We hypothesized that important differences may exist in urethral cancer ASR in contemporary patients, according to gender, age, race, histological subtype, region and stage. We tested this hypothesis within the SEER database 2004–2016 and arrived at several noteworthy observations.
First, we corroborated an important difference in ASR, relative to the previous figures reported by Swartz et al . Overall, ASR in urethral cancer was 1.69/1,000,000. After stratification according to patient sex, ASR was 2.70 vs. 0.55/1,000,000 in males vs. females, respectively. Moreover, in temporal trend analyses, ASR decreased in both sexes at a similar rate. Although, the absolute ASR is different in contemporary urethral cancer patients, relative to more historic controls, our findings are comparable to Swartz et al., with respect to sex distribution . Specifically, ASR was higher in males than in females. However, comparisons of absolute rates cannot be made, due to methodological and patient population differences.
Second, we identified important differences according to race, as well as patient sex. Specifically, stratification according to race differed between males and females. In consequence, sex-specific results focusing on race were reported. In males, highest ASR was recorded in African Americans, followed by Caucasians and Hispanics, in that order. The same relationship was recorded in females. However, in females, the absolute numbers were lower in African Americans and Caucasians than those reported in males. Finally, ASR could not be computed for Hispanic females due to insufficient numbers. Despite those differences, the temporal trends were highly comparable between males and females, in African American and Caucasian patient groups. Our findings are comparable to Swartz et al., who also reported higher historic incidence rates in African American males and females, relative to Caucasian males and females .
Third, we identified important differences according to histological subtypes, as well as according to patient sex. Specifically, stratification according to histological subtypes differed between males and females. In consequence, sex-specific results focusing on histological subtypes were reported. In males, highest incidence rates were recorded in urothelial histological subtype, followed by SCC and adenocarcinoma. In females, incidence rates were comparable between all histological subtype groups. In temporal trend analyses, in both males and females no ASR differences were recorded according to histological subtype. To the best of our knowledge, no contemporary study reported incidence rates according to histological subtype of urethral cancer. In consequence, our data cannot directly be compared to contemporary studies. However, our observations are comparable with previous reports, where urothelial histological subtype was predominant in male urethral cancer patients and were more equal distribution of histological subtype (urothelial, SCC, adenocarcinoma and other) was recorded in female urethral cancer patients [8, 9, 14–18].
Fourth, we tested for differences in ASR according to four SEER regions, namely Midwest, Northeast, South and West. It is of note that important sample size differences exist between those four regions. Specifically, Midwest included 205 observations vs. 901 in West vs. 481 in South vs. 320 in Northeast. Despite numeric and regional membership differences, we corroborated ASR regional differences. These were in agreement with regional differences described by Swartz et al. . Neither Swartz et al. nor the current data can provide firm indications to explain those differences. Moreover, similar to Swartz et al., we also observed the highest incidence of urethral cancer patients in the age category of patients ≥ 75 years . However, no significant changes were observed over time in age category incidences. These observations are noteworthy, since with demographic changes an increasing incidence in the oldest age category may have been expected.
Fifth, important differences in stage stratified analyses were recorded. Overall ASR was highest in T1N0M0, followed by T3 − 4N0M0, T1 − 4N1 − 2M0, T1 − 4N0 − 2M1 and T2N0M0 stage. After stratification according to male sex, highest ASR was also reported in T1N0M0 stage, followed by T3 − 4N0M0. Due to limited sample size, incidence rates could not be computed in females. In consequence, the overall rates very closely approximated those recorded in males. In temporal trend analyses, T1N0M0 stage significantly decreased over time (-3.00%, p = 0.02) in favor of T1-4N1-2M0 stage (+ 2.11%, p = 0.02). In temporal trend analyses that focused on males, the same pattern of stage distribution was observed. To the best of our knowledge, we are the first to report ASR according to stage at presentation in urethral cancer. In consequence, our data cannot be compared to previous investigations. Nonetheless, our findings require consideration in clinical practice, due to the increase in unfavorable stage T1 − 4N1 − 2M0 rate.
Taken together, our results provided important observations about urethral cancer incidence and its trends over time. First, urethral cancer ASR is very low, relative to other urologic primaries [19–22]. Its ASR is highest in males, elderly patients, African Americans and in urothelial histological subtype. Most incident cases are stage T1N0M0. However, over time, the importance of T1N0M0 decreased in favor of T1 − 4N1 − 2M0. This observation is worrisome and may be indicative in diagnostic delays.
Our work has limitations and should be interpreted in the context of its retrospective and population-based design. Second, our results relied on US population and may not be generalizable to other western countries. Third, our cohort relies on a small sample that resulted in lack of significant differences in some subgroup comparisons. Fourth, histologic diagnoses in the SEER database are derived from medical records, without central review. However, it should be emphasized that the SEER database is designed to providing proportional representation of the United States’ population and only the National Cancer Data Base can provide a larger sample of urethral cancer patients, without providing cancer-specific mortality rates that are required in any cancer analysis.