Quantification and molecular correlates of tertiary lymphoid structures in primary prostate cancer.

OBJECTIVE: To morphologically describe tertiary lymphoid structures (TLS) in prostatectomy specimens and correlate them with clinical and transcriptomic features. METHODOLOGY: A total of 72 consecutive cases of entirely submitted radical prostatectomy (RP) patients tested with the Decipher Genomic Classifier were included in the study. Images were manually annotated using QuPath tools to denote tumor regions and each cluster of TLS. Clusters of lymphocytes that were surrounded on all four sides by tumor were defined as intra-tumor TLS (IT-TLS). Clusters of lymphocytes at the leading edge of carcinoma with either the prostatic pseudocapsule or benign parenchyma at one end were defined as peri-tumor TLS (PT-TLS). A classification algorithm to distinguish lymphocytes from non-lymphocytic cells using a supervised machine learning model was used. The associations between TLS formation and 265 gene expression-based signatures were examined. RESULTS: The magnitude of total TLS correlations with primary tumor gene expression signatures was moderate (~0.35-0.5) with several HLA, T-cell and B-cell Cluster signatures, showing positive correlation with various metrics for quantification of TLS. On the other hand, immune suppressive signatures (Treg, MDSC) were negatively correlated. While signatures for macrophages, NK cells and other immune cell types were uncorrelated for the most part. PT-TLS was associated with MHC signatures while IT TLS correlated with MHC and T-cell signatures. CONCLUSIONS: Clusters of inflammatory cells in the RP specimen can be divided spatially into PT TLS and IT-TLS, each with its unique molecular correlates of tumor immune microenvironment. The presence of TLS is positively correlated with MHC signatures, T- cell and B-cell cluster signatures but, negatively correlated with immune suppressive signatures. A subset of prostate cancer demonstrate a robust inflammatory response, and warrant further characterization in larger cohorts.

MRI-based radiomic features of the urinary bladder wall identify patients with moderate-to-severe international prostate symptom score.

BACKGROUND: The International Prostate Symptom Score (IPSS) is a patient-reported measurement to assess the lower urinary tract symptoms of bladder outlet obstruction. Bladder outlet obstruction induces molecular and morphological alterations in the urothelium, suburothelium, detrusor smooth muscle cells, detrusor extracellular matrix, and nerves. We sought to analyze MRI-based radiomics features of the urinary bladder wall and their association with IPSS. METHOD: In this retrospective study, 87 patients who had pelvic MRI scans were identified. A biomarker discovery approach based on the optimal biomarker (OBM) method was used to extract features of the bladder wall from MR images, including morphological, intensity-based, and texture-based features, along with clinical variables. Mathematical models were created using subsets of features and evaluated based on their ability to discriminate between low and moderate-to-severe IPSS (less than 8 vs. equal to or greater than 8). RESULTS: Of the 7,666 features per patient, four highest-ranking optimal features were derived (all texture-based features), which provided a classification accuracy of 0.80 with a sensitivity, specificity, and area under the receiver operating characteristic curve of 0.81, 0.81, and 0.87, respectively. CONCLUSION: A highly independent set of urinary bladder wall features derived from MRI scans were able to discriminate between patients with low vs. moderate-to-severe IPSS with accuracy of 80%. Such differences in MRI-based properties of the bladder wall in patients with varying IPSS's might reflect differences in underlying molecular and morphological alterations that occur in the setting of chronic bladder outlet obstruction.

Gender inequality in genitourinary malignancies clinical trials leadership.

BACKGROUND: Over the past 2 decades, there has been a growing interest in the significance of gender roles in healthcare and several efforts and initiatives have focused on increasing female representation in the medical field. Clinical trials play a very important role in shaping medical practice; moreover, the leaders of clinical trials often represent the upper echelon of researchers in any designated field. Presently, there is no data regarding women's representation in urological oncology clinical trials leadership. Therefore, the aim of this study is to examine the extent of female representation in leading urological clinical trials. METHODOLOGY: To thoroughly examine the representation of females as principal investigators (PIs) in urological cancer clinical trials between 2000 and 2020, we conducted a comprehensive search of completed trials focused on kidney, prostate, and bladder cancer on ClinicalTrials.gov. We extracted relevant information regarding the PIs and analyzed the data using univariate analyses to identify any significant differences between male and female PIs. RESULTS: A total of 9145 cancer clinical trials were conducted over the last 2 decades, and 11.3% (n = 1033) of them were urological cancer clinical trials. We were able to obtain detailed information about the principal investigators (PI) in 79.0% (n = 816) of the clinical trials, and we found that 16.8% (n = 137) of them were led by female investigators. Upon evaluating the characteristics of the PIs, female PIs had a significantly lower median age and median total citations as compared to male PIs (55.0 vs 59.0 and 5333 vs 7902; p-value < 0.001 and 0.006, respectively). However, there was no statistically significant difference between the termination rate, publication rate, funding source, cancer type, and the subject of conducting the clinical trials between male and female PIs. CONCLUSION: Between 2000 and 2020, only 16.8% of urological cancer clinical trials were led by a female PI, perhaps reflective of a low percentage of senior female researchers in the fields of urology, oncology and radiation oncology. Universities, research institutes and funding agencies should work to improve mentorship, representation and opportunities for female investigators to encourage more involvement for female researchers in these clinical trials.

