Venous Thromboembolism and Peri-Operative Chemotherapy for Muscle-Invasive Bladder Cancer: A Population-based Study

Abstract

Background:Chemotherapy and major pelvic surgery are established risk factors for venous thromboembolism (VTE). We evaluate the incidence rate, timing, and factors associated with VTE in patients with bladder cancer who underwent radical cystectomy and peri-operative chemotherapy in routine clinical practice.Methods:Electronic records of treatment were linked to the population-based Ontario Cancer Registry to identify all patients who underwent cystectomy for bladder cancer in Ontario 1994–2013. VTE events within 6 months of before or after cystectomy were identified using diagnostic codes recorded on hospital admissions and emergency department visits. Multivariable logistic regression was used to analyze factors associated with VTE prior to surgery, within 90-days of cystectomy, and 120-days after the start of adjuvant chemotherapy.Results:4205 patients had cystectomy and 26% (1084/4205) received peri-operative chemotherapy. The overall incidence rate of VTE within 6 months of cystectomy was 9% (363/4205). VTE rate was highest among those patients treated with neoadjuvant chemotherapy (NACT) compared to patients treated with no chemotherapy or only adjuvant chemotherapy (ACT) (12% vs 8% vs 9%, p = 0.002). Among all VTE events, 10%, 28%, and 61% occurred before, during, and after hospitalization for cystectomy. Pre-operative VTE rate was highest among cases treated with NACT (4%) compared to patients with no chemotherapy (<1%) or ACT (<1%) (p < 0.001). VTE within 90 days of surgery was associated with greater length of hospital admission (p < 0.001) across all treatment groups.Conclusions:A substantial proportion of patients treated with peri-operative chemotherapy will develop VTE. The majority of these occur after discharge from hospital following cystectomy. Extended thromboprophylaxis treatment in high-risk patients including those who receive peri-operative chemotherapy should be considered.

Thromboembolism in Muscle-Invasive Bladder Cancer. A Population-based Nationwide Study

“…The results in the present and other series indicate that neoadjuvant or adjuvant chemotherapy might have a further prolonged effect on the occurrence of VTE [20][21][22][23][29][30][31], possibly due to cisplatin-induced apoptosis and vascular necrosis mediated by the cytotoxic effect of caspases and calpain or vascular damage from central venous catheters or other mechanisms of hypercoagulability [17,18]. Similar results have been found with carboplatin and gemcitabine [19].…”

“…Such treatment must include cisplatin, which may induce damage to the vascular endothelium, in conjunction with central venous catheters and other tumour-related factors, which may all increase the risk of VTE [17,18]. This might explain some of the pathophysiology behind the reported 90-or 180-day cumulative incidences for VTE between 9.6%-26% related to such treatment [19][20][21][22][23].…”

Population‐based analysis of perioperative chemotherapy use, interventions requiring hospitalization and atheroembolic events among patients with non‐metastatic muscle‐invasive bladder cancer

“…The sizable amount of patients whom commence chemotherapy and never make it to RC is an interesting group to hypothesize upon. These findings call into question the generalizability of prior publications in this space that have utilized the actual RC as a start point for cohort assembly 19‐21,29 . When comparing predictors of initiation versus completion of NC, we see a significant difference in baseline characteristics.…”

“…Chemotherapy is associated with a significantly increased risk of atheroembolic events in bladder cancer patients 14‐19 . Numerous additional factors contribute to the risk of thromboembolic events in this patient population including the following: age, frailty, smoking history, pelvic surgery, immobility, obesity, and cardiovascular comorbidities 11‐13,16 .…”

Venous Thromboembolism Rate in Patients With Bladder Cancer According to the Type of Treatment: A Systematic Review

“…There are many possible explanations for the large variations in the rates of VTE observed within this group: for example, the heterogeneity of risk factors in this population that could affect the rate of VTE such as minimal invasive (robotic) cystectomy or open radical cystectomy [10]. Additionally, 33 of the included studies did not state, discuss or categorise BC patients according to confounding factors that alter the rate of VTE such as receiving surgical thromboprophylaxis for 14 or 28 days, which then makes it difficult to compare rates between studies [13,[15][16][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53]. All included studies, with the exception of two [19][20], did not clearly discuss or state the thromboprophylaxis measures employed.…”