Targeting Trop-2 in Advanced Urothelial Carcinoma - Episode 2

Germline Mutations in Advanced Urothelial Carcinoma

The relationship between germline mutations in DNA repair genes and advanced urothelial carcinoma, and tips for counseling patients who are candidates for germline testing.

Petros Grivas, MD, PhD: Neeraj, you covered it so nicely. It’s a very important medical issue worldwide. You mentioned that smoking tobacco, cigarettes, cigars, and pipes is the most important risk factor. It significantly increases the risk for bladder cancer as well as many other cancers and problems, including cardiovascular disease. Older age is another risk factor. You mentioned the median age of diagnosis is 73 years old. Most patients are men, but it can still affect women. That’s an important point. We have sometimes seen delayed diagnosis, especially in younger women, because it’s lower in the list of the differential diagnoses. It’s important to think about bladder cancer in patients with relevant symptoms and send those patients for a further diagnosis work-up. That applies to both men and women across all ages.

Exposure to certain chemicals is a relevant risk factor. There’s a list of those chemicals that the audience can look at online. Previous cancer treatments with specific chemotherapy drugs, like cyclophosphamide or ifosfamide, can increase the risk. Chronic bladder inflammation can also increase the risk. You mentioned in other countries, like Egypt, there is a higher frequency of squamous cell bladder cancer as opposed to urothelial cancer, which is the most common type in other areas and in the United States. Squamous cell bladder cancer can be associated with chronic inflammation, irritation, and Schistosoma haematobium, a parasite that can be found there. Patients with neurogenic bladder, chronic irritation, and catheterization are also at higher risk.

With family history and personal history of cancer, germline mutations have become more the focus of our attention. I send patients for genetic counseling more often than before, especially with upper tract disease, but also for bladder cancer because we tend to see more germline mutations. Neeraj, I want to recognize how much work you are doing at the University of Utah with germline mutations. We are seeing other genes. Do you refer patients to genetic counseling based on the personal history or family history side of disease?

Neeraj Agarwal, MD: If they have significant family history or are relatively young, if there are no offending factors or obvious causative agent out there, especially, for example, a nonsmoker who presents to us with bladder cancer really early, in their 40s or 50s, that definitely raises a flag. I would like that patient to be seen by our genetic counselor. But in general, I do not send all patients with bladder cancer to the genetic counseling clinic.

Petros Grivas, MD, PhD: Thank you so much, Neeraj. It’s an emerging theme that we see more germline mutations, so I wanted to make sure the audience thinks about that and takes into account the age of the patient, upper vs lower tract, and personal and family history of cancer. We need more genetic counselors across cancers, including prostate cancer, kidney cancer, and urothelial cancer.

Transcript edited for clarity.