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SYMPOSIUM-EDITORIAL
Year : 2011  |  Volume : 27  |  Issue : 2  |  Page : 215-217
 

The management of urothelial cancer in 2010 and beyond


Professor and Chairman Emeritus, University of Miami Miller School of Medicine, FL, USA

Date of Web Publication8-Jul-2011

Correspondence Address:
Mark S Soloway
Professor and Chairman Emeritus, University of Miami Miller School of Medicine, FL
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0970-1591.82840

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How to cite this article:
Soloway MS. The management of urothelial cancer in 2010 and beyond. Indian J Urol 2011;27:215-7

How to cite this URL:
Soloway MS. The management of urothelial cancer in 2010 and beyond. Indian J Urol [serial online] 2011 [cited 2019 Oct 21];27:215-7. Available from: http://www.indianjurol.com/text.asp?2011/27/2/215/82840


It is an honor to be asked to serve as the guest editor of this edition of the Indian Journal of Urology. Bladder cancer (BC) has been a major focus of my basic and clinical research starting with my fellowship in the Surgery Branch of the National Cancer Institute. There I had the good fortune to develop an animal model for BC. Mice were given a carcinogen in their diet which caused many to develop urothelial cancer of the bladder almost identical to human BC. Not only was I able to study the development in this primary tumor model but since the mice were genetically identical I was able to transplant some of these primary tumors to syngeneic mice and develop what I termed the MBT 2 murine transplantable BC model which is still in use today. Using this animal model I was able to demonstrate the sensitivity of this urothelial cancer to the then investigational drug, cis-diamminedichloro platinum later known as cisplatin and today the most active chemotherapeutic agent for locally advanced and metastatic BC. I saw treating people with BC as a major challenge. The judgments are often difficult and the quality of life impact for the patient often substantial.

The authors of the articles in this special issue have been given topics related to urothelial cancer. Each manuscript provides insight into a specific area that requires attention by all urologists who are involved with the treatment of this cancer.

M et al discuss the rationale for an early detection program for BC. I find the contrast between BC and prostate cancer (PC) most striking. Physicians, led by urologists, have made a major impact in the diagnosis and management of PC in many parts of the world largely through the use of PSA coupled with a public education campaign to stress the possibility of this relatively simple method of highlighting which men are more likely to have PC an thus lead to an earlier diagnosis compared to waiting for symptoms to occur. Several decades ago about 10% of men were diagnosed with locally confined PC. That figure now approaches 90% in regions where there is an emphasis on early detection. There is ample evidence the death rate from PC has declined as a result. In contrast to BC a high percentage of men with PC are diagnosed by requesting testing for this cancer. They have been largely educated by a long list of celebrities who have been treated for PC and have advocated for testing. In contrast public awareness of BC is virtually nonexistent. Although we can identify high-risk groups who could be targeted for screening for BC this approach has rarely been tested. This might start with men over 60 who have an extensive cigarette smoking history or have been exposed to other known carcinogens. Not only is the public and most physicians unaware of the association of cigarettes and BC but there are no "poster boys" who are willing to come forward and educate them. How then do we instruct those who have hematuria and have smoked cigarettes to be evaluated to see if BC is the cause of their hematuria? The authors list the urinary markers including cytology which could serve as the "PSA" for BC. We have few studies to determine the feasibility of an early diagnosis strategy for a high-risk population, e.g., men over 50 who have smoked over 15 pack/yrs. The authors suggest beginning with a urinalysis and possibly an inexpensive marker. It would be wonderful if the government would provide funding for such a study to determine the feasibility and effectiveness of an early detection program for BC. One benefit would be public education of the relationship of cigarettes to BC.

Cauberg et al. discuss the emerging advances in endoscopy. Until recently we have had few modifications of our endoscopic instruments designed to examine the lower urinary tract and remove tumors. The introduction of the flexible cystoscope in the 1980s was the last major development. This was a benefit for the patient in terms of surveillance as it provided the same or better ability to survey the lower urinary tract with much less discomfort.

Evidence suggests that the endoscopic resection of bladder tumors is often incomplete. It is one of the most common operations performed by urologists and yet, until quite recently, there has been a paucity of literature on how one can improve upon the staging of BC or the ability to completely remove all tumors. The authors of this article highlight three emerging technologies that may allow us to identify bladder tumors more readily and thus perform a more complete resection. Intravesicalinstillation of hexaminolevulinic acid along with a blue light source allows the endoscopist to identify tumors more readily as they fluoresce when the blue light is used. In a large multi-institutional prospective randomized trial the recurrence rate was lower in patients in which the photodynamic treatment was used compared to patients who had only standard white light endoscopy and resection. Endoscopes equipped with narrow band imaging are also designed to highlight bladder tumors and serves as another method to enhance our ability to identify and thus resect all bladder tumors. A more thorough resection will enhance the effectiveness of subsequent treatments, e.g., BCG, chemotherapy.

