Radical cystectomy is the most commonly used definitive local treatment for muscle-invasive bladder cancer (MIBC), yet it carries substantial perioperative complication risk, alongside major changes in urinary and sexual function. Chemoradiotherapy (CRT) is used as a bladder-sparing alternative but is usually reserved for small, solitary tumors. Highly active systemic induction therapy could enable bladder preservation for patients with more advanced tumors and reduce recurrence risk. We previously demonstrated high activity of preoperative ipilimumab (3 mg kg-1) plus nivolumab in patients with stage III MIBC. Given this high activity, the single-arm, multicenter phase 2 INDIBLADE trial aimed to provide effective bladder-sparing treatment to patients with stage II/III (cT2-4aN0-2, n = 50) MIBC, using induction ipilimumab (3 mg kg-1) plus nivolumab followed by CRT. After a median follow-up of 28.7 months, the primary endpoint of estimated 2-year bladder-intact event-free survival (BI-EFS) was met at 78% (95% confidence interval (CI): 0.67-0.9, P < 0.001). Secondary endpoints included overall survival, safety and the predictive value of circulating tumor DNA (ctDNA). Two-year overall survival was 96% (95% CI: 0.91-1). Grade 3-4 immune-related adverse events occurred in 24% of patients; grade 3-4 CRT-related adverse events occurred in 7% of patients. Absence of detectable ctDNA after induction immunotherapy was associated with BI-EFS (hazard ratio 8.3, 95% CI: 1.38-50.36, P = 0.02). In conclusion, our results show that induction combination immunotherapy followed by CRT is an effective bladder-sparing treatment in MIBC, and response can be monitored by ctDNA. ClinicalTrials.gov identifier: NCT05200988 .

Background and objective: Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT) and new treatment modalities have expanded the possibilities for diagnosing and managing metastatic prostate cancer, but have also raised questions about their implementation in daily clinical practice. We sought consensus on definitions, preferred imaging modality for staging, and treatment selection in the era of next-generation imaging. Methods: A modified Delphi method involved two voting rounds and a face-to-face multidisciplinary meeting with 40 Dutch prostate cancer (PCa) experts. Consensus was reached if ≥75% of the panellists chose the same option. Appropriateness was assessed by the RAND Corporation/University of California Los Angeles appropriateness method. Key findings and limitations: There was consensus on performing metastatic screening with PSMA-PET/CT for unfavourable intermediate- or high-risk PCa. PSMA-PET/CT findings were considered feasible for determining treatment in synchronous metastatic hormone-sensitive prostate cancer, but there was no agreement on the validity of the CHAARTED criteria for interpreting the PSMA-PET/CT findings. If the PSMA-PET/CT findings led to upstaging after conventional imaging, 76% of panellists would opt for treatment intensification. In case of downstaging, 71% would choose for deintensification. Panellists would generally treat patients based on metastatic disease volume as per the CHAARTED criteria, except for bulky low-volume disease (LVD) and LVD with multiple (more than ten) bone metastases, all within the axial skeleton. This would be classified as LVD but treated as high-volume disease. Limitations are that the statements are largely consensus based and originate from a national (Dutch) perspective. Conclusions and clinical implications: PSMA-PET/CT was considered the preferred modality for initial PCa staging, which is nowadays the standard of care in The Netherlands. The majority of panellists would incorporate PSMA-PET/CT findings for treatment planning, including intensification and deintensification, but the criteria for interpreting metastatic disease volume on PSMA-PET/CT are still uncertain. Patient summary: A group of Dutch medical specialists discussed on how to diagnose metastatic hormone-sensitive prostate cancer and choose the most appropriate treatment for patients with this condition. It was concluded that imaging based on Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) helps determine appropriate treatment options, with most experts supporting treatment adjustments based on PSMA-PET/computed tomography (CT) results. However, there is still some uncertainty about the criteria for interpreting the extent of metastatic disease with PSMA-PET/CT.

