Predictive Role of GATA3, CD44, p53, and Ki-67 in Recurrence and Progression of Bacillus Calmette–Guérin-Treated Papillary Non-Muscle-Invasive Bladder Cancer

Background: Intravesical Bacillus Calmette–Guérin (BCG) therapy remains the standard adjuvant treatment for intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC). However, substantial rates of recurrence and progression continue to represent major clinical challenges. Therefore, reliable prognostic markers are needed to identify patients who may benefit from closer surveillance or early definitive treatment. This study aimed to evaluate the prognostic value of p53, Ki-67, CD44, and GATA3 expression in predicting recurrence and progression in papillary NMIBC patients treated with intravesical BCG. Methods: Histopathological specimens from patients with papillary NMIBC who underwent transurethral resection of the bladder tumor followed by at least six intravesical BCG instillations, completing the standard induction course, between 2015 and 2020 were retrospectively re-evaluated by a single uropathologist using immunohistochemistry (IHC) for p53, Ki-67, CD44, and GATA3. Positivity thresholds were defined as ≥25% for p53 and Ki-67, and ≥50% for GATA3 and CD44. Associations between marker expression and clinical outcomes were analyzed. Results: Among 156 patients treated with intravesical BCG, 106 met the inclusion criteria and were included in the study. Complete response to BCG therapy was observed in 71 patients (67.0%), while tumor recurrence occurred in 28 patients (26.4%) and disease progression in 7 patients (6.6%). GATA3 negativity was significantly associated with higher recurrence and progression rates (p < 0.001). Elevated p53 and Ki-67 expression levels were significantly associated with disease progression (p = 0.034 and p = 0.017, respectively). Neither p53 nor Ki-67 expression was significantly associated with tumor recurrence (p = 0.461 and p = 0.278, respectively). Conclusions: High p53 and Ki-67 expression levels appear to be associated with an increased risk of disease progression in BCG-treated papillary NMIBC patients, whereas low GATA3 expression may predict both recurrence and progression. These findings suggest that selected IHC markers may contribute to risk stratification in selected patients or consideration of definitive treatment strategies. Larger prospective multicenter studies are warranted to validate the prognostic significance of these markers.