To evaluate the long-term efficacy of one-shot neoadjuvant IAC versus NIAC before RC for bladder cancer, we retrospectively reviewed all patients treated with RC/PLND between October 2006 and November 2015 for urothelial carcinoma of the bladder without distant metastasis in the Department of Urology, Beijing Chao-Yang Hospital. This study was approved by the Institutional Review Board of Beijing Chao-Yang Hospital. To prevent selection bias of the learning curve, we chose patients whose operations were performed by the same laparoscopic surgeon (Xing).
2.1. Patient eligibility and selection
The diagnosis of bladder cancer was made using imaging findings [ultrasonography, computed tomography (CT), magnetic resonance imaging], chest radiography with or without cystoscopic biopsy, and routine laboratory analysis. The TNM classification was staged according to the American Joint Committee on Cancer staging system (7th 2010). Clinical staging was based on the physical examination, imaging findings, and biopsies of bladder tumours before the start of therapy. All patients had pathologic documentation of urothelial carcinoma, which was defined as local disease (pT2-4N0/+M0) or non-muscle-invasive bladder cancer (NMIBC), but the patients were at high risk for tumours [T1G3 with concurrent carcinoma in situ (CIS) at diagnosis, multiple and/or large T1G3, recurrent T1G3]. The pathological results were reviewed by the two genitourinary pathologists after matching the two groups. Patients with pelvic lymph node metastasis diagnosed by imaging studies were eligible. Patients who underwent neoadjuvant intravesical chemotherapy but not adjuvant chemotherapy were ineligible. Patients who had nonurothelial carcinoma (n=11), preoperative pelvic irradiation (n=5), missing clinical information (n=11) or who were lost to follow-up (n=17) were excluded, leaving 149 patients available for analysis.
2.2. IAC treatment protocol
Gemcitabine (700-1000 mg/m2) and cisplatin (35-70 mg/m2) were infused into the femoral artery to the internal iliac artery using the Seldinger technique. The approach in 15 patients was from the bilateral internal iliac artery, while the unilateral internal iliac artery was used in 11 patients, and the approach was based on tumour location as determined by imaging tests, cystoscopy and digital subtraction angiography. Complete blood counts and biochemical studies were performed every 2 weeks. Patients were evaluated for treatment responses using imaging tests and were assigned to receive RC/PLND 4 weeks after IAC to allow adequate recovery.
2.3. Statistical analysis
2.3.1. Baseline comparison between the intra-arterial chemotherapy and no intra-arterial chemotherapy groups
Key baseline characteristics [gender, age, body mass index (BMI), hypertension, diabetes, age-adjusted Charlson comorbidity index (CCI), American Society of Anesthesiologists (ASA) score, Eastern Cooperative Oncology Group performance status (ECOG PS), smoking history, time between tumour confirmation and RC, preoperative irradiations, and follow-up duration)] were compared between the IAC and NIAC groups.
Continuous characteristics were compared by independent samples t-tests when the data were normally distributed and by Wilcoxon rank sum tests when the data were nonnormally distributed. The Pearson chi-square test or Fisher’s exact test was performed to calculate p values for categorical factors. The Wilcoxon rank sum test was performed to compare ordinal values.
2.3.2. Propensity-score matching
We performed matched group analysis to control for differences between groups due to selection bias and confounding factors. Propensity-score matching was performed based on key characteristics, including gender, age, BMI, hypertension, diabetes, age-adjusted CCI, ASA score, ECOG PS, smoking history, time between tumour confirmation and RC, preoperative irradiations and follow-up duration. Propensity scores were estimated using a logistic regression model. A 1:3 matching with no replacement was applied using the nonrandom package in R (http://www.r-project.org). A t-test or Wilcoxon rank sum test, or Pearson’s chi-square test or Fisher’s exact test, was applied to compare differences in covariates after matching to demonstrate that matching enhanced the balance between groups.
2.3.3. Oncological outcomes in the matched group
We compared oncological outcomes in a matched cohort using t-tests, Wilcoxon rank sum tests, Pearson’s chi-square tests and Fisher’s exact tests. The Kaplan-Meier method was utilized to estimate survival probabilities, and the log-rank test was used to compare survival outcomes between different groups. A multivariable Cox proportional hazards model was used to estimate survival outcomes.
All statistical analyses, except for propensity-score matching, were performed with IBM SPSS version 19.0 (IBM Corp., Armonk, NY). The threshold for statistical significance was a two-sided p value of <0.05. All statistical plots were drawn in GraphPad Prism version 6.0 (GraphPad Software Inc., La Jolla, CA 92037 USA).