Primary urethral cancer (PUC) is a rare urological malignancy. Prior research linked a higher prevalence of bulbomembranous adenocarcinoma in Taiwan to historical chronic arsenic exposure in drinking water. However, recent decades have seen successful public health measures to reduce this exposure. This study aimed to investigate the changing trends of male PUC in Taiwan compared to the United States of America (USA).

We conducted a retrospective analysis of data on male PUC patients at National Cheng Kung University Hospital (NCKUH), the only medical center near the black foot disease endemic area between 1975 to 2020. We also identified male PUC patients within Surveillance, Epidemiology and End Results (SEER) database to evaluate trends of PUC in the USA. To investigate potential trends over time, we categorized male PUC patients into two groups based on their diagnosis year. The year 2003 served as the dividing point.

From 1975 to 2020, 24 and 641 male PUC patients were diagnosed in NCKUH and in SEER database respectively. Within NCKUH, a marked decrease in the prevalence of adenocarcinoma (43% to 0%) and a corresponding increase in transitional cell carcinoma (TCC, 21% to 90%) were observed. The predominant site of male PUC shifted from the bulbomembranous urethra (50%) to the penile urethra (50%). The SEER data, on the other hand, showed TCC remaining the most prevalent histological type (65% to 56%). However, a trend towards more advanced stages (31% to 38%, p= 0005) and increase of chemotherapy (13% to 29%, p < 0.001) was seen. Additionally, the SEER database exhibited a significant decrease in the incidence rate of male PUC cases (3 to 1.4 per 1,000,000, p < 0.001), particularly for TCC (2 to 0.8 per 1,000,000, p < 0.001), with an annual percentage change of -3.7 per 1,000,000.

Our analysis identified three significant trends in male PUC: 1. Over time, the histologic patterns of PUC at NCKUH evolved to resemble those observed in the USA, likely reflecting the success of public health measures in reducing chronic arsenic exposure in Taiwan. 2. The incidence rate of PUC in the USA decreased significantly, potentially linked to the declining prevalence of Human papillomavirus infection in the United States, a risk factor for PUC. Additionally, bladder cancer exhibits similar temporal trends, suggesting a possible shared carcinogenic pathway between these malignancies. 3. There has been an increase in the proportion of advanced-stage diagnoses, which may be attributed to stage migration as advanced diagnostic tools like computed tomography allowed more sensitive detection.