Paweł Kiełb

Background/Objectives: Prostate cancer remains one of the most common malignancies in men, and prognosis remains particularly challenging in patients with lymph node metastases. Cyclooxygenase-2 (COX-2), an inducible enzyme involved in inflammation and tumor progression, has been investigated as a potential prognostic biomarker and therapeutic target, but its expression in lymph node metastases remains unclear. While COX-2 overexpression in primary prostate tumors has been reported, its expression in lymph node metastases has not been thoroughly investigated. Therefore, this study aimed to compare COX-2 expression in primary prostate tumors and corresponding lymph node metastases and to evaluate its association with clinicopathological characteristics and survival. Methods: This study included 77 treatment-naïve patients with prostate cancer and histologically confirmed lymph node metastases who underwent radical prostatectomy with extended lymphadenectomy. COX-2 expression was assessed using immunohistochemistry in paired samples from primary tumors and corresponding lymph node metastases. Statistical comparisons were conducted using the Mann–Whitney U test and survival analyses were performed using Kaplan–Meier curves with the log-rank test. Results: COX-2 expression was detected in both primary tumors and lymph node metastases, with no significant difference in staining intensity between the two sites. High COX-2 expression in primary tumors was significantly associated with a higher percentage of involved lymph nodes (30.0% vs. 11.8%, p = 0.026), elevated postoperative PSA levels (1.98 vs. 0.10 ng/mL, p = 0.007), and reduced surgical radicality (11.1% vs. 63.2%, p = 0.008). Moreover, elevated COX-2 expression in both primary and metastatic tissues correlated with worse five-year overall survival (41.7% vs. 92.8%, p = 0.033; and 40.0% vs. 95.6%, p < 0.001, respectively). Conclusions: High COX-2 expression is associated with adverse clinicopathological features and poorer survival in lymph node–positive prostate cancer. The association of COX-2 expression with the extent of lymph node involvement and survival suggests that COX-2 may have prognostic value in this setting. However, the present findings do not establish a causal role of COX-2 in disease progression or lymphangiogenesis. Further studies are warranted to validate the prognostic significance of COX-2 and to clarify its potential biological and therapeutic relevance in lymph node–positive prostate cancer.

Background: Prostate cancer remains one of the most common malignancies in men, and prognosis remains particularly challenging in patients with lymph node metastases. Cyclooxygenase-2 (COX-2), an inducible enzyme involved in inflammation and tumor progression, has been proposed as a potential prognostic biomarker and therapeutic target. While COX-2 overexpression in primary prostate tumors has been reported, its expression in lymph node metastases has not been thoroughly investigated. Methods: This study included 77 treatment-naïve patients with prostate cancer and histologically confirmed lymph node metastases who underwent radical prostatectomy with extended lymphadenectomy. COX-2 expression was assessed using immunohistochemistry in paired samples from primary tumors and corresponding lymph node metastases. Statistical comparisons were conducted using the Mann–Whitney U test and survival analyses were performed using Kaplan–Meier curves with the log-rank test. Results: COX-2 expression was detected in both primary tumors and lymph node metastases, with no significant difference in staining intensity between the two sites. High COX-2 expression in primary tumors was significantly associated with a higher percentage of involved lymph nodes (30.0% vs. 11.8%, p = 0.026), elevated postoperative PSA levels (1.98 vs. 0.10 ng/ml, p = 0.007), and reduced surgical radicality (11.1% vs. 63.2%, p = 0.008). Moreover, elevated COX-2 expression in both primary and metastatic tissues correlated with worse five-year overall survival (41.7% vs. 92.8%, p = 0.033; and 40.0% vs. 95.6%, p < 0.001, respectively). Conclusions: High COX-2 expression is associated with adverse clinicopathological features and poorer survival in lymph node–positive prostate cancer. These findings suggest that COX-2 is not only a marker of tumor aggressiveness, but may also contribute to disease progression through facilitating lymphangiogenesis. Given its strong association with adverse outcomes, COX-2 may serve as a clinically relevant prognostic biomarker in lymph node-positive PC. Further prospective studies are needed to validate its prognostic utility and assess its potential as a therapeutic target.

