Radical cystectomy or trimodality therapy for muscle-invasive bladder cancer: a qualitative study exploring patient priorities and counselling needs when making a treatment choice.

BACKGROUND: This study aims to explore the priorities and counselling needs of patients with muscle-invasive bladder cancer faced with a decision between radical cystectomy and trimodality therapy. METHODS: We performed a qualitative study according to the phenomenological approach. Sixteen muscle-invasive bladder cancer survivors who underwent radical cystectomy or trimodality therapy completed a semi-structured interview between May 2022 and February 2023. Patients were recruited via Ghent University Hospital and a patient organisation. Data were analysed with inductive thematic analysis by a multi-disciplinary team using an iterative approach and investigators' triangulation. RESULTS: Four main priorities determining the treatment decision were identified. (1) curing the disease; (2) health-related quality of life (physical, mental and social); (3) confidence in the treatment, which was mainly based on trust in the clinician; and (4) personal attributes. Trust in the clinician can be achieved by fulfilling the patient's information needs (accurate, complete, clear, impartial, personalised, realistic, and transparent information), ensuring accessibility of the clinician, and creating a clear and personalised treatment plan, involving patients to the extend they desire. Many patients considered a patient decision aid as a valuable asset in this process. CONCLUSION: Priorities vary between patients with muscle-invasive bladder cancer. Identifying individual priorities and offering personalised information about them is crucial for ensuring trust in the clinician and confidence in the treatment. Use of a patient decision aid can be beneficial in this process.

Supportive care needs and utilization of bladder cancer patients undergoing radical cystectomy: A longitudinal study.

OBJECTIVES: Investigating supportive care (SC) needs and utilization/willingness to use SC services from diagnosis to one year after radical cystectomy in bladder cancer (BC) patients. MATERIALS & METHODS: A longitudinal cohort study was conducted in 90 BC patients at Ghent/Leuven University Hospitals between April 2017 and December 2020. The Supportive Care Needs Survey-short form (SCNS-SF34) was used before radical cystectomy, one, three, six and 12 months after radical cystectomy. Additional questions assessed utilization/willingness to use SC services. Linear mixed models were performed. RESULTS: The majority of BC patients report at least one moderate or high SC need at diagnosis (82%), month 1 (84%), month 3 (86%), month 6 (64%), and month 12 (60%). Significant decreases over time were seen for all domains (p < 0.001), except for sexuality (p = 0.275). From baseline to month 1, physical needs first significantly increased (p = 0.001) after which they decreased. Psychological (e.g. fears about the future) and informational (e.g. information on how to get better) needs were most common at baseline whereas physical (e.g. lack of energy) and informational needs were more common in the early postoperative phases. The majority of patients (ranging from 81% (month 1) to 91% (month 12)) did not make use of SC services and the majority of the patients (ranging from 81% (month 1) to 88% (month 12)) did not wish to talk about their problems to someone. Those willing to talk to someone preferred their physician. CONCLUSIONS: A clear gap exists between the large proportion of SC needs experienced by BC patients undergoing radical cystectomy and the low use of SC services.

Elective nodal radiotherapy in prostate cancer.

In patients with prostate cancer who have a high risk of pelvic nodal disease, the use of elective whole pelvis radiotherapy is still controversial. Two large, randomised, controlled trials (RTOG 9413 and GETUG-01) did not show a benefit of elective whole pelvis radiotherapy over prostate-only radiotherapy. In 2020, the POP-RT trial established the role of elective whole pelvis radiotherapy in patients who have more than a 35% risk of lymph node invasion (known as the Roach formula). POP-RT stressed the importance of patient selection. In patients with cN1 (clinically node positive) disease or pN1 (pathologically node positive) disease, the addition of whole pelvis radiotherapy to androgen deprivation therapy significantly improved survival compared with androgen deprivation therapy alone, as shown in large, retrospective studies. This patient population might increase in the future because use of the more sensitive prostate-specific membrane antigen PET-CT will become the standard staging procedure. Additionally, the SPORTT trial suggested a benefit of whole pelvis radiotherapy in biochemical recurrence-free survival in the salvage setting. A correct definition of the upper field border, which should include the bifurcation of the abdominal aorta, is key in the use of pelvic radiotherapy. As a result of using modern radiotherapy technology, severe late urinary and intestinal toxic effects are rare and do not seem to increase compared with prostate-only radiotherapy.

