Current Perspectives in the Treatment of Bladder Cancer
Today, there are more options for the treatment of bladder cancer than ever before. Christopher B. Anderson, MD, MPH, and G. Joel DeCastro, MD, MPH, urologic oncologists in the Department of Urology at NewYork-Presbyterian/
Strategies in Bladder Preservation
Muscle Invasive Cancer Most patients with aggressive cancer invading the deep muscular layer of the bladder wall are recommended to have intravenous chemotherapy and bladder removal. “However, there is a very select group of patients for whom perhaps we can salvage the bladder,” says Dr. Anderson. “These are patients who were told that they needed to have their bladder removed, and they say, ‘I hear what you’re saying, but I don’t want that. I want you to do something less aggressive.’ After counseling them extensively, we can sometimes create treatment plans to preserve the bladder.”
As Dr. Anderson explains, “We have described in a recent paper that if you’re really good at selecting patients for bladder preservation, you have an excellent multidisciplinary team, and if the patients respond very well to chemotherapy, then it may be reasonable to consider not removing the bladder.”
In a multicenter study, the Columbia urology team retrospectively reviewed the records of 148 patients with muscle invasive bladder cancer who elected surveillance following a clinically complete response to cystoscopic bladder resection and neoadjuvant chemotherapy from 2001 to 2017. These patients were advised to have a radical cystectomy but elected to preserve their bladders instead. A clinically complete response was defined as absent tumor on post-chemotherapy transurethral resection, negative cytology, and normal cross-sectional imaging. The researchers observed high rates of overall and disease specific survival in patients who achieved a clinically complete response to neoadjuvant chemotherapy, and few patients required bladder removal for a subsequent recurrence.
“At the very least, this is a controversial treatment, but there is considerable patient interest in bladder preservation,” says Dr. Anderson. “Patients who are more likely to succeed with this approach have smaller tumors, a solitary tumor, tumors that are not blocking the kidney, and tumors that don’t have any associated carcinoma in situ.”
The trade-off with bladder preservation for patients that have a complete response to chemotherapy is a small increased risk of cancer death that may have been avoidable with an immediate surgery. However, this risk must be weighed against the risks of the surgery itself, which include major complications and even death. The Columbia researchers concluded that future studies are needed to improve patient selection for bladder preservation by identifying biomarkers predicting invasive relapse and developing novel imaging methods of early detection.
Bladder Cancer Staging
Non-Muscle Invasive Cancer Bacillus Calmette-Guerin or BCG is the most common intravesical immunotherapy for treating urothelial carcinoma of the bladder. “Historically, bladder-infused immunotherapy for cancer that has not invaded into the muscle reduces the chance that the cancer will progress to worse disease or recur,” says Dr. DeCastro, noting that patients with cancers that are high grade and just shy of invading the muscle can also undergo BCG therapy.
“Cystectomy is the standard of care for muscle invasive disease, as well as the standard of care for patients with non-muscle invasive disease that has recurred after getting BCG,” continues Dr. DeCastro. “For patients who have BCG refractory bladder cancer and who refuse or can’t tolerate cystectomy, we can offer a novel multidrug intravesical regimen consisting of cabazitaxel, gemcitabine, and cisplatin — CGC.”
“Removing a bladder and doing a urinary diversion is a major undertaking. There’s a subset of patients that we can actually prevent from having to undergo that surgery and that’s very exciting.”
— Dr. G. Joel DeCastro
Dr. DeCastro and his colleagues, who just completed a five-year phase 1 clinical trial of CGC with 18 patients, are reporting very good results. “The underlying enthusiasm for CGC is that while we can perform cystectomy robotically with fewer incisions and less pain, it is still a major and life-changing surgery. Additional studies are necessary, but we’re very excited about helping this BCG-unresponsive population. If we can actually prevent these patients from having to undergo major surgery, that is a big deal.”
While the Columbia investigators believe this to be a promising new treatment, they note that it is yet to be fully investigated and that additional studies are needed. “We hope to be starting phase 1b/2 of the study this year,” says Dr. DeCastro.
MRI versus CT for Greater Accuracy
The tools used to determine how aggressive and the extent of bladder cancer include cystoscopy and computed tomography. “The issue is that our ability to accurately stage the disease or estimate the extent of disease is somewhat limited because CT scans are not perfect,” says Dr. Anderson. “A possible solution or improvement would be the use of MRI. The question is can MRI do a better job than CT of characterizing the extent or stage of disease to estimate risk and direct treatment? We’re exploring that now — as are other investigators around the world — and have made some promising early observations.”
Increasing Role of Robotics
Radical cystectomy is the surgical standard for invasive bladder cancer. At Columbia, Dr. Anderson and Dr. DeCastro are increasingly offering patients robot-assisted cystectomy. “We have found in our experience that patients do very well — they recover faster, the blood loss is less, and the pain after surgery is less,” says Dr. DeCastro.
“Evidence now suggests that robotic surgery benefits patients in numerous ways,” agrees Dr. Anderson. “There’s a huge patient demand for it depending on the type of surgery, for example, with prostate cancer and kidney cancer. Given our expertise, we’ve been able to push the envelope and offer it to patients who might not be offered it elsewhere.”
Both physicians emphasize that the robot is only a tool, but when used appropriately it does offer many advantages. “However, it’s considered on a case-by-case basis,” says Dr. DeCastro. “Some patients are not eligible for robotic surgery, and we may not recommend it. But that’s part of the discussion we have in the clinic, and part of the difficult decisions we have to make.”
Mazza P, Moran GW, Li G, Robins DJ, Matulay JT, Herr HW, DeCastro GJ, McKiernan JM, Anderson CB. Conservative management following complete clinical response to neoadjuvant chemotherapy of muscle invasive bladder cancer: Contemporary outcomes of a multi-institutional cohort study. Journal of Urology. 2018 Nov;200(5):1005-13.