To Örebro University

OBJECTIVES: The objective of this study is to compare the use of lymph node surgery and complication rates before and after centralization of penile cancer (PeCa) surgery in Sweden. In January 2015, curative surgical care for PeCa was centralized to the Skåne University Hospital in Malmö and the Örebro University Hospital in Örebro.

PATIENTS AND METHODS: All 1079 patients with invasive PeCa in the Swedish National Penile Cancer Register (NPECR) diagnosed between 2009 and 2020 were included, 458 before and 621 after centralization. The proportion of patients subjected to lymph node surgery 2009-2014 versus 2015-2020 was compared using Pearson's Chi-squared test. Odds ratios (ORs) for complications were calculated using a logistic regression model adjusting for age, nodal stage and extent of penile surgery. Continuous variables were presented as medians and compared using Wilcoxon's rank sum test.

RESULTS: Before centralization, 270/458 (59%) of patients were subjected to lymph node surgery compared to 474/621 (76%) after 2014. Overall complication rate for patients undergoing such surgery was unaltered before and after centralization. The incidence of any complications increased after Dynamic Sentinel Lymph Node Biopsy from 18% (22/122) to 36% (91/256), corresponding to an adjusted OR of 1.89 (95% confidence interval [CI] 1.09-3.27). For lymphocele, lymphedema or infection after modified or radical inguinal or pelvic lymphadenectomy, the adjusted OR was 0.47 (95% CI 0.29-0.75) after centralization. The register-based setting is a study limitation.

CONCLUSIONS: The proportion of men undergoing lymph node surgery increased, and the risk of lymphocele, lymphedema and infection after inguinal and pelvic lymph node surgery decreased after centralization of PeCa care.

Introduction & Objectives: Penile cancer (PeCa) surgery was in 2015 centralized to two hospitals in Sweden. This study compares the use of lymph node surgery and complication rates before and after centralization.

Materials & Methods: All 1079 patients with invasive PeCa in the Swedish National Penile Cancer Register (NPECR) diagnosed between 2009 and 2020 were included, 458 before and 621 after centralization. The proportion of patients subjected to lymph node surgery 2009-2014 vs 2015-2020 was compared using Pearson’s Chi-squared test. Odds ratios (OR) for complications were calculated using a logistic regression model adjusting for age, nodal stage, and extent of penile surgery. Continuous variables were presented as medians with inter quartile ranges and compared with Wilcoxon’s rank sum test.

Results: Before centralization 270/458 (59 %) of patients were subjected to lymph node surgery compared to 474/621 (76 %) after 2014. Overall complication rate for patients undergoing such surgery was unaltered (35 %) before and after centralization. Complications after Dynamic Sentinel Lymph Node Biopsy increased from 17 % (22/126) to 32 % (91/288), corresponding to an adjusted OR of 1.89 (95 % confidence interval (CI) 1.09-3.27). For lymphocele, lymphedema or infection after modified or radical inguinal or pelvic lymphadenectomy, the adjusted OR was 0.47 (95 % CI 0.29-0.75) after centralization. The register-based setting is a study limitation.

Conclusions: The proportion men undergoing lymph node surgery increased, and risk of lymphocele, lymphedema and infection after inguinal and pelvic lymph node surgery decreased after centralization of PeCa care.

BACKGROUND: Muscle invasive bladder cancer (MIBC) is an aggressive disease with a high mortality rate. Radical cystectomy (RC) is the standard treatment for MIBC and selected non-muscle invasive bladder -cancer (NMIBC) cases. The NorCys-study (NCT04523038, NCT04537221 and NCT04523025) aims to validate biomarkers predicting RC outcomes. This report describes RC practice patterns across the Nordic countries.

MATERIALS AND METHODS: This prospective, multi-institutional study included bladder cancer patients undergoing RC with or without preoperative chemotherapy in all five Nordic countries from 5/2020 to 1/2025. Clinical and pathological data were collected prospectively into REDCap database and analysed using descriptive statistics, Wilcoxon rank sum and Pearson's Chi-squared tests.

