Lymph Node Dissection in Testicular Cancer: The State of the Art and Future Perspectives.

PURPOSE OF REVIEW: This narrative review provides a comprehensive overview of the evolving role of retroperitoneal lymph node dissection (RPLND) in the management of testicular cancer (TC). It explores the significance of RPLND as both a diagnostic and therapeutic tool, highlighting its contribution to accurate staging, its impact on oncological outcomes, and its influence on subsequent treatment decisions. RECENT FINDINGS: RPLND serves as an essential diagnostic procedure, aiding in the precise assessment of lymph node involvement and guiding personalized treatment strategies. It has demonstrated therapeutic value, particularly in patients with specific risk factors and disease stages, contributing to improved oncological outcomes and survival rates. Recent studies have emphasized the importance of meticulous patient selection and nerve-sparing techniques to mitigate complications while optimizing outcomes. Additionally, modern imaging and surgical approaches have expanded the potential applications of RPLND. In the context of TC management, RPLND remains a valuable and evolving tool. Its dual role in staging and therapy underscores its relevance in contemporary urological practice. This review highlights the critical role of RPLND in enhancing patient care and shaping treatment strategies, emphasizing the need for further research to refine patient selection and surgical techniques.

Effect of HVEM/CD160 Variations on the Clear Cell Renal Carcinoma Risk and Overall Survival.

Renal cell carcinoma (RCC) accounts for approximately 90-95% of all kidney cancers in adults, with clear cell RCC (ccRCC) being the most frequently identified subtype. RCC is known for its responsiveness to immunotherapy, making it an area of significant research interest. Immune checkpoint (IC) molecules, which regulate immune surveillance, are established therapeutic targets in RCC. The aim of this study was to analyze the influence of HVEM and CD160 gene polymorphisms on ccRCC susceptibility and patient overall survival (OS) over a ten-year period of observation. We genotyped three HVEM single nucleotide polymorphisms (SNPs): rs1886730, rs2234167, and rs8725, as well as two CD160 SNPs: rs744877 and rs2231375, in 238 ccRCC patients and 521 controls. Our findings indicated that heterozygosity within rs2231375 and/or rs2234167 increases ccRCC risk. Furthermore, in women, heterozygosity within HVEM SNPs rs8725 and rs1886730 is also associated with an increased ccRCC risk. The presence of a minor allele for rs1886730, rs2234167, rs8725, and rs2231375 was also correlated with certain clinical features of ccRCC. Moreover, rs1886730 was found to be associated with OS. In conclusion, our study highlights an association between HVEM and CD160 polymorphisms and the risk of developing ccRCC as well as OS.

Preoperative Factors for Lymphovascular Invasion in Prostate Cancer: A Systematic Review and Meta-Analysis.

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.

Lymph Node Dissection in Upper Tract Urothelial Carcinoma: Current Status and Future Perspectives.

PURPOSE OF REVIEW: This narrative review aims to evaluate the role of lymph node dissection (LND) in upper tract urothelial carcinoma (UTUC) and its implications for staging and management outcomes, as well as future perspectives. RECENT FINDINGS: Multiple studies have demonstrated the limitations of conventional imaging techniques in accurately localizing lymph node metastasis (LNM) in UTUC. While 18F-fluorodeoxyglucose positron emission tomography with computed tomography (18FDG-PET/CT) shows promise for preoperative LNM detection, its specificity is low. Alternative methods such as choline PET/CT and sentinel lymph node detection are under consideration but require further investigation. Additionally, various preoperative factors associated with LNM hold potential for predicting nodal involvement, thereby improving nodal staging and oncologic outcomes of LND. Several surgical approaches, including segmental ureterectomy and robot-assisted nephroureterectomy, provide a possibility for LND, while minimizing morbidity. LND remains the primary nodal staging tool for UTUC, but its therapeutic benefit is still uncertain. Advances in imaging techniques and preoperative risk assessment show promise in improving LNM detection. Further research and multi-center studies are needed to comprehensively assess the advantages and limitations of LND in UTUC, as well as the long-term outcomes of alternative staging and treatment strategies.

The Variations' in Genes Encoding TIM-3 and Its Ligand, Galectin-9, Influence on ccRCC Risk and Prognosis.