Evaluating the impact of 18F-FDG-PET-CT on risk stratification and treatment adaptation for patients with muscle-invasive bladder cancer (EFFORT-MIBC): a phase II prospective trial.

BACKGROUND: The outcome of patients with muscle-invasive bladder cancer (MIBC) remains poor, despite aggressive treatments. Inadequate primary staging, classically performed by computed tomography (CT)-imaging, could lead to inappropriate treatment and might contribute to these poor results. Although not (yet) adapted by international guidelines, several reports have indicated the superiority of 18F-fluorodeoxyglucose-positron emission tomography-CT (18F-FDG-PET-CT) compared to CT in the detection of lymph node and distant metastases. Thereby the presence of extra-vesical disease on 18F-FDG-PET-CT has been correlated with a worse overall survival. This supports the hypothesis that 18F-FDG-PET-CT is useful in stratifying MIBC patients and that adapting the treatment plan accordingly might result in improved outcome. METHODS: EFFORT-MIBC is a multicentric prospective phase II trial aiming to include 156 patients. Eligible patients are patients with histopathology-proven MIBC or ≥ T3 on conventional imaging treated with MIBC radical treatment, without extra-pelvic metastases on conventional imaging (thoracic CT and abdominopelvic CT/ magnetic resonance imaging (MRI)). All patients will undergo radical local therapy and if eligible neo-adjuvant chemotherapy. An 18F-FDG-PET-CT will be performed in addition to and at the timing of the conventional imaging. In case of presence of extra-pelvic metastasis on 18F-FDG-PET-CT, appropriate intensification of treatment with metastasis-directed therapy (MDT) (in case of ≤3 metastases) or systemic immunotherapy (> 3 metastases) will be provided. The primary outcome is the 2-year overall survival rate. Secondary endpoints are progression-free survival, distant metastasis-free survival, disease-specific survival and quality of life. Furthermore, the added diagnostic value of 18F-FDG-PET-CT compared to conventional imaging will be evaluated and biomarkers in tumor specimen, urine and blood will be correlated with primary and secondary endpoints. DISCUSSION: This is a prospective phase II trial evaluating the impact of 18F-FDG-PET-CT in stratifying patients with primary MIBC and tailoring the treatment accordingly. We hypothesize that the information on the pelvic nodes can be used to guide local treatment and that the presence of extra-pelvic metastases enables MDT or necessitates the early initiation of immunotherapy leading to an improved outcome. TRIAL REGISTRATION: The Ethics Committee of the Ghent University Hospital (BC-07456) approved this study on 11/5/2020. The trial was registered on ClinicalTrials.gov (NCT04724928) on 21/1/2021.

Exercise prescription dose for castrate-resistant prostate cancer patients: a phase I prescription dose escalation trial.

PURPOSE: To determine the start exercise prescription dose in metastatic castrate-resistant prostate cancer (mCRPC) patients receiving second-line hormone treatment and recommended phase II exercise prescription. METHODS: Patients were enrolled in a 3 + 3 dose escalation phase I trial of aerobic, resistance, and flexibility exercises to evaluate dose-limiting tolerance and safety. Tolerance was defined as Borg score ≤ 16 and safety (pain) as a visual analogue scale score (VAS) ≤ 3 and CTCAE grade < 2. Dose level 1 (escalation start dose) was set at 15 min. Aerobic training (50-80% HRmax warm-up and cooling-down; and 65-80% HRmax. core), 1 set with 8-10 repetitions (reps.) resistance training (50-60% 1-RM, 8 exercises), and 1 set (30s) with 2 reps flexibility training (5 exercises). The prescription dose escalation was designed in four levels (from dose -1 to 3), with a dose escalation in volume and intensity of the exercises. RESULTS: Nine patients were included in two dosing cohorts and were under active treatment (n = 4 abiraterone acetate and n = 5 enzalutamide). Dose limiting safety concerns were observed in 2 out of 3 patients in dose level 2 and 1 patient out of 6 in dose level 1 due to VAS > 3 during resistance training and/or flexibility training. No tolerance issues were observed in the two dosing cohorts. The optimal start exercise prescription dose was set at dose level 1 due to safety issues at dose level 2. CONCLUSION: Our findings suggest that exercise is perceived tolerable in mCRPC patients receiving second-line hormone therapy. Caution is indicated on safety during performance of the exercises.