RESULTS: A total of 1,642 patients from 15 centres were enrolled. Of these, 35% (531) had clinical NMIBC (T1-Tis-Ta), and 65% (999) had cT2-4 disease. Preoperative chemotherapy was administered to 398/929 (43%) cT2-4 or node-positive patients. The most common neoadjuvant chemotherapy (NAC) regimens were gemcitabine - cisplatin (GC) (275/475 [58%]) and dose-dense methotrexate, vinblastine, doxorubicin and cisplatin (dd-MVAC) (144/475 [30%]). Robot-assisted RC was the most common surgical approach administered in 886 of 1,472 (60%) cases, with variation between centres. Ileal conduit was the predominant diversion method in 1,375 out of 1,465 cases (94%). Median surgical time was 322 min, blood loss was 300 mL and hospital stay was 9 days. Final pathology demonstrated pT0 in 29%, ≥pT2 in 43% and lymph node metastases 203 (17%).

CONCLUSION: This study reports current RC practices amongst Nordic countries. Patient cohorts did not differ between countries, and although the practices were generally similar, some differences were noted in chemotherapy regimens, the use of robotic-assisted surgery and rates of early RC.

BACKGROUND: Penile cancer (PeCa) is a rare but aggressive disease where lymph node metastases (LNM) represent the most significant prognostic factor. Accurate identification of LNM remains a clinical priority, but traditional imaging and clinical parameters often fail to detect occult LNM. Soluble immune checkpoint proteins (sICs) have recently emerged as potential non-invasive biomarkers in various malignancies, although unexplored in PeCa. The primary aim of this study was to explore the value of a panel of 14 sICs for predicting LNM in PeCa. The secondary aim was to compare plasma sIC levels between PeCa patients and cancer-free controls.

METHODS: Using ProcartaPlex immunoassays, BTLA, IDO, LAG-3, HVEM, PD-1, PD-L1, PD-L2, TIM-3, CD80, CTLA-4, GITR, CD27, CD28, and CD137 were measured in plasma from 284 PeCa patients and 45 cancer-free controls. PeCa patients were divided into a training set (n=202) and a test set (n=82). A prediction model for LNM was created using logistic regression.

RESULTS: Overall accuracy of the prediction model reached 77.5% (95% CI: 70.9 - 83.3) for the training set, yielding 8.9% sensitivity and 99.3% specificity in predicting LNM. Upon validation using the test set, the accuracy decreased to 62.2% (95% CI: 50.8-72.7) with 17.9% sensitivity and 85.2% specificity. When comparing PeCa patients and cancer-free controls, four inhibitory sICs (IDO, TIM-3, CD80, and CTLA-4) were found at significantly higher levels in the PeCa group. Due to the rarity of the disease, the main limitation of the study is the small number of patients with LNM.

CONCLUSION: Our study provides no evidence that sICs can predict LNM in PeCa, although four inhibitory sICs were significantly elevated in PeCa patients compared to cancer-free controls, suggesting systemic immunosuppression associated with tumor presence, consistent with findings in other malignancies. Studies with larger cohorts are warranted to clarify the prognostic significance of sICs in PeCa.

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.

Introduction: Curative penile cancer (PeCa) surgery was in 2015 centralized to two hospitals in Sweden. This study compares the use of lymph node surgery and complication rates before and after the centralization.

Method: All 1079 patients with invasive PeCa in the Swedish National Penile Cancer Register (NPECR) diagnosed between 2009 and 2020 were included, 458 before and 621 after centralization. Proportion of patients subjected to lymph node surgery 2009-2014 vs 2015-2020 was compared with Pearson’s Chi-squared test. Odds ratios (OR) for complications were calculated using a logistic regression model adjusting for age, nodal stage, and extent of penile surgery. Continuous variables were presented as medians with inter quartile ranges (IQR) and compared with Wilcoxon’s rank sum test.

