BackgroundNeuroendocrine carcinomas of the prostate (NEPCs) are rare tumors with poor prognosis. While platinum and etoposide-based chemotherapy regimens (PE) are commonly applied in first-line for advanced disease, evidence for second-line therapy and beyond is very limited.MethodsRetrospective analysis of all patients with NEPCs including mixed differentiation with adenocarcinoma component and well differentiated neuroendocrine tumors (NETs, carcinoids) at two high-volume oncological centers between 12/2000 and 11/2017.ResultsOf 46 identified patients 39.1 % had a prior diagnosis of prostatic adenocarcinoma only, 43.5 % had a mixed differentiation at NEPC diagnosis, 67.4 % developed visceral metastases, 10.9 % showed paraneoplastic syndromes. Overall survival (OS) from NEPC diagnosis was 15.5 months, and significantly shorter in patients with a prior prostatic adenocarcinoma (5.4 vs. 32.7 months, p=0.005). 34 patients received palliative first-line systemic therapy with a median progression-free survival (PFS) of 6.6 months, mostly PE. Overall response rate (ORR) for PE was 48.1 %. 19 patients received second-line therapy, mostly with poor responses. Active regimens were topotecan (1 PR, 3 PD), enzalutamide (1 SD), abiraterone (1 SD), FOLFIRI (1 SD), and ipilimumab+nivolumab (1 PR). One patient with prostatic carcinoid was sequentially treated with octreotide, peptide receptor radionuclide therapy and everolimus, and survived for over 9 years.ConclusionsEP in first-line shows notable ORR, however limited PFS. For second-line therapy, topotecan, FOLFIRI, enzalutamide, abiraterone and immune checkpoint blockade are treatment options. Prostatic carcinoids can be treated in analogy to well differentiated gastrointestinal NETs.

The “Cellular Dissociation Grade” (CDG) is based on tumor cell budding and cell nest size. Many studies have examined the CDG in squamous cell carcinomas of other organs such as the lungs, oral cavity, pharynx, larynx, cervix and esophagus. In this study, the CDG was examined in 109 cases of invasive penile squamous cell carcinoma that were treated at the University Medicine Rostock between 2014 and 2022. Furthermore, its correlation with the pathologic status of regional lymph nodes (pN) as the main prognostic factor was verified. Finally, cellular dissociation grading was compared with classic WHO grading. The results showed that pN in penile squamous cell carcinoma showed a highly significant association with the CDG and no statistically significant association with WHO grading. These results support the notion that cellular dissociation grading is an important prognostic factor for squamous cell carcinoma.

The predictive potential of immunological markers are not fully understood in head and neck squamous cell carcinomas (HNSCC). We retrospectively analyzed 129 treatment-naive HNSCCs for programmed death ligand 1 (PD-L1) and CKLF-like MARVEL transmembrane domain-containing 6 (CMTM6) expression, tumor-infiltrating leukocytes (TILs), and tumor-associated macrophages (TAMs). We evaluated mutual relationships among these markers, HPV-status, and overall survival (OS). PD-L1 and CMTM6 expression (combined positive score ≥ 1 and ≥ 5) was detected in ~ 75% of HNSCCs. The HPV-status had a minor impact on expression of either marker. Nearly all PD-L1-positive cases showed simultaneous CMTM6 expression in comparable staining patterns. Tumors with PD-L1 (p < 0.0001) and/or CMTM6 (p < 0.05) expression showed the best OS. A high density of TILs (p < 0.01), CD8+ T cells (p < 0.001), and a CD68/CD163 ratio > 1 had prognostic relevance. PD-L1 and CMTM6 correlated with density of TILs and CD8+ cells (Spearman r = range from 0.22 to 0.34), but not with HPV-status. Our results identify CMTM6 as an important interaction partner in the crosstalk between TILs, CD8+ T cells, and PD-L1, mediating anticancer efficacies. CMTM6 evaluation may be helpful for prognostic prediction and additionally serve as a reliable biomarker for selecting HNSCC patients eligible for ICIs treatment.