Renal cell cancer is the most common type of kidney cancer in adults, and clear cell renal cell carcinoma (ccRCC) is the most diagnosed type. T cell immunoglobulin and mucin-domain-containing-3 (TIM-3) belongs to immunological checkpoints that are key regulators of the immune response. One of the known TIM-3 ligands is galectin-9 (LGALS9). A limited number of studies have shown an association between TIM-3 polymorphisms and cancer risk in the Asian population; however, there is no study on the role of LGALS9 polymorphisms in cancer. The present study aimed to analyze the influence of TIM-3 and LGALS9 polymorphisms on susceptibility to ccRCC and patient overall survival (OS), with over ten years of observations. Using TaqMan probes, ARMS-PCR, and RFPL-PCR, we genotyped two TIM-3 single-nucleotide polymorphisms (SNPs): rs1036199 and rs10057302, and four LGALS9 SNPs: rs361497, rs3751093, rs4239242, and rs4794976. We found that the presence of the rs10057302 A allele (AC + AA genotypes) as well as the rs4794976 T allele (GT + TT genotypes) decreased susceptibility to ccRCC by two-fold compared to corresponding homozygotes. A subgroup analysis showed the association of some SNPs with clinical features. Moreover, TIM-3 rs1036199 significantly influenced OS. Our results indicate that variations within TIM-3 and LGALS9 genes are associated with ccRCC risk and OS.

Pro-Inflammatory Cytokine Gene Expression in Penile Cancer: Preliminary Studies.

Background and Objectives: Penile cancer is a rare neoplasm in developed countries with an incidence of 0.8/100,000 per male inhabitant. Despite the development of personalized medicine and multimodal treatment, the outcome of penile cancer treatment is insufficient. Our study aimed to assess the levels of pro-inflammatory cytokines' mRNA such as interleukin 1-A (encoded by IL1A gene, alias IL-1A), interleukin 1-B (IL1B, IL-1B), interleukin 1 receptor antagonist (IL1RN, IL-1RN), interleukin 6 (IL6, IL-6), transforming growth factor ß1 (TGFB1, TGFß-1), and Interferon-gamma (INFG, INF-γ) in penile cancer tissue and associate them with tumor progression and patient survival. Material and Methods: Skin biopsies from patients suffering from penile cancer (n = 6) and unchanged foreskin from 13 healthy adult males undergoing circumcision due to a short frenulum were obtained. Pro-inflammatory cytokine mRNA levels were quantified through qPCR. Results: We observed higher expression of pro-inflammatory cytokine genes (IL-1A, IL-1B, IL-6, INF-γ, TGF-ß) in penile cancer tissue. The average follow-up period was 48 months (range: 38-54 months), during which only one penile tumor progression was observed However, this was without association with the nature of tumor (patient refused radical treatment). Conclusions: This is the first study to show increased expression of cytokines such as IL-1A, IL-1B, IL-6, INF-γ, and TGF-ß in penile cancer with positive correlation between TNM staging and INF-γ levels in tumor samples (rs = 0.672, p = 0.045), which may be associated with the immunosuppressive role of the tumor environment.

The Usefulness of Lymphadenectomy in Bladder Cancer-Current Status.

The purpose of this review is to present the current status of lymph node dissection (LND) during radical cystectomy in patients with bladder cancer (BCa). Despite the growing body of evidence of LND utility at the time of radical cystectomy (RC) in high-risk nonmuscle-invasive and muscle-invasive BCa (MIBC), therapeutic and prognostic value and optimal extent of LND remain unsolved issues. Recently published results of the first prospective, a randomized trial assessing the therapeutic benefit of extended versus limited LND during RC, failed to demonstrate survival improvement with the extended template. Although LND is the most accurate staging procedure, the direct therapeutic effect is still not evident from the current literature, limiting the possibility of establishing clear recommendations. This indicates the need for robust and adequately powered clinical trials.

The presence of prostate cancer at biopsy is predicted by a number of genetic variants.

