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Bladder Cancer symptoms and treatment

The most common symptom in over 80% of patients is painless and usually intermittent haematuria (blood in the urine), which is also often a sign of less serious problems.1 However, haematuria should always be investigated if early diagnosis is to be achieved. Other symptoms include urinary frequency and pain on passing urine, but again these often indicate the presence of non-malignant conditions such as urinary tract infections.

Around three-quarters of patients present with superficial tumours (i.e. confined to the bladder mucosa or submucosal layer without muscle invasion) which are treated by transurethral resection and have a very good prognosis2. Unfortunately, superficial recurrence is a problem and regular cystoscopies are required to manage this condition.

Progression occurs in approximately 15-25% of patients. To prevent or postpone superficial recurrence, intravesical therapy is used (treatment inside the bladder), either with drugs (chemotherapy) or with the bacillus Calmette-Guèrin (BCG) (immunotherapy). BCG is particularly useful for transitional cell carcinoma in situ where it has a significant effect on reducing its high rate of progression to invasive carcinoma.3

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More advanced tumours which have invaded the muscle require treatment with surgery and/or radiotherapy. Radical cystectomy, which involves removing the bladder, is standard treatment in most countries.

In women, radical cystectomy involves removing the bladder, urethra, lower end of ureters, front wall of vagina, uterus, fallopian tubes and ovaries. In younger women the ovaries may be preserved.

In men, cystectomy involves removal of the bladder, prostate, lower end of ureters and sometimes the urethra. The operation has to be extensive due to the likelihood of local invasion from the original site. For most patients the ureters are then attached to a piece of bowel (ileum) the other end of which comes out of the abdominal wall and the urine is collected in a bag on the abdominal wall.

Recent advances in surgical techniques now mean that the bladder can be removed and an internal bladder replacement (called a neo-bladder) can be fashioned in some patients. Full dose external beam radiotherapy may permit bladder preservation and seems to offer similar long-term survival to surgery.

It is possible that the results of radiotherapy could be further improved by combining this with mild chemotherapy, an approach currently being tested in a clinical trial.4 However, it suffers from the disadvantage that some patients have recurrent disease requiring subsequent surgery.

Neoadjuvant chemotherapy (chemotherapy before local treatment) has been shown to improve survival in recent overviews of randomised trials. Best estimates suggest that using multi-agent platinum-based chemotherapy reduces the risk of dying of bladder cancer by about 15%.5, 6.

Using chemotherapy after local treatment is more controversial though a recent overview suggests that this approach may have similar value to neoadjuvant treatment.7 Confirmation for this is being sought from a large international trial. Response to neoadjuvant chemotherapy has been used to select patients who may benefit most from radiotherapy.8 This approach is being tested against a policy of cystectomy in a UK trial.9

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Patients with metastatic disease can benefit from palliative radiotherapy which improves symptoms.

Intensive cisplatin-based chemotherapy has been shown to provide a survival advantage compared to less intensive chemotherapy.10 Recent advances in chemotherapy schedules using either growth factor support 11 or schedules including gemcitabine 12 mean that this treatment can be administered with lower toxicity than previously used schedules.

Guidelines on improving the outcome for bladder and other urological cancers have been published and stress the importance of multidisciplinary urological teams with specialised skills at each level of the service and the need to provide timely and relevant information to patients.13 2

It is recommended that radical surgery should only be undertaken by specialist teams who carry out a minimum of 50 radical operations (cystectomies or radical prostatectomies) per annum. The NICE guidance identifies the need for more active treatment of bladder cancer patients and predicts the need for additional intravesical chemotherapy for superficial cancers and an additional 850 cystectomies per annum.13

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The future of bladder cancer treatment

Improved surgery has increased the quality of life for patients with invasive bladder cancer. But although the disease can be controlled locally by surgery or radiotherapy, the problem of occult metastases, which may ultimately kill half the patients with invasive disease remains and some form of systemic therapy is needed.14

New treatments using radiotherapy or chemotherapy alone, or in combination, as well as a number of immunotherapies are being tested in clinical trials. The best use of intravesical chemotherapy and BC for early bladder cancer is also being investigated. Further improvements in neoadjuvant chemotherapy may lead to improved survival.

References for bladder cancer symptoms and treatment

1. De Vita VC, H.S., Rosenberg SA, Management of transitional cell carcinoma of the bladder. Cancer: principles and practice of oncology(6th edition). 2001: Lippincott, Williams and Wilkins.
2. Scottish Intercollegiate Guidelines Network (SIGN), 2005.
3. Alexandroff, A.B., et al., BCG immunotherapy of bladder cancer: 20 years on. Lancet, 1999. 353(9165): p. 1689-94.
4. Coppin, C.M., et al., Improved local control of invasive bladder cancer by concurrent cisplatin and preoperative or definitive radiation. The National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol, 1996. 14(11): p. 2901-7.
5. Neoadjuvant chemotherapy in invasive bladder cancer: a systematic review and meta-analysis. Lancet, 2003. 361(9373): p. 1927-34.
6. Neoadjuvant chemotherapy in invasive bladder cancer: update of a systematic review and meta-analysis of individual patient data advanced bladder cancer (ABC) meta-analysis collaboration. Eur Urol, 2005. 48(2): p. 202-5; discussion 205-6.
7. Adjuvant chemotherapy in invasive bladder cancer: a systematic review and meta-analysis of individual patient data Advanced Bladder Cancer (ABC) Meta-analysis Collaboration. Eur Urol, 2005. 48(2): p. 189-199; discussion 199-201.
8. Shipley, W.U., et al., Selective bladder preservation by trimodality therapy for patients with muscularis propria-invasive bladder cancer and who are cystectomy candidates--the Massachusetts General Hospital and Radiation Therapy Oncology Group experiences. Semin Radiat Oncol, 2005. 15(1): p. 36-41.
9. Neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: a randomised controlled trial. International collaboration of trialists. Lancet, 1999. 354(9178): p. 533-40.
10. Mead, G.M., et al., .A randomized trial comparing methotrexate and vinblastine (MV) with cisplatin, methotrexate and vinblastine (CMV) in advanced transitional cell carcinoma: results and a report on prognostic factors in a Medical Research Council study. MRC Advanced Bladder Cancer Working Party. Br J Cancer, 1998. 78(8): p. 1067-75.
11. Sternberg, C.N., et al., Randomized phase III trial of high-dose-intensity methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) chemotherapy and recombinant human granulocyte colony-stimulating factor versus classic MVAC in advanced urothelial tract tumors: European Organization for Research and Treatment of Cancer Protocol no. 30924. J Clin Oncol, 2001. 19(10): p. 2638-46.
12. von der Maase, H., et al., .Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol, 2000. 18(17): p. 3068-77.
13. NICE, Guidance on Cancer Services. Improving Outcome in Urological Cancers. 2002, National Institute for Clinical Excellence.
14. Raghavan D, Quinn D, Skinner DG, Stein JP. Surgery and adjunctive chemotherapy for invasive bladder cancer. Surg Oncol 2002;11(1-2):55-63.

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