SSAT - THE IMPACT OF MULTIAGENT CHEMORADIATION TREATMENT VS RADIATION WITH OR WITHOUT MONOAGENT CHEMOTHERAPY ON THE PROGNOSIS OF ANAL SQUAMOUS CELL CARCINOMA.

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THE IMPACT OF MULTIAGENT CHEMORADIATION TREATMENT VS RADIATION WITH OR WITHOUT MONOAGENT CHEMOTHERAPY ON THE PROGNOSIS OF ANAL SQUAMOUS CELL CARCINOMA.
Paolo Goffredo^*¹, Alan Utria¹, Jacklyn Engelbart¹, Jessica Frakes², Timothy Robinson², Imran Hassan¹
¹Surgery, University of Iowa, Iowa City, IA; ²Radiation Oncology, Moffitt Cancer Center, Tampa, FL

Introduction: The standard treatment for anal squamous cell carcinoma is multiagent chemotherapy (5-FU and mitomycin-C) with radiation. This regimen, in part, is based on three randomized clinic trials (RTCs) comparing this approach to radiation alone (UKCCCR Anal Cancer Trial I and EORTC22861) or to radiation with monoagent chemotherapy (RTOG87-04). While these trials have shown significantly lower colostomy and locoregional failure rates in patients who received multiagent chemotherapy with radiation, they have failed to demonstrate an overall survival benefit with this regimen. We hypothesized that the lack of evidence of survival benefit in these RCTs may be due to limited sample sizes or length of follow-up and that multiagent chemotherapy with radiation is in fact associated with an improved overall survival as compared to radiation alone or with monoagent chemotherapy.
Methods: The National Cancer Database was queried to identify patients with anal squamous cell cancers from 2004 to 2015. Analyses were limited to patients who received radiation therapy with a total dose between 45 and 59 Gy, and did not undergo abdominoperineal resection (2.5% of this selected cohort). The survival impact of multiagent chemoradiation treatment vs radiation with or without monoagent chemotherapy was analyzed for AJCC stages I, II, and III. Data were examined using simple summary statistics, Kaplan-Meier analyses, and Cox proportional hazards regression analysis.
Results: A total of 16,975 patients met inclusion criteria: 14,496 received multiagent chemotherapy with radiation, 1,721 had monoagent chemotherapy with radiation, and 758 received radiation alone. Compared to the other two groups, patients who received multiagent chemotherapy with radiation had significantly younger age at diagnosis, higher proportions of females and private insurance, lower number of comorbidities, and more advanced disease, defined by higher rates of poorly differentiated histology, larger tumor size, and lymph node metastases (all p<0.01). In univariate analysis, after stratification by stage, receiving multiagent chemotherapy with radiation was consistently associated with improved overall survival (all p<0.001, Table 1). After adjustment for available confounders, multiagent chemotherapy with radiation remained independently associated with more favorable outcomes across all stages (all p<0.001, Table 2).
Conclusions: Notwithstanding the limitations of this dataset, our data suggest that multiagent chemotherapy with radiation is associated with an overall survival benefit compared to radiation alone or with monoagent chemotherapy. Absent mitigating circumstances, the potential survival benefit associated with multiagent chemotherapy should be considered in the management of patients diagnosed with anal squamous cell carcinoma.

5 year overall survival by stage
Stage 5 year Overall Survival, % p-value
Radiation alone Monoagent chemoradiation Multiagent chemoradiation
I 76 80 87 <0.001
II 54 70 77 <0.001
III 43 56 66 <0.001

Multivariate analysis for overall survival by stage
Risk factor Stage I Stage II Stage III
HR (95% CI) p-value HR (95% CI) p-value HR (95% CI) p-value
Gender, male 1.34 (1.08-1.67) 0.008 1.48 (1.32-1.65) <0.001 1.73 (1.55-1.94) <0.001
Age, years 1.04 (1.03-1.05) <0.001 1.03 (1.02-1.03) <0.001 1.02 (1.01-1.02) <0.001
Institution
Academic Reference
Comprehensive N/A 1.19
(1.05-1.34)
0.007 1.10
(0.98-1.23)
0.097
Community N/A 1.54
(1.29-1.83) <0.001 1.24
(1.02-1.50)
0.030
Insurance
Medicare Reference
Private 0.37
(0.23-0.60) 0.67
(0.42-1.09) 0.66
(0.51-0.85) 0.001 0.64
(0.52-0.78) <0.001
None 0.67
(0.42-1.09) 0.106 1.00
(0.77-1.29) 0.990 1.00
(0.82-1.23) 0.973
Comorbidities
None Reference
1
1.47
(1.11-1.95)
0.008
1.36
(1.18-1.57)
<0.001
1.14
(0.98-1.33)
0.088
≥2
2.20
(1.57-3.10)
<0.001
2.05
(1.73-2.43)
<0.001
1.64
(1.36-1.98)
<0.001
Treatment
Multiagent chemoradiation Reference
Monoagent chemoradiation 1.35
(1.02-1.79)
0.036 1.24
(1.06-1.45)
0.006 1.28
(1.09-1.51)
0.003
Radiation alone 1.49
(1.10-2.04)
0.011 2.12
(1.71-2.63)
<0.001 1.72
(1.29-2.30)
<0.001

HR indicates Hazard Ratio; CI, Confidence Interval, N/A, not applicable

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