Several single nucleotide polymorphisms (SNPs) have been associated with an elevated risk of prostate cancer risk. It is not established if they are useful in predicting the presence of prostate cancer at biopsy or if they can be used to define a low-risk group of men. In this study, 4,548 men underwent a prostate biopsy because of an elevated prostate specific antigen (PSA; ≥4 ng/mL) or an abnormal digital rectal examination (DRE). All men were genotyped for 11 selected SNPs. The effect of each SNP, alone and in combination, on prostate cancer prevalence was studied. Of 4,548 men: 1,834 (40.3%) were found to have cancer. A positive association with prostate cancer was seen for 5 of 11 SNPs studied (rs1800629, rs1859962, rs1447295, rs4430796, rs11228565). The cancer detection rate rose with the number of SNP risk alleles from 29% for men with no variant to 63% for men who carried seven or more risk alleles (OR = 4.2; p = 0.002). The SNP data did not improve the predictive power of clinical factors (age, PSA and DRE) for detecting prostate cancer (AUC: 0.726 vs. 0.735; p = 0.4). We were unable to define a group of men with a sufficiently low prevalence of prostate cancer that a biopsy might have been avoided. In conclusion, our data do not support the routine use of SNP polymorphisms as an adjunct test to be used on the context of prostate biopsy for Polish men with an abnormal screening test.

Expression of Immunotherapy Target PRAME in Cancer Correlates with Histone H3 Acetylation and Is Unrelated to Expression of Methylating (DMNT3A/3B) and Demethylating (TET1) Enzymes.

Background/Objectives: Preferentially expressed antigen in melanoma (PRAME), a member of the cancer testis antigen family, is a promising target for cancer immunotherapy. Understanding the epigenetic mechanisms involved in the regulation of PRAME expression might be crucial for optimizing anti-PRAME treatments. Methods: Three malignancies of different lineages (sinonasal melanoma, testicular seminoma, and synovial sarcoma), in which immunohistochemical (IHC) reactivity for PRAME is a common yet variable feature, were studied. The expression of PRAME, ten-eleven translocation demethylase 1 (TET1), and DNA methyltransferase (DNMT) 3A and 3B were evaluated using immunohistochemistry. Moreover, the expression of two epigenetic marks, 5-hydroxymethylcytosine (5hmC) and histone 3 acetylation (H3ac), was tested. Results: All PRAME-positive tumors expressed medium-to-high levels of H3ac but differed considerably with respect to other markers. In seminomas, PRAME expression correlated with TET1, but in melanomas and synovial sarcomas, it correlated with both DNMTs and DNMT3A, respectively. Conclusions: PRAME expression was not determined by a balance between the global expression of DNA methylating/demethylating enzymes. However, histone acetylation may be one of the epigenetic mechanisms involved in PRAME regulation. Thus, the therapeutic combination of histone deacetylase inhibitors and PRAME immunotherapy merits further investigation.

Prognostic Value of Postneoadjuvant Chemotherapy Neutrophil-to-Lymphocyte Ratio in Patients undergoing Radical Cystectomy.

Background: Neutrophil-to-lymphocyte ratio (NLR), a widely assessed biomarker in most common diseases, is typically evaluated before treatment initiation. However, data on NLR in the post-treatment setting is limited. Therefore, we assessed the NLR calculated after neoadjuvant chemotherapy (NAC) initiation in patients with bladder cancer (BC). We hypothesised that changes in blood cells after NAC could be a marker of tumour response and long-term survival. Materials and Methods: Our study included 214 patients who underwent NAC followed by radical cystectomy (RC) in two urological departments, wherein post-NAC NLR was used to categorize patients into the low (NLR ≤ 1.75) and high (NLR > 1.75) groups. Results: Logistic regression analysis indicated that a post-NAC NLR ≥ 1.75 is a good biomarker for pathologic response (odds ratio (OR), 0.045; p <0.001), emphasizing its ability to predict patient survival. The HRs for overall survival and cancer-specific survival were 2.387 (p = 0.048) and 2.342 (p < 0.001), respectively. Conclusions: We believe that post-NAC NLR can be used for patient stratification after NAC. Consequently, the post-NAC NLR may serve as a guide for the decision-making process regarding RC versus bladder-preserving strategies.

Association of Lymphovascular Invasion with Lymph Node Metastases in Prostate Cancer-Lateralization Concept.

