Cancers

Background/Objectives: The present study aimed to compare the efficacy and safety of intravesical gemcitabine versus Bacillus Calmette–Guérin administered after transurethral resection of bladder tumor in patients with non-muscle-invasive bladder cancer. Methods: A comprehensive literature search was conducted using PubMed, Embase, and the Cochrane Library databases up to September 2025. Studies were eligible for inclusion if they were comparative studies evaluating intravesical gemcitabine versus Bacillus Calmette–Guérin following transurethral resection of bladder tumor. The primary outcomes were recurrence-free survival, progression-free survival, and incidence of adverse events. Pooled hazard ratios were calculated using a random-effects model based on log hazard ratios and standard error values. Results: Seven studies comprising approximately 774 patients were included in this analysis. The pooled hazard ratio was 0.80 (95% confidence interval, 0.42–1.53) for recurrence-free survival and 0.76 (95% confidence interval, 0.46–1.26) for progression-free survival, indicating no significant difference between gemcitabine and Bacillus Calmette–Guérin. However, gemcitabine was associated with a significantly lower incidence of adverse events, with a pooled odds ratio of approximately 0.48 (95% confidence interval, 0.27–0.86). Risk-of-bias assessment revealed that most randomized trials had “some concerns” based on the Risk of Bias 2 tool, whereas non-randomized studies were rated as having “moderate to serious” risk of bias according to the Risk of Bias in Non-randomized Studies of Interventions tool. Conclusions: Gemcitabine demonstrated an oncologic efficacy comparable to that of Bacillus Calmette–Guérin in terms of recurrence and progression outcomes while showing a substantially lower incidence of treatment-related toxicities.

Objective: Radiotherapy remodels the tumor microenvironment (TME) and may enhance the efficacy of immunotherapy in cancer treatment, particularly in patients with large, unresectable hepatocellular carcinoma (HCC) complicated by portal vein tumor thrombus (PVTT). Because of these unique effects, a growing body of research has found that stereotactic body radiation therapy (SBRT) combined with transcatheter arterial chemoembolization (TACE) or programmed death protein 1 (PD-1) inhibitors has a synergistic impact on unresectable advanced hepatocellular carcinomas (HCCs) larger than 5 cm in diameter. We aim to explore the efficacy of these treatment modalities through a network meta-analysis (NMA). Methods and Analysis: We evaluated the efficacy and safety of different SBRT-based treatment modalities for large advanced HCCs with PVTT (tumor diameter ≥ 5 cm), with primary endpoints including overall survival (OS), progression-free survival (PFS), and grade 3–4 severe adverse events (SAEs). Results: Eighteen studies comprising 2303 patients were included. SBRT combined with transcatheter arterial chemoembolization (SBRT + TACE) demonstrated significantly superior overall survival compared with other monotherapy or combination strategies. Most other treatment regimens showed comparable PFS outcomes. Notably, SBRT alone and SBRT combined with PD 1 inhibitors (SBRT + PD 1) were associated with significantly lower incidences of severe adverse events compared with other treatment modalities; all of these reported SAEs were manageable with appropriate clinical intervention. Conclusions: For patients with large (≥5 cm) advanced HCC with PVTT, SBRT combined with TACE was associated with superior OS and PFS compared with other treatment strategies. These findings suggest potential synergistic interactions between SBRT and TACE or immunotherapy. Further high-quality prospective trials are warranted to validate these observations and clarify the underlying molecular mechanisms. Our results provide evidence to inform therapeutic decision-making in advanced HCC.

Purpose: HER2-targeted therapy has been incorporated into the standard neoadjuvant treatment (NAT) regimen for HER2-positive early-stage breast cancer, yet a subset of patients have shown a limited pathological response. This study aimed to evaluate clinicopathological factors associated with NAT sensitivity and to develop a predictive model. Methods: This retrospective study included 13,004 HER2-positive breast cancer patients from the National Cancer Database (2010–2022) who received neoadjuvant chemotherapy plus HER2-targeted therapy. Pathological complete response (pCR) was defined as no residual invasive carcinoma in the breast and axillary lymph nodes (ypT0/is, ypN0). NAT sensitivity was additionally defined using clinical-to-pathologic stage migration according to the AJCC 8th edition criteria. Baseline characteristics and overall survival (OS) were compared between NAT-sensitive and NAT-insensitive groups. A multivariable logistic regression model was developed based on age, clinical T stage, clinical N stage, histologic subtype, tumor grade, and hormone receptor (HR) status. Model performance was assessed using the area under the receiver operating characteristic curve and calibration curves. Results: Among the patients included, 3660 (28.1%) achieved pCR. Based on the predefined stage-based criteria, 10,451 (80.4%) were classified as NAT-sensitive and 2553 (19.6%) as NAT-insensitive. NAT-insensitive patients were older and more likely to present with clinical T1c and node-negative disease, whereas NAT-sensitive patients more frequently had higher clinical T and N stages. HR-positive and lower tumor grades were significantly associated with treatment insensitivity. NAT-insensitive patients demonstrated significantly worse OS compared with NAT-sensitive patients (p < 0.001). The predictive model showed acceptable discrimination with AUCs of 0.762 in the training cohort and 0.776 in the validation cohort, demonstrating good calibration. Conclusions: NAT sensitivity in HER2-positive early-stage breast cancer exhibited substantial biological and clinical heterogeneity in real-world practice. A younger age, higher clinical stage, invasive ductal histology, higher tumor grade, and HR-negative status were associated with improved responses. A predictive model based on routinely available baseline variables demonstrated reasonable performance for estimating treatment sensitivity, supporting its potential utility for baseline risk stratification pending external validation.