Where are the ‘poster boys’ for bladder cancer?


High-grade bladder cancer should and must be considered potentially lethal. If a high-grade bladder cancer cannot be successfully resected transurethrally, either because it is too deep or its location is not amenable to a complete endoscopic resection, treatment must either consist of removing the bladder, or a combination of chemotherapy and radiation therapy as a bladder-preserving approach. The purpose of these comments is not to debate the relative efficacy of either of these two methods but to emphasize that despite all the current treatments, less than a half of patients with muscle-invasive bladder cancer survive for 5 years, and there has been little improvement over the last two decades. One of my greatest frustrations as a urological oncologist is to face the patient with locally advanced bladder cancer and be unable to be realistically optimistic about cure.

In contrast to bladder cancer the progress in prostate cancer is relatively pleasing; from 1974 to 1998 the 5-year survival rate for white men with prostate cancer improved from 68% to 98% for all stages [1]. In 1982, less than half of patients with prostate cancer were diagnosed when the cancer was clinically organ-confined [2]; currently it is nearly 90%. I think that there are two critical reasons for the changes, i.e. a minimally invasive, if imperfect, blood test which identifies prostate cancer at a relatively early stage, and an impressive public information campaign led by the American Cancer Society and AUA, that has effectively used several ‘poster boys’ to encourage ‘others’ to be checked.

In the USA there will be 57 400 new cases of bladder cancer this year (42 200 men and 15 200 women) [1]; 12 500 of them will die. The number is higher if other urothelial cancers are included. Many patients who have a cystectomy for muscle invasive bladder cancer present at that stage, i.e. no prior history of bladder cancer. Has this changed in the past 20 years? We analysed 184 consecutive patients who had a cystectomy for muscle-invasive bladder cancer between 1992 and 1999 [3]; 51% of men and an astonishing 85% of women had de novo muscle-invasive bladder cancer, and no previous diagnosis of bladder cancer. Twenty years ago, 80% of men and women had de novo muscle-invasive bladder cancer [4]. There has been a modest improvement for men and none for women. Of equal importance was the finding that the disease-free survival was far superior if a patient had a previous noninvasive (Ta, T1 or CIS) bladder cancer and later developed muscle-invasive bladder cancer. Thus, there is a better chance of curing the patient if the diagnosis is made when the cancer is ‘superficial’ and these patients closely monitored, and cystectomy urged when the initial endoscopically based approach fails.

A recent analysis indicated a modicum of improvement in the overall survival of bladder cancer [1]. A reduction in the perioperative mortality and the incorporation of systemic chemotherapy into the multimodal treatment of bladder cancer may account for some gains in the 5-year survival rate for bladder cancer from 1974 to 1998. These values for all stages of bladder cancer show an increase from 74% to 80% for whites and 48 to 65% for African-Americans [1]. The results are not so encouraging if this is contrasted with the same survival rates for prostate cancer over the 25 year interval; 68% to 98% for whites and 58% to 93% for African-Americans.

Why has their been so little improvement in the survival rate with bladder cancer? There are a few possible reasons. Patients may have no symptoms or signs until the cancer has metastasized (as with lung and pancreatic cancers). In some instances the signs or symptoms may be ignored and assumed to be a benign condition, e.g. irritative symptoms or haematuria may be treated as a UTI. In instances where it is apparent that the local treatment has been ineffective, urologists or the patient may delay a more effective treatment by avoiding a cystectomy or chemotherapy plus radiation therapy. The window of opportunity is lost. For high-grade invasive bladder cancer, delay matters.

Radical cystectomy is a formidable procedure. Many patients with bladder cancer do not have normal cardiac, vascular and respiratory systems because they have been adversely affected by years of cigarette smoking. Many are overweight and> 65 years old, presenting additional risk factors for major surgery. The perioperative morbidity is ≈ 25%. Consequently, this does not encourage a climate in which the patient or physician is eager to make critical life-altering decisions. In contrast, faced with a diagnosis of clinically organ-confined prostate cancer, there are various relatively low-morbidity treatments.

What can be done? First, for those who are diagnosed with locally advanced bladder cancer, we must emphasize the improvements that have been made in treatment options, and aggressively encourage the patient to proceed earlier with cystectomy or an approach using chemotherapy plus radiation to preserve the bladder. The orthotopic neobladder has decreased the effects on quality of life of radical cystectomy while gemcitabine, combined with cisplatin, has decreased the morbidity of multi-agent chemotherapy [5]. Also, radiation therapy is far better tolerated than it was several years ago.

Unfortunately, these measures will not help those with asymptomatic, aggressive bladder cancer. The time has come to initiate exploratory protocols for early diagnosis. Unlike prostate cancer, most patients with bladder cancer share an important risk factor, i.e. cigarette smoking or other carcinogen exposure. There are urinary markers with reasonable sensitivity and specificity that can be tested, along with more traditional methods of identifying those who may have bladder cancer, i.e. blood in the urine and cytology [6,7]. Public education is a critical part of the equation. I am constantly amazed at how few patients with bladder cancer realise that cigarette smoking is associated with the development of their cancer. What we need is to identify a ‘poster boy’ for bladder cancer! The healthcare decision-makers must recognise the needs of patients with bladder cancer and explore methods for identifying this cancer earlier, when there is an opportunity to provide effective treatment.