BACKGROUND: Lymphovascular invasion (LVI) is a vital but often overlooked prognostic factor in prostate cancer. As debates on lymphadenectomy's overtreatment emerge, understanding LVI laterality gains importance. This study pioneers the investigation into PCa, aiming to uncover patterns that could influence tailored surgical strategies in the future. METHODS: Data from 96 patients with both LVI and lymph node invasion (LNI) were retrospectively analyzed. All participants underwent radical prostatectomy (RP) with modified-extended pelvic lymph node dissection (mePLND). All specimens underwent histopathological examination. The assessment of LVI was conducted separately for the right and left lobes of the prostate. Associations within subgroups were assessed using U-Mann-Whitney and Kruskal-Wallis tests, as well as Kendall's tau-b coefficient, yielding p-values and odds ratios (ORs). RESULTS: Out of the 96 patients, 61 (63.5%) exhibited exclusive left-sided lymphovascular invasion (LVI), 24 (25.0%) had exclusive right-sided LVI, and 11 (11.5%) showed bilateral LVI. Regarding nodal involvement, 23 patients (24.0%) had LNI solely on the left, 25 (26.0%) exclusively on the right, and 48 (50.0%) on both sides. A significant correlation was observed between lateralized LVI and lateralized LNI (p < 0.001), particularly in patients with right-sided LVI only. LN-positive patients with left-sided LVI tended to have higher pT stages (p = 0.047) and increased odds ratios (OR) of bilateral LNI (OR = 2.795; 95% confidence interval [CI]: 1.231-6.348) compared to those with exclusive right-sided LVI (OR = 0.692; 95% CI: 0.525-0.913). CONCLUSIONS: Unilateral LVI correlates with ipsilateral LNI in PCa patients with positive LNs, notably in cases of exclusively right-sided LVI. Left-sided LVI associates with higher pT stages and a higher percentage of bilateral LNI cases.

Retrograde intrarenal surgery using the ILY robotic flexible ureteroscope: a single centre experience.

Introduction: The ILY robotic flexible ureteroscope has been introduced in order to improve intraoperative ergonomics, reduce operator distance from radiation and shorten the learning curve. In this study we aimed to assess the clinical performance and feasibility of the ILY robot during retrograde intrarenal surgery (RIRS) and combined endoscopic procedures (miniECIRS). Material and methods: The RIRS procedures were performed using the ILY robotic arm in 57 adult patients (46 RIRS and 11 miniECIRS) from 2022 to 2023. All procedures were performed in the supine position. Pre-stenting was not the standard of care. Results: Turning on and calibration of the device took approximately 100 s. Average draping time was 93 s using original ILY drapes and 47 s using classic drapes designed for C-arm covering. Mean docking time was 73 s in procedures with ureteral access sheath (UAS) and 61 s in procedures without it. The undocking took less than 60 s in every case. Average procedure time was 63 min for RIRS and 55 min for miniECIRS. Endoscopically proven stone-free rate was achieved in 37 (80.4%) RIRS and 10 (90.9%) miniECIRS patients. A total of 17 (36.9%) RIRS and 8 (72.7%) miniECIRS procedures required conversion in order to perform basketing and stone fragments retrieval/transposition. Conclusions: The use of ILY robot during endourological procedures is feasible and urologists that are familiar with the device controller do not require extensive training. The time needed for device draping, docking and undocking was approximately 4 minutes. Moreover, use of the robot resulted in satisfactory stone-free rates.

The clinical meaning of lymphovascular invasion: preoperative predictors and postoperative implications in prostate cancer - a retrospective study.

Introduction: Lymphovascular invasion (LVI) is a pivotal histopathological parameter in prostate cancer (PCa), holding significant prognostic implications. Our study pursued a dual objective: firstly, to identify preoperative factors associated with LVI, aiming to unveil markers facilitating the recognition of patients prone to LVI during postoperative examination; and secondly, to assess postoperative outcomes correlated with LVI. Methods: We retrospectively analyzed 861 nonmetastatic PCa patients who underwent radical prostatectomy (RP), investigating preoperative factors and postoperative outcomes. Surgical specimens were processed following established guidelines. Statistical analyses utilized non-parametric tests to assess the association between LVI and both pre- and postoperative factors. Furthermore, logistic regression analyses were utilized to develop models aimed at identifying the most significant predictors of LVI and pN1 status, respectively. Results: Numerous preoperative factors exhibited significant correlations with LVI, offering valuable clinical insights. Logistic regression identified magnetic resonance imaging (MRI)-based clinical tumor stage (cT) 3-4, biopsy Gleason Grading Group (GGG) 3-5, preoperative prostate specific antigen (PSA) ≥20 and percentage of positive biopsy cores (PPBC) ≥50% as the strongest preoperative predictors of LVI. Additionally, the study uncovered an association between LVI and postoperative outcomes, including postoperative PSA (p value <0.001), extracapsular extension (ECE) (<0.001), positive surgical margins (PSM) (<0.001), perineural invasion (PNI) (<0.001), pathological tumor stage (pT) (<0.001), pathological lymph node status (pN) (<0.001), postoperative GGG (<0.001), and operative time (0.023). Notably, the study revealed a novel and substantial association between LVI and an increased number of positive lymph nodes in pN+ patients in the univariate analysis (<0.001). Furthermore, we have found an association between LVI and pN1 status in the logistic regression analysis (odds ratio [OR] = 23.905; p <0.001). Conclusion: Our findings underscore the pivotal role of LVI in influencing the prognosis of prostate cancer (PCa). The study acknowledges the challenges associated with preoperative LVI assessment and emphasizes the need for future research to unravel the factors associated with this histopathological finding. Significantly, our research stands out as the first, to the best of our knowledge, to reveal the association between LVI and the number of positive lymph nodes in pN+ patients.