INTRODUCTION:Adjuvant chemotherapy in the treatment of endometrial cancer can be difficult to tolerate for older women. This study examined age-related differences in patient preferences for chemotherapy in women with high-risk endometrial cancer. METHODS:We re-analyzed data from the cross-sectional patient preference study PRETEC-2 to determine the difference between three age groups in minimally desired survival benefit of chemotherapy. For this, patients with high-risk endometrial cancer treated with adjuvant pelvic radiotherapy with or without chemotherapy completed a treatment trade-off questionnaire. Patients also rated the importance they attributed to treatment duration and acute and late side-effects for their decision on chemotherapy, which we analyzed by age group. RESULTS:A total of 171 patients (23% <60 years, 40% 60-69 years and 37% ≥70 years) were included in the analysis. Older patients had a significantly higher median minimally desired survival benefit for preferring chemoradiotherapy (5% for <60 years, 8% for 60-69 years and 15% for patients ≥70 years; (p<0.001)), and had the largest variability in minimally desired survival benefit. For a real-life five-year survival benefit of 5%, fewer older patients preferred the addition of chemotherapy to their treatment regimen (61.5% for <60 years, 45.6% for 60-69 years and 21.9% for ≥70 years; p<0.001). Furthermore, older patients rated both treatment duration (p=0.001) and long-term tingling or numbness (p=0.005) as significantly more important than their younger counterparts. CONCLUSION:There is more heterogeneity in the desired benefit of chemotherapy among patients aged 70 years or more compared to younger patients. This underlines the importance of recognizing individual differences and the need for shared decision-making.

Background and purpose: The target structures for cervix brachytherapy are segmented by radiation oncologists using imaging and clinical information. At the first fraction, this is performed manually from scratch. For subsequent fractions the first fraction segmentations are rigidly propagated and edited manually. This process is time-consuming while patients wait immobilized. In this work, we evaluate the potential clinical impact of using population-based and patient-specific auto-segmentations as a starting point for target segmentation of the second fraction. Materials and method: For twenty-eight patients with locally advanced cervical cancer, treated with MRI-guided brachytherapy, auto-segmentations were retrospectively generated for the second fraction image using two approaches: 1) population-based model, 2) patient-specific models fine-tuned on first fraction information. A radiation oncologist manually edited the auto-segmentations to assess model-induced bias. Pairwise geometric and dosimetric comparisons were performed for the automatic, edited and clinical structures. The time spent editing the auto-segmentations was compared to the current clinical workflow. Results: The edited structures were more similar to the automatic than to the clinical structures. The geometric and dosimetric differences between the edited and the clinical structures were comparable to the inter-observer variability investigated in literature. Editing the auto-segmentations was faster than the manual segmentation performed during our clinical workflow. Patient-specific auto-segmentations required less edits than population-based structures. Conclusions: Auto-segmentation introduces a bias in the manual delineations but this bias is clinically irrelevant. Auto-segmentation, particularly patient-specific fine-tuning, is a time-saving tool that can improve treatment logistics and therefore reduce patient burden during the second fraction of cervix brachytherapy.

Background and purpose: Existing methods for quality assurance of the radiotherapy auto-segmentations focus on the correlation between the average model entropy and the Dice Similarity Coefficient (DSC) only. We identified a metric directly derived from the output of the network and correlated it with clinically relevant metrics for contour accuracy.Materials and Methods: Magnetic Resonance Imaging auto-segmentations were available for the gross tumor volume for cervical cancer brachytherapy (106 segmentations) and for the clinical target volume for rectal cancer external-beam radiotherapy (77 segmentations). The nnU-Net's output before binarization was taken as a score map. We defined a metric as the mean of the voxels in the score map above a threshold (lambda). Comparisons were made with the mean and standard deviation over the score map and with the mean over the entropy map. The DSC, the 95th Hausdorff distance, the mean surface distance (MSD) and the surface DSC were computed for segmentation quality. Correlations between the studied metrics and model quality were assessed with the Pearson correlation coefficient (r). The area under the curve (AUC) was determined for detecting segmentations that require reviewing.Results: For both tasks, our metric (lambda = 0.30) correlated more strongly with the segmentation quality than the mean over the entropy map (for surface DSC, r > 0.65 vs. r < 0.60). The AUC was above 0.84 for detecting MSD values above 2 mm.Conclusions: Our metric correlated strongly with clinically relevant segmentation metrics and detected segmentations that required reviewing, indicating its potential for automatic quality assurance of radiotherapy target auto-segmentations.