When to order genomic tests: development and external validation of a model to predict high-risk prostate cancer at the genotypic level.

PURPOSE: The aim of this study was to develop a model to predict high-genomic-risk prostate cancer (PCa) according to Decipher score, a validated 22 gene prognostic panel. By doing so, one might select the individuals who are likely to benefit from genomic testing and improve pre-op counseling about the need for adjuvant treatments. METHODS: We retrospectively reviewed IRB-approved databases at two institutions. All patients had preoperative magnetic resonance imaging (MRI) and Decipher prostate radical prostatectomy (RP), a validated 22 gene prognostic panel. We used binary logistic regression to estimate high-risk Decipher (Decipher score > 0.60) probability on RP specimen. Area under the curve (AUC) and calibration were used to assess the accuracy of the model in the development and validation cohort. Decision curve analysis (DCA) was performed to assess the clinical benefit of the model. RESULTS: The development and validation cohort included 622 and 185 patients with 283 (35%) and 80 (43%) of those with high-risk Decipher. The multivariable model included PSA density, biopsy Gleason Grade Group, percentage of positive cores and MRI extracapsular extension. AUC was 0.73 after leave-one-out cross-validation. DCA showed a clinical benefit in a range of probabilities between 15 and 60%. In the external validation cohort, AUC was 0.70 and calibration showed that the model underestimates the actual probability of the outcome. CONCLUSIONS: The proposed model to predict high-risk Decipher score at RP is helpful to improve risk stratification of patients with PCa and to assess the need for additional testing and treatments.

Outcome of Mini-PCNL Under Loco-Regional Anesthesia: Outcomes of a Systematic Review.

PURPOSE OF REVIEW: Miniaturized PCNL (mi-PCNL) for stone disease is performed under a general anesthesia. However, the role of loco-regional anesthesia in mi-PCNL and its outcomes are not well defined yet. Here, we review the outcomes and complications of loco-regional anesthesia for mi-PCNL. A Cochrane-style review was performed in accordance with the preferred reporting items for systematic reviews to evaluate the outcomes of loco-reginal anesthesia for URS in stone disease, including all English language articles from January 1980 and October 2021. RECENT FINDINGS: Ten studies with a total of 1663 patients underwent mi-PCNL under loco-regional anesthesia. The stone-free rate (SFR) for mi-PCNL under neuro-axial anesthesia ranged between 88.3 and 93.6%, while it ranged between 85.7 and 93.3% for mi-PCNL under local anesthesia (LA). The conversion rate to another anesthesia modality was 0.5%. The complications ranged widely between 3.3 and 85.7%. The majority were Grade I-II complications and none of the patients had grade V complications. Our review shows that mi-PCNL under loco-regional anesthesia is feasible with good SFR and a low risk of major complications. The conversion to general anesthesia is needed in a small minority, with the procedure itself being well tolerated and a big step towards establishing an ambulatory pathway for these patients.

Robotic Surgery for Stone Disease.

PURPOSE OF REVIEW: To evaluate recent literature regarding the role of robotic technology in the treatment of nephrolithiasis with particular attention to complex technical procedures. RECENT FINDINGS: Robotic platforms including single-port robotics have been widely adopted in urological practice for the treatment of both malignant and benign conditions and has led to an expansion of the utilization of robot-assisted surgery to tackle challenging clinical scenarios such as bladder neck reconstruction, upper urinary tract reconstruction, and more recently complex stone disease. Presently, the American Urological Association guidelines on the surgical management of stones advise against using robotic, open, or laparoscopic techniques as a first-line approach for most patients with stone disease with the exception for patients with anatomical abnormalities, large or complex stones, or patients requiring a concomitant reconstructive operation. Clinicians have demonstrated the safety and feasibility of surgical robotics in the treatment of stone disease for a variety of operations including robotic pyeloplasty, pyelolithotomy, ureterolithotomy, and surgical interventