ABSTRACT
INTRODUCTION: To mirror guideline-adherence for pT1 bladder cancer treatment in Northern Germany. MATERIALS AND METHODS: Overall, 111 patients with pT1 diagnosis were treated at 4 institutions. Guideline-adherence was defined as repeat resection, instillation, and quarterly cystoscopy. Patient characteristics and pathological parameters were assessed. We summarized patients using descriptive analyses and evaluated guideline-adherence within selected subgroups. We created a multivariable model to identify predictors of guideline-adherence. RESULTS: Median age was 75 years (range 39-94 years), multifocal tumors were found in 44.1%, early instillation was performed in 33.3%, and repeat resection was performed in 77.5%. Of 62.2% who underwent instillation, 59.4% received BCG, while 40.6% received Mitomycin C or other agents. Cystoscopic follow-up was performed in 81.8%. Guideline-adherence was met in 56.8%. Patients aged below the median met adherence metrics more often compared to those above the median (66.7 vs. 46.3%; p = 0.030). Men more frequently met adherence metrics compared to women (62.1 vs. 37.5%; p = 0.038). More patients with multifocal tumors met all 3 adherence metrics (69.4 vs. 48.0%; p = 0.050), as compared to those with unifocal lesions. In multivariable analyses, age-adjusted comorbidity (OR 0.75; 95% CI 0.59-0.94; p = 0.011) and multifocality (OR 2.62; 95% CI 1.09-6.27; p = 0.031) were predictors of guideline-adherence. CONCLUSIONS: We found non-adherence in more than one-third of patients and disparities among patients of different age and according to tumor focality. Larger samples and prospective studies are needed to delineate and eradicate treatment disadvantages in these high-risk patients.
Subject(s)
Guideline Adherence , Medical Oncology/standards , Urinary Bladder Neoplasms/diagnosis , Urinary Bladder Neoplasms/therapy , Administration, Intravesical , Adult , Aged , Aged, 80 and over , Cystoscopy/methods , Female , Humans , Male , Medical Oncology/methods , Middle Aged , Multivariate Analysis , Neoplasm Recurrence, Local/pathology , Prospective Studies , Retrospective Studies , Urinary Bladder/pathologyABSTRACT
BACKGROUND: The identification of protein biomarkers to guide treatment decisions regarding adjuvant therapies for high-risk non-muscle-invasive bladder cancer (NMIBC) has been of increasing interest. Evidence of the impact of tumor suppressor gene product p53 and cell proliferation marker Ki-67 on oncologic outcomes in bladder cancer patients at highest risk of recurrence and progression is partially contradictory. We sought to mirror contemporary expression patterns of p53 and Ki-67 in a select cohort of patients with pT1 bladder cancer. METHODS: Patients from four Northern German institutions with a primary diagnosis of pT1 bladder cancer between 2009 and 2016 and complete data regarding p53 or Ki-67 expression status were included for final analyses. Baseline patient characteristics (age, gender, age-adjusted Charlson comorbidity index) and tumor characteristics [diagnostic sequence, tumor focality, concomitant carcinoma in situ, 1973 World Health Organization (WHO) grading, lymphovascular invasion, adjuvant instillation therapy] were abstracted by retrospective chart review. Immunohistochemistry for detection of p53 and Ki-67 expression was performed according to standardized protocols. Microscopic analyses were performed by central pathologic review. First, we compared patients with positive vs. negative p53 expression and Ki-67 labeling index [>40% vs. ≤40%; cutoffs based on best discriminative ability in univariable Cox regression analysis with disease-free survival (DFS) as endpoint] with regard to baseline and tumor characteristics. Second, we evaluated the effect of biomarker positivity on DFS by plotting univariable Kaplan-Meier curves and performing uni- and multivariable Cox regression analyses. RESULTS: Of 102 patients with complete information on p53 status, 44 (43.1%) were p53 positive, and they more often harbored concomitant carcinoma in situ (50.0% vs. 27.6%; P=0.032) and 1973 WHO grade 3 (97.7% vs. 69.0%; P=0.001) compared to their p53 negative counterparts. Of 79 patients with complete information on Ki-67 expression status, 30 (38.0%) had a labeling index >40%. Mean Ki-67 labeling index was higher in WHO grade 3 vs. grade 2 tumors (45.8 vs. 29.7; P=0.004). At a median follow-up of 51.0 months, 31/91 patients with complete follow-up information (34.1%) suffered from disease recurrence or progression. In univariable Kaplan-Meier analyses, no difference regarding DFS was found in p53 positive vs. negative (P=0.8) or Ki-67 labeling index >40% vs. ≤40% (P=0.078) patients. In multivariable analyses, Ki-67 labeling index >40% remained an independent predictor of DFS [hazard ratio (HR), 2.66; 95% confidence interval (CI), 1.02-6.95; P=0.046], after adjusting for p53 expression and lymphovascular invasion. However, p53 status was not associated with our endpoint (P=0.8). CONCLUSIONS: While we found an association of a Ki-67 labeling index >40% and shorter DFS in pT1 bladder cancer patients, this did not hold true for p53 positivity. Future research is needed to identify additional microscopic and molecular risk factors and biomarker panels to improve risk stratification and guide adjuvant therapies in those patients.