Editor's Note: Patients with metastatic castration-resistant prostate cancer (mCRPC) who experience disease progression following novel endocrine therapy have very limited treatment options, presenting a major clinical challenge. In recent years, China has made substantial advances in innovative drug development, continuously reshaping treatment strategies. Novel TROP2 antibody-drug conjugates (ADCs), represented by sacituzumab tirumotecan, have demonstrated promising potential in prostate cancer. When combined with immunotherapy, the regimen achieved an overall objective response rate (ORR) of 47.4%, a disease control rate (DCR) of 89.5%, a duration of response (DoR) of 24.7 months, and a PSA50 response rate of 39.1% in the overall population. Median radiographic progression-free survival (rPFS) was 13.1 months, and median overall survival (OS) reached 22.8 months, potentially opening up a new treatment pathway for patients with mCRPC.In this issue, Oncology Frontier – UroStream invited Professor Dingwei Ye and Professor Xiaojie Bian of Fudan University Shanghai Cancer Center to provide an in-depth analysis of the current challenges in mCRPC diagnosis and treatment in China, discuss the clinical value of the sacituzumab tirumotecan combination regimen, and share their team’s efforts and achievements in advancing the field of uro-oncology in collaboration with the Chinese Society of Clinical Oncology (CSCO). Their insights aim to expand treatment options for mCRPC and continuously improve patient survival outcomes.
Limited Treatment Options for mCRPC: An Urgent Need for Innovative Strategies
Oncology Frontier – UroStream
mCRPC refers to the stage of disease progression following treatment for metastatic hormone-sensitive prostate cancer (mHSPC). It represents the terminal stage of prostate cancer, with limited treatment options and poor patient prognosis. Could you discuss the unmet clinical needs of patients with mCRPC in China?
Professor Dingwei Ye: mCRPC represents the terminal stage of prostate cancer progression. Once the disease reaches this stage, the tumor is highly aggressive, and treatment options become increasingly limited as the disease progresses, resulting in poor overall prognosis. Existing studies indicate that median overall survival ranges from only 17.5 to 34.7 months.
Therefore, the core treatment goals in mCRPC are, on the one hand, to extend overall survival as much as possible and, on the other, to delay symptom worsening and maintain or improve patients’ quality of life.
Historically, treatment options for mCRPC have included sequential use of endocrine therapies and chemotherapy, particularly docetaxel. However, most patients inevitably face rapid development of tumor resistance after entering later lines of treatment.
For patients with mCRPC whose disease has progressed following novel endocrine therapy, new options such as olaparib, ^177Lu-PSMA, and deuterated enzalutamide are available in clinical practice. Nevertheless, overall treatment options remain limited, and there is still a lack of sufficient, effective, and innovative subsequent therapies capable of prolonging survival, delaying disease progression, and improving quality of life.
In China in particular, access to, affordability of, and standardized use of novel drugs, radioligand therapies, and precision diagnostic testing vary across regions and medical centers, making unmet needs in real-world practice even more pronounced.
Meanwhile, the European Association of Urology (EAU) guidelines recommend that the ideal time to change treatment should be before symptom progression. However, high-quality evidence supporting this approach remains insufficient in current clinical practice. There are no clear, universally accepted standards for selecting drugs or determining the optimal timing of treatment changes in second-line and later-line settings.
More importantly, China still lacks sufficient real-world data from Chinese populations, precise risk-stratification systems, and comprehensive management pathways covering the entire course of the disease.
Therefore, the unmet needs of patients with mCRPC in China go beyond simply “a lack of drugs.” They encompass multiple dimensions, including access to precision diagnostics, affordability of novel therapies, standardization of treatment sequencing and timing of treatment changes, management of bone metastases and symptoms, preservation of quality of life, and the development of locally generated clinical evidence. These remain key areas of ongoing exploration in China’s prostate cancer field.
Sacituzumab Tirumotecan Combination Therapy Demonstrates Clinical Potential in Efficacy and Safety
Oncology Frontier – UroStream
At the prostate cancer session of this year’s CSCO Annual Meeting, an oral presentation was delivered on the Phase II study (SKB264-II-06) of sacituzumab tirumotecan combined with immunotherapy for metastatic castration-resistant prostate cancer. The study enrolled patients with mCRPC who had previously received one or two novel endocrine therapies and no more than one prior chemotherapy regimen. Could you discuss the rationale behind the study design and its key highlights?