Clinical and Oncological Outcomes Following Percutaneous Cryoablation vs. Partial Nephrectomy for Clinical T1 Renal Tumours: Systematic Review and Meta-Analysis.

Percutaneous cryoablation (PCA) can be an alternative to partial nephrectomy (PN) in selected patients with stage T1 renal tumours. Existing meta-analyses regarding ablative techniques compared both laparoscopic and PCA with PN. That is why we decided to perform a meta-analysis that focused solely on PCA. The aim of this study was to compare the complications and functional and oncological outcomes between PCA and PN. A systematic literature search was performed in January 2024. Data for dichotomous and continuous variables were expressed as pooled odds ratios (ORs) and mean differences (MDs), both with 95% confidence intervals (CIs). Effect measures for the local recurrence-free survival (LRFS), metastasis-free survival (MFS), cancer-specific survival (CSS) and overall survival (OS) were expressed as pooled hazard ratios with 95% CIs. Among 6487 patients included in the 14 selected papers, 1554 (23.9%) and 4924 (76.1%) underwent PCA and PN, respectively. Compared with the PN group, patients undergoing PCA had significantly lower overall and major postoperative complication rates. There was no difference in renal function between PCA and PN groups. When analysing collective data for cT1 renal carcinoma, PCA was associated with worse LRFS compared with PN. However, subgroup analysis revealed that in the case of PCA, LRFS was not decreased in patients with cT1a tumours. Moreover, patients undergoing robotic-assisted PN had improved LRFS compared with those undergoing PCA. No significant differences were observed between PCA and PN in terms of MFS and CSS. Finally, PCA was associated with worse OS than PN in both collective and subgroup analyses. In conclusion, PCA is associated with favourable postoperative complication rates relative to PN. Regarding LRFS, PCA is not worse than PN in cT1a tumours but has a substantially relevant disadvantage in cT1b tumours. Also, RAPN might be the only surgical modality that provides better LRFS than PCA. In cT1 tumours, PCA shows MFS and CSS comparable to PN. Lastly, PCA is associated with a shorter OS than PN.

The Impact of Venous Thromboembolism on Upper Tract Urothelial Carcinomas Undergoing Open or Minimally Invasive Radical Nephroureterectomy in the USA: Perioperative Outcomes and Health Care Costs from Insurance Claims Data.

