SIU 2024: (SYMP-09) Systemic Treatment in the Perioperative Period of Upper Tract Urothelial Carcinoma (UTUC)
Speaker: Yige Bao, West China Hospital, Sichuan University, Chin
Important Takeaways
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Neoadjuvant and Adjuvant Chemotherapy: Effective for high-risk UTUC in reducing recurrence and metastasis, but patient selection is crucial.
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Advantages of Neoadjuvant Chemotherapy: Better tolerance and earlier prognosis assessment, though clinical staging inaccuracies limit its effectiveness.
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Adjuvant Chemotherapy Impact: Supported by the POUT study, it enhances disease-free and metastasis-free survival but does not significantly improve overall survival.
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Kidney Function Considerations: Post-nephrectomy kidney function often affects the feasibility of adjuvant chemotherapy, making neoadjuvant therapy a valuable alternative.
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Future Directions: Emphasis on biomarker-guided treatments to predict chemotherapy responses and enhance perioperative decision-making.
Key Highlights
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Risk Stratification of UTUC |
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Low Risk |
High Risk |
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Monofocal disease |
Multifocal disease |
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Tumor size < 2 cm |
Tumor size > 2 cm |
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Low grade in urine cytology |
High level in urinary exfoliated cells |
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Low-grade ureteroscopic biopsy |
High-grade ureteroscopic biopsy |
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CT scans reveal no signs of local invasions |
CT scans reveal localized invasions |
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Hydronephrosis |
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Previous MIBC history with Radical cystectomy (RC) |
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Department of Urology in West China Hospital |
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UTUC and Risk Stratification:
Dr. Bao highlighted that while UTUC is relatively rare, it exhibits unique biological behaviors compared to bladder cancer. Low-risk UTUC can often be managed with kidney-sparing treatments, while high-risk cases typically necessitate radical nephroureterectomy. Given the high recurrence risk, systemic therapies in the perioperative period are critical.
Neoadjuvant vs. Adjuvant Chemotherapy:
Both approaches aim to minimize recurrence and manage post-operative metastasis. Neoadjuvant therapy is well-tolerated and allows for early prognosis assessment, though it may face challenges due to inaccurate clinical staging. Conversely, adjuvant therapy benefits from accurate pathological staging post-surgery, as illustrated by the POUT study, which indicated significant improvements in disease-free and metastasis-free survival. However, post-nephrectomy kidney function can limit the tolerance for adjuvant chemotherapy.
POUT Study and Real-World Data:
The POUT study focused on patients with pathological staging from T2 to T4 and N1 to N3, showing improved disease-free and metastasis-free survival with adjuvant chemotherapy, although overall survival benefits were less conclusive. Real-world data suggests that patients undergoing neoadjuvant chemotherapy tolerated treatment better due to decreased kidney function post-surgery, underscoring the importance of timing in chemotherapy administration.
Predicting Chemotherapy Response:
Dr. Bao emphasized the need for predicting chemotherapy responses to tailor treatment approaches effectively. Neoadjuvant therapy is more beneficial for patients demonstrating good responses, while upfront surgery followed by adjuvant chemotherapy suits those with poor responses.
Clinical Trials and Future Directions:
Ongoing trials at West China Hospital are investigating antibody-drug conjugates (ADCs) such as RC48 combined with PD-1 inhibitors, showing promising interim results with around 20% pathological complete response rates. These trials seek to refine neoadjuvant therapies for high-risk patients and explore primary culture and organoid models for predicting treatment responses.
Conclusion:
In conclusion, Dr. Bao reaffirmed that both neoadjuvant and adjuvant chemotherapy are pivotal in managing high-risk UTUC during the perioperative phase. However, advancements in predictive tools are crucial for optimizing treatment strategies. The future of systemic treatment lies in personalized, biomarker-guided approaches that can identify patients who will benefit most from neoadjuvant or adjuvant therapies.
Société Internationale d'Urologie Congress, 23-26 October 2024, New Delhi, India.