BACKGROUND:Current treatment options for patients with locally advanced vulvar cancer are limited and associated with high morbidity. Therefore, it is important to develop new and safe treatment strategies for this vulnerable patient group. PRIMARY OBJECTIVE:To compare the efficacy and safety of neoadjuvant chemotherapy followed by surgery with definitive chemoradiation in patients with locally advanced vulvar cancer. STUDY HYPOTHESIS:Neoadjuvant chemotherapy followed by surgery is oncologically safe, potentially more effective than primary chemoradiation in establishing long lasting locoregional control, and associated with an improved quality of life. TRIAL DESIGN:This study is a multicenter, prospective, phase II randomized controlled trial. Patients will be randomized 1:1 to the standard treatment arm (primary chemoradiation, consisting of a tumor dose of 64.5 Gy in 30 fractions of external beam radiotherapy with weekly cisplatin for 6 weeks) or the experimental treatment arm (neoadjuvant chemotherapy, consisting of carboplatin and paclitaxel in a 3 weekly scheme, followed by surgery). MAJOR INCLUSION/EXCLUSION CRITERIA:Eligible patients must have a histologically confirmed primary or recurrent locally advanced squamous cell carcinoma of the vulva (International Federation of Gynecology and Obstetrics (FIGO) stages Ib-Iva; Lesions larger than 2 cm in size or stromal invasion larger than 1 mm (T1b or higher), any status of lymph node involvement (any N), no distant metastasis including pelvic lymph nodes (M0)) with the size or localization of the tumor requiring treatment through primary chemoradiation or extensive surgery. Patients with documented metastases of the pelvic lymph nodes will be excluded from participation in this study. PRIMARY ENDPOINT:Locoregional control at 24 months. SAMPLE SIZE:98 patients will be included in the study. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS:Expected complete accrual in 2028 with presentation of results by 2030. TRIAL REGISTRATION:ClinicalTrials.gov NCT05905315.