Professor Xiaojie Bian: Treatment options for mCRPC in later lines are limited, and resistance develops readily. For patients who have experienced treatment failure following novel endocrine therapy and chemotherapy, new therapeutic strategies are urgently needed. The rationale for this Phase II study was to investigate the efficacy and safety of sacituzumab tirumotecan combined with pembrolizumab in this challenging patient population, based on the synergistic antitumor mechanisms of ADCs and immunotherapy.
The study has several key highlights.
First, it precisely targets a population with significant unmet clinical needs. The study enrolled patients with histologically confirmed mCRPC who had previously received one or two second-generation antiandrogen therapies and no more than one chemotherapy regimen. Patients were required to have experienced disease progression within six months before screening and to have an ECOG performance status of 0–1. These patients were at a critical point in second-line or later-line treatment, where clinical needs remain far from being met.
Second, it introduces an innovative ADC-plus-immunotherapy combination. As a China-developed TROP2 ADC, sacituzumab tirumotecan has the potential to deliver potent antitumor activity through its unique dual-function linker and topoisomerase I inhibitor payload. Preclinical studies have confirmed that combining an ADC with a PD-1 inhibitor can produce synergistic antitumor effects.
The treatment regimen consisted of sacituzumab tirumotecan administered once every two weeks, combined with pembrolizumab once every six weeks. Treatment continued until disease progression or the occurrence of unacceptable toxicity.
Third, it incorporates systematic dose exploration and comprehensive endpoint assessment. The study included two dose cohorts: 4 mg/kg (10 patients) and 5 mg/kg (36 patients), aiming to achieve a favorable balance between efficacy and safety.
The primary endpoints were adverse events (AEs), objective response rate (ORR), and PSA50 response rate. Secondary endpoints included disease control rate (DCR), duration of response (DoR), radiographic progression-free survival (rPFS), and overall survival (OS).
Oncology Frontier – UroStream
The combination of sacituzumab tirumotecan and pembrolizumab offers a new option for second-line and later-line treatment of mCRPC. Considering the clinical needs of this population and the efficacy data from this study, how would you interpret the clinical value of sacituzumab tirumotecan in second-line and later-line mCRPC treatment?
Professor Xiaojie Bian: Following progression on novel endocrine therapy, patients with mCRPC commonly face limited treatment options and a plateau in treatment efficacy. Innovative regimens that combine high efficacy with an acceptable safety profile are urgently needed.
TROP2 is highly expressed in prostate cancer, making it an ideal therapeutic target for TROP2 ADCs such as sacituzumab tirumotecan. This provides a new avenue for exploring ways to improve clinical outcomes in patients with mCRPC.
In terms of key efficacy outcomes, the overall ORR reached 47.4%, including 75.0% in the 4 mg/kg dose cohort. The overall DCR was as high as 89.5%, and the DoR reached 24.7 months. The PSA50 response rate in the overall population was 39.1%, rising to 50.0% in the cohort receiving sacituzumab tirumotecan at 4 mg/kg plus pembrolizumab, demonstrating the potential for deep responses and early tumor control. Long-term survival data were also encouraging: median rPFS was 13.1 months, reaching 24 months in the 4 mg/kg cohort, while median OS reached 22.8 months. These results suggest that the regimen can effectively delay rapid disease progression and improve survival, potentially delivering long-term survival benefits.
This combination demonstrated substantial antitumor activity in second-line and later-line treatment of previously treated patients with mCRPC. It achieved sustained tumor control and deep PSA responses, potentially overcoming the efficacy ceiling of conventional later-line therapies.
Furthermore, through the synergistic mechanisms of ADCs and immunotherapy, the regimen may help address resistance and extend survival benefits. In terms of safety, overall adverse reactions were manageable, and long-term tolerability was favorable.
As a China-developed TROP2 ADC, sacituzumab tirumotecan combined with immunotherapy addresses an unmet need in later-line treatment following failure of novel endocrine therapy. It provides clinical evidence to support the optimization of second-line and later-line treatment strategies and the improvement of survival outcomes in patients with mCRPC.
Oncology Frontier – UroStream
As an innovative TROP2 ADC developed in China, sacituzumab tirumotecan has achieved encouraging efficacy results in the mCRPC study. What value and impact do you believe this study will have on clinical practice in mCRPC treatment?
Professor Dingwei Ye: The study has demonstrated that sacituzumab tirumotecan combined with immunotherapy can provide deep and durable tumor responses and meaningful survival benefits for patients with mCRPC receiving second-line and later-line treatment. Subgroup data also suggest that both dose cohorts have favorable antitumor activity.
