Introduction: The accurate assessment and grading of adverse events (AE) is essential to ensure comparisons between surgical procedures and outcomes. The current lack of a standardized severity grading system may limit our understanding of the true morbidity attributed to AEs in surgery. The aim of this study is to review the prevalence in which intraoperative adverse event (iAE) severity grading systems are used in the literature, evaluate the strengths and limitations of these systems, and appraise their applicability in clinical studies. Methods: A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. PubMed, Web of Science, and Scopus were queried to yield all clinical studies reporting the proposal and/or the validation of iAE severity grading systems. Google Scholar, Web of Science, and Scopus were searched separately to identify the articles citing the systems to grade iAEs identified in the first search. Results: Our search yielded 2957 studies, with 7 studies considered for the qualitative synthesis. Five studies considered only surgical/interventional iAEs, while 2 considered both surgical/interventional and anesthesiologic iAEs. Two included studies validated the iAE severity grading system prospectively. A total of 357 citations were retrieved, with an overall self/nonself-citation ratio of 0.17 (53/304). The majority of citing articles were clinical studies (44.1%). The average number of citations per year was 6.7 citations for each classification/severity system, with only 2.05 citations/year for clinical studies. Of the 158 clinical studies citing the severity grading systems, only 90 (56.9%) used them to grade the iAEs. The appraisal of applicability (mean%/median%) was below the 70% threshold in 3 domains: stakeholder involvement (46/47), clarity of presentation (65/67), and applicability (57/56). Conclusion: Seven severity grading systems for iAEs have been published in the last decade. Despite the importance of collecting and grading the iAEs, these systems are poorly adopted, with only a few studies per year using them. A uniform globally implemented severity grading system is needed to produce comparable data across studies and develop strategies to decrease iAEs, further improving patient safety.

Penile squamous cell carcinoma (PSCC) represents a malignancy with low incidence. Despite advances in chemotherapy-based management, outcomes for patients with locally advanced and metastatic disease remain poor, with 5-year survival rates of 51% and 9%, respectively. Early diagnosis is crucial, yet psychosocial/structural barriers often delay it. Treatment strategies are stage-dependent, ranging from organ-sparing surgery and targeted radiotherapy for early-stage disease to cisplatin-based chemotherapy for locally advanced and metastatic cases. However, systemic therapies provide modest survival benefits and can expose the patient to unnecessary toxicities. Immunotherapy has emerged as a promising area, given the high expression of PD-L1 in PSCC and the significant proportion of HPV-driven tumors. Although initial results from immunotherapy-based trials are limited, preliminary trials such as HERCULES, ALPACA, PULSE, and PERICLES aim to define their role better. Similarly, combination regimens utilizing toripalimab in combination with nimotuzumab and taxane-based chemotherapy (TNT) followed by consolidative surgery are currently underway. Furthermore, the development of therapeutic HPV vaccines offers a novel strategy to enhance local antitumor immunity. Antibody–drug conjugates (ADCs) targeting HER-2, Trop-2, and Nectin-4 antigens represent another evolving therapeutic avenue that has shown preliminary promising results. As the landscape of penile cancer treatment continues to grow, incorporating these novel strategies could further improve survival outcomes and/or offer improved quality of life. This review provides a comprehensive overview of emerging systemic therapies in PSCC, underscoring ongoing research efforts to address unmet needs.