To Örebro University

BACKGROUND AND OBJECTIVE: To improve treatment for patients with penile cancer, there is a need for prognostic and treatment predictive biomarkers. The objective of this study was to examine the expression of checkpoint proteins (programmed cell death ligand 1 [PD-L1], T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain [TIGIT], and cluster of differentiation 155 [CD155]) and human papillomavirus (HPV) status in primary tumors of penile cancer patients with indication for perioperative oncological treatment. As a secondary aim, we evaluated the associations between these biomarkers and penile cancer-specific survival.

METHODS: Fifty-two patients who underwent surgical treatment during 2009-2018 were included. HPV status was determined by polymerase chain reaction, and tissue microarray sections from primary tumors were subjected to immunohistochemistry to evaluate the expression of PD-L1, TIGIT, and CD155.

KEY FINDINGS AND LIMITATIONS: PD-L1, TIGIT, and CD155 were expressed widely. Specifically, 75% of patients had PD-L1-positive tumors, 80% had TIGIT-positive tumors, and 98% had CD155-positive tumors. Additionally, 47% of patients had HPV-positive tumors. Patients with HPV-positive tumors had better survival than those with HPV-negative tumors. Patients with indication for perioperative oncological therapy who received such treatment and whose tumors exhibited low PD-L1 expression demonstrated better survival than those with higher PD-L1 expression levels. The main limitations of this study include the small number of patients, retrospective design, and use of tissue microarrays rather than whole tissue sections.

CONCLUSIONS AND CLINICAL IMPLICATIONS: We found high expressions of the investigated checkpoint proteins, suggesting an immunosuppressed tumor microenvironment in patients with advanced penile cancer. These findings imply that checkpoint proteins could serve as prognostic and treatment predictive biomarkers. Patients with HPV-positive tumors had better prognosis.

PATIENT SUMMARY: In this report, we investigated tumor tissue from patients with penile cancer and identified a high prevalence of proteins that play an important role in the immune system's defense against cancer. The findings suggest that these proteins can be important in understanding and developing treatments for patients with lymph node metastasized penile cancer.

OBJECTIVE: The Swedish national guidelines on penile cancer were first published in 2013. The objective of the present study is to present the 2023 update of these guidelines and highlight the differences to the European Association of Urology (EAU) / American Association of Clinical Oncology (ASCO) guidelines on penile cancer.

MATERIAL AND METHODS: A review of the literature and a comparison to the EAU / ASCO guideline on penile cancer was performed. Differences between the EAU / ASCO guidelines and the Swedish national guidelines are highlighted.  

Results: The Swedish national guidelines on penile cancer emphasized the consultation of a national multidisciplinary treatment conference for all patients diagnosed with both primary and recurrent penile cancer or penile intraepithelial neoplasia (PeIN). Clinically lymph node negative patients diagnosed with >pT1G1 are offered dynamic sentinel node biopsy (DSNB). In the EAU / ASCO guidelines the DSNB is optional for T1aG2 patients. Penile cancer surgery is centralized to two hospitals. Perioperative chemotherapy is offered to patients with ≥N2. In the EAU / ASCO guidelines the use of perioperative chemotherapy for N2 patients is optional. A structured follow-up program is advocated to find recurrences at an early stage.

CONCLUSIONS: The Swedish national guidelines on penile cancer have been updated and compared to the EAU / ASCO guidelines. The national multidisciplinary treatment conference, centralization of surgery, the use of perioperative chemotherapy and a structured follow-up are the cornerstones of the Swedish national guidelines on penile cancer.

BACKGROUND: The benefit of perioperative oncological treatment in men with penile cancer is uncertain. In 2015, treatment recommendations were centralised in Sweden and treatment guidelines were updated. OBJECTIVE: To evaluate if the use of oncological treatment in men with penile cancer increased after the introduction of centralised recommendations, and whether such therapy is associated with better survival.

DESIGN SETTING AND PARTICIPANTS: This was a retrospective cohort study including a total of 426 men diagnosed with penile cancer with lymph node or distant metastases in Sweden during 2000-2018.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We first assessed the change in the proportion of patients with an indication for perioperative oncological treatment who actually received such treatment. Second, we used Cox regression to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for disease-specific mortality associated with perioperative treatment. Comparisons were made for both all men without perioperative treatment and for those who did not receive treatment but who lacked apparent contraindications for treatment.

