The Risk of Thromboembolism in Patients with Muscle Invasive Bladder Cancer before and after Cystectomy Depending on Blood Group and Neoadjuvant Chemotherapy-A Multicentre Retrospective Cohort Study.

PURPOSE: Previous studies have indicated that patients with muscle-invasive bladder cancer with non-O blood types have an increased risk of experiencing thromboembolic events (TEEs). This is finding is in relation to neoadjuvant-chemotherapy (NAC)-naïve patients. AIM: to establish the risk of TEEs and any association with blood types among NAC patients as well as NAC-naïve patients. METHODS: Cystectomized patients at four centres treated from 2009 to 2018 (n = 244) were analysed. The quantities of patients corresponding to each blood group were as follows: A-108 (44%); O-99 (41%); B-30 (12%); and AB-7 (3%). NAC patients (n = 167) and NAC-naïve NAC-eligible patients (n = 77) were assessed. In total, 54 women (22%) and 190 men (78%), with a median age of 69 years, were included in the study. The occurrence of any type of TEE from six months pre-cystectomy to 12-24 months after was analysed using logistic regression adjusted for NAC and confounders. RESULTS: Sixty-six TEEs were detected in 21% of the patients (n = 52). Pulmonary embolus (n = 33) and deep venous thrombosis (n = 11) were the most common forms. No significant differences between blood types were found in the analysis, although B blood type had a nearly significant increased crude risk compared with O blood type, for which there was an OR of 2.48 (95% CI 0.98-6.36). Adjustment for NAC and covariates weakened the OR, which plummeted to 1.98 (95% CI 0.71-5.51). CONCLUSIONS: No significant associations were found between blood types and TEE occurrences in this cohort including both NAC and NAC-naïve NAC-eligible patients.

A prospective multicenter study of visual response-evaluation by cystoscopy in patients undergoing neoadjuvant chemotherapy for muscle invasive urinary bladder cancer.

PURPOSE: To evaluate a method of transurethral visual response-staging in patients with urothelial muscle-invasive urinary bladder cancer (MIBC), undergoing neoadjuvant chemotherapy (NAC) and radical cystectomy (RC). METHODS: A prospective study at four Swedish cystectomy centers, cystoscopy was performed after final NAC-cycle for MIBC. Fifty-six participants underwent cystoscopy for visual staging of the tumor immediately pre-RC. Visual assessments were correlated to pathoanatomical outcomes post-RC. RESULTS: Seventeen tumors were classified as complete response (CR), i.e. pT0. Twenty-five patients had residual MIBC and 14 had non-muscle invasive residual tumors (NMIBC). Of the 39 patients with residual tumor, 25 were correctly identified visually (64%). Eleven patients were pN+. The diagnostic accuracy of cystoscopy to correctly identify complete response or remaining tumor was 70% (CI = 56-81%) with a sensitivity of 64% (CI = 47-79%), specificity 82% (CI = 57-96%), PPV 89% (CI = 74-96%) and NPV 50% (CI =38-61%). Twenty-eight cystoscopy evaluations showed signs of residual tumors and 3/28 (11%) were false positive. In 4/14 patients assessed having residual NMIBC the estimates were correct, 8/14 had histopathological MIBC and 2/14 had CR. In 11/14 patients (79%), the suggested visual assessment of MIBC was correct, 2/14 had NMIBC and 1/14 had CR. Twenty-eight cystoscopies had negative findings, 14 were false negatives (50%), when cystoscopy falsely predicted pT0. Among them there were eight patients with pTa, pT1 or pTis and six MIBC-tumors. In 17 patients with histopathological pT0, 14 were correctly identified with cystoscopy (82%). CONCLUSION: Cystoscopy after the final NAC-cycle cannot robustly differentiate between NAC-responders and non-responders. Visually, negative MIBC-status cannot be determined safely.

The increased risk for thromboembolism pre-cystectomy in patients undergoing neoadjuvant chemotherapy for muscle-invasive urinary bladder cancer is mainly due to central venous access: a multicenter evaluation.

PURPOSE: To investigate if patients receiving neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) had an increased risk of thromboembolic events (TEE) and to evaluate when these events occur on a timeline starting from 6 months pre-cystectomy, during NAC-administration and 60 months post-cystectomy. METHODS: Two hundred and fifty five patients undergoing radical cystectomy during 2009-2014 at three Swedish cystectomy centers (Umeå, Linköping and Sundsvall) were in-detail reviewed retrospectively, using individual medical records. One hundred and twenty nine patients were ineligible for analysis. NAC patients (n = 67) were compared to NAC-naïve NAC-eligible patients (n = 59). The occurrence of TEE was divided into different periods pre-cystectomy and post-cystectomy. Statistical analyses included Chi-squared and logistical regression tests. RESULTS: Significant associations were found between receiving NAC and acquiring a TEE during NAC therapy pre-cystectomy. All but one pre-cystectomy event was venous and all but one of the patients received NAC. 31% (14/45) of TEEs occurred pre-cystectomy. The incidence of TEEs pre-cystectomy in NAC-naive NAC-eligible patients was only 10% (2/20), whereas the incidence of TEEs in NAC patients occurred pre-cystectomy in 48% (12/25) and 11/12 incidents were detected during NAC therapy-this including 7/11 (64%) incidents affecting veins in anatomical conjunction with the placement of central venous access for chemotherapy administration. CONCLUSIONS: There is a significantly increased risk for TEE pre-cystectomy during chemotherapy administration in MIBC patients receiving NAC, compared to the risk in NAC-naïve NAC-eligible MIBC patients. In 64% of the pre-RC TEEs in NAC patients, there was a clinical connection to placement of central venous access.