BACKGROUND AND OBJECTIVE: Venous thromboembolism (VTE) is a significant predictor of worse postoperative morbidity in cancer surgeries. No data have been available for patients with preoperative VTE and upper tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU). Our aim was to assess the impact of a preoperative VTE diagnosis on perioperative outcomes in the RNU context. METHODS: Patients aged 18 yr or older with a UTUC diagnosis undergoing RNU were identified in the Merative Marketscan Research deidentified databases between 2007 and 2021. Multivariable logistic regression adjusted by relevant perioperative confounders was used to investigate the association between a diagnosis of VTE prior to RNU and 90-d complication rates, postoperative VTE, rehospitalization, and total costs. A sensitivity analysis on VTE severity (pulmonary embolism [PE] and/or deep venous thrombosis [DVT]) was examined. KEY FINDINGS AND LIMITATIONS: Within the investigated cohort of 6922 patients, history of any VTE preceding RNU was reported in 568 (8.21%) cases, including DVT (n = 290, 51.06%), PE (n = 169, 29.75%), and superficial VTE (n = 109, 19.19%). The history of VTE before RNU was predictive of higher rates of complications, the most prevalent being respiratory complications (odds ratio [OR]: 1.78, 95% confidence interval [CI]: 1.43-2.22). Preoperative VTE was found to be associated with an increased risk of VTE following RNU (OR: 14.3, 95% CI: 11.48-17.82), higher rehospitalization rates (OR: 1.26, 95% CI 1.01-1.56) other than home discharge status (OR: 1.44, 95% CI: 1.18-1.77), and higher costs (OR 1.42, 95% CI: 1.20-1.68). Limitations include the retrospective nature and the use of an insurance database that relies on accurate coding and does not include information such as pathologic staging. CONCLUSIONS AND CLINICAL IMPLICATIONS: The presented findings will contribute to the counseling process for patients. These patients may benefit from enhanced pre/postoperative anticoagulation. More research is needed before the following results can be used in the clinical setting. PATIENT SUMMARY: Patients aged 18 yr or older with an upper tract urothelial carcinoma (UTUC) diagnosis undergoing radical nephroureterectomy (RNU) were identified in the Merative Marketscan Research deidentified databases between 2007 and 2021. Multivariable logistic regression adjusted by relevant perioperative confounders was used to investigate the association between a diagnosis of venous thromboembolism (VTE) prior to RNU and 90-d complication rates, postoperative VTE, rehospitalization, and total costs. A sensitivity analysis on VTE severity (pulmonary embolism and/or deep venous thrombosis) was examined. The presented findings will contribute to the counseling of patients with UTUC and preoperative VTE.

The Prognostic Role of Preoperative PSMA PET/CT in cN0M0 pN+ Prostate Cancer: A Multicenter Study.

CONTEXT: Despite negative preoperative conventional imaging, up to 10% of patients with prostate cancer (PCa) harbor lymph-node involvement (LNI) at radical prostatectomy (RP). The advent of more accurate imaging modalities such as PET/CT improved the detection of LNI. However, their clinical impact and prognostic value are still unclear. We aimed to investigate the prognostic value of preoperative PET/CT in patients node positive (pN+) at RP. EVIDENCE SYNTHESIS: We retrospectively identified cN0M0 patients at conventional imaging (CT and/or MRI, and bone scan) who had pN+ PCa at RP at 17 referral centers. Patients with cN+ at PSMA/Choline PET/CT but cN0M0 at conventional imaging were also included. Systemic progression/recurrence was the primary outcome; Cox proportional hazards models were used for multivariate analysis. EVIDENCE ACQUISITION: We included 1163 pN+ men out of whom 95 and 100 had preoperative PSMA and/or Choline PET/CT, respectively. ISUP grade ≥4 was detected in 66.6%. Overall, 42% of patients had postoperative PSA persistence (≥0.1 ng/mL). Postoperative management included initial observation (34%), ADT (22.7%) and adjuvant RT+/-ADT (42.8%). Median follow-up was 42 months. Patients with cN+ on PSMA PET/CT had an increased risk of systemic progression (52.9% vs. 13.6% cN0 PSMA PET/CT vs. 21.5% cN0 at conventional imaging; P < .01). This held true at multivariable analysis: (HR 6.184, 95% CI: 3.386-11-295; P < .001) whilst no significant results were highlighted for Choline PET/CT. No significant associations for both PET types were found for local progression, BCR, and overall mortality (all P > .05). Observation as an initial management strategy instead of adjuvant treatments was related with an increased risk of metastases (HR 1.808; 95% CI: 1.069-3.058; P < .05). CONCLUSIONS: PSMA PET/CT cN+ patients with negative conventional imaging have an increased risk of systemic progression after RP compared to their counterparts with cN0M0 disease both at conventional and/or molecular imaging.

The G84E mutation in the HOXB13 gene is associated with an increased risk of prostate cancer in Poland.

BACKGROUND: The G84E mutation in the HOXB13 gene has been associated with a high lifetime risk of prostate cancer in North America (about 20-fold). The geographical and ethnic extent of this recurrent allele has not yet been determined. METHODS: We assayed for the presence of the G84E mutation in 3,515 prostate cancer patients and 2,604 controls from Poland and estimated the odds ratio for prostate cancer associated with the allele. RESULTS: The G84E mutation was detected in 3 of 2,604 (0.1%) individuals from the general population in Poland and in 20 of 3,515 (0.6%) men with prostate cancer (Odds ratio [OR] = 5.0; 95% CI: 1.5-16.7; P = 0.008). The allele was present in 4 of 416 (1.0%) men with familial prostate cancer (OR = 8.4, 95% CI: 1.9-37.7; P = 0.005). CONCLUSIONS: The G84E mutation predisposes to prostate cancer in Poland, but accounts for only a small proportion of cases. We expect that the G84E founder mutation might be present in other Slavic populations.

