Retrospective Single Center Assessment of Routes to Penile Cancer Diagnosis and the Role of Penile Biopsy.

OBJECTIVE: To examine the routes to penile cancer diagnosis and the role of penile biopsy. MATERIALS AND METHODS: This retrospective observational study from a tertiary referral center included 625 patients referred as urgent suspected penile cancer within the Danish Cancer Patient Pathway (CPP) and 216 patients undergoing penile biopsy outside the CPP between January 1, 2021 and March 31, 2025. The main outcomes were the number of patients diagnosed within and outside the CPP and secondary outcomes included biopsy findings, the ratio between urgent suspected penile cancer referrals and the number of patients subsequently diagnosed with penile cancer. RESULTS: Among 529 patients referred under the CPP for suspected penile cancer, only 10% were diagnosed with cancer. Biopsy confirmed cancer was more frequent within the CPP, though overall cancer detection rates were similar (~10%). Patients biopsied outside the CPP were younger and more often had prior biopsies. Complication rates after penile biopsy were low and comparable between groups. Diagnostic concordance between clinical suspicion and histology was slight (κ = 0.20, SE 0.04) for cancer and fair (κ = 0.33, SE 0.05) for PeIN. Biopsies demonstrated both diagnostic and therapeutic value, occasionally altering clinical management. CONCLUSION: The CPP identifies a higher proportion of malignancies but with a low overall conversion ratio, and some cancers are still diagnosed outside the pathway. Penile biopsy is safe and essential for accurate diagnosis due to low clinical-histological concordance, with added therapeutic value. Continued focused penile biopsy use, including re-biopsy in uncertain cases, is warranted to ensure optimal management and oncological safety.