RESULTS AND LIMITATIONS: The use of perioperative oncological treatment increased from 2000 to 2018, from 32% of patients with an indication for treatment during the first 4 yr to 63% during the last 4 yr. In comparison to patients potentially eligible for oncological treatment who did not receive it, those who were treated had a 37% lower risk of disease-specific death (HR 0.63, 95% CI 0.40-0.98). Stage migration because of improvements in diagnostic tools over time may have inflated the more recent survival estimates. An influence of residual confounding due to comorbidity and other potential confounders cannot be excluded.

CONCLUSIONS: The use of perioperative oncological treatment increased after the centralisation of penile cancer care in Sweden. Although the observational study design precludes causal inference, the findings suggest that perioperative treatment in patients with penile cancer eligible for treatment may be associated with better survival.

PATIENT SUMMARY: In this study, we looked at the use of chemotherapy and radiotherapy for men with penile cancer and lymph node metastases in Sweden during 2000-2018. We found an increase in the use of cancer therapy and an increase in survival for patients who received such therapy.

BACKGROUND: Penile cancer is an uncommon disease with poor prognosis when spread to more than one inguinal lymph node. Recommendations on chemo- and radiotherapy in treatment guidelines are based on low-grade evidence. There are to our knowledge no described population-based cohort with detailed information on given oncological treatment and survival data. The aim of this study is to investigate in detail how men with metastatic penile cancer have been treated with chemotherapy and radiotherapy over time, and how survival varies with N-stage and given treatment.

MATERIAL AND METHODS: For this observational cohort study all men in Sweden diagnosed with penile cancer with lymph node- or distant metastases 2000-2015 were identified through the Swedish National Penile Cancer Register (NPECR). Medical records were retrieved and 325 men were confirmed to have metastatic penile cancer (T-any, c or pN1-3 and/or M1). Information on treatments was collected. Causes of death were retrieved from the National Cause of Death Register (CDR).

RESULTS: Chemotherapy and/or radiotherapy were given to 172 (53%) of all men. The use of oncological treatments with curative intent increased significantly during the study period, from 30% of men with c/pN2-3 diagnosed 2000-2003 compared with 57% of men diagnosed 2012-2015. Ninety-three (29%) men received oncological treatments with curative intent of whom 85/93 (91%) had stage c/pN2-3M0. Survival decreased with higher N-stage, M1-stage, and absence of oncological treatment with curative intent. For men with c/pN3-stage, the engagement of pelvic lymph nodes was entailed with lower survival than pN3 based on extra-nodal extension (ENE).

CONCLUSION: The use of oncological treatment was below recommendations in guidelines but increased during the study period. Treatment was given predominantly to men with c/pN2-3 and M1-disease. Survival was higher among men treated with curative intent; this could be due to patient selection bias.

OBJECTIVE: The aims of this study were to create a cohort of retrospectively collected renal cell carcinoma (RCC) specimens to be used a basis for prognostic molecular studies, and to investigate the outcome and time trends in patients surgically treated for RCC in a single-centre cohort.

MATERIALS AND METHODS: Patients undergoing surgery for RCC between 1986 and 2010 were included in the study. Medical records were reviewed, and the diagnostic tissue was re-evaluated according to a modern classification. The change in patient and tumour characteristics over time was analysed.

RESULTS: The study included 345 patients. Smaller tumours, as indicated by primary tumour diameter, tumour (T) stage and American Joint Committee on Cancer (AJCC) stage, were found more frequently in later years compared to the early 1990s. No changes in the clinical outcome for the patients were seen among the time periods investigated. Increasing T stage, AJCC stage, primary tumour diameter and decreasing haemoglobin levels were associated with cancer-specific mortality in univariate analysis. A high calcium level was significantly associated with increased cancer-specific mortality (hazard ratio = 4.25, 95% confidence interval 1.36-13.28) in multivariate analysis.

CONCLUSIONS: This study on patients who underwent surgery for RCC from 1986 to 2010 at a single institution in Sweden indicates that there has been a change in tumour characteristics of patients diagnosed with RCC over time. It was also shown that calcium levels were an independent prognostic factor for cancer-specific mortality in this cohort. This cohort could provide a valuable basis for further molecular studies.