Lymphovascular invasion (LVI) is one of the most important prognostic factors in prostate cancer (PCa) and is correlated with worse survival rates, biochemical recurrence (BCR), and lymph node metastasis (LNM). The ability to predict LVI preoperatively in PCa may be useful for proposing variations in the diagnosis and management strategies. We performed a systematic review and meta-analysis to identify preoperative clinicopathological factors that correlate with LVI in final histopathological specimens in PCa patients. Systematic literature searches of PubMed, Embase, and Web of Science were performed up to 31 January 2023. A total of thirty-nine studies including 389,918 patients were included, most of which were retrospective and single-center. PSA level, clinical T stage, and biopsy Gleason score were significantly correlated with LVI in PCa specimens. Meta-analyses revealed that these factors were the strongest predictors of LVI in PCa patients. Prostate volume, BMI, and age were not significant predictors of LVI. A multitude of preoperative factors correlate with LVI in final histopathology. Meta-analyses confirmed correlation of LVI in final histopathology with higher preoperative PSA, clinical T stage, and biopsy Gleason score. This study implies advancements in risk stratification and enhanced clinical decision-making, and it underscores the importance of future research dedicated to validation and exploration of contemporary risk factors in PCa.

Introduction: Prostate cancer (PCa) is the second most commonly diagnosed cancer in men worldwide. Lymph node metastasis is a poor prognostic factor for PCa. Previous studies have found that Golgi phosphoprotein 3 (GOLPH3) is overexpressed in various cancers, including PCa. We examined GOLPH3 expression in PCa cells from primary tumor and, as the first, also in metastatic lymph nodes to assess its potential as a new risk factor for PCa progression.Methods: The study included 78 patients diagnosed with lymph node-positive PCa confirmed in the postoperative material. All the patients underwent radical prostatectomy (RP) with extended lymphadenectomy. The clinical data of the patients were retrospectively analyzed, and their histopathological specimens were selected for further analysis. Immunohistochemistry (IHC) staining was performed and the expression of GOLPH3 was assessed by an experienced uropathologist using an immunoreactive scale (IRS). A correlational analysis of the obtained data with the clinicopathological data of patients was performed.Results: A positive IHC reaction for GOLPH3 was observed in all samples. IRS score for GOLPH3 expression was higher in the metastatic lymph nodes than in the prostate (not statistically significant; p=0.056). Several significant correlations were identified in connection with GOLPH3 expression levels in the prostate and metastatic lymph node tissues. No significant correlations were found between GOLPH3 expression and patient characteristics (e.g. BMI, EAU risk group, or preoperative PSA level), pathological features, or postoperative outcomes. However, we found that lymphovascular invasion (LVI) tended to be more common in patients with a higher percentage of GOLPH3-positive cells (p=0.02). We also found a positive association between the intensity of GOLPH3 staining in metastatic lymph nodes and the EAU classification. Finally, we found a significant negative correlation between the GOLPH3 expression and the efficacy of RP – the higher the expression of GOLPH3, the lower the efficacy of RP was (p<0.05).Conclusion: GOLPH3 is expressed in both prostate and metastatic lymph nodes, with higher expression in metastatic lymph nodes. High GOLPH3 expression was associated with the occurrence of LVI, higher-risk group in the EAU classification, and lower efficacy of the RP, but there was no significant correlation with other pathological features or postoperative outcomes.

