Guru Sonpavde, MD
In the era of immunotherapy, particularly considering its impact on genitourinary malignancies, many experts are looking to PD-1/PD-L1 inhibitors for their patients with urothelial carcinoma. However, chemotherapy is still a big player in the advanced-disease setting, making the treatment landscape quite varied.
State of the Science Summit™ on Genitourinary Cancers.
The biggest unmet need in the bladder cancer space is the treatment of cisplatin-ineligible patients, says Sonpavde. Patients with urothelial carcinoma who are ineligible to receive cisplatin have suboptimal survival with chemotherapy. Given that cisplatin plus chemotherapy improves survival in the advanced disease setting, it makes sense to give neoadjuvant chemotherapy before radical cystectomy in high-risk locally advanced or muscle-invasive bladder cancer, Sonpavde explains.
Patients less than 1 year out of preoperative platinum therapy receive a different second-line therapy.
“This is the era of immunotherapy,” said Sonpavde. “There is a lot of ‘push and pull’ in the immune system, and there are pathways that are inhibiting the immune system” from working in patients with bladder cancer.
Urothelial carcinoma has a high somatic mutation burden; it has the fourth highest of all cancers behind melanoma, squamous cell carcinoma of the lung, and lung adenocarcinoma, Sonpavde noted. Therefore, it is rational to expect immunotherapy to work well in this setting. Second-line therapy has been revolutionized by the approvals of 5 PD-1/PD-L1 inhibitors, he added.
In muscle-invasive bladder cancer, an increased infiltration of CD8-positive T cells can signify a good prognosis. In nonmuscle- invasive bladder cancer, PD-L1 expression is associated with poor outcomes when patients receive Bacillus Calmette-Guérin (BCG). PD-L1 also correlated with stage and grade—meaning that the higher the stage, the higher the expression.
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