The clinical significance of lymphangiogenesis in renal cell carcinoma.

BACKGROUND: The formation of lymphatic vessels (lymphangiogenesis) occurs in tumor tissues and is crucial for tumor development and progression in some cancers. Lymphangiogenesis and its clinical effect on renal cell carcinoma have been less thoroughly investigated in comparison with angiogenesis. The aim of this study was to evaluate the role of lymphangiogenesis as a prognostic factor in renal cell carcinoma (RCC). MATERIAL AND METHODS: The expression of peritumoral/intratumoral lymphatics was studied by immunohistochemical methods in paraffin-embedded nephrectomy specimens from 133 patients with clear cell carcinoma. Patients were divided into 3 groups depending on postoperative follow-up: I) patients without metastases, II) patients with metastases during follow-up, and III) patients with metastases during the operation. Peritumoral lymphatics (PTL) and intratumoral lymphatics (ITL) were immunostained with a D2-40 antibody. RESULTS: The mean number of PTL present in each group was I=14.1, II=10.6, III=12.1. The mean number of ITL present in each group was I=0.7, II=2.3, III=2.3. The 3 groups showed statistically significant differences only in the case of ITL. A mean count of ITL ≥1 is significantly associated with an increased risk of regional lymph node involvement and distant metastasis. Patients with expression ITL >0.2 and PTL ≤15.2 had a significantly shorter cancer-specific survival. CONCLUSIONS: The number of ITL showed an association with more aggressive cases of RCC and progression of disease. Therefore, the level of expression ITL, together with stage and histological grading, may provide valuable predictive information about the outcome of treatment.

Adequate Pelvic Lymph Node Dissection in Radical Cystectomy in the Era of Neoadjuvant Chemotherapy: A Meta-Analysis and Systematic Review.

Radical cystectomy (RC) with pelvic lymphadenectomy (PLND) serves as the gold-standard treatment for muscle-invasive bladder cancer (MIBC). Numerous studies have shown that the number of lymph nodes (LN) removed during RC could affect patient prognosis. However, these studies confirmed the association between PLND and survival outcomes prior to the widespread adoption of neoadjuvant chemotherapy (NAC). Consequently, this study aimed to investigate the prognostic role of PLND in patients previously pretreated with NAC. A systematic review and meta-analysis were performed using PubMed, Web of Knowledge, and Scopus databases. The selected studies contained a total of 17,421 participants. The meta-analysis indicated a significant correlation between adequate PLND and overall survival in the non-NAC group. However, a survival benefit was not observed in patients undergoing RC with preoperative systemic therapy, regardless of the LN cut-off thresholds. The pooled HR for ≥10 and ≥15 LN were 0.87 (95% CI 0.75-1.01) and 0.87 (95% CI 0.76-1.00), respectively. The study results suggest that NAC mitigates the therapeutic significance of PLND, as patients pre-treated with NAC no longer gain oncological benefits from more extensive lymphadenectomy. This highlights the analogous roles of NAC and PLND in eradication of micrometastases and in prevention of distal recurrence post-RC.

Influence of Neoadjuvant Chemotherapy on Survival Outcomes of Radical Cystectomy in Pathologically Proven Positive and Negative Lymph Nodes.

Patients receiving neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC) typically show better survival outcomes than those undergoing immediate surgery for muscle-invasive bladder cancer. However, most studies have not considered the lymph node (LN) status when evaluating NAC's survival benefits. This study sought to delineate the impact of NAC on patients based on their pathologically determined LN status at the time of RC. We examined data from 1395 patients treated at two departments between 1991 and 2022. Of them, 481 had positive LNs. A comparison of overall survival (OS) outcomes revealed that patients without LN involvement ((y)pN0) benefited from NAC with a hazard ratio (HR) of 0.692 (95% confidence interval [CI] 0.524-0.915). In contrast, patients with (y)pN+ showed no improvement with NAC (HR 0.927, 95%CI 0.713-1.205). Notably, patients treated with NAC for stage