Development of a pre- and postoperative physical activity promotion program integrated in the electronic health system of patients with bladder cancer (The POPEYE study): An intervention mapping approach.

INTRODUCTION: Uptake of sufficient physical activity before and after radical cystectomy is important to improve physical and psychosocial outcomes in bladder cancer (BC) patients. METHODS: In this paper, we describe the development of an evidence-based and theory-informed intervention, guided by the steps of the Intervention Mapping approach, to promote physical activity before and after radical cystectomy in patients with BC. RESULTS: The intervention is a home-based physical activity program. The preoperative timeframe of the intervention is 4 or 12 weeks, depending on administration of neoadjuvant chemotherapy. Postoperatively, the intervention will last for 12 weeks. The intervention consists of a digital oncological platform (DOP), several consultations with healthcare professionals, personal booklet and follow-up phone calls. DOP includes information, diaries, visual representation of progress, mailbox, videos of peers and treating physician explaining the benefits of physical activity, photo material of exercises and a walking program with an activity tracker. Individual goals will be set and will be self-monitored by the patient through DOP. Patients will receive alerts and regular feedback. CONCLUSIONS: Intervention Mapping ensures transparency of all intervention components and offers a useful approach for the development of behaviour change interventions for cancer patients and for translation of theories into practice.

Phase II open-label study investigating apalutamide in patients with biochemical progression after radical prostatectomy.

Apalutamide, a competent inhibitor of the androgen receptor, has shown promising clinical efficacy results for patients with advanced prostate cancer. Here, we describe the rationale and design for the SAVE trial, a multi-center, Phase II study, wherein 202 men with biochemical progression after radical prostatectomy are randomly assigned 1:1 to apalutamide plus salvage radiotherapy (SRT) or androgen-deprivation therapy with an luteinizing hormone-releasing hormone agonist or antagonist plus SRT. The primary objective is to compare sexual function between the two treatment arms based on the expanded prostate cancer index-26 sexual domain score at nine months after start of hormonal treatment. The key secondary objectives are to assess quality of life, to evaluate the safety profile and the short-term efficacy of apalutamide in combination with SRT. ClinicalTrials.gov identifier: NCT03899077.

Health-related quality of life overview after different curative treatment options in muscle-invasive bladder cancer: an umbrella review.

PURPOSE: This umbrella review aims to evaluate the quality, summarize and compare the conclusions of systematic reviews investigating the impact of curative treatment options on health-related quality of life (HRQoL) in muscle-invasive bladder cancer (MIBC). METHODS: The Cochrane Library, MEDLINE, Embase and Web of Science were searched independently by two authors from inception until 06 January 2020. Systematic reviews and meta-analyses assessing the impact of any curative treatment option on HRQol in MIBC patients were eligible. Risk of bias was assessed using the AMSTAR 2 tool. RESULTS: Thirty-two reviews were included. Robot-assisted RC with extracorporeal urinary diversion and open RC have similar HRQoL (n = 10). Evidence for pelvic organ-sparing RC was too limited (n = 2). Patients with a neobladder showed better overall and physical HRQoL outcomes, but worse urinary function in comparison with ileal conduit (n = 17). Bladder-preserving radiochemotherapy showed slightly better urinary and sexual but worse gastro-intestinal HRQoL outcomes in comparison with RC patients (n = 6). Quality of the reviews was low in more than 50% of the available reviews and most of the studies included in the reviews were nonrandomized studies. CONCLUSION: This umbrella review gives a comprehensive overview of the available evidence to date.

Hyperbaric oxygen therapy for radiation cystitis after pelvic radiotherapy: Systematic review of the recent literature.