Possibly the most difficult decision in the area of BC is the optimal approach for the patient with a high-grade urothelial cancer which invades beyond the basement membrane (T1). Many of these tumors can be completely resected endoscopically. It is a recommendation to perform a repeat resection to ensure that all tumor has been removed and to be certain the initial T1 tumor was not understaged. This second resection is usually followed by BCG. Unfortunately this strategy is not uniformally effective and approximately 50% of these patients will develop a new tumor. If this "recurrence" is high grade and occurs within 3-6 months then the urologist should strongly consider abandoning a bladder preservation strategy. We have reported that approximately 15% of patients who have high-grade T1 BC and are initially treated by a TUR then BCG and have a cystectomy die of urothelial cancer. It is likely that each of these patients would have had a better prognosis had a RC been performed when the T1 cancer was first diagnosed. Thus rises the dilemma of an initial bladder preservation strategy or an early RC. Mandhani nicely reviews the arguments involving these HG T1 BCs and emphasizes the role of the reTUR in helping to make the best decision in terms of bladder preservation.

Patients who develop a BC are at high risk for the development of a subsequent tumor. There are several reasons for this: Incomplete resection, implantation of residual tumor cells which may implant on the altered urothelial surface and the continued effect of the carcinogen(s) which have affected the bladder urothelium. Intravesical instillation of chemotherapeutic agents or BCG immunotherapy has been shown to have some effect on reducing the chance of a true recurrence (due to incomplete resection or implantation) or a new tumor. Manoharan reviews the literature on intravesical agents currently being used and others which are in clinical trials. Although the added benefit is modest in some situations, e.g., post-TUR single instillation chemotherapy, I believe the risk of recurrence compared to the low side-effects of properly delivered chemotherapy or BCG favors its use. Avoiding a trip to the operating room by reducing the recurrence rate reduces anxiety and cost if not morbidity.

Ayyathurai discusses another important topic, namely the risk of an upper tract tumor after the discovery of a bladder tumor. Once such a patient is in our care how should we monitor the upper tract to discover an upper tract urothelial tumor in a timely fashion. As he indicates the risk of a subsequent upper tract tumor is low in patients with a low grade, low-stage bladder tumor and in fact so low that it does not seem worthwhile to routinely monitor the upper tract. On the other hand the risk of an upper tract tumor is not inconsequential for those with a high grade or invasive BC. It does not seem feasible, however, to monitor the upper tract at too frequent intervals by IVP or CAT scan because of the expense, inconvenience and cumulative side effects of imaging. In practical terms high-grade upper tract tumors develop, invade and cause symptoms before being detected by any routine monitoring study which are usually performed annually. If one really wanted to monitor the upper tract we should probably obtain urine for cytology at frequent intervals, possibly every 3 months, for all patients with CIS or other high-grade BC. This would be particularly true for high-risk patients who have frequent new tumors or urothelial carcinoma in the prostatic urethra.

Another important manuscript discusses the perioperative morbidity of radical cystectomy. Kulkarni details the myriad list of complications associated with this technically demanding operation. Not only is it a lengthy surgery but the patients are often elderly with cardiovascular and pulmonary problems due in part to their history of cigarette smoking. He emphasizes that although the perioperative mortality has been substantially reduced over the last decades the perioperative morbidity remains high (average 25%). Much of this is related to the age and comorbidity of the patients but also the length and technical demands of the surgery. Those of us who perform this procedure frequently have developed perioperative pathways which we hope will standardize the care and apply new strategies to reduce untoward events. His chapter emphasizes most of these. I use the cell saver to minimize the need for allogeneic blood. I do not see evidence that this alters the cure rate. The ligasure and endovascular stapler, although expensive, serve to limit the blood loss when compared to standard sutures. The postoperative ileus varies among patients and I have not found a successful method to limit this despite removing the nasogastric tube early, early ambulation, gum chewing etc. Some have advocated limiting the time the peritoneal cavity is exposed. A radical cystectomy and urinary diversion remains a difficult and lengthy procedure and should probably be performed in referral centers which have the interest and personnel to take care of these high-risk patients. This includes the entire team, i.e., anesthesia, nursing.

One of the ways we may be able to impact the progression free and overall survival of patients with locally advanced and metastatic BC is with the appropriate incorporation of systemic chemotherapy into the treatment plan. Nayyar and Gupta provide the rationale for both induction or neoadjuvant chemotherapy for patients who are at especially high risk of micrometastases, e.g., hydronephrosis, LVI, cT3. The alternative is adjuvant chemotherapy for those who have metastasis to regional lymph nodes or other adverse prognostic factors following radical cystectomy, e.g., positive margin, extensive LVI. Although we have Level 1 evidence showing a modest survival advantage for neoadjuvant chemotherapy the evidence in favor of adjuvant chemotherapy is less robust. At the University of Miami we have found that patients are far more likely to receive adequate chemotherapy when given before surgery when compared to relaying on adjuvant chemotherapy. The postoperative complication rate of 25% is a major impediment to relying on chemotherapy after this major operation. We have been impressed that at least 30% of patients have a dramatic response (often to pT0) after initial chemotherapy with little morbidity and no delay to proceeding with surgery.

I salute the urologists who take care of men and women with BC. Although we have not made impressive strides in the areas of early diagnosis or in curing more patients who present with locally advanced BC we have made some inroads with technical improvements in endoscopic resection and staging as well as incorporating systemic chemotherapy into a multidisciplinary approach to patients with cT2 - CT4 or node-positive urothelial cancer.




 

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