New Bladder-Sparing Approaches Emerge at ASCO 2021

In this exclusive MedPage Today video, Matthew Galsky, MD, of Icahn School of Medicine at Mount Sinai in New York City, highlights data he presented at the 2021 virtual American Society of Clinical Oncology (ASCO) annual meeting, evaluating an approach to treating muscle-invasive bladder cancer that spares patients from undergoing cystectomy or a directed, definitive local therapy.

Following is a transcript of his remarks:

I’m Matt Galsky, a medical oncologist at the Icahn School of Medicine at Mount Sinai in New York. And at ASCO this year, I presented the results of GU 16-257, which was a phase II trial of gemcitabine, cisplatin, plus nivolumab [Opdivo] with selective bladder-sparing in patients with muscle-invasive bladder cancer.

The standard treatment for muscle-invasive bladder cancer involves neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy. We’ve known for decades that a subset of patients treated with new adjunctive chemotherapy will achieve a pathological complete response — that is, when the bladder is removed, there’s no evidence of cancer under the microscope.

While that’s associated with a very favorable long-term prognosis, unfortunately that information is only obtained after the bladder has already been removed. And so this raises the key question: are there a subset of patients that can be treated definitively with systemic therapy plus transurethral resection of bladder tumor alone, without having to have their bladders removed?

So we set out to test this concept prospectively. There have only been a few trials testing this prospectively in the past, and a few ongoing trials as well.

Patients with muscle-invasive clinically localized urothelial cancer of the bladder were enrolled. Patients received four cycles of the combination of chemotherapy with gemcitabine and cisplatin, plus the immunotherapy drug nivolumab, an anti-PDL1 antibody.

After four cycles of treatment, patients underwent a restaging evaluation, which included imaging of the abdomen, including the bladder, which could include an MRI, or if an MRI was contraindicated, a CT scan. Patients had urine cytology collected and underwent a cystoscopy with biopsies of the bladder.

If there was no evidence of cancer on those assessments — and that was stringently defined — that is, if there was a clinical complete response, then patients were offered the opportunity to not have their bladders removed and proceed with an additional 4 months of nivolumab followed by observation. Or patients could opt to proceed with cystectomy, as that is the standard of care. If there was no complete clinical response, then cystectomy was recommended.

There were co-primary endpoints of this study. The first endpoint was what was the clinical complete response rate with this regimen? Because clinical complete response rigorously defined has not been well tested in the context of cisplatin-based chemotherapy or chemotherapy plus immune checkpoint blockade.

The second co-primary endpoint was to determine the performance characteristics of clinical complete response as a biomarker — that is, does clinical complete response predict which patients will remain disease free with their bladders intact long-term?

So, 76 patients were enrolled on the study. At the time of the data lock for the ASCO presentation, 64 patients had completed four cycles of treatment and underwent restaging. Among those 64 patients, 31 achieved a complete clinical response, for a clinical complete response rate of 48%.

Among those 31 patients, only one patient opted to undergo immediate cystectomy. The remaining 30 opted for bladder sparing. Of note, the one patient who opted for an immediate cystectomy had a low-grade papillary tumor residual on pathology.

Of the 30 patients who opted not to have their bladders removed initially and received an additional 4 months of immune checkpoint blockade, we have a median follow-up of about a year. And so our long-term outcomes, our second co-primary endpoint, has not yet been reached because we really are waiting for a 2-year follow-up time point from that dataset. That said, we do have many patients now out 1 year beyond the start of treatment who are disease free with their bladders intact.

So in conclusion, in patients with clinically localized muscle-invasive bladder cancer, transurethral resection of bladder tumor plus cisplatin-based chemotherapy plus immune checkpoint blockade achieves a stringently defined clinical complete response in a relatively high proportion of patients — 48% of patients to date. A subset of patients can remain with their bladder intact disease-free with relatively long follow-up — although we need much longer follow-up to know if this is indeed a tractable approach.

This is not yet a standard approach. There are other studies seeking to test a variation on this theme using genomic biomarkers to identify which patients might meet criteria for leaving their bladders intact.

But I think a combination of all of these data sets in all of these studies will help us determine whether or not this approach should be integrated into our standard treatment algorithms in the future.