The present study assessed the efficacy of hyperbaric oxygen therapy in reducing symptoms of radiation cystitis, a specific type of iatrogenic injury to the bladder, by systematic review of recent literature. The MEDLINE, Embase and Web of Science databases were searched using combinations of the terms "radiation," "cystitis" and "hyperbaric oxygen" to identify articles evaluating patients with radiation cystitis, treated with hyperbaric oxygen therapy. Only recent (≤10 years) original studies were included. Data were extracted and pooled in order to calculate descriptive weighted averages. Articles were evaluated on their level of evidence. A total of 20 papers were obtained, resulting in a cohort of 815 patients who were treated with hyperbaric oxygen therapy for radiation cystitis. Overall and complete response rates varied from 64.8% to 100% and 20% to 100%, respectively. The weighted average overall and complete response rates were 87.3% and 65.3%, respectively. Adverse events were observed in 9.6% of the patients, but permanent side-effects were rare. The most prominent limitations were high cost and low availability. Hyperbaric oxygen therapy is effective in the treatment of radiation-induced cystitis, with minimal adverse events, but low availability and high cost. At present, evidence is low; therefore, more prospective studies are required.

Patient- versus physician-reported outcomes in prostate cancer patients receiving hypofractionated radiotherapy within a randomized controlled trial.

PURPOSE: The risk of developing acute radiotherapy(RT)-induced side effects may increase with hypofractionated RT. To detect treatment-related side effects, patient-reported outcomes (PROs) might be more reliable than physician-reported outcomes. Therefore, we tried to evaluate the rate of agreement between urinary and gastrointestinal (GI) side effects and the prevalence of side effects reported by patients and by physicians. METHODS: Data from a randomized controlled trial (RCT) comparing two hypofractionated RT schedules were used. Urinary (nocturia, incontinence, frequency, dysuria, and urgency) and GI (obstruction, diarrhea, vomiting, nausea, bloating, hemorragia, and incontinence) symptoms measured by the EORTC QLQ-C30 and PR-25 were used for PROs. The same symptoms were scored by the physician using the Common Terminology Criteria Adverse Events v4.0. Outcomes were reported at baseline, end of treatment, month 1, and month 3. PROs and physician-reported outcomes were converted in two categories (0 = no symptoms; 1 = symptoms of any severity) and were correlated using the kappa (κ) correlation statistics. Values below 0.40 were considered low agreement. In addition, the prevalence of symptoms was calculated. RESULTS: Data from 160 patients were used. The mean value for Cohen's κ was 0.31 (ranging between 0.04 and 0.55) and 0.23 (ranging between 0.04 and 0.47) for urinary and GI symptoms, respectively. Except for three symptoms at baseline, all symptoms reported by patients were higher than those reported by physicians. CONCLUSION: There is low agreement between symptoms reported by patients and physicians, with high rates of underreporting by the physician.

Importance of metastatic volume in prognostic models to predict survival in newly diagnosed metastatic prostate cancer.

PURPOSE: To explore the prognostic importance of metastatic volume in a contemporary daily practice cohort of patients with newly diagnosed metastatic hormone-naive prostate cancer (mHNPC) and to develop a pragmatic prognostic model to predict survival for these patients. METHODS: Since 2014, 113 patients with newly diagnosed mHNPC were prospectively registered. Statistical analysis was performed using SPSS 25.0™ with two-sided p value < 0.05 indicating statistical significance. Univariate and multivariate cox regression analyses were performed to identify prognostic risk factors. Kaplan-Meier method with log-rank statistics was constructed to analyze difference in survival in the prognostic groups. Model performance was assessed using the Concordance-index (C-index) and cross-validated in R v3.4.1. High-volume mHNPC (HVD) was defined as the presence of visceral metastasis or ≥ 4 bone metastases with ≥ 1 appendicular lesion. RESULTS: Multivariate analysis identified HVD (p = 0.047) and elevated alkaline phosphatase (ALP) (p = 0.018) as independent prognostic risk factors for overall survival (OS). Consequently, three prognostic groups were created: a good (no risk factors), intermediate (1 risk factor) and poor prognosis group (2 risk factors). Median OS for the good, intermediate and poor prognosis group was not reached, 73 and 20 months (95% CI 9-31 months with p < 0.001 and Correspondence-index of 0.78), respectively. CONCLUSIONS: We developed a pragmatic and qualitative prognostic model consisting of three prognostic risk groups for OS in a daily practice cohort of patients with newly diagnosed mHNPC. Independent prognostic risk factors included in the model were HVD and abnormal ALP.

