Objective:To investigate the clinical characteristics and prognostic factors of primary urethral cancer.Methods:The clinical data of 35 patients with primary urethral cancer admitted to the First Affiliated Hospital of Zhengzhou University from January 2011 to April 2022 were retrospectively analyzed. There were 12 males (34.3%) and 23 females (65.7%). The average age was 61.1 ± 13.0 years old. The clinical symptoms included 13 cases of urethral obstruction (37.1%), 7 cases of hematuria (20.0%), 6 cases of urethral bleeding (17.1%), 5 cases of urinary tract irritation (14.3%), 1 case of Urinary incontinence (2.9%), 1 case of low back pain (2.9%), 1 case of scrotal ulcer (2.9%), and 1 case (2.9%) by self examination. All patients underwent cystourethroscopy and tissue biopsy. The biopsy pathology showed 16 cases of urothelial carcinoma, 7 cases of squamous carcinoma, 4 cases of adenocarcinoma, 3 cases of malignant melanoma, 1 case of urothelial carcinoma with squamous carcinoma, 1 case of Signet ring cell carcinoma, 1 case of sarcomatoid carcinoma, 1 case of embryonic Rhabdomyosarcoma, and 1 case of epithelioid angiosarcoma. The tumors were located in the proximal urethra in 13 cases (37.1%) and in the distal urethra in 22 cases (62.9%). There were 14 cases (40.0%) with a maximum diameter of less than 3 cm, 16 cases (45.7%) with a diameter of ≥ 3 cm, and 5 cases (14.3%) with mucosal abnormalities. There were 12 cases of T 1 stage, 9 cases of T 2 stage, 7 cases of T 3 stage, and 7 cases of T 4 stage in tumor staging. Imaging evaluation of lymph nodes showed 25 cases of N 0 stage, 2 cases of N 1 stage, and 8 cases of N 2 stage; A total of 11 cases of lymph node biopsy were performed (including 8 cases of intraoperative lymph node dissection and 3 cases of preoperative lymph node biopsy), of which 6 cases had lymph node metastasis, and 1 case was initially diagnosed with distant metastasis. Thirty-one cases underwent surgical treatment, of which 16 cases underwent radical urethrectomy, and 8 cases underwent intraoperative pelvic and bilateral inguinal lymph node dissection, 8 cases underwent resection of urethral tumors, and 7 cases underwent transurethral resection of tumors. Four cases did not undergo surgical treatment, while 1 case had epithelioid angiosarcoma and received radiotherapy combined with chemotherapy, 2 cases received chemotherapy with GC (Gemcitabine+ cisplatin) regimen, and 1 case received immunotherapy with immune checkpoint inhibitors. The risk factors that affected patient prognosis were analyzed. Results:All 35 cases in this group were followed up, with a median follow-up time of 22 (2, 122) months. Seventeen cases survived, 18 cases died, and the overall median survival duration was 23 (13 to not reached) months. The overall 5-year survival rate was 45%. The results of univariate analysis showed that clinical T-stage ( P=0.019), maximum tumor diameter ( P=0.016), and tumor location ( P=0.006) were independent risk factors affecting patient prognosis. Result of multivariate analysis showed that the maximum diameter of the tumor ≥ 3 cm ( HR=2.673, P=0.029) and the proximal location of the tumor ( HR=3.064, P=0.023) were independent risk factors affecting patient survival. Gender, age, treatment method, lymph node dissection, adjuvant radiotherapy, adjuvant chemotherapy, clinical manifestations, pathological type, clinical N staging, and pathological N staging had no significant impact on patient survival rate ( P>0.05). Single factor analysis was conducted on female patients separately, and only tumor location was found to be a prognostic factor ( χ2=17.246, P<0.01). Conclusions:Primary urethral cancer is a rare disease with various symptoms and poor prognosis. The maximum diameter of the tumor ≥3 cm and the tumor located at the proximal end of the urethra are clinical risk factors affecting the prognosis of patients with primary urethral cancer.