Penile cancer represents 0.2% of all malignant neoplasms, with 34,500 cases worldwide in 2018 compared to 1,270,000 cases of prostate cancer. There are few active studies in penile cancer care, with only 23 actively recruiting currently. This is an unmet need in genitourinary cancer care and research.
HPV infection is associated with both better prognosis and radiation sensitivity in other cancers such as head & neck carcinoma and may also be associated with better prognosis in penile cancer. Optimal perioperative management of patients with node-positive disease is unclear, and the impact of HPV-status on treatment strategy is also unknown. To address this question in penile cancer, Dr. Andrea Necchi and colleagues in abstract 706MO utilized an international database of men who underwent inguinal lymph node dissection for management of node+ penile cancer and explored the association between HPV infection and outcome. Unlike in head and neck carcinoma and in contrast to a previously published pooled analysis of smaller patient cohorts with penile cancer, no difference in overall survival was found by HPV infection status. The authors also explored whether HPV status impacted the response to radiotherapy and found that HPV positivity was associated with longer survival in patients who received radiation, though patient numbers were small in this analysis. This may be explained in part by the finding that HPV-negative tumors are associated with a higher incidence of TP53 alteration (75.2%) compared to HPV-positive tumors. These genomic analyses are also relevant to ongoing clinical research questions around the role of immunotherapy in the management of penile cancer. While patients with MSI-H status were rare in the 706MO cohort, a subset of patients (more in the HPV positive population) has tumor mutational burden higher than 10 or 20 mutations/megabase. Prior studies have shown PD-L1 expression in tumor and microenvironment cells. Multiple trials are ongoing evaluating the role of immunotherapy in penile cancer after platinum chemotherapy.
Abstract 707MO illustrated the clinical characteristics and treatment patterns of patients with metastatic penile cancer. The findings in this abstract showed that more than half of patients with metastatic disease had progressive disease even with standard of care platinum chemotherapy, though patient survival was longer if they received any chemotherapy as opposed to best standard of care. Given the poor outcomes in metastatic disease, studies optimizing adjuvant and neoadjuvant strategies to limit the risk of developing metastatic disease are needed. To this end, Dr. Baciarello discussed the InPACT study exploring optimal implementation of neoadjuvant therapies, inguinal lymph node dissection, and adjuvant therapies for intermediate and high-risk penile cancer patients.
Dr. Baciarello then discussed abstract 708MO, focusing on the risk of contralateral metachronous testicular cancer. It has been known for some time that patients with metastatic testicular cancer, who receive platinum-based chemotherapy, have a 50% lower risk of developing a second testicular cancer relative to patients diagnosed with only localized disease that is managed surgically. This study found that platinum chemotherapy decreased the risk of contralateral testicular cancer, with a greater decrease in incidence with more cycles of chemotherapy. Diagnosis at age less than 30 was also associated with a higher risk of metachronous second testicular cancer. These results may have implications for surveillance programs for patients diagnosed with testicular cancer, especially those diagnosed with localized disease before they are 30 years old.
Presented by: Guilia Baciarello, MD, Medical Oncologist at the Institut Gustave Roussy, Villejuif, France
Written by: Alok Tewari, MD, PhD, Medical Oncologist at the Dana-Farber Cancer Institute, at the 2020 European Society for Medical Oncology Virtual Congress (#ESMO20), September 19th-September 21st, 2020.