Currently, patients with metastatic castration-resistant prostate cancer whose disease has progressed following novel endocrine therapy have limited treatment options and generally poor prognosis. The updated results of this study address a gap in later-line mCRPC treatment by introducing an ADC-plus-immunotherapy regimen and providing a new therapeutic strategy for these patients.
With this novel approach combining a TROP2 ADC and immunotherapy, the regimen achieved a median OS of 22.8 months, representing particularly encouraging survival data in the later-line mCRPC setting.
More importantly, the combination of a TROP2 ADC and immunotherapy does not depend on specific gene mutations, making it potentially applicable to a broader patient population and representing a major advance in second-line and later-line mCRPC treatment.
Oncology Frontier – UroStream
Considering the safety profile of sacituzumab tirumotecan observed in this study, how should potential adverse reactions be managed in clinical practice to ensure that treatment proceeds smoothly and patients can achieve longer-term survival benefits?
Professor Xiaojie Bian: From a safety perspective, the combination of sacituzumab tirumotecan and pembrolizumab had a manageable adverse-event profile and favorable tolerability, supporting the safety and feasibility of the combination regimen.
Treatment-related adverse events (TRAEs) were predominantly mild to moderate. The incidence of grade ≥3 adverse events was 67%, and the incidence of serious TRAEs was 41%. The most common grade ≥3 TRAEs were anemia, neutropenia, decreased neutrophil count, oral mucositis, and decreased white blood cell count.
Compared with the toxicity associated with conventional later-line chemotherapy for mCRPC, the safety profile of the ADC-plus-immunotherapy regimen appears clinically manageable. It may help improve quality of life in patients with advanced, difficult-to-treat disease while maintaining treatment efficacy.
In terms of specific management strategies, clinicians already have considerable experience managing the common adverse reactions associated with TROP2 ADCs, as well as immune-related adverse events caused by PD-1 inhibitors.
With sacituzumab tirumotecan, particular attention should be paid to the prevention, monitoring, and treatment of hematologic toxicity and oral mucositis. For grade 1–2 adverse events, close observation and symptomatic management are generally recommended, while avoiding premature dose reductions or treatment interruptions.
Overall, selecting an appropriate dose, establishing a comprehensive toxicity monitoring system throughout treatment, and implementing standardized management through multidisciplinary collaboration can minimize the impact of adverse reactions, help patients remain on treatment, and ultimately support longer-term survival benefits.
Innovation in Uro-Oncology: Prostate Cancer Enters a New Era of Personalized Treatment
Oncology Frontier – UroStream
What major advances and research directions in prostate cancer are worth watching at this year’s CSCO Annual Meeting?
Professor Xiaojie Bian: In recent years, the most noticeable development has been China’s transition into the era of personalized prostate cancer treatment.
The updates in the 2026 edition of the CSCO Guidelines for the Diagnosis and Treatment of Prostate Cancer reflect this trend. In diagnosis, the recommendation level for MRI combined with prostate-specific antigen density (PSAD) has been upgraded, and AI-assisted image interpretation has been incorporated. Multimodal diagnostic approaches are gradually replacing reliance on PSA testing alone.
In treatment, mHSPC has officially entered the era of intensified combination therapy. ^177Lu-PSMA-617, niraparib for patients with BRCA mutations, and capivasertib for patients with PTEN deficiency have been incorporated into the recommendations. The treatment paradigm of combining PARP inhibitors with novel hormonal therapy (NHT) has successfully moved from the mCRPC setting to the mHSPC setting.
As clinical evidence for sacituzumab tirumotecan, our TROP2-targeted therapy, continues to accumulate, it may also be incorporated into future guideline recommendations, providing Chinese patients with additional treatment options.
I believe three areas are particularly promising for future clinical breakthroughs.
First, implementation of early screening. The proportion of newly diagnosed patients with advanced disease in China is significantly higher than in Europe and the United States. Standardized and widespread PSA screening is an important pathway to reducing mortality.
Second, clinical translation of novel drugs, including ADCs, bispecific antibodies, and radiopharmaceuticals. The indications for ^177Lu-PSMA are expanding from mCRPC toward mHSPC and potentially even the perioperative setting.
Third, translating advances into broader clinical practice. Through the CSCO professional committee’s approach of “serving primary care, serving patients, and engaging internationally,” we aim to bring the latest standards and recommendations to primary-level medical institutions and ensure that original research from China translates into meaningful survival benefits for patients. This is also the mission of our generation of young scholars in uro-oncology.
Professor Dingwei Ye
Professor Xiaojie Bian
