From the first glimmer of insight in 1941, when Professor Charles Huggins discovered the hormone dependence of prostate cancer, to today’s flourishing era of precision oncology, the field of genitourinary cancers has traveled an extraordinary path—from silence and therapeutic limitation to an age of precision-driven breakthroughs. As both a participant in and witness to this journey, I feel deeply honored and profoundly inspired.This Chronicles of Genitourinary Oncology is more than a retrospective of landmark milestones over the past seven decades. It is a testament to the collective wisdom, perseverance, and courage of researchers, clinicians, and patients around the world. From the early days of androgen deprivation therapy (ADT) and chemotherapy, through the rise of targeted therapy and immunotherapy, to the explosive emergence of antibody-drug conjugates (ADCs), radioligand therapy, and bispecific antibody combinations, we have witnessed the transformation of genitourinary oncology from a “one-size-fits-all” approach to the era of truly personalized medicine.
Particularly noteworthy are the revolutionary advances seen in urothelial carcinoma in recent years. ADCs represented by disitamab vedotin are reshaping the treatment landscape for HER2-expressing advanced urothelial carcinoma through their unique bystander effect and precise targeting capabilities. Most excitingly, on April 10, 2026, the indication for disitamab vedotin combined with toripalimab as first-line treatment for HER2-expressing (IHC 1+/2+/3+) locally advanced or metastatic urothelial carcinoma was officially approved.
This “China-developed strategy,” published in the New England Journal of Medicine, not only fills a major gap in first-line immunotherapy-targeted combination treatment for HER2-expressing patients, but also marks a pivotal moment in China’s emergence as a global leader in precision therapy for genitourinary cancers.
A chronicle records the past, but more importantly, it illuminates the future. I hope every reader can see not only the footprints of medical progress, but also the direction in which we continue to move forward. The road toward precision oncology is long and challenging, but perseverance will take us there. Together, may we continue writing the next great chapter in genitourinary cancer treatment.
Urothelial Carcinoma
Professor Jun Guo
Jun Guo
“As a principal investigator of the RC48-C016 study, my center was deeply involved in this multicenter randomized phase III clinical trial. This was the world’s first randomized phase III study evaluating first-line treatment for HER2-expressing advanced urothelial carcinoma (UC). The results, published in the New England Journal of Medicine in 2025, marked a historic transition for Chinese investigators—from followers to global leaders in this field.
The study enrolled 484 patients and demonstrated that disitamab vedotin combined with toripalimab achieved a median progression-free survival (PFS) of 13.1 months, doubling that of the chemotherapy group (6.5 months), with a 64% reduction in the risk of progression or death (HR=0.36). Median overall survival (OS) reached 31.5 months versus 16.9 months with chemotherapy, translating into a 46% reduction in mortality risk (HR=0.54). The objective response rate (ORR) reached an impressive 76.1%, substantially higher than the 50.2% observed with chemotherapy.
This regimen established the second international first-line standard for advanced UC following the EV regimen and carries truly era-defining significance. Although large randomized trials in the neoadjuvant setting are still pending, I look forward to further breakthroughs in earlier-stage disease.”
Professor Jiwei Huang
Jiwei Huang
“This event is particularly significant because the pivotal study was published in the New England Journal of Medicine and has already influenced both Chinese and international clinical guidelines.
RC48-C016 was the first randomized phase III trial worldwide evaluating first-line therapy for HER2-expressing advanced urothelial carcinoma, enrolling 484 patients. The study showed that disitamab vedotin plus toripalimab achieved a median PFS of 13.1 months, doubling that of chemotherapy (6.5 months). Median OS reached 31.5 months compared with 16.9 months for chemotherapy. The ORR was as high as 76.1%, while the disease control rate (DCR) reached 91.4%.
Based on these groundbreaking data, the regimen became the world’s first approved HER2-ADC plus immunotherapy combination for first-line treatment of advanced UC.”
Professor Hao Zeng
Hao Zeng
“Over the past five years, the field of genitourinary oncology has witnessed numerous transformative advances, but what excites me most is the success of ADCs combined with immunotherapy in bladder cancer.
Compared with kidney and prostate cancers, patients with advanced bladder cancer historically had significantly poorer outcomes. Before the advent of ADCs, median overall survival was less than 18 months. The breakthrough results of the RC48-C016 study completely changed this landscape: disitamab vedotin combined with toripalimab extended median OS in advanced urothelial carcinoma to 31.5 months—nearly three years—almost doubling survival compared with conventional platinum-based chemotherapy (16.9 months).
This China-originated, globally pioneering ADC-plus-immunotherapy regimen has brought new hope to patients with metastatic bladder cancer. I look forward to seeing even more breakthroughs across the entire spectrum of genitourinary oncology in the future.”
Renal Cell Carcinoma
Professor Liangyou Gu
Liangyou Gu
“I place great importance on this milestone because pembrolizumab combined with axitinib has long been one of the most widely adopted first-line targeted-immunotherapy regimens for renal cell carcinoma (RCC) in China.
The KEYNOTE-426 study demonstrated a 47% reduction in mortality risk (HR=0.53) and a 31% reduction in progression risk (HR=0.69) in advanced RCC patients treated with this combination.
More importantly, this regimen became the template for subsequent domestic innovation. The RENOTORCH study, modeled after KEYNOTE-426, successfully validated the efficacy of toripalimab plus axitinib in Chinese patients, extending median PFS from 9.8 months to 18.0 months (HR=0.65), with a favorable trend in overall survival as well (HR=0.61).
For these reasons, this event may represent a true milestone—or even a foundational cornerstone—in the field of renal cancer.”
Professor Cuijian Zhang
Cuijian Zhang
“In 2018, the FDA approved nivolumab combined with ipilimumab as first-line treatment for intermediate- and poor-risk advanced renal cell carcinoma based on the CheckMate 214 study.
Long-term follow-up demonstrated the unique ‘tail effect’ of dual immunotherapy in these patients. Eight-year follow-up data showed that median OS reached 46.7 months in the combination arm compared with 26.0 months in the sunitinib group (HR=0.69). The ORR was 42.4% versus 27.5%, respectively.
Importantly, extended follow-up also suggested meaningful survival benefits in favorable-risk patients. The durability and reliability of this regimen have provided long-term survival hope for patients with advanced RCC.”
Prostate Cancer
Professor Xiongjun Ye
Xiongjun Ye
“In June 2025, the FDA approved darolutamide for adult patients with metastatic hormone-sensitive prostate cancer (mHSPC). This marked a major milestone in the treatment landscape for metastatic prostate cancer and brought significant clinical benefits to patients with mHSPC.
The approval was based on the ARANOTE study, which demonstrated that darolutamide plus ADT reduced the risk of radiographic progression or death by 46% compared with placebo plus ADT (HR=0.54). Median radiographic progression-free survival (rPFS) had not yet been reached, representing a substantial leap beyond the 25 months observed in the control group.
In addition, the ARASENS study confirmed that the triplet regimen of darolutamide, ADT, and docetaxel reduced mortality risk by 32% (HR=0.68).
As a next-generation androgen receptor inhibitor (ARi), darolutamide offers several advantages, including higher androgen receptor affinity, lower blood-brain barrier penetration, and fewer drug-drug interactions.”
Which breakthrough would you choose as the year’s most important milestone? Share your thoughts and join the discussion.
