Vogelzang Emphasizes Aggressive Biopsies, Novel Therapies in Urothelial Carcinoma

Nicholas J. Vogelzang, MD

Diagnostic practices are not aggressive enough in the field of bladder cancer, according to Nicholas J. Vogelzang, MD. Prevalence and incidence of bladder cancer in the United States is high, with mortality rates remaining constant since 1975.

In his presentation, “Updates in Urothelial Carcinoma and the Role of the Immune System,” during the 2017 Genitourinary Cancers Symposium, Vogelzang, a professor at the University of Nevada School of Medicine, emphasized that the biggest mistake made in the diagnosis of bladder cancer is that surgeons do not go deep enough into the muscle during tumor biopsy.

Bladder cancer is categorized by level of invasion into the bladder wall. Non—muscle-invasive bladder cancer has a lower risk of mortality than muscle-invasive bladder cancer (MIBC). So, if surgeons do not go deep enough, they risk misdiagnosing.

Diagnosis of the tumor type in bladder cancer is imperative, said Vogelzang, as there is a great divide between tumor degrees, as the survival rate drops dramatically between T1 and T2.

When performing a transurethral resection (TUR), surgeons must go into the muscle tissue to get a proper reading, said Vogelzang, “The risk of going deeper is that [surgeons] perforate the bladder, and it does happen—there’s muscle and a little bit of fat in the specimen. It’s not a sin to do that…the bladder will heal itself. In fact, there is very good evidence that if your second TUR has muscle and no tumor, you’ve done the patient a huge favor. You’ve eradicated the tumor and you’ve accurately staged them.”

The best way to screen for bladder cancer would be a PET scan, said Vogelzang, as it can potentially answer the 2 most important questions of whether tumor is in the muscle, or if there is a tumor in the lymph node.

Vogelzang believes that calls for a multidisciplinary approach in MIBC and metastatic bladder cancer are positive, but unrealistic anywhere other than large cancer centers, “We have these nice pictures of everyone playing together in the sandbox, but it doesn’t happen.” New drugs though, could be the next step toward multidisciplinary care.

Alternative treatments must be developed, said Vogelzang, as the current treatment recommendations of surgery, chemotherapy, and radiation are too extreme for most patients with MIBC, as they often tend to be elderly or in too poor health overall.

Currently, first-line treatment for metastatic bladder cancer is cisplatin-containing combination chemotherapy of either gemcitabine or DDMVAC (dose-dense methotrexate + vinblastine + doxorubicin + cisplatin). Recommended second-line treatment is participating in clinical trials.

The future holds promise though, as immunotherapy becomes better understood and utilized in this disease. An effective antitumor immune response depends on neoantigen presentation, but the high mutational load of bladder cancer may correlate with immunogenicity, said Vogelzang.

T-cell function throughout the cancer immunity cycle is regulated by activating and inhibiting signals, and according to Vogelzang, PD-L1 may limit T-cell activation. The goal, he said, is to “wake up”—or activate—these T-cells by either monotherapy or through combination trials.

As opposed to the historically toxic side effects of chemotherapy, immunotherapy is seen as a more tolerable option by patients. Although chemotherapy does have significant toxicity, so does immunotherapy, said Vogelzang. It is important that physicians inform their patients about immunotherapy side effects, as they occur where the immune system lives—the mouth, nose, lungs, gastrointestinal tract, endocrine system—and toxicities can be anywhere from flu-like, to severe dehydration paired with colitis.

“One of the things that we all need to do when we are treating bladder cancer, is give knowledge about bladder cancer to the patients. We must also raise awareness in the urology community that these tumors need to be very clearly identified.”

<<<

View more from the 2017 Genitourinary Cancers Symposium