Background and objective: Owing to the greater use of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) in patients with biochemical recurrence (BCR) of prostate cancer (PCa) after robot-assisted radical prostatectomy (RARP), patient selection for local salvage radiation therapy (sRT) has changed. Our objective was to determine the short-term efficacy of sRT in patients with BCR after RARP, and to develop a novel nomogram predicting BCR-free survival after sRT in a nationwide contemporary cohort of patients who underwent PSMA PET/CT before sRT for BCR of PCa, without evidence of metastatic disease. Methods: All 302 eligible patients undergoing PCa sRT in four reference centers between September 2015 and August 2020 were included. We conducted multivariable logistic regression analysis using a backward elimination procedure to develop a nomogram for predicting biochemical progression of PCa, defined as prostate-specific antigen (PSA) >= 0.2 ng/ml above the post-sRT nadir within 1 yr after sRT. Key findings and limitations: Biochemical progression of disease within 1 yr after sRT was observed for 56/302 (19%) of the study patients. The final predictive model included PSA at sRT initiation, pathological grade group, surgical margin status, PSA doubling time, presence of local recurrence on PSMA PET/CT, and the presence of biochemical persistence (first PSA result >= 0.1 ng/ml) after RARP. The area under the receiver operating characteristic curve for this model was 0.72 (95% confidence interval 0.64-0.79). Using our nomogram, patients with a predicted risk of >20% had a 30.8% chance of developing biochemical progression within 1 yr after sRT. Conclusions: Our novel nomogram may facilitate better patient counseling regarding early oncological outcome after sRT. Patients with high risk of biochemical progression may be candidates for more extensive treatment. Patient summary: We developed a new tool for predicting cancer control outcomes of radiotherapy for patients with recurrence of prostate cancer after surgical removal of their prostate. This tool may help in better counseling of these patients with recurrent cancer regarding their early expected outcome after radiotherapy. (c) 2024 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Our objective was to assess the diagnostic value of the sentinel node (SN) procedure for lymph node staging in primary intermediate- and high-risk prostate cancer patients with node-negative results on prostate-specific membrane antigen PET/CT (miN0). Methods: From 2016 to 2022, 154 patients with primary, miN0 PCa were retrospectively included. All patients had a Briganti nomogram-assessed nodal risk of more than 5% and underwent a robot-assisted SN procedure for nodal staging. The prevalence of nodal metastases at histopathology and the occurrence of surgical complications according to the Clavien-Dindo classification were evaluated. Results: The SN procedure yielded 84 (14%) tumor-positive lymph nodes with a median metastasis size of 3 mm (interquartile range, 1-4 mm). In total, 55 patients (36%) were reclassified as pN1. A complication of Clavien-Dindo grade 3 or higher occured in 1 patient (0.6%). Conclusion: The SN procedure classified 36% of patients with miN0 prostate cancer with an elevated risk of nodal metastases as pN1.

Background: Penile cancer (PeCa) is rare, and the survival of patients with advanced disease remains poor. A better understanding of where treatment fails could aid the development of new treatment strategies.Objective: To describe the disease course after pelvic lymph node (LN) treatment for PeCa. Design, setting, and participants: We retrospectively analysed 228 patients who underwent pelvic LN treatment with curative intent from 1969 to 2016. The main treatment modalities were neoadjuvant chemotherapy, chemoradiation, and pelvic LN dissection. Outcome measurements and statistical analysis: In the case of multiple recurrence locations, the most distant location was taken and recorded as follows: local (penis), regional (inguinal and pelvic LN), and distant (any other location). A com-peting risk analysis was used to calculate the time to recurrence per location, and a Kaplan-Meier analysis was used for overall survival (OS).Results and limitations: The median follow-up of the surviving patients was 79 mo. The reason for pelvic treatment was pelvic involvement on imaging (29%), two or more tumour-positive inguinal LNs (61%), or inguinal extranodal extension (52%). More than half of the patients (61%) developed a recurrence. The median recurrence-free survival was 11 mo. The distribution was local in 9%, regional in 27%, and distant in 64% of patients. The infield control rate of nonsystemically treated patients was 61% (113/184). From the start of pelvic treatment, the med-ian OS was 17 mo (95% confidence interval 12-22). After regional or distant recurrence, all but one patient died of PeCa with median OS after a recurrence of 4.4 (regional) and 3.1 (distant) mo. This study is limited by its retrospective nature. Conclusions: The prognosis of PeCa patients treated on their pelvis who recur despite locoregional treatment is poor. The tendency for systemic spread empha-sises the need for more effective systemic treatment strategies. Patient summary: In this report, we looked at the outcomes of penile cancer patients in an expert centre undergoing various treatments on their pelvis. We found that survival is poor after recurrence despite locoregional treatment. Therefore, better systemic treatments are necessary.(c) 2022 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4.0/).