Discovery and validation of a serum microRNA signature to characterize oligo- and polymetastatic prostate cancer: not ready for prime time.

PURPOSE: Patients with oligometastatic prostate cancer (PC) may benefit from metastasis-directed therapy (MDT), delaying disease progression and the start of palliative systemic treatment. However, a significant proportion of oligometastatic PC patients progress to polymetastatic PC within a year following MDT, suggesting an underestimation of the metastatic load by current staging modalities. Molecular markers could help to identify true oligometastatic patients eligible for MDT. METHODS: Patients with asymptomatic biochemical recurrence following primary PC treatment were classified as oligo- or polymetastatic based on 18F-choline PET/CT imaging. Oligometastatic patients had up to three metastases at baseline and did not progress to more than three lesions following MDT or surveillance within 1 year of diagnosis of metastases. Polymetastatic patients had > 3 metastases at baseline or developed > 3 metastases within 1 year following imaging. A model aiming to prospectively distinguish oligo- and polymetastatic PC patients was trained using clinicopathological parameters and serum-derived microRNA expression profiles from a discovery cohort of 20 oligometastatic and 20 polymetastatic PC patients. To confirm the models predictive performance, it was applied on biomarker data obtained from an independent validation cohort of 44 patients with oligometastatic and 39 patients with polymetastatic disease. RESULTS: Oligometastatic PC patients had a more favorable prognosis compared to polymetastatic ones, as defined by a significantly longer median CRPC-free survival (not reached versus 38 months; 95% confidence interval 31-45 months with P < 0.001). Despite the good performance of a predictive model trained on the discovery cohort, with an AUC of 0.833 (0.693-0.973; 95% CI) and a sensitivity of 0.894 (0.714-1.000; 95% CI) for oligometastatic disease, none of the miRNA targets were found to be differentially expressed between oligo- and polymetastatic PC patients in the signature validation cohort. The multivariate model had an AUC of 0.393 (0.534 after cross-validation) and therefore, no predictive ability. CONCLUSIONS: Although PC patients with oligometastatic disease had a more favorable prognosis, no serum-derived biomarkers allowing for prospective discrimination of oligo- and polymetastatic prostate cancer patients could be identified.

Understanding physical activity behavior in patients with bladder cancer before and after radical cystectomy: a qualitative interview study.

OBJECTIVE:: To explore the determinants of physical activity in patients with bladder cancer before and after radical cystectomy. DESIGN:: A qualitative research design using semi-structured face-to-face interviews. SETTING AND SUBJECTS:: A total of 30 interviews were conducted with people diagnosed with bladder cancer and treated with radical cystectomy at Ghent University Hospital. MAIN MEASURES:: The interviews were audiotaped and transcribed verbatim. Framework analysis with constant comparison between and within interviews was applied until final topics were derived from interpreting the data. RESULTS:: Physical activity behavior in patients with bladder cancer is determined multifactorial with condition-related (e.g. urinary symptoms, comorbidities), therapy-related (e.g. fatigue, diarrhea), patient-related (e.g. outcome expectations, coping skills, definitions of physical activity), social/economic-related (e.g. social support, attractive environment) and health system-related (e.g. physicians' advice, information) factors. CONCLUSION:: The results of this study can guide the development of theory-based behavior change interventions to increase physical activity in bladder cancer patients.

Pelvic lymph node dissection in prostate cancer staging: evaluation of morbidity and oncological outcomes.

