# Novel Immune Checkpoint Inhibitor and Antibody–Drug Conjugate Approaches in the Perioperative Management of Muscle-Invasive Bladder Cancer

**Authors:** Joseph Vento, Tian Zhang, Yair Lotan, Solomon Woldu, Qian Qin

PMC · DOI: 10.3390/curroncol33030162 · 2026-03-12

## TL;DR

This paper reviews how immunotherapy and antibody-drug conjugates are changing treatment for muscle-invasive bladder cancer before and after surgery.

## Contribution

The paper provides a review of recent clinical trials and treatment shifts involving immune checkpoint inhibitors and antibody-drug conjugates in muscle-invasive bladder cancer.

## Key findings

- Immunotherapy and antibody-drug conjugates are now standard in perioperative care for muscle-invasive bladder cancer.
- Combination therapies improve survival outcomes in advanced urothelial carcinoma.
- Ongoing trials may further change treatment approaches for this cancer type.

## Abstract

The approach to treating muscle-invasive bladder cancer is shifting toward immunotherapy-based regimens and increasing use of antibody drug conjugates before and after surgery. In this paper, we review the key studies that led to these shifts in the perioperative management of muscle-invasive bladder cancer.

Immune checkpoint inhibitors and antibody drug conjugate combinations have revolutionized the management of patients with advanced and metastatic urothelial carcinoma, offering unprecedented survival outcomes. These treatments are now moving into earlier stages of disease, including perioperative treatments for patients with muscle-invasive bladder cancer planning for curative-intent radical cystectomy. In this setting, there are now standard-of-care options for adjuvant immune checkpoint inhibitors with or without prior neoadjuvant chemotherapy, perioperative immune checkpoint plus cytotoxic chemotherapy combinations, and perioperative immune checkpoint inhibitor plus antibody drug conjugate combinations. This review will evaluate key clinical trials that led to modern standards of care involving these classes of drugs and highlight ongoing clinical trials that may further shift treatment paradigms for muscle-invasive bladder cancer. Key efficacy and toxicity considerations will be reviewed, and available evidence for biomarkers will be evaluated. As immune checkpoint inhibitors and antibody drug conjugates continue to demonstrate improved outcomes across the spectrum of bladder cancer treatment, understanding their role in the muscle-invasive disease state is crucial to managing patients with this condition.

## Linked entities

- **Diseases:** urothelial carcinoma (MONDO:0040679)

## Full-text entities

- **Genes:** CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, PDCD1 (programmed cell death 1) [NCBI Gene 5133] {aka ADMIO4, AIMTBS, CD279, PD-1, PD1, SLEB2}, GGT1 (gamma-glutamyltransferase 1) [NCBI Gene 2678] {aka CD224, D22S672, D22S732, GGT, GGT 1, GGTD}, ERBB2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 2064] {aka CD340, HER-2, HER-2/neu, HER2, MLN 19, MLN-19}, UGT1A1 (UDP glucuronosyltransferase family 1 member A1) [NCBI Gene 54658] {aka BILIQTL1, GNT1, HUG-BR1, UDPGT, UDPGT 1-1, UGT1}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, TACSTD2 (tumor associated calcium signal transducer 2) [NCBI Gene 4070] {aka EGP-1, EGP1, GA733-1, GA7331, GP50, M1S1}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, CTLA4 (cytotoxic T-lymphocyte associated protein 4) [NCBI Gene 1493] {aka ALPS5, CD, CD152, CELIAC3, CTLA-4, GRD4}, NECTIN4 (nectin cell adhesion molecule 4) [NCBI Gene 81607] {aka EDSS1, LNIR, PRR4, PVRL4, nectin-4}, LAG3 (lymphocyte activating 3) [NCBI Gene 3902] {aka CD223}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}
- **Diseases:** cancer (MESH:D009369), MIBC (MESH:D000093284), pCR (MESH:D005598), ocular disorders (MESH:D005128), death (MESH:D003643), pneumonitis (MESH:D011014), motor and sensory nerve toxicities (MESH:D010523), ocular toxicity (MESH:D000081028), upper-tract disease (MESH:D012141), injury to (MESH:D014947), la (MESH:D049310), pruritis (MESH:D011537), urinary tract infections (MESH:D014552), hematuria (MESH:D006417), cerebrovascular accident (MESH:D020521), invasive (MESH:D009361), Stevens-Johnson Syndrome (MESH:D013262), skin reactions (MESH:D012871), hypersensitivity (MESH:D004342), neuropathy (MESH:D009422), endocrine toxicities (MESH:D004700), hypoesthesia (MESH:D006987), gastrointestinal toxicity (MESH:D005767), Bladder Cancer (MESH:D001749), alopecia (MESH:D000505), gastric cancer (MESH:D013274), neutropenia (MESH:D009503), anemia (MESH:D000740), neurotoxicity (MESH:D020258), hypokalemia (MESH:D007008), rash (MESH:D005076), hyperglycemia (MESH:D006943), upper tract urothelial cancer (MESH:D014523), cardiotoxicity (MESH:D066126), diarrhea (MESH:D003967), toxicities (MESH:D064420), -related adverse (MESH:D002318)
- **Chemicals:** methotrexate (MESH:D008727), T (MESH:D014316), trastuzumab (MESH:D000068878), atezolizumab (MESH:C000594389), tremelimumab (MESH:C520704), paclitaxel (MESH:D017239), vinblastine (MESH:D014747), creatinine (MESH:D003404), ipilimumab (MESH:D000074324), CTLA4 antibody (-), GC (MESH:C057580), SN-38 (MESH:D000077146), doxorubicin (MESH:D004317), disitamab vedotin (MESH:C000722994), DV (MESH:D004028), nivolumab (MESH:D000077594), pembrolizumab (MESH:C582435), cisplatin (MESH:D002945), gemcitabine (MESH:D000093542), EV (MESH:C000632577), SG (MESH:C000608132), trastuzumab deruxtecan (MESH:C000614160), carboplatin (MESH:D016190), docetaxel (MESH:D000077143), durvalumab (MESH:C000613593), MMAE (MESH:C495575), vinflunine (MESH:C111217), avelumab (MESH:C000609138), platinum (MESH:D010984), relatlimab (MESH:C000721227), toripalimab (MESH:C000656314)
- **Species:** Homo sapiens (human, species) [taxon 9606]

---
Source: https://tomesphere.com/paper/PMC13025583