Wojciech A. Cieslikowski

Extraprostatic extension (EPE) is an important prognostic factor in prostate cancer and influences nerve-sparing decisions during radical prostatectomy. Multiparametric MRI (mpMRI) is the standard for local staging, but its sensitivity for EPE remains limited, and its interpretation is subject to inter-reader variability. In this narrative review, we aim to create an overview of contemporary strategies for the preoperative detection of EPE. We searched PubMed, Embase, Web of Science, and Google Scholar, focusing on studies published between 2015 and 2025 including articles evaluating clinical parameters, mpMRI features, nomograms, radiomics, machine learning, and deep learning models for EPE prediction. The analyzed literature was compared with respect to diagnostic performance, validation strategy, and clinical applicability of individual methods. Clinical parameters and traditional nomograms provide moderate accuracy for EPE detection. mpMRI improves staging, with tumor–capsule contact length as the most important single imaging marker. Radiomics-based and machine-learning models matched and occasionally outperform conventional approaches, achieving AUC values ranging from 0.75 to 0.85. Deep-learning models demonstrated similar performance by directly analyzing imaging data, although most lacked external validation and were sensitive to dataset heterogeneity. Several radiomics and deep learning models demonstrated performance comparable to, and in selected studies exceeding, expert radiologist assessment. Binary EPE classification has limited clinical value, while side-specific and graded EPE assessment offers a more clinically relevant approach. Translation of these tools into routine practice will require multimodal, side-specific, and externally validated models supported by automated segmentation and explainable artificial intelligence frameworks.

The aim of the present study was to verify whether the baseline circulating tumor cell (CTC) count might serve as a predictor of overall survival (OS) and metastasis-free survival (MFS) in patients with high-risk prostate cancer (PCa) during a follow-up period of at least 5 years. CTCs were enumerated using three different assay formats in 104 patients: the CellSearch^® system, EPISPOT assay and GILUPI CellCollector. A total of 57 (55%) patients survived until the end of the follow-up period, with a 5 year OS of 66% (95% CI: 56–74%). The analysis of univariate Cox proportional hazard models identified a baseline CTC count ≥ 1, which was determined with the CellSearch^® system, a Gleason sum ≥ 8, cT ≥ 2c and metastases at initial diagnosis as significant predictors of a worse OS in the entire cohort. The CTC count ≥ 1 was also the only significant predictor of a worse OS in a subset of 85 patients who presented with localized PCa at the baseline. The baseline CTC number did not affect the MFS. In conclusion, the baseline CTC count can be considered a determinant of survival in high-risk PCa and also in patients with a localized disease. However, determining the prognostic value of the CTC count in patients with localized PCa would optimally require longitudinal monitoring of this parameter.

The aim of the present study was to identify the reasons behind the delayed diagnosis of testicular cancer in a group of Polish males diagnosed with this malignancy in 2015–2016. The study included data from 72 patients aged between 18 and 69 years. Based on the median time elapsed to the testicular cancer diagnosis, the study patients were divided into the timely diagnosis group (diagnosis within 10 weeks from initial manifestation, n = 40) and the delayed diagnosis group (diagnosis > 10 weeks from initial manifestation, n = 32). Diagnosis of testicular cancer > 10 weeks after its initial manifestation was associated with less favorable survival (5-year overall survival: 78.1% [95% CI: 59.5–88.9%] vs. 92.5% [95% CI: 78.5–97.5%], p = 0.087). Multivariate logistic regression analysis identified two independent predictors of the delayed diagnosis, age > 33 years (OR = 6.65, p = 0.020) and residence in the countryside (OR = 7.21, p = 0.012), with another two parameters, the lack of a regular intimate partner (OR = 3.32, p = 0.098) and the feeling of shame (OR = 8.13, p = 0.056), being at the verge of statistical significance. All the factors mentioned above should be considered during planning social campaigns aimed at the early detection of testicular malignancies, along with improving the quality and trustfulness of Internet-based information resources.