Background: Accurate identification of men who harbor nodal metastases is neces-sary to select patients who most likely benefit from whole pelvis radiotherapy (WPRT). Limited sensitivity of diagnostic imaging approaches for the detection of nodal micrometastases has led to the exploration of the sentinel lymph node biopsy (SLNB). Objective: To evaluate whether SLNB can be used as a tool to select pathologically node-positive patients who likely benefit from WPRT. Design, setting, and participants: We included 528 clinically node-negative primary prostate cancer (PCa) patients with an estimated nodal risk of >5% treated between 2007 and 2018. Intervention: A total of 267 patients were directly treated with prostate-only radio-therapy (PORT; non-SLNB group), while 261 patients underwent SLNB to remove lymph nodes directly draining from the primary tumor prior to radiotherapy (SLNB group); pN0 patients were treated with PORT, while pN1 patients were offered WPRT. Outcome measurements and statistical analysis: Biochemical recurrence-free survival (BCRFS) and radiological recurrence-free survival (RRFS) were compared using propensity score weighted (PSW) Cox proportional hazard models. Results and limitations: The median follow-up was 71 mo. Occult nodal metastases were found in 97 (37%) SLNB patients (median metastasis size: 2 mm). Adjusted 7-yr BCRFS rates were 81% (95% confidence interval [CI] 77-86%) in the SLNB group and 49% (95% CI 43-56%) in the non-SLNB group. The corresponding adjusted 7-yr RRFS rates were 83% (95% CI 78-87%) and 52% (95% CI 46-59%), respectively. In the PSW multivariable Cox regression analysis, SLNB was associated with improved BCRFS (hazard ratio [HR] 0.38, 95% CI 0.25-0.59, p < 0.001) and RRFS (HR 0.44, 95% CI 0.28-0.69, p < 0.001). Limitations include the bias inherent to the study's Conclusions: SLNB-based selection of pN1 PCa patients for WPRT was associated efit from the addition of pelvis radiotherapy. This strategy results in a longer dura (c) 2023 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY license (http://creativecommons.

Background Segmentation of the Gross Tumor Volume (GTV) is a crucial step in the brachytherapy (BT) treatment planning workflow. Currently, radiation oncologists segment the GTV manually, which is time-consuming. The time pressure is particularly critical for BT because during the segmentation process the patient waits immobilized in bed with the applicator in place. Automatic segmentation algorithms can potentially reduce both the clinical workload and the patient burden. Although deep learning based automatic segmentation algorithms have been extensively developed for organs at risk, automatic segmentation of the targets is less common. The aim of this study was to automatically segment the cervical cancer GTV on BT MRI images using a state-of-the-art automatic segmentation framework and assess its performance. Methods A cohort of 195 cervical cancer patients treated between August 2012 and December 2021 was retrospectively collected. A total of 524 separate BT fractions were included and the axial T2-weighted (T2w) MRI sequence was used for this project. The 3D nnU-Net was used as the automatic segmentation framework. The automatic segmentations were compared with the manual segmentations used for clinical practice with Sørensen–Dice coefficient (Dice), 95th Hausdorff distance (95th HD) and mean surface distance (MSD). The dosimetric impact was defined as the difference in D98 (ΔD98) and D90 (ΔD90) between the manual segmentations and the automatic segmentations, evaluated using the clinical dose distribution. The performance of the network was also compared separately depending on FIGO stage and on GTV volume. Results The network achieved a median Dice of 0.73 (interquartile range (IQR) = 0.50–0.80), median 95th HD of 6.8 mm (IQR = 4.2–12.5 mm) and median MSD of 1.4 mm (IQR = 0.90–2.8 mm). The median ΔD90 and ΔD98 were 0.18 Gy (IQR = -1.38–1.19 Gy) and 0.20 Gy (IQR =-1.10–0.95 Gy) respectively. No significant differences in geometric or dosimetric performance were observed between tumors with different FIGO stages, however significantly improved Dice and dosimetric performance was found for larger tumors. Conclusions The nnU-Net framework achieved state-of-the-art performance in the segmentation of the cervical cancer GTV on BT MRI images. Reasonable median performance was achieved geometrically and dosimetrically but with high variability among patients.

