Adjuvant Therapy for Muscle-Invasive Urothelial Cancer: Current Evidence and Future Directions  

Authors: Charbel Hobeika, Fuat Bicer, Khaled Abouelezz, Shilpa Gupta

Published in Advances in Oncology on April 6.

The battle against muscle-invasive bladder cancer (MIBC) and upper tract urothelial carcinoma (UTUC) has seen significant advancements, with neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy marking the current standard of care. Despite these measures, the risk of recurrence remains high, highlighting the critical need for effective adjuvant therapies.

What we learned:

• Neoadjuvant and Adjuvant Cisplatin-Based Chemotherapy: Neoadjuvant cisplatin-based chemotherapy (NAC) followed by radical cystectomy is standard for MIBC, despite many patients being ineligible due to various contraindications.

Evidence supports adjuvant cisplatin-based chemotherapy’s role in reducing recurrence, but definitive randomized data is lacking. A meta-analysis of 10 trials showed a modest 6% improvement in 5-year OS with adjuvant cisplatin-based chemotherapy. Over 50% of MIBC patients are ineligible for cisplatin, underscoring the need for alternative therapies that are effective and have manageable side effects.

• Rise of Immunotherapy: ICIs represent a significant shift towards immunotherapy in adjuvant treatments, with ongoing research focused on solidifying their role and identifying patients who would benefit the most. While the IMvigor010 trial failed to show improved DFS with adjuvant atezolizumab, CheckMate 274 demonstrated a DFS benefit with adjuvant nivolumab, especially in those who received prior therapy. The AMBASSADOR trial reported a 31% reduction in DFS risk with adjuvant pembrolizumab. More research is needed to optimize patient selection and outcomes.
• Challenges with UTUC: UTUC remains a challenging field, with limited data supporting the benefits of neoadjuvant chemotherapy. The landmark POUT trial demonstrated the efficacy of adjuvant platinum-based chemotherapy in improving disease-free survival, marking a significant advancement. However, the role of adjuvant immunotherapy in UTUC is less clear, pointing to an urgent need for tailored therapeutic strategies.
• Importance of Biomarkers: Biomarkers, such as PD-L1 expression and circulating tumor DNA (ctDNA), hold the key to unlocking personalized adjuvant therapies, with ongoing trials aiming to refine patient selection and improve outcomes.

Key Take home Messages:

• Advancements and Limitations: The advancement in adjuvant therapies for MIBC and UTUC, particularly through ICIs, marks a significant step forward, yet the journey for an ideal, universally effective adjuvant therapy continues.
• The Critical Role of Biomarkers: The future of adjuvant therapy lies in the identification and utilization of biomarkers to tailor treatments to individual patient needs, potentially transforming the landscape of MIBC and UTUC treatment.
• The Need for Continued Research: Ongoing and future clinical trials are necessary to explore the complexities of adjuvant therapy, with the ultimate goal of improving survival rates and quality of life for patients battling MIBC and UTUC.

Summary by Amalya Sargsyan, MD

Adjuvant Therapy for Muscle-Invasive Urothelial Cancer: Current Evidence and Future Directions/Charbel Hobeika, Fuat Bicer, Khaled Abouelezz, Shilpa Gupta/