Given the low specificity of the routinely used biomarker prostate-specific antigen, circulating tumor cell (CTC) enumeration seems to be particularly useful in the monitoring of prostate cancer. In this review, we focused on a few aspects of CTC enumeration in prostate malignancies: prognostic value in metastatic and non-metastatic tumors, role in the monitoring of treatment outcomes, use as a surrogate marker for survival, and other applications, mostly for research purposes. CTC enumeration, without a doubt, offers an attractive perspective in the management of prostate cancer. However, the vast majority of available data about the role of CTC in this malignancy originate from randomized studies of anticancer agents and do not necessarily translate into real-world clinical practice. Further, most studies on the application of CTC in prostate cancer patients were limited to advanced stages of this malignancy. Meanwhile, the role of CTC in the early stages of prostate cancer, in which some patients may present with occult disseminated disease, is still relatively poorly understood, and should thus be studied extensively. Other obstacles in the widespread application of CTC enumeration in routine clinical practice include considerable discrepancies in the number of cells determined with various commercially available systems.

After prostatectomy due to prostate carcinoma, patients often develop metastases. Although prostate cancer is susceptible to hormonal manipulation, many patients become castration-resistant. Therefore, new therapies are the focus of investigations. We analyzed the effect of the tyrosine kinase inhibitors (TKIs), sorafenib and sunitinib, in combination with rottlerin, a PKC inhibitor, on metastatic mechanisms in prostate carcinoma cells. LNCaP and PC-3 prostate carcinoma cells were treated with sorafenib or sunitinib alone at various concentrations (1-20 mu M) or in combination with rottlerin (10 mu M) for 24 h. Then, cell toxicity (MTT test) and cell proliferation (BrdU incorporation assay) were quantified. The study demonstrated a dose-dependent inhibitory effect of sorafenib and sunitinib on PC-3 and LNCaP cell activity and proliferation. Both agents showed significantly stronger cytotoxic effects in LNCaP cells. At the highest concentrations, sorafenib and sunitinib inhibited the viability of LNCaP cells up to 2 % and 31 %, respectively, and the viability of PC-3 cell line up to 20 % and 43 %, respectively. The proliferation of both cell lines was significantly stronger inhibited by sorafenib than by sunitinib. In LNCaP cells, sorafenib and sunitinib at the highest concentrations inhibited cell proliferation up to 46 % and 49 %, respectively, and the proliferation of PC-3 line up to 40 % and 47 %, respectively. Rottlerin reduced the viability and proliferation of PC3 cells to 81 % and 42 %, whereas the viability and proliferation of LNCaP cells were reduced to 25 % and 57 %, respectively. Sorafenib and sunitinib at low concentrations partly neutralized the inhibitory effect of rottlerin on cell viability and proliferation. On the other hand, in PC-3 cells, rottlerin reduced the inhibitory effects of sorafenib and sunitinib at the highest concentrations on cell viability from 20 % to 30 % and from 43 % to 61 %, respectively. An additive effect on cell activity was observed after treating LNCaP cells with both sunitinib at high concentrations and rottlerin. This combination increased the cytotoxic effect from 31 % to 13 % at the highest sunitinib concentration. Our results showed that monotherapy with sorafenib was the most efficient in both PCa cell lines. A marginally additive effect of rottlerin was only observed in LNCaP cells treated with sunitinib at a high concentration. Sorafenib and sunitinib reduced cell migration in PC-3 cells to 10 % and 32 % of untreated cells, respectively. Co-treatment with sorafenib/sunitinib and rottlerin did not result in a significantly stronger anti migratory effect than the treatment with each TKI alone. Given the strong cytotoxic effect of TKIs, especially sorafenib, on LNCaP cells, the results of the migration assay in this line were severely biased and not considered in the analysis. Unlike in other malignancies, combination therapy with TKI and rottlerin seems not beneficial in prostate cancer. More promising seems to be monotherapy with rottlerin, but further studies are needed to confirm this observation.