Prostate cancer (PCa) is the second most frequently diagnosed cancer among men. The use of IL-17A and its receptor IL-17RA as prognostic markers for PCa has shown promising results. We analyzed the clinical data of 77 patients with PCa after radical prostatectomy with lymphadenectomy and lymph node metastasis (LN+). We assessed the expression levels of IL-17A and IL-17RA in cancer cells in prostate and, for the first time, also in LN+. Prostate IL-17A expression positively correlated with BMI (p = 0.028). In LN+, the expression of IL-17A was positively correlated with the percentage of affected lymph nodes (p = 0.006) and EAU risk groups (p = 0.001). Additionally, in the group with high IL-17A expression in LN+, the extracapsular extension (ECE) of the prostate was significantly more frequent (p = 0.033). Also, significant correlations with the level of IL-17RA expression was found—expression was higher in prostate than in LN+ (p = 0.009); in LN+, expression positively correlated with the EAU risk group (p = 0.045), and in the group of high expression in LN+ ECE of lymph nodes was detected significantly more often (p = 0.009). Our findings support the potential role of IL-17A and IL-17RA as PCa markers; however, further studies are needed to determine their roles and potential clinical applications.

Prostate cancer (PCa) is the second most frequently diagnosed cancer in men. Despite the significant progress in cancer diagnosis and treatment over the last few years, the approach to disease detection and therapy still does not include histopathological biomarkers. The dissemination of PCa is strictly related to the creation of a premetastatic niche, which can be detected by altered levels of specific biomarkers. To date, the risk factors for biochemical recurrence include lymph node status, prostate-specific antigen (PSA), PSA density (PSAD), body mass index (BMI), pathological Gleason score, seminal vesicle invasion, extraprostatic extension, and intraductal carcinoma. In the future, biomarkers might represent another prognostic factor, as discussed in many studies. In this review, we focus on histopathological biomarkers (particularly CD169 macrophages, neuropilin-1, cofilin-1, interleukin-17, signal transducer and activator of transcription protein 3 (STAT3), LIM domain kinase 1 (LIMK1), CD15, AMACR, prostate-specific membrane antigen (PSMA), Appl1, Sortilin, Syndecan-1, and p63) and their potential application in decision making regarding the prognosis and treatment of PCa patients. We refer to studies that found a correlation between the levels of biomarkers and tumor characteristics as well as clinical outcomes. We also hypothesize about the potential use of histopathological markers as a target for novel immunotherapeutic drugs or targeted radionuclide therapy, which may be used as adjuvant therapy in the future.

Lymph node (LN) metastases have a significant negative impact on the prognosis of urological malignancies. Unfortunately, current imaging modalities are insufficient when it comes to detecting micrometastases; thus, surgical LN removal is commonly used. However, there is still no established ideal lymph node dissection (LND) template, leading to unnecessary invasive staging and the possibility of missing LN metastases located outside the standard template. To address this issue, the sentinel lymph node (SLN) concept has been proposed. This technique involves identifying and removing the first group of draining LNs, which can accurately stage cancer. While successful in breast cancer and melanoma, the SLN technique in urologic oncology is still considered experimental due to high false-negative rates and lack of data in prostate, bladder, and kidney cancer. Nevertheless, the development of new tracers, imaging modalities, and surgical techniques may improve the potential of the SLN procedures in urological oncology. In this review, we aim to discuss the current knowledge and future contributions of the SLN procedure in the management of urological malignancies.

