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

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 F-18-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

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

Early biomarkers related to secondary primary cancer risk in radiotherapy treated prostate cancer patients: IMRT versus IMAT

AbstractPurposeTo investigate whether rotational techniques (Volumetric Modulated Arc Therapy – VMAT) are associated with a higher risk for secondary primary malignancies compared to step-and-shoot Intensity Modulated Radiation Therapy (ss-IMRT). To this end, radiation therapy (RT) induced DNA double-strand-breaks and the resulting chromosomal damage were assessed in peripheral blood T-lymphocytes of prostate cancer (PCa) patients applying γH2AX foci and G0 micronucleus (MN) assays.Methods and materialsThe study comprised 33PCa patients. A blood sample was taken before start of therapy and after the 1st and 3rd RT fraction to determine respectively the RT-induced γH2AX foci and MN. The equivalent total body dose (DETB) was calculated based on treatment planning data.ResultsA linear dose response was obtained for γH2AX foci yields versus DETB while MN showed a linear-quadratic dose response. Patients treated with large volume (LV) VMAT show a significantly higher level of induced γH2AX foci and MN compared to IMRT and small volume (SV) VMAT (p<0.01). Assuming a linear-quadratic relationship, a satisfactory correlation was found between both endpoints (R2 0.86).ConclusionsBiomarker responses were governed by dose and irradiated volume of normal tissues. No significant differences between IMRT and rotational therapy inherent to the technique itself were observed