We retrospectively collected information on MIBC patients treated in Tianjin Union Medical Center from January 2019 to January 2022.

Inclusion criteria were: (1) MIBC cases with stages T2 to T3, with pathological biopsy confirming urothelial carcinoma; (2) maximal transurethral resection of bladder tumor (cTURBT) and postoperative intravenous chemotherapy with gemcitabine combined with cisplatin (GC) or RC48-ADC, including 6 cycles for the postoperative GC chemotherapy or 6 cycles for RC48-ADC treatment.

Exclusion criteria were: (1) MIBC with distant metastasis; (2) completion of less than 6 cycles of postoperative GC chemotherapy or RC48-ADC; (3) incomplete follow-up information.

A total of 217 eligible MIBC patients were included in this study. Of these patients, 112 refused RC and actively requested bladder-preservation comprehensive therapy, while 105 were unable to tolerate RC due to old age, severe cardiopulmonary or cerebral diseases, or coagulation dysfunction. Patients and their families provided signed informed consent. All patients underwent preoperative urological ultrasound, abdominal CT, CTU, pelvic MRI, cystoscopy, and tissue biopsy to confirm the diagnosis and to determine the clinical stage and pathological grade.

The research roadmap of bladder-preservation comprehensive treatment is shown in Fig. 1. All 217 patients underwent cTURBT, of whom 175 received GC chemotherapy, while the remaining 42, due to intolerance to GC chemotherapy and HER2 positivity (IHC 2 + or 3 +), received RC48-ADC treatment. The clinicopathological characteristics and survival data collected included gender, age, smoking history, primary tumor site, tumor size, single or multiple, clinical stage, pathological grade, pelvic lymph node metastasis, HER2 expression levels, ECOG score, treatment status, and follow-up of patient recurrence status and survival time. During the follow-up period, B-mode ultrasound was performed every 3 months for the first year; pelvic MRI and cystoscopy were carried out every 3 to 6 months and after 24 months postoperatively; and B-mode ultrasound, pelvic MRI, and cystoscopy were conducted every 6 months. This study was approved by the Ethics Committee of Tianjin People's Hospital.

Research Roadmap. MIBC, muscle-invasive bladder cancer; cTURBT, maximal transurethral resection of bladder tumor; GC, intravenous chemotherapy of gemcitabine combined with cisplatin; RFS, recurrence-free survival; OS, overall survival

In cTURBT, resection of grossly visible tumors was performed, and patients with T3 stage disease underwent resection to visible extravesical fat. Electrocoagulation of the bladder mucosa was performed within 1 cm around the tumor base. In GC chemotherapy, patients received intravenous chemotherapy with the GC regimen one week postoperatively, with each 21 days constituting one chemotherapy cycle, for a total of six cycles. RC48-ADC was administered at a dose of 2 mg/kg, once every two weeks, for a total of six administrations.

All bladder tumor tissue specimens from patients were assessed for HER2 expression by immunohistochemical staining (IHC). At least two experienced pathologists evaluated HER2 expression per the 2018 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines. Immunohistochemical staining of HER2 expression levels at 0, 1 + , 2 + , and 3 + is shown in Fig. 2. HER2 expression at 2 + or 3 + was defined as HER2 positive, while 0 or 1 + was defined as HER2 negative. The rate of HER2 positivity and its correlations with clinical characteristics were analyzed.

Immunohistochemical staining of HER2 expression levels at 0, 1 + , 2 + , and 3 +

Of the 175 patients administered cTURBT combined with GC chemotherapy for bladder-preservation comprehensive treatment, 92 and 83 were HER2-negative and HER2-positive, respectively. Recurrence-free survival (RFS) and overall survival (OS) in HER2-negative and HER2-positive patients were compared to analyze the correlation between HER2 expression and prognosis after bladder-preservation comprehensive treatment.

RFS and OS in the 83 HER2-positive patients administered cTURBT combined with GC chemotherapy and the 42 HER2-positive patients administered cTURBT combined with RC48-ADC chemotherapy were compared to analyze the differences in prognosis between the two treatment methods; the adverse reactions of both chemotherapy methods were also compared. Adverse reactions after chemotherapy were evaluated per the grading standards set by the World Health Organization [14].

Count data with normal distribution were represented by mean ± standard deviation compared by the t-test or analysis of variance. Categorical variables were represented by frequency and compared by the chi-square test or Fisher’s exact test. The Kaplan–Meier method was used to analyze RFS and OS, with P < 0.05 indicating a statistically significant difference. Statistical analysis was performed with the SPSS software (SPSS Inc., Chicago, Illinois) version 22.0.