BACKGROUND: To evaluate the morbidity of different surgical approaches for pelvic lymph node dissection (PLND), to evaluate the influence of morbidity on radiotherapy (RT) planning and to evaluate a possible therapeutic effect of a more extensive yield of PLND. METHODS: From 2000-2016, 228 patients received staging PLND before primary RT in a single tertiary care center. Nine patients were excluded for the evaluation of morbidity. Fifty patients were operated in an open approach, 96 laparoscopic and 73 robot-assisted (RA). Clavien-Dindo classification was used for evaluating complications. Predictors of biochemical recurrence (BCR), clinical relapse (CR), cancer-specific survival (CSS) and overall survival (OS) were evaluated by regression analyses to determine a possible therapeutic effect. RESULTS: Minimal invasive surgery (laparoscopic or RA) caused five times less major complications (22% vs. 4.3%, p = .001) and a median 3 days shorter hospital stay (5 days versus 2 days, p < .001). Major complications resulted in a delayed (23 days, p < .001) RT start but no oncological effect was seen. Independent oncological predictors were the number of positive nodes (BCR, CR, CSS, OS), a lower age (CR), a higher level of initial prostate-specific antigen (PSA) (BCR) and post-RT PSA (BCR). CONCLUSION: Minimal invasive surgery can diminish major complications which delay RT start. Nodal staging proved to be of importance for prognosis but no therapeutic effect was seen of performing PLND as such.

Clinical pathway improves implementation of evidence-based strategies for the management of androgen deprivation therapy-induced side effects in men with prostate cancer.

OBJECTIVES: To assess the effects of a prostate cancer (PCa) clinical pathway on the implementation of evidence-based strategies for the management of androgen deprivation therapy (ADT)-induced side effects. PATIENTS AND METHODS: A clinical pathway was introduced at hospital level in 2015. The pathway consists of evidence-based strategies for the management of ADT-induced side effects. All patients with PCa receiving ADT for >6 months were eligible to enter the clinical pathway. Data on recommended evidence-based strategies were retrospectively extracted from the electronic health records of all eligible patients in the year before (2014) and the year of implementation of the pathway (2015). Descriptive statistics were used for patient characteristics. The chi-squared test (or Fisher's exact test) and Mann-Whitney U-test were used to compare results in the control group with those in the intervention group. RESULTS: In total, 126 patients were included in the control group and 132 patients in the intervention group. Baseline patient characteristics were well balanced. After implementation of the pathway, metabolic, bone and cardiac risk assessment screenings were more frequently applied in the intervention group (metabolic 46% vs 4%; bone 58% vs 10%; cardiac 61% vs 16%; P < 0.001). Advice on strategies preventing ADT-induced side effects was more frequently provided in the intervention group (exercise 62% vs 11%; nutrition 58% vs 10%; psycho-education 54% vs 13%; P < 0.001). CONCLUSION: A clinical pathway for patients with PCa improved the implementation of evidence-based strategies for the management of ADT-induced side effects. A clinical pathway could serve as a method to bridge the gap between evidence-based guidelines and daily clinical practice.

A systematic review of exercise and psychosocial rehabilitation interventions to improve health-related outcomes in patients with bladder cancer undergoing radical cystectomy.

OBJECTIVE: Summarizing the evidence on the effects of pre- and postoperative exercise and psychosocial rehabilitation interventions on patient-reported outcomes (PROs) and physical fitness in bladder cancer patients undergoing radical cystectomy. DATA SOURCES: The Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Web of Science and the Physiotherapy Evidence Database were searched independently by two authors from inception until 10 November 2017. Cited references of the studies and citing references retrieved via Web of Science were also checked. REVIEW METHODS: Randomized controlled trials (RCTs) and non-randomized studies assessing effects of exercise and psychosocial interventions in bladder cancer patients undergoing radical cystectomy were eligible. Primary outcome measures were PROs and physical fitness. Risk of bias was assessed using the Cochrane Collaboration tool and the Newcastle-Ottawa Scale. RESULTS: Five RCTs (three exercise and two psychosocial studies) and one non-randomized psychosocial study comprising 317 bladder cancer patients were included. Timing of the intervention was preoperative ( n = 2), postoperative ( n = 2) or both pre- and postoperative ( n = 2). Positive effects of exercise were found for physical fitness ( n = 3), some health-related quality-of-life (HRQoL) domains ( n = 2), personal activities in daily living ( n = 1) and muscle strength ( n = 1). Psychosocial interventions showed positive effects on anxiety ( n = 1), fatigue ( n = 1), depression ( n = 1), HRQoL ( n = 1) and posttraumatic growth ( n = 1). Quality assessment showed most shortcomings with sample sizes and strong heterogeneity was observed between studies. CONCLUSION: The evidence relating to the effects of exercise in bladder cancer is very limited and is even less for psychosocial interventions.

