Penile cancer management: from primary tumor to distant metastasis

In 2021, approximately 122,651 people in the Netherlands were diagnosed with cancer, and one in five of these cases were classified as rare cancers. This research focuses on penile cancer, with 178 new patients in the Netherlands in 2021. Penile cancer has an extensive impact on quality of life. The investigations in this thesis aim to reduce morbidity and improve survival for penile cancer patients and consist of three parts: Primary Tumour: EMI-137, a fluorescent tracer, is used to help identify the primary tumour. Outcomes of perineal urethrostomy are also discussed. Dynamic Sentinel Node Biopsy: The use of the hybrid (fluorescent and radioactive) tracer Indocyanine Green–99mTechnetium-nanocolloid is evaluated. We conclude that blue dye is not of added value. Complications of the procedure are seen more often when more lymph nodes are resected. After a tumor positive sentinel node biopsy, histopathological outcomes cannot be used to reliably predict the patients who have to undergo completion lymph node dissection. Treatment of Locoregional and Distant Metastases: Improved systemic therapy is necessary to reduce recurrences. Chemoradiation turns out to be a less toxic treatment in comparison to neo-adjuvant chemotherapy. The rationale for immunotherapy in penile cancer is discussed and the efficacy of immunotherapy for penile cancer is evaluated. In conclusion, investigations in this thesis show c-MET to be a potential penile cancer-specific tracer, confirm the reliability and low morbidity and illustrate the continuing evolution of dynamic sentinel node biopsy, propose chemoradiation in stead of neo-adjuvant chemotherapy and pave the way for immunotherapy treatment alternatives in penile cancer

Defining the Tumor Microenvironment of Penile Cancer by Means of the Cancer Immunogram

CD8 + T-cell infiltration and PD-L1 expression are commonly observed in penile cancers, providing the rationale for immunotherapeutic treatment, particularly in advanced disease. Clinical trials testing checkpoint blockade are ongoing

Clinicopathological predictors of finding additional inguinal lymph node metastases in penile cancer patients after positive dynamic sentinel node biopsy: a European multicentre evaluation

Objective: To develop a predictive model for additional inguinal lymph node metastases (LNM) at inguinal lymph node dissection (ILND) after positive dynamic sentinel node biopsy (DSNB) using DSNB characteristics to identify a patient group in which ILND might be omitted. Patients and Methods: We conducted a retrospective study of 407 inguinal basins with a positive DSNB in penile cancer patients who underwent subsequent ILND from seven European centres. From the histopathology reports, the number of positive and negative lymph nodes, presence of extranodal extension and size of the metastasis were recorded. Using bootstrapped logistic regression, variables were selected for the clinical prediction model based on the optimization of Akaike's information criterion. The area under the curve (AUC) of the receiver-operating characteristic curve was calculated for the resulting model. Decision curve analysis (DCA) was used to evaluate the clinical utility of the model. Results: Of the positive DSNBs, 64 (16%) harboured additional LNM at ILND. Number of positive nodes at positive DSNB (odds ratio [OR] 2.19, 95% confidence interval (CI) 1.17–4.00; P = 0.01) and largest metastasis size in mm (OR 1.06, 95% CI 1.03–1.10; P = 0.001) were selected for the clinical prediction model. The AUC was 0.67 (95% CI 0.60–0.74). The DCA showed no clinical benefit of using the clinical prediction model. Conclusion: A small but clinically important group of basins harbour additional LNM at completion ILND after positive DSNB. While DSNB characteristics were associated with additional LNM, they did not improve the selection of basins in which ILND could be omitted. Thus, completion ILND remains necessary in all basins with a positive DSNB