Adjuvant Chemoradiotherapy May Provide Benefit in Locally Advanced Bladder Cancer

July 2016, Vol 7, No 6

In the United States, the standard of care for locally advanced bladder cancer after radical cystectomy is to “consider” adjuvant chemotherapy and ad­juvant radiation. Results of a 3-arm randomized clinical trial showed that adjuvant radiation therapy alone or combined with chemotherapy (ie, chemoradiotherapy) did not significantly improve disease-free survival compared with adjuvant chemotherapy alone. However, the findings hint at benefits for chemoradiotherapy that should be studied further. Brian Baumann, MD, a radiation oncology resident at the University of Pennsylvania, Philadelphia, presented the findings at the 2016 Genitourinary Cancers Symposium.

The study included 2 main comparisons of adjuvant chemoradiotherapy versus radiation and adjuvant chemoradiotherapy versus chemotherapy alone. The 3-year disease-free survival rate was 68% for adjuvant chemoradiotherapy versus 53% for radiation alone, but this 5% difference was not statistically significant. The 3-year disease-free survival rate in the second comparison was 68% for chemoradiotherapy versus 56% for chemotherapy alone, a numerical trend toward improved survival with chemoradiotherapy.

The rate of local recurrence was significantly reduced with adjuvant chemoradiation versus chemotherapy, which was the only significant difference between the arms in this trial. However, the improved control of local recurrence did not lead to improved disease-free survival or metastasis-free survival.

The study was conducted in Egypt, where adjuvant radiation therapy is the standard of care for pelvic failure after radical cystectomy. Also, Egyptian patients have more mixed histology, with a higher percentage of squamous-cell bladder cancer than in the United States, explained Dr Baumann. Investigators from the University of Pennsylvania provided help in analyzing and interpreting the data.

“This is one of the largest trials to be presented, and it provides more evidence that adjuvant chemoradiation may have some benefit in locally advanced bladder cancer. Chemoradiation led to improvement in local control in the second randomization. We think the results are intriguing, and larger studies are needed. Four organizations [worldwide] are currently considering such trials adding radiation to neoadjuvant chemotherapy,” Dr Baumann said.

Study Details

The study enrolled 198 patients with bladder cancer who were treated between 2002 and 2008 at the National Cancer Institute in Cairo. The patients were treated with radical cystectomy and pelvic node dissection with negative margins and at least 1 high-risk feature for local failure (ie, stage pathologic T3b disease or higher, grade 3 tumors, and positive lymph nodes).

The patients were aged <70 years (median age, 54 years), had adequate ECOG performance status, and adequate organ function. Patients with evidence of distant metastasis or second malignancies were excluded from the study.

The patients were randomized 3 to 6 weeks after radical cystectomy to adjuvant radiation 45 Gy given twice daily over 3 weeks or chemotherapy with 2 cycles of gemcitabine (Gemzar, Eli Lilly) plus cisplatin (Platinol, Corden Pharma Latina S.p.A.), followed by adjuvant radiation and then by 2 more cycles of gemcitabine plus cisplatin. There were 78 patients in the radiation-alone arm and 75 patients in the chemoradiation arm. A total of 45 patients were later enrolled in the chemotherapy-alone arm and received 4 cycles of gemcitabine plus cisplatin.

Overall, 53% of patients had urothelial carcinoma, and 41% had squamous-cell carcinoma. The median follow-up was 19 months.

In the initial randomization, the disease-free survival rate was 68% for the chemoradiation arm and 63% for the radiation arm, a nonsignificant difference. The rate of freedom from local disease-free recurrence was 96% at 3 years with chemoradiation versus 87% for radiation, which was again a nonsignificant difference.

The rate of distant metastases-free survival was 73% for chemoradiation versus 72% for radiation, and the overall survival rate was 64% versus 48% respectively, which were nonsignificant differences.

In the second comparison between chemoradiation and chemotherapy alone, a trend was seen toward improved disease-free survival with chemoradiation versus chemotherapy alone (68% vs 56%, respectively), and a significant benefit was seen for chemoradiation on local recurrence-­free survival (96% vs 69%, respectively; P <.001).

No significant differences were found between these 2 arms in patients with 3-year metastasis-free survival (64% for chemoradiation vs 51% for chemotherapy alone) or overall survival; however, the overall survival analysis numerically favored chemoradiation over chemotherapy alone (64% vs 51%, respectively).

“The small size of these arms limits the ability to detect clinically meaningful differences between the chemotherapy and chemoradiation arms,” Dr Baumann said, which is “something that has plagued many adjuvant chemotherapy trials."

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