ADJUVANT CHEMOTHERPY HELPFUL IN HIGH RISK BLADDER CANCER

NEW YORK (Reuters Health) Aug 13 - Adjuvant chemotherapy (AC) after radical cystectomy will benefit the highest risk bladder cancer patients, according to a retrospective analysis of data on nearly 4,000 patients at 11 centers.

While existing evidence has suggested a survival advantage with post-surgery chemotherapy, Dr. Colin Dinney of the M.D. Anderson Cancer Center in Houston and his colleagues write, methodological issues and small sample size have made it difficult to draw conclusions from this research.

"As a result, the routine use of AC for patients undergoing radical cystectomy has not gained widespread acceptance," Dr. Dinney and his team note in a July 22 online paper in Clinical Cancer Research.

To get a better sense of the potential benefit of adjuvant chemotherapy in routine clinical practice, the researchers gathered data on 3,947 patients treated for transitional cell carcinoma of the bladder from 1979 to 2008, 932 of whom received off-protocol adjuvant chemotherapy. All had undergone radical cystectomy with lymphadenectomy, and none received neoadjuvant chemotherapy.

The researchers used a shared-frailty survival model to reduce bias due to differences between centers.

Median follow-up was 32 months, with median overall survival of 6.6 years. The median cancer-specific survival wasn't reached.

For the entire cohort, five and 10-year cancer-specific survival estimates were 66.7% and 60.3%, respectively, while recurrence-free survival estimates were 59.2% at five years and 55.3% at 10 years.

Multivariate analysis showed improved survival in patients given adjuvant chemotherapy, but the benefit was greatest for the highest risk patients. Overall, the hazard ratio for survival with adjuvant chemotherapy was 0.83, while it was 0.75 for the patients in the highest risk quintile.

Dr. Dinney and his team also found significant associations with survival for pathologic stage, gender, lymphovascular invasion, status of surgical margins, adjuvant radiation, and nodal status.

Five-year disease-specific survival was 94.2% among patients in the first quintile of risk, based on cancer-specific survival probability, and 81.3% for patients in the second quintile. Thus, for patients at the lowest risk of death, chemotherapy actually decreased survival (HR 6.21 for the first quintile, HR 2.20 for the second quintile, P<0.001). There was no association between chemotherapy and survival in the third and fourth quintiles.

But for patients in the top quintile, whose probability of disease-specific survival at five years was 32.8%, adjuvant chemotherapy had a significant benefit (HR 0.75, P = 0.002). For patients in this quintile, the median survival was 25 weeks with chemotherapy and 19 weeks without it.

While the results don't rule out benefits of adjuvant chemotherapy for a subgroup of patients with less advanced disease, the researchers say their findings "do not support routine administration of AC to patients with pathologic T2, node-negative disease, but we recognize that a benefit from AC for this subgroup of patients may require a larger number of patients and events."

In the meantime, Dr. Dinney and his team conclude, "Selective administration in patients at the highest risk for disease progression such as those with advanced pathologic stage and nodal involvement may optimize the therapeutic benefit of AC."

Clin Cancer Res. Posted online July 22, 2010. Abstract