Background: The optimal limits of the bilateral pelvic lymph node dissection (PLND) template in bladder cancer treatment remain controversial. This study aimed to investigate whether radio-guided sentinel node (SLN) detection is a reliable technique for the perioperative localisation of potential lymphatic metastasis during cystectomy for muscle-invasive bladder cancer (MIBC). Materials and Methods: We studied 54 patients with pT2-pT4 MIBC who underwent cystectomy with extended PLND (ePLND) augmented by the SLN technique. The identification of SLN was performed by preoperative SPECT/CT hybrid lymphoscintigraphy using peritumoral injection of nanocolloid-Tc-99m, followed by intraoperative navigation with a handheld γ-probe. All nodal specimens were collected separately and then fixed in formalin, stained with haematoxylin and eosin, and examined by an experienced uropathologist. Results: A total of 1414 LNs were resected and examined for the presence of metastases. The mean number of harvested LNs was 26 (range: 11–50) per patient. In 51 of 54 patients, 192 SLNs were resected. In addition, 20/192 (10.4%) SLNs were located outside of the ePLND area. Overall, 72 metastatic LNs (LN+) were found in 22 of 54 patients (40.7%) and in 24/192 SLNs (12.5%). The SLN technique detected LN+ in 14 of 22 (64%) patients. The SLNs were the only sites of metastasis (SLN+ = LN+) in 6 of 22 (27.3%) LN+ patients, including two cases with foci located in the pararectal region. The diagnostic values for the sensitivity, specificity, positive predictive value, and false-negative rate for the SLN technique were 66.66%, 4.16%, 28.57%, and 33.33%, respectively. Extended lymphadenectomy and its combination with the SLN technique enabled the correct assessment in 96.3 and 100% of patients, respectively. Conclusions: The combination of ePLND and SLN provides a better pN assessment compared to ePLND alone. Although the SLN technique has restrictions that limit its diagnostic value, its use as an addition to lymphadenectomy allows for the visualisation of nonstandard lymph drainage pathways that may be potential metastatic routes.

Background. In many malignancies, sentinel lymph node dissection (SLND) is being used as a nodal staging tool. We prospectively evaluated the diagnostic value of radio-guided sentinel lymph node (SLN) detection in patients with prostate cancer (PCa). This study aimed to investigate the reliability of the radio-guided SLN detection technique for perioperative localization of LNs metastases as well as to map lymphatic drainage patterns of the prostate. Methods. Forty-three patients with intermediate- or high-risk cN0cM0 PCa at conventional imaging underwent radical prostatectomy with modified-extended pelvic lymph node dissection (mePLND). A day before the planned surgery, a Tc-99m nanocolloid was injected into the prostate under the control of transrectal ultrasonography (TRUS). Preoperative single-photon emission computed tomography (SPECT-CT) imaging and intraoperative gamma-probe were used to identify SLNs. All positive lesions were excised, followed by mePLND. The excised lymph nodes (LNs) were then submitted for histopathological examination, which was used as a reference for the calculation of diagnostic parameters of the SLN technique for SPECT-CT and the intraoperative gamma-probe. Results. In total, 119 SLNs were detected preoperatively (SPECT-CT) and 118 intraoperatively (gamma-probe). The study revealed that both SLN detection techniques showed a sensitivity of 90% and a specificity of 6.06%. The negative predictive value (NPV) was 66.67%. SLN technique would have correctly staged nine of 10 patients, which is the same result as in the case of limited LND. However, it allowed the removal of all metastatic nodes only in four of them. SLND would have comprised 69.7% of preoperatively detected LNs, and removed 13 out of 19 positive LNs (68.42%), respectively. Conclusions. Radio-guided SLND has a low diagnostic rate and is a poor staging tool. ePLND remains the gold standard in nodal metastases assessment in PCa. Our study indicates that lymphatic drainage of the prostate and actual metastasis routes may vary significantly.

Nowadays, molecular and immunological research is essential for the better understanding of tumor cells pathophysiology. The increasing number of neoplasms has been taken under ‘the molecular magnifying glass’ and, therefore, it is possible to discover complex relationships between the cytophysiology and immune system action. An example could be renal cell carcinoma (RCC) which has deep interactions with immune mediators such as Interleukin 17 (IL-17)—an inflammatory cytokine reacting to tissue damage and external pathogens. RCC is one of the most fatal urological cancers because of its often late diagnosis and poor susceptibility to therapies. IL-17 and its relationship with tumors is extremely complex and constitutes a recent topic for numerous studies. What is worth highlighting is IL-17’s dual character in cancer development—it could be pro- as well as anti-tumorigenic. The aim of this review is to summarize the newest data considering multiple connections between IL-17 and RCC.