBRT on StPF in patients with surgically staged EC

The number of metastatic sites for stage IIIA endometrial carcinoma, endometrioid cell type, is a strong negative prognostic factor

The aim of this study was to look at the impact of the number of sites with tumour involvement on outcome for patients with stage IIIA endometrioid-type endometrial carcinoma.\ud \ud Patients and methods: 141 patients stage IIIA were included. A central histopathological review was performed. Patients staged solely on the presence of a positive peritoneal washing were excluded. Follow-up ranged from 2 to 217 months with a median of 43 months. Endpoints of the study were locoregional recurrence rates, distant metastasis-free survival (DMFS), disease-free survival (DFS) and disease-specific survival (DSS).\ud \ud Results: In multivariate analyses the number of involved sites showed to be the only independent significant variable for DMFS, DFS, and DSS with a Hazard Ratio of 2.1, 2.2, and 2.2, respectively. The DSS was significantly related to the number of involved sites, with a 5-year DSS of 70.4% for one site, 42.8% for two sites, and 43.9% for three sites, respectively (p = 0.001).\ud \ud Conclusion: The number of involved sites outside the corpus uterine for stage IIIA seems to be a strong negative prognostic factor for stage IIIA endometrial carcinoma