Introduction:

Prior pelvic radiation is an oncogenic risk, and radiation dose is a well-established factor in mutation burden. While studies exist correlating outcomes in muscle-invasive disease (MIBC) to prior radiation, there is a lack of data on the genetics of bladder cancer associated with prior radiation. This project investigates the genetic, demographic, pathological, and surgical characteristics of cystectomy patients with and without prior pelvic radiation.

Methods:

Data were gathered from a single-institution cystectomy database. A 161 gene solid tumor panel performed by SEMA4 identified mutation type, area, and quantity. Total mutational burden was estimated by calculating the mutational sum. Group comparisons between the two cohorts were performed with the Kruskal-Wallis test (due to lack of normality) for continuous variables, and Fisher’s exact test for categorical comparisons. Kaplan-Meier curves were calculated for survival differences between those with and without prior radiation.

Results:

            Data from 339 cystectomy patients (from year to year), 276 without and 63 with prior radiation were analyzed. Of these, 142 patients without and 27 with a history of prior radiation had sequencing results from the solid tumor panel. Patients with prior radiation were statistically older (median of 75 vs 68 years), had higher Charlson comorbidity scores (median of 6 vs 5), and lower estimated blood loss (median of 300 vs 200 mL). Patients with prior radiation also had higher rates of discharge to non-home, discharge to home with home health aides, and open surgery as compared to patients without prior radiation. MYC mutations (11.1 vs. 1.4%, p = 0.030) and TP53 mutations (77.8% vs 53.2%, p = 0.031) were significantly more frequent in the radiation group than the non-radiation group. Mutational burdens were not significant between the groups. Overall survival was not statistically significant between the groups.

Conclusion:

            Certain mutations seem to be more prevalent in those with prior pelvic radiation. The lack of difference between the two cohorts may be due to an underlying history of smoking in both groups, which is a proven predictor of TMB, driving mutational burden more so than prior pelvic radiation. The higher rate of MYC and TP53 mutations in patients with prior pelvic radiation is interesting in light of MYC’s role in inhibiting urothelial carcinoma progression and TP53’s ubiquitous presence in cancer. TP53 has been shown to correlate with a worse cancer prognosis, which is supportive of our finding that these patients have higher ASA and Charleson comorbidity coefficient.

Funding: N/A