Francesco Lasorsa,1,2 Gabriele Bignante,1,3 Angelo Orsini,1,4 Sofia S Rossetti,1 Michele Marchioni,4 Francesco Porpiglia,3 Pasquale Ditonno,2 Giuseppe Lucarelli,2 Riccardo Autorino,1 Celeste Manfredi5 1Department of Urology, Rush University, Chicago, IL, USA; 2Department of Precision and Regenerative Medicine and Ionian Area- Urology, Andrology and Kidney Transplantation Unit, University of Bari ‘Aldo Moro’, Bari, Italy; 3Division of Urology, Department of Oncology, University of Turin, San Luigi Gonzaga Hospital, Orbassano, Turin, Italy; 4Urology Unit, Department of Medical, Oral and Biotechnological Sciences, “G. d’Annunzio” University, Chieti, Italy; 5Department of Woman, Unit of Urology, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli” Naples ItalyCorrespondence: Riccardo Autorino, Director of Surgical Innovation & Clinical Research, Department of Urology, Rush University Medical Center, 1725 W. Harrison Street, Suite 970, Chicago, IL, 60612, USA, Tel +1 312-563-7622, Email ricautor@gmail.com; riccardo_autorino@rush.eduAbstract: Penile cancer (PeCa) is a rare urologic tumor worldwide. In 2024, 2100 new cases and 500 deaths are estimated in the United States. Radical surgery via total penectomy has historically been the cornerstone of treatment, since it provides excellent long-term oncological control. The rationale of surgery for penile cancer was to achieve a 2 cm macroscopic surgical margin that is historically advocated to reduce recurrences. Over time, numerous studies have demonstrated that resection margin status does not affect patients’ survival. Different penile-sparing techniques are currently recommended in the European Association of Urology-American Society of Clinical Oncology (EAU-ASCO) guidelines for the treatment of localized primary PeCa. Centralization of care could yield multiple benefits, including improved disease awareness, higher rates of penile-sparing surgery, enhanced detection rates, increased utilization of less invasive lymph node staging techniques, enhanced quality of specialized histopathological examinations, and the establishment of specialized multidisciplinary teams. Compared to more aggressive treatments, the higher recurrence rates after penile-sparing surgery do not hamper neither the metastasis-free survival nor the overall survival. Repeated penile-sparing surgery could be considered for selected cases. The psychological impact of penile cancer is not negligible since the perceived loss of masculinity might adversely affect mental health and overall well-being. Quality of life may be compromised by sexual and urinary dysfunction which may be the result either of the loss of penile tissue or the psychological status of the patient. It is of utmost importance to offer rehabilitative treatment as sexual therapy, physical therapy, occupational therapy, family and peer counseling.Keywords: penile cancer, penile-sparing surgery, quality of life, sexual function, survival