BACKGROUND:Radiolabeled prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) has shown superior diagnostic accuracy to conventional imaging for the detection of prostate cancer deposits . Consequently, clinical management changes have been reported in patients with biochemical recurrence (BCR) of disease after robot-assisted radical prostatectomy (RARP). We hypothesized that, due to the exclusion of patients with metastatic disease on PSMA-PET/CT, those who underwent local salvage radiation therapy (SRT) after restaging PSMA-PET/CT for BCR may have better oncological outcomes than patients who underwent "blind" SRT. OBJECTIVE:To compare the oncological outcome of a patient cohort that underwent PSMA-PET imaging prior to SRT with that of a patient cohort that did not have PSMA-PET imaging before SRT. DESIGN, SETTING, AND PARTICIPANTS:We included 610 patients who underwent SRT, of whom 298 underwent PSMA-PET/CT prior to SRT and 312 did not. No additional hormonal therapy was prescribed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:To compare both cohorts, case-control matching was performed, using the prostate-specific antigen (PSA) value at the initiation of SRT, pathological grade group, pathological T stage, surgical margin status, and biochemical persistence after RARP as matching variables. The outcome variable was biochemical progression at 1 yr after SRT, defined as either a rise of PSA ≥0.2 ng/ml above the nadir after SRT or the start of additional treatment. RESULTS AND LIMITATIONS:After case-control matching, 216 patients were matched in both cohorts (108 patients per cohort). In the patient cohort without PSMA-PET/CT prior to SRT, of 108 patients, 23 (21%) had biochemical progression of disease at 1 yr after SRT, compared with nine (8%) who underwent restaging PSMA-PET/CT prior to SRT (p = 0.007). CONCLUSIONS:PSMA-PET/CT is found to be associated with an improved oncological outcome in patients who undergo SRT for BCR after RARP. PATIENT SUMMARY:Performing prostate-specific membrane antigen positron emission tomography/computed tomography imaging in patients with biochemical recurrence of disease after robot-assisted radical prostatectomy, before initiating salvage radiation therapy, resulted in improved short-term oncological outcomes.

3 Background: Patients (Pts) with advanced squamous cell carcinoma of the penis (aPeCa) have a poor prognosis (21% 2-year overall survival from moment of diagnosis) and high morbidity, due to progressive locoregional disease. Pre-clinical studies show high rates of infiltrating immune cells and high PD-L1 expression, suggesting that immunotherapy may be beneficial for these patients. In the PERICLES study, we assess the activity of atezolizumab (atezo) in aPeCa pts, with or without radiotherapy (RT) to control locoregional lymph node disease. Methods: A single-centre phase 2 study with two treatment arms (non-randomized) was conducted in 32 histologically confirmed aPeCa pts with a WHO performance status of 0-1 (NCT03686332). Any previous treatment except for immunotherapy was allowed. Study treatment consisted of atezo 1200 mg every 3 weeks (all pts). Pts expected to benefit from RT for locoregional disease control (cohort A) additionally received 33 fractions of 1.5 Gy (locoregional affected lymph node regions and penile region) and 1.8 Gy (macroscopic tumor + margin) irradiation. Response was evaluated with 12-weekly CT scans of the abdomen and thorax using RECIST1.1. Toxicity was scored by NCI-CTCAE V4. The primary endpoint was 1-year progression free survival (PFS) for the full cohort. Results: From Oct 2018 to Aug 2021, 20 pts were included in cohort A (RT + atezo) and 12 pts in cohort B (only atezo). Median follow-up was 22 months (interquartile range (IQR) 4.3-14). Median age was 67 years (IQR 60-72) and all patients had stage IV aPeCa. Pts received no prior treatment (25%), or prior RT (34%), chemoradiation (22%), chemotherapy (6%) or surgery (69%). An immunotherapy or radiotherapy-related grade 3-4 AE was observed in 3/32 (9.4%) and 1/20 (5.0%) patients, respectively. There were no grade 5 treatment-related AEs. One-year PFS was 12% (95% confidence interval (CI) 4.0-33), which did not meet the primary objective. The response rate of RECIST1.1 evaluable pts was 30% (see table). In two patients with pulmonary metastases, a complete response was observed. Initial responses with early progression were seen in 5 pts. Median overall survival (OS) was 12 months (95% CI 5.4-19). Conclusions: Anti-tumor activity of atezo was observed in aPeCa, including complete and durable responses. The trial failed to meet its primary objective (PFS). Our results suggest that a subset of aPeCa pts has incomplete immunological activity and/or early resistance to atezo. Analysis of tumor tissue collected in this trial (including on-treatment biopsies) could suggest new therapeutic strategies to overcome resistance and improve clinical outcome to immunotherapy in aPeCa. Clinical trial information: NCT03686332. [Table: see text]

