Approaches in High-Risk Non-Muscle Invasive Bladder Cancer

Transcript:Raoul S. Concepcion, MD: Urothelial carcinoma of the bladder really comes in essentially two types. We know that in about 80% of patients present who have bladder cancer, 80% present with non-muscle invasive bladder cancer and 20% present with muscle-invasive bladder cancer. So, this next case we’re going to talk about is a 63-year-old white male who presents to urology with painless gross hematuria and urinary urgency symptoms. He has no history of kidney stones. He’s a two-pack per day smoker for 20 years. His AUA (American Urological Association) symptom score is 23, post-void on ultrasound is only 5 cc, PSA is 0.9 ng/ml, and digital rectal exam is a 2+ prostate with no nodules. Because of his painless gross hematuria, according to AUA Guidelines, he undergoes a traditional workup. And his CT scan shows normal upper tracks with a filling defect to the left-lateral wall of the bladder, but no obvious thickening. He undergoes cystoscopy, which shows a large broad-based tumor, lateral to the right orifice with some questionable erythema on regular cystoscopy to the posterior wall. He, at that point, is scheduled by the urologist to undergo transurethral resection (TUR) of the bladder tumor under general anesthesia. He undergoes complete resection, as well as bladder biopsy. And, his final pathology shows a grade 3 urothelial cancer, invasion through the lamina propria, but not into the muscularis mucosa, which pathologically is a pT1 lesion. Biopsy of the posterior wall of the erythematous area is consistent with carcinoma in situ (CIS) of the bladder, and random biopsies to the rest of the bladder really are negative for tumor.

So, at this point, in summary, we have a healthy 63-year-old. He has a long-time smoking history with a pathologic T1 lesion of the right-lateral wall of the bladder with concomitant CIS, as well. Mike, again, where do we stand with this gentleman? What do the guidelines say about the management of not only CIS, but, as well as, T1 disease?

Michael S. Cookson, MD, MMHC: Well, first of all, I think it’s important to note that no matter what we do to the bladder, if he doesn’t stop smoking, he’s at risk for a lot of problems including recurrence. So, I think we have to employ smoking cessation programs in these patients. With respect to his bladder cancer, this gentleman has a high-grade T1. You mentioned 80% of cancers are noninvasive. This gentleman has that 25% of that 80% pie that’s high risk; high risk not only for recurrence but for progression—and left untreated and unaccounted for could even lead to death. These are not too far distant from the muscle-invasive bladder cancers that we see. They need to be handled appropriately. The first thing that the guidelines would recommend in this scenario would be a restaging TUR to try and determine if there is either residual T1 disease, or an invasive component that just wasn’t determined in his first resection. The other thing that would be useful in this patient would be enhanced imaging. So, those who have it available to them would probably use a fluorescent cystoscopy, which not only can pick up additional satellite papillary tumors, but also CIS. And so, another alternative would be narrow band imaging, some enhanced detection for that flat, more subtle lesion. His main threat, currently, would be to reassess the T1 component.

Raoul S. Concepcion, MD: It’s my understanding—again, because I think you’re on this committee also—that for T1, the recommendation was made for re-resection because we knew, historically, that 30% went on to develop muscle-invasive disease. But, then, didn’t they functionally realize that they were just incomplete resections and you actually were leaving behind muscle-invasive disease, and that was some of the drive for re-resection? Is that correct?

Michael S. Cookson, MD, MMHC: Just as a clarification, I’m not on the bladder cancer guidelines panel. Dr. Sam Chang is chairing that, and they’ll be presented this year at the AUA. But, I have reviewed them, and I’m aware of them. And the goals of the re-resection are, as you stated, to make sure that we haven’t incompletely resected, but also to make sure that we don’t have a more deeply invasive tumor. Depending on the size of the tumor, you might be underrepresenting this to the pathologist. And, then, there are unique challenges to the pathologist even with the cautery artifact. Sometimes with a large tumor, if it’s all sent as a single specimen, they have trouble determining what was up, what was down. Sometimes sending patients’ tumors, superficial and deep, help them to determine that. Other uses, such as monopolar cautery, sometimes can give the pathologist a better chance to really see what’s going on at that level. But, the advantage of the re-resection is you’re only at the base. So, any residual tumor is likely to give them that information about the presence or absence of muscle and whether it’s involved.

Raoul S. Concepcion, MD: So, he undergoes re-resection 6 weeks later. He has no evidence of muscle-invasive disease at the time of his re-resection, but he still obviously has this posterior wall biopsy that was consistent with carcinoma in situ of the bladder, CIS. What about in terms of initial therapeutic management at this point?

Michael S. Cookson, MD: I think there are two options for this patient, who is relatively young. The most aggressive surgical option would be a radical cystectomy. These patients often don’t want to undergo cystectomy as the first option because it’s a life-changing and potentially morbid operation. The alternative would be to consider intravesical therapy. The standard in the United States would be an induction course of BCG (bacillus Calmette-Guerin) with recommendation to follow with a maintenance course, if he responds.

Transcript Edited for Clarity