Bladder Cancer Newer Treatments

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[edit] Bladder Cancer Newer Treatments

Carcinoma in situ: For early bladder cancer (carcinoma in situ lesions) treatment with a solution containing a live anti-tuberculous vaccine (called BCG) leads to superior survival figures. This is done through a bladder catheter and is called "intravesical therapy with BCG" or "BCG treatment" for short. This local therapy for superficial bladder cancer is apparently superior to intravesical chemotherapy (Ref. 4). However, phase III trials are needed to establish, which dosage schedule gives the largest survival advantage.

Radical transurethral resection of the prostate (TURP): It seems that superficial disease (Tis and T1 stage) and also T2 (which invades the muscle) can be handled with radical TURP. There was no 10-year survival advantage for a group of patients who had a radical cystectomy (=cutting the bladder out) initially (see Ref. 5).

This author, when reviewing the data of the Memorial Sloan-Kettering Cancer Centre in New York, found that the group with initial radical cystectomy had a 10-year cancer survival rate of 71%, whereas the radical TURP group had an overall cancer survival rate of 76%. The key in this study is that the patients had initially 3-monthly and then 6-monthly follow-up examinations where they were scrutinized for recurrences. If a recurrence was found, then immediate action was taken to deal with this. Re-resection or radical cystectomy was now done and the surgical specimens were then pathologically examined. Now the bladder cancers were restaged pathologically, which is much more accurate than clinical staging, and the appropriate treatment was given. 34% of the initial TURP group had a recurrence and were then restaged. Their 10-year survival with stage T0 ( no more tumor found) was 82%, whereas for patients with restaged T1 bladder cancer it was 57% (Ref.5). This is a superb longterm result for bladder cancer!

Radiation seems to be used mostly in combination with some other treatment modality. Even though it has good effects on its own in terms of reducing bulk of the disease and in treating pelvic lymph nodes and paraaortic lymp nodes, it is even more effective when combined with surgery or chemotherapy.

Some groups do presurgical radiation and remove the remaining cancer tissue 4 weeks after radiation. Other groups prefer to do surgery and then radiate after that to treat possible local cancer spread and/or pelvic and paraaortic lymph nodes that could not be removed technically. The patient needs to be informed why a certain combination would be more advantantageous in a certain situation than the other. The key is to individualize and do what is best for the patient.

Combination chemotherapy has been found to be much more effective in delaying tumor growth than any single chemotherapeutic agent.

However, even though short term responses can be obtained in 30 to 50 % of patients, the longterm survival has only marginally improved. Ref. 6 explains that attempts concentrate presently on improving the survival rates by stimulating the immune system with granulocyte colony stimulating factor (colony-forming unit factor or CFU-C factor) and other immune stimulants in order to be able to treat with higher doses of combination chemotherapy.

This has already been very successful with testicular cancer in improving survival rates. However, bladder cancer is a type of cancer that is inherently more resisitant to both radiation and chemotherapy. The authors in Ref.7 have shown that even with "incurable" stage 4 bladder cancer patients it is possible to achieve survivals at 5-years with an aggressive protocol.

Using a combination chemotherapy with trexall (=methotrexate), vinblastine, doxorubicin, and cisplatin (M-VAC) these urological oncologists from New York were able to cure 41% of these patients with chemotherapy alone. 33% of patients survived 5 years by treating with this combination regimen first and subsequently removing the remaining cancer tissue surgically. They also found that the better 5-year survival rates were obtained in those patients who had localized, but non operable primary tumors initially or who had metastases restricted to lymph node sites rather than those patients who had distant metastases.

Biological therapies: There is a tendency lately to explore less toxic modalities of treatment. However, one has to remain critical of the effectiveness (called "efficacy") of these treatments. On the other hand the researchers are very much aware that many of the present therapies known to improve survival have been labeled in the past as "hoax therapies". I would like to summarize some of the steps that could be taken right now:

What we can do now re. prevention of bladder cancer

Any smoker can quit smoking. This is a proven cancer preventing step. Also anybody who is presently inhaling second hand smoke should lobby for a smoke free work environment. Some jurisdictions have this law in place and the majority of people like it. People can change their diet. If a person eats more vegetables and less refined carbohydrates, the amount of natural anti-cancer substances in the food intake are increased and the negative effect on the cyclic AMP from hyperinsulinism is removed. This zone-type diet will lead to a much stronger immune system, which will prevent or reduce the development of many cancers (Ref.8). Chromosomal abnormalities that have been found in many bladder cancers tend to lead to a higher resistance to treatment as the cells are deficient for the normal cell functions. In order to get a lasting break-through for the patients who do not respond to the presently known treatment modalities, newer methods such as monoclonal antibodies attached to the patient's own activated macrophages or genetic vaccines etc.will have to be employed. Several Cancer Agencies around the world are investigating these methods, but nothing concrete, which would stand up to the test of prolonging long-term survival has yet been found. Watch out though as it is there that break throughs will come from.

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References:

1. Cancer: Principles&Practice of Oncology. 5th edition, volume 1. Edited by Vincent T DeVita, Jr. et al. Lippincott-Raven Publ., Philadelphia,PA, 1997.

2. Cancer: Principles &Practice of Oncology, 4^th edition, by V.T. De Vita,Jr., et al. J.B. Lippincott Co.,Philadelphia,1993. Chapter 34, page 1054 (data from text arranged as a table).

3. M Simoneau et al. Oncogene 2000 Dec 19(54): 6317-6323.

4. G Dalbagni , HW Herr Urol Clin North Am 2000 Feb 27(1): 137-146.

5. HW Herr J Clin Oncol 2001 Jan 1;19(1): 89-93.

6. DA Corral, CJ Logothetis World J Urol 1997; 15(2): 139 - 143.

7. PM Dodd et al. J Clin Oncol 1999 Aug;17 (8): 2546- 2552.

8. B. Sears: "The age-free zone".Regan Books, Harper Collins, 2000.

9. Conn's Current Therapy 2004, 56th ed., Copyright © 2004 Elsevier

10. Ferri: Ferri's Clinical Advisor: Instant Diagnosis and Treatment, 2004 ed., Copyright © 2004 Mosby, Inc