Despite treatment with cisplatin‐based chemotherapy and surgical resection, clinical outcomes of patients with locally advanced urothelial carcinoma (UC) remain poor. We compared neoadjuvant/induction platinum‐based combination chemotherapy (NAIC) with combination immune checkpoint inhibition (cICI). We identified 602 patients who attended our outpatient bladder cancer clinic in 2018 to 2019. Patients were included if they received NAIC or cICI for cT3‐4aN0M0 or cT1‐4aN1‐3M0 UC. NAIC consisted of cisplatin‐based chemotherapy or gemcitabine‐carboplatin in case of cisplatin‐ineligibility. A subset of patients (cisplatin‐ineligibility or refusal of NAIC) received ipilimumab plus nivolumab in the NABUCCO‐trial (NCT03387761). Treatments were compared using the log‐rank test and propensity score‐weighted Cox regression models. We included 107 Stage III UC patients treated with NAIC (n = 83) or cICI (n = 24). NAIC was discontinued in 11 patients due to progression (n = 6; 7%) or toxicity (n = 5; 6%), while cICI was discontinued in 6 patients (25%) after 2 cycles due to toxicity (P = .205). After NAIC, patients had surgical resection (n = 50; 60%), chemoradiation (n = 26; 30%), or no consolidating treatment due to progression (n = 5; 6%) or toxicity (n = 2; 2%). After cICI, all patients underwent resection. After resection (n = 74), complete pathological response (ypT0N0) was achieved in 11 (22%) NAIC‐patients and 11 (46%) cICI‐patients (P = .056). Median (IQR) follow‐up was 26 (20‐32) months. cICI was associated with superior progression‐free survival (P = .003) and overall survival (P = .003) compared to NAIC. Our study showed superior survival in Stage III UC patients pretreated with cICI if compared to NAIC. Our findings provide a strong rationale for validation of cICI for locally advanced UC in a comparative phase‐3 trial.

Abstract Background Decision making regarding future fertility can be very difficult for female cancer patients. To support patients in decision making, fertility preservation decision aids (DAs) are being developed. However, to make a well‐informed decision, patients need personalized information tailored to their cancer type and treatment. Tailored cancer‐specific DAs are not available yet. Methods Our DA was systematically developed by a multidisciplinary steering group (n = 21) in an iterative process of draft development, three rounds of alpha testing, and revisions. The drafts were based on current guidelines, literature, and patients' and professionals' needs. Results In total, 24 cancer‐specific DAs were developed. In alpha testing, cancer survivors and professionals considered the DA very helpful in decision making, and scored an 8.5 (scale 1–10). In particular, the cancer‐specific information and the tool for recognizing personal values were of great value. Revisions were made to increase readability, personalization, usability, and be more careful in giving any false hope. Conclusions A fertility preservation DA containing cancer‐specific information is important in the daily care of female cancer patients and should be broadly available. Our final Dutch version is highly appraised, valid, and usable in decision making. After evaluating its effectiveness with newly diagnosed patients, the DA can be translated and adjusted according to (inter)national guidelines.

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 0.87-0.97]; p = 0.003) with comorbidity (OR 0.34 [95% CI 0.12-0.89]; p = 0.035) had lower preference for chemoradiotherapy, while patients with better numeracy skills (OR 1.2 [95%CI 1.05-1.36], p = 0.011) and chemoradiotherapy history (OR 25.0 [95%CI 8.8-91.7]; p < 0.001) had higher preference for chemoradiotherapy. 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/).