A phase I/II trial of fixed-dose stereotactic body radiotherapy with sequential or concurrent pembrolizumab in metastatic urothelial carcinoma: evaluation of safety and clinical and immunologic response.

BACKGROUND: Current first-line standard of therapy for metastatic urothelial carcinoma is platinum-based combination chemotherapy. Pembrolizumab in phase III has demonstrated a promising overall response rate of 21.1% in patients with progression or recurrence after platinum-based chemotherapy. Preclinical and clinical evidence suggests that radiotherapy has a systemic anti-cancer immune effect and can increase the level of PD-L1 and tumor infiltrating lymphocytes in the tumor microenvironment. These findings gave rise to the hypothesis that the combination of radiotherapy with anti-PD1 treatment could lead to a synergistic effect, hereby enhancing response rates. METHODS: The phase I part will assess the dose limiting toxicity of the combination treatment of stereotactic body radiotherapy (SBRT) with four cycles of pembrolizumab (200 mg intravenously, every 3 weeks) in patients with metastatic urothelial carcinoma. The dose of both pembrolizumab and SBRT will be fixed, yet the patients will be randomized to receive SBRT either before the first cycle of pembrolizumab or before the third cycle of pembrolizumab. SBRT will be delivered (24 Gy in 3 fractions every other day) to the largest metastatic lesion. Secondary objectives include response rate according to RECIST v1.1 and immune related response criteria, progression-free survival and overall survival. The systemic immune effect triggered by the combination therapy will be monitored on various time points during the trial. The PD-L1/TIL status of the tumors will be analyzed via immunohistochemistry and response rates in the subgroups will be analyzed separately. A Simon's two-stage optimum design is used to select the treatment arm associated with the best response rate and with acceptable toxicity to proceed to the phase II trial. In this phase, 13 additional patients will be accrued to receive study treatment. DISCUSSION: The progress made in the field of immunotherapy has lead to promising breakthroughs in various solid malignancies. Unfortunately, the majority of patients do not respond. The current trial will shed light on the toxicity and potential anti-tumor activity of the combination of radiotherapy with anti-PD1 treatment and may identify potential new markers for response and resistance to therapy. Trial registration this trial is registered on clinicaltrials.gov (NCT02826564).

Whole pelvis radiotherapy for pathological node-positive prostate cancer : Oncological outcome and prognostic factors.

PURPOSE: The goal of this work was to investigate the oncological outcome of whole pelvis radiotherapy (wpRT) in pathologic pelvic lymph node-positive (pN1) prostate cancer (PCa), evaluate the location of relapse, and identify potential prognostic factors. PATIENTS AND METHODS: All patients undergoing pelvic lymph node dissection (PLND) since the year 2000 at a single tertiary care center were evaluated. A total of 154 patients with pN1 PCa were treated with wpRT (39 in an adjuvant setting) and 2-3 years of androgen deprivation therapy (ADT). Kaplan-Meier analysis was performed to estimate biochemical recurrence-free survival (bRFS), clinical progression-free survival (cPFS), and prostate cancer-specific survival (CSS). Uni- and multivariate regression analyses were performed to identify prognostic factors. RESULTS: Estimated bRFS was 67%, cPFS was 71%, and CSS was 96% at 5 years. Median follow-up was 55 months (interquartile range 25-87). Multivariate analysis identified having only 1 positive lymph node, a shorter time between diagnosis and PLND, and older age as independent favorable prognostic factors for biochemical and clinical recurrence. The number of positive lymph nodes was prognostic for CSS (hazard ratio [HR] 1.34, 95% confidence interval 1.17-1.54) and OS (HR 1.22, 95% confidence interval 1.10-1.36). Bone metastases were the most frequent location of PCa relapse (n = 32, 64%). CONCLUSIONS: Patients with pN1 PCa treated with wpRT and 2-3 years ADT have an encouraging 5­year CSS. Understaging of the disease extent may be the most important enemy in definitive pN1 PCa treatment.

