Neoadjuvant Chemo New SOC Option in Urothelial Carcinoma

Roxanne Nelson, RN, BSN

February 24, 2022

Neoadjuvant chemotherapy with a regimen of gemcitabine-cisplatin for high-risk upper tract urothelial carcinoma (UTUC) resulted in a high rate of downstaging, and should now be considered a new standard of care option in these patients, say experts discussing new data.

The new results come from a study of 57 patients, which found that two thirds (63%) of them achieved a pathological response.

Longer-term follow-up showed that patients who achieved a pathological response had significantly better outcomes than those who did not; 2-year overall survival rates were 100% vs 80%, P < 0.001).

Based on these results, neoadjuvant chemotherapy should be considered a new standard of care option for patients with high-risk UTUC, concluded lead author Wesley Yip, MD, a fellow at Memorial Sloan Kettering Cancer Center in New York City.

UTUC is a rare but deadly disease, with 5-year cancer-specific mortality rates for T2 to T4 disease that range from 21% to 59%. He noted that, as observed from data at their institution, patients with high-grade disease have significantly worse prognosis.

He presented the study at the 2022 ASCO Genitourinary Cancers Symposium, held in San Francisco and virtually because of the pandemic.

Patients with upper tract urothelial carcinoma are difficult to stage accurately, and often have aggressive disease, said Daniel Geynisman, MD, associate professor in the Department of Hematology/Oncology at Fox Chase Cancer Center, Philadelphia, Pennsylvania, who was approached for comment.

Neoadjuvant chemotherapy is often underutilized for these patients, even though previous studies have shown it to be effective in downstaging them, he told Medscape Medical News. This new trial shows that a combination of gemcitabine and cisplatin also leads to a high rate of downstaging, and that downstaging is associated with improved long-term outcomes.

"Neoadjuvant cisplatin-based chemotherapy should be considered for all eligible patients with high-grade upper tract urothelial carcinoma," Geynisman added.

Study Details

The study conducted by Yip and colleagues assessed the use of neoadjuvant therapy with gemcitabine and cisplatin in patients with high-risk UTUC prior to extirpative surgery. The regimen used was a split-dose gemcitabine-cisplatin regimen administered over 12 weeks and four cycles. This was followed by surgical resection and lymph node dissection.

A total of 58 patients were enrolled in the study, all underwent neoadjuvant chemotherapy, and all patients except for one also underwent surgery, and so 57 patients were evaluable for the primary endpoint.

Almost two thirds (n = 36, 65%) achieved a pathologic response, meeting the primary endpoint of the study. Of this group, a complete response was observed in 11 patients (19%), defined as pT0N0 (ie, no evidence of disease).

At a median follow up of 42.3 months, six patients had died. For the group overall, progression-free survival (PFS) at 2 years was 76% and 61% at 5 years. The overall survival (OS) rate was 93% at 2 years and 79% at 5 years.

Patients with a pathologic response had a better outcome than those who did not; 2-year PFS rates were 91% vs 52% (log-rank P < .001) and 2-year overall survival rates were 100% vs 80% (log-rank P < 0.001).

Serious surgical complications (grade 3 or higher) at 90 days were seen in only 7% of patients. When looking at drug toxicity, 89% of patients were able to receive at least three cycles. The most common grade 3 or higher toxicities were lymphedema (33%), neutropenia (32%), and hyperglycemia (14%). Nearly one third (30%) of patients required a dose delay or reduction, and 14% discontinued treatment early.

Yip commented that "neoadjuvant chemotherapy was well tolerated, with minimal delay to surgery or impact on perioperative outcomes."

Yip and Geynisman have disclosed no relevant financial relationships.

2022 Genitourinary Cancers Symposium: Abstract 440. Presented February 18, 2022.

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