Background: In patients with oligometastatic recurrent prostate cancer, standard treatment is androgen deprivation therapy (ADT). However, ADT has many potential side effects that may result in impaired quality of life. Early identification to select patients suitable for stereotactic ablative radiotherapy (SABR) is of utmost importance to prevent or delay start of ADT and its side effects. Because Prostate-Specific Membrane Antigen-11 Positron Emission Tomography (PSMA-11-PET) has a higher sensitivity than choline-PET, we hypothesise that PSMA-11-PET based SABR results in longer response duration and subsequent longer delay in starting ADT than choline-PET. Methods: Patients with oligometastatic (<= 4 metastases) recurrent prostate cancer (with no local recurrence) based on PSMA-11-PET or choline-PET treated with SABR from January 2012 until December 2017 were included. Primary endpoint was ADT-free survival. Secondary endpoints were Prostate Specific Antigen (PSA) response after SABR and time to PSA rise after SABR. Results: Fifty patients (n = 40 PSMA-11-PET and n = 10 choline-PET) with in total 72 lesions were included. Median follow-up was 24.3 months. PSMA-11-PET enabled eligibility of patients with lower PSA levels than choline-PET (median 1.8 versus 4.2 ng/mL, p = 0.03). The PSMA-11-PET group had a significant longer PSA response duration (median 34.0 months (95% confidence interval (CI), 16.0-52.0) versus 14.7 months (95% CI 4.7-24.7), p = 0.004) with a subsequent longer ADT-free survival (median 32.7 months (95% CI, 20.8-44.5) versus 14.9 months (95% CI, 5.7-24.1), p = 0.01). Conclusions: With PSMA-11-PET we are able to select patients with oligometastatic recurrent prostate cancer suitable for SABR in an earlier disease stage at lower PSA levels. PSMA-11-PET guided SABR resulted in a significant longer response duration and ADT-free survival compared with choline-PET and can therefore prevent or delay ADT related side effects.

Background and purpose: Chemoradiation (CRT) with mitomycin-C (MMC) and 5-fluorouracil (5-FU) has been shown to be superior to radiation alone in patients with muscle-invasive bladder cancer (MIBC). MMC/capecitabine is an effective replacement for 5FU as a radiosensitizer in other malignancies but has not been studied in bladder cancer. We evaluated the outcomes of MIBC patients treated with concurrent radiation and MMC/capecitabine. Materials and methods: MIBC patients treated with CRT (60 Gy in 5 weeks with single-dose MMC and capecitabine orally twice daily) between 2014 and 2019 were identified. Acute (<90 days) and late toxicity were registered. Endpoints were clinical complete response (cCR) in the bladder assessed by cystoscopy 3 months after CRT, locoregional disease-free survival (LDFS) and the number of salvage cystectomies. Results: We analysed 71 cT2-4aN0-2 M0 MIBC patients (median age 70 years). Twenty-one (30%) patients received neoadjuvant or induction chemotherapy and 14 (20%) patients underwent a pelvic lymph node dissection prior to CRT. All patients received the full dose of planned radiation. Seven (10%) patients experienced acute grade 3-4 toxicities and 2 (3%) patients experienced late grade 3-4 toxicities. Sixty-eight (96%) patients achieved cCR. Eight (11%) patients had a bladder recurrence, of whom 3 (4%) required salvage cystectomy. Two-year LDFS was 79% (95% CI: 68-88) at a median follow-up of 23 (95% CI: 17-28) months. Conclusion: Radiation with concurrent MMC/capecitabine is a well-tolerated bladder-sparing treatment. Severe toxicity is infrequent and locoregional tumor control and short-term disease free survival appear similar to previous studies with MMC/5FU. (c) 2020 Elsevier B.V. All rights reserved.