Adjuvant radiotherapy after radical cystectomy for patients with muscle invasive bladder cancer: a phase II trial.

BACKGROUND: Neo-adjuvant chemotherapy followed by radical cystectomy with extended pelvic lymph node dissection is considered to be the treatment of choice for patients with muscle invasive bladder cancer (MIBC). Despite this aggressive treatment the outcome is poor and ultimately, 30% of the patients with ≥pT3 tumors develop a pelvic recurrence. We hypothesize that postoperative adjuvant external beam radiotherapy (EBRT) might prevent local and lymph node recurrence and improve disease free- and overall survival as loco-regional recurrence is linked to the development of distant metastasis. METHODS: We plan to perform a multicentric prospective phase two study including 76 patients. Eligible patients are patients with MIBC, treated with radical cystectomy and presenting with ≥1 of the following characteristics: Pathological (p)T3 stage + presence of lymphovascular invasion on pathological examination pT4 stage <10 lymph nodes removed positive lymph nodes positive surgical margins Patients will have a 18F-FDG PET-CT to rule out the presence of distant metastasis prior to EBRT. A median dose of 50 Gy in 25 fractions is prescribed to the pelvic lymph node regions with inclusion of the operative bladder bed in case of a positive surgical margin. Patients with suspected lymph nodes on PET- CT can still be included in the trial, but a simultaneous integrated boost to 74Gy to the positive lymph nodes will be delivered. Blood and urine samples will be collected on day-1 and last day of EBRT for evaluation of biomarkers. The primary endpoint is evaluation of acute ≥Grade 3 intestinal or grade 4 urinary toxicity, in case of a neo-bladder reconstruction, within 12 weeks after EBRT. Secondary endpoints are: assessment of QOL, late RTOG toxicity, local control, disease free survival and overall survival. Biomarkers in urine and blood will be correlated with secondary survival endpoints. DISCUSSION: This is a prospective phase 2 trial re-assessing the feasibility of adjuvant radiotherapy in high-risk MIBC. TRIAL REGISTRATION: The Ethics committee of the Ghent University Hospital (EC2014/0630) approved this study on 31/07/2014. Trial registration on Clinicaltrials.gov ( NCT02397434 ) on November 19, 2014.

Prevalence and prognosis of low-volume, oligorecurrent, hormone-sensitive prostate cancer amenable to lesion ablative therapy.

OBJECTIVES: To describe the anatomical patterns of prostate cancer (PCa) recurrence after primary therapy and to investigate if patients with low-volume disease have a better prognosis as compared with their counterparts. MATERIALS AND METHODS: Patients eligible for an 18-F choline positron-emission tomography (PET)-computed tomography (CT) were enrolled in a prospective cohort study. Eligible patients had asymptomatic biochemical recurrence after primary PCa treatment and testosterone levels >50 ng/mL. The number of lesions was counted per scan. Patients with isolated local recurrence (LR) or with ≤3 metastases (with or without LR) were considered to have low-volume disease and patients with >3 metastases to have high-volume disease. Descriptive statistics were used to report recurrences. Cox regression analysis was used to investigate the influence of prognostic variables on the time to developing castration-resistant PCa (CRPC). RESULTS: In 208 patients, 625 sites of recurrence were detected in the lymph nodes (N1/M1a: 30%), the bone (18%), the prostate (bed; 11%), viscera (4%), or a combination of any of the previous (37%). In total, 153 patients (74%) had low-volume recurrence and 55 patients (26%) had high-volume recurrence. The 3-year CRPC-free survival rate for the whole cohort was 79% (95% confidence interval 43-55), 88% for low-volume recurrences and 50% for high-volume recurrences (P < 0.001). Longer PSA doubling time at time of recurrence and low-volume disease were associated with a longer time to CRPC. CONCLUSIONS: Three out of four patients with PCa with a 18-F choline PET-CT-detected recurrence have low-volume disease, potentially amenable to local therapy. Patients with low-volume disease have a better prognosis as compared with their counterparts. Lymph node recurrence was the most dominant failure pattern.