Results: Before centralization 270/458 (59%) of patients were subjected to lymph node surgery compared to 474/621 (76%) after 2014. Overall complication rate for patients undergoing such surgery was similar (35%) before and after centralization. After Dynamic Sentinel Node Biopsy (DSNB) overall complications increased from 17% (22/126) to 32% (91/288) after centralization corresponding to an adjusted OR of 1.89 (95% confidence interval (CI) 1.09-3.27). For lymphocele, lymphedema or infection after modified or radical inguinal lymphadenectomy or pelvic lymphadenectomy, the adjusted OR was 0.47 (95% CI 0.29-0.75) after centralization. The register-based setting is a study limitation.

Conclusion: The proportion men receiving lymph node surgery increased and risk of lymphedema, lymphocele and infection after inguinal and pelvic lymph node surgery decreased after centralization of PeCa care. 

Introduction & Objectives: Immune checkpoint proteins are recognized as critical regulators of the immune system and play an important role in the defence against cancer. Unfortunately, cancer cells evade the immune destruction by overexpressing inhibitory checkpoint proteins, hence creating a favourable tumour microenvironment. Recently, it has been proposed that immune checkpoint proteins can be detected in soluble form in body fluids. This is important since a blood sample is less invasive than a tissue sample and hypotheticall yhas the potential to be more representative. The aim of the study was to evaluate the concentrations of soluble immune inhibitory checkpoint proteins (sICs) in men with and without penile cancer.

Materials & Methods: The circulating levels of ten soluble immune inhibitory checkpoint proteins (TIM-3, CD152, HVEM, IDO, LAG-3, BTLA, CD80, PD-1, PD-L1 and PD-L2) were assessed in plasma of 206 men with penile cancer (cases) and 46 men free from penile cancer (controls) using a multiplex Luminex assay. Mean concentrations of sICs were calculated and bootstrap resampling together with Welch's t-tests were used to assess differential expression and distribution of sICs between cases and controls.

Results: HVEM was detectable in 87% of the samples. PD-L1 was only detectable in 43.3% and therefore excluded from further analyses. The remaining markers were detectable in all samples. When comparing the mean concentrations of soluble immune inhibitory checkpoint proteins, nine sICs were found in higher concentrations in cases compared to controls, out of which seven reached statistical significance (Table 1).

Conclusions: Our study indicates that men with penile cancer have higher concentrations of soluble immune inhibitory checkpoint proteins in plasma compared to penile cancer-free men. Further studies are needed to evaluate their prognostic value

OBJECTIVES: This work aims to present epidemiological data on penile cancer from the Nordic region (Denmark, Finland, Iceland, Norway, Sweden) and discuss the results in light of the present knowledge and possible future treatment strategies.

PATIENTS AND METHODS: All patients diagnosed with penile cancer in the Nordic countries between 2000 and 2022 were identified in the NORDCAN database. Data on the number of new cases per year, incidence (presented as an age-standardized rate using the Nordic population as a reference), prevalence, mortality, relative survival and predictions on the future societal impact of this cancer was retrieved.

RESULTS: A total of 6106 cases of penile cancer were registered in a population that increased from about 12-14 million men over the period. The age-standardized incidence has significantly increased over time and is now above 2.0 per 100 000 men. Currently, more than 300 new cases are diagnosed each year, and more than 3000 men live with a penile cancer diagnosis. Mortality, as well as both 1-year and 5-year relative survival have, however, remained nearly unchanged. Using the NORPRED model, it is predicted that the yearly number of penile cancer cases will continue to increase in all the countries investigated over the next decade.

CONCLUSION: Penile cancer incidence and prevalence have increased in the Nordic region over the last 20 years. Mortality and survival, however, have remained unchanged. The number of new penile cancer cases is predicted to increase over the next decade. Better treatment options for these patients are therefore urgently needed.

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.