From the moment Charles Huggins first demonstrated the hormone dependence of prostate cancer in 1941, genitourinary oncology has evolved from an era of limited treatment possibilities into one defined by precision medicine and therapeutic innovation.The Urologic Oncology Chronicle 2026 revisits the landmark discoveries, transformative clinical trials, and paradigm-shifting therapies that have shaped the field over the past decades. From androgen deprivation therapy and chemotherapy to targeted therapy, immunotherapy, antibody-drug conjugates (ADCs), radioligand therapy, and bispecific combinations, GU oncology has entered an era of increasingly personalized care.
Among the most striking advances has been the rapid transformation of urothelial carcinoma management. ADC-based therapies—particularly those targeting HER2—have dramatically expanded treatment possibilities for patients with advanced disease.
A major milestone came on April 10, 2026, when the combination of disitamab vedotin plus toripalimab received approval as first-line treatment for HER2-expressing locally advanced or metastatic urothelial carcinoma. Published in the The New England Journal of Medicine, this China-developed strategy marked a major breakthrough in precision therapy for urothelial carcinoma and demonstrated China’s growing leadership in global GU oncology innovation.
Urothelial Carcinoma: Entering the ADC-Immunotherapy Era
Professor Zhisong He
For many years, platinum-based chemotherapy represented the standard first-line treatment for advanced urothelial carcinoma (UC), but its efficacy had reached a therapeutic plateau, while toxicity limited eligibility for many patients.
The approval of enfortumab vedotin plus pembrolizumab fundamentally changed this landscape.
The EV-302 study showed that the combination extended median overall survival from 16.1 months with platinum chemotherapy to 31.5 months, reducing the risk of death by 53% (HR=0.47). This landmark result signaled the beginning of a new ADC-immunotherapy era in UC.
As research continues, this treatment paradigm is expected to expand beyond metastatic disease into later-line settings, perioperative therapy, and even neoadjuvant treatment for muscle-invasive bladder cancer.
Professor Jianming Guo
Across the three major GU malignancies, new drugs and combination strategies have nearly doubled patient survival outcomes in recent years.
In renal cell carcinoma, toripalimab plus axitinib improved first-line accessibility for advanced disease in China. In prostate cancer, intensified androgen receptor-targeted therapy, chemotherapy, and radioligand therapy significantly prolonged survival.
But one of the most exciting breakthroughs came from the RC48-C016 study in urothelial carcinoma.
Disitamab vedotin plus toripalimab achieved a median OS of 31.5 months—comparable to EV-based therapy—with substantially improved tolerability compared with chemotherapy. Grade ≥3 treatment-related adverse events occurred in 55.1% of patients versus 86.9% in the chemotherapy arm.
This China-developed ADC-immunotherapy combination not only introduced a precision treatment option for HER2-expressing UC, but also demonstrated that Chinese innovation can influence international treatment standards.
Professor Xiaojie Bian
The approval of disitamab vedotin plus toripalimab as first-line treatment for HER2-expressing advanced UC represents more than a domestic success story—it delivered one of the highest response rates ever observed in a biomarker-selected UC population globally.
In RC48-C016:
- Median progression-free survival reached 13.1 months versus 6.5 months with chemotherapy
- Median OS reached 31.5 months versus 16.9 months
- Objective response rate reached 76.1%
- Disease control rate reached 91.4%
- Median duration of response reached 14.6 months
Importantly, the regimen benefits the entire HER2-expressing population (IHC 1+/2+/3+), regardless of cisplatin eligibility.
Beyond prolonging survival, the regimen also significantly improved tolerability, allowing patients not only to live longer, but to live better.
Renal Cell Carcinoma: The Era of IO-TKI Combination Therapy
Professor Juan Li
Advanced RCC treatment has now fully entered the immunotherapy-targeted combination era.
The RENOTORCH study established the benefit of toripalimab plus axitinib in intermediate- and poor-risk populations, while the positive ETER100 study expanded evidence to the broader RCC population.
ETER100 demonstrated that cadonilimab plus anlotinib significantly improved outcomes versus sunitinib in first-line advanced RCC, with median PFS reaching 19 months (HR=0.53).
Based on these findings, the combination received regulatory approval in China in 2025, expanding access to effective IO-TKI therapy.
Professor Yi He
I chose to highlight belzutifan because I personally participated in its phase III development program.
During the study, I witnessed patients who had already progressed after targeted therapy and immunotherapy achieve remarkable responses after treatment with belzutifan.
The drug received FDA approval in 2021 for VHL-associated RCC and later expanded into advanced RCC treatment in 2023, becoming the first approved HIF-2α inhibitor.
Some patients experienced tumor shrinkage exceeding 50%, offering renewed hope in heavily pretreated disease.
Prostate Cancer: Earlier Intensification, Better Outcomes
Professor Benkang Shi
The use of next-generation androgen receptor inhibitors has steadily moved earlier into hormone-sensitive disease settings.
This shift has been particularly beneficial for younger patients, those with high Gleason scores, and patients with biologically aggressive tumors.
Darolutamide was approved in China in 2021 for high-risk non-metastatic castration-resistant prostate cancer (nmCRPC), based on the ARAMIS study.
Compared with ADT alone, darolutamide extended median metastasis-free survival from 18.4 months to 40.4 months (HR=0.41), while reducing all-cause mortality risk by 31% (HR=0.69).
Importantly, adverse event rates remained comparable to placebo.
In the Chinese Society of Clinical Oncology prostate cancer guidelines, darolutamide is now listed as a Class I recommendation with Level 1A evidence for nmCRPC patients with PSA doubling time ≤10 months.
We hope these innovative therapies will become increasingly accessible through broader reimbursement coverage in the future.
Conclusion
The evolution of GU oncology has accelerated dramatically in recent years, driven by ADCs, immunotherapy combinations, molecular stratification, and novel targeted therapies.
From urothelial carcinoma to RCC and prostate cancer, the field is rapidly moving away from “one-size-fits-all” treatment toward increasingly individualized precision care.
The advances highlighted in this chronicle not only reflect scientific progress, but also symbolize the growing influence of Chinese clinical research and innovation on the global oncology landscape.