The aim of this study was to investigate whether the enumeration of circulating tumor cells (CTCs) in blood can differentiate between true localized and metastatic prostate cancer. A cross-sectional study of 104 prostate cancer patients with newly diagnosed high-risk prostate cancer was conducted. In total, 19 patients presented metastatic disease and 85 were diagnosed with localized disease. Analyses included intergroup comparison of CTC counts, determined using the CellSearch^® system, EPISPOT assay and GILUPI CellCollector^®, and ROC analysis verifying the accuracy of CTC count as a maker of disseminated prostate cancer. The vast majority (94.7%) of patients with advanced-stage cancer tested positively for CTCs in at least one of the assays. However, significantly higher CTC counts were determined with the CellSearch^® system compared to EPISPOT assay and GILUPI CellCollector^®. Identification of ≥4 CTCs with the CellSearch^® system was the most accurate predictor of metastatic disease (sensitivity 0.500; specificity 0.900; AUC (95% CI) 0.760 (0.613–0.908). Furthermore, we tried to create a model to enhance the specificity and sensitivity of metastatic prediction with CTC counts by incorporating patient’s clinical data, including PSA serum levels, Gleason score and clinical stage. The composite biomarker panel achieved the following performance: sensitivity, 0.611; specificity, 0.971; AUC (95% CI), 0.901 (0.810–0.993). Thus, although the sensitivity of CTC detection needs to be further increased, our findings suggest that high CTC counts might contribute to the identification of high-risk prostate cancer patients with occult metastases at the time of diagnosis.

The characterization of circulating tumor cells (CTCs) can lead to a promising strategy for monitoring residual or relapsing prostate cancer (PCa) after local therapy. The aim of this study was to compare three innovative technologies for CTC enumeration in 131 high-risk patients with PCa, before and after radiotherapy, combined with androgen deprivation. The CTC number was tested using the FDA-cleared CellSearch^® system, the dual fluoro-EPISPOT assay that only detects functional CTCs, and the in vivo CellCollector^® technology. The highest percentage of CTC-positive patients was detected with the CellCollector^® (48%) and dual fluoro-EPISPOT (42%) assays, while the CellSearch^® system presented the lowest rate (14%). Although the concordance among methods was only 23%, the cumulative positivity rate was 79%. A matched-pair analysis of the samples before, and after, treatment suggested a trend toward a decrease in CTC count after treatment with all methods. CTC tended to be positivity correlated with age for the fluoro-EPISPOT assay and with PSA level from the data of three assays. Combining different CTC assays improved CTC detection rates in patients with non-metastatic high-risk PCa before and after treatment. Our findings do not support the hypothesis that radiotherapy leads to cancer cell release in the circulation.

VHL inactivation is the most established molecular characteristic of clear cell renal cell carcinoma (ccRCC), with only a few additional genes implicated in development of this kidney tumor. In recently published ccRCC gene expression meta-analysis study we identified a number of deregulated genes with limited information available concerning their biological role, represented by gene transcripts belonging to transmembrane proteins family (TMEMs). TMEMs are predicted to be components of cellular membranes, such as mitochondrial membranes, ER, lysosomes and Golgi apparatus. Interestingly, the function of majority of TMEMs remains unclear. Here, we analyzed expression of ten TMEM genes in the context of ccRCC progression and development, and characterized these proteins bioinformatically. The expression of ten TMEMs (RTP3, SLC35G2, TMEM30B, TMEM45A, TMEM45B, TMEM61, TMEM72, TMEM116, TMEM207 and TMEM213) was measured by qPCR. T-test, Pearson correlation, univariate and multivariate logistic and Cox regression were used in statistical analysis. The topology of studied proteins was predicted with Metaserver, together with PSORTII, Pfam and Localizome tools. We observed significant deregulation of expression of 10 analyzed TMEMs in ccRCC tumors. Cluster analysis of expression data suggested the down-regulation of all tested TMEMs to be a descriptor of the most advanced tumors. Logistic and Cox regression potentially linked TMEM expression to clinical parameters such as: metastasis, Fuhrman grade and overall survival. Topology predictions classified majority of analyzed TMEMs as type 3 and type 1 transmembrane proteins, with predicted localization mainly in ER. The massive down-regulation of expression of TMEM family members suggests their importance in the pathogenesis of ccRCC and the bioinformatic analysis of TMEM topology implies a significant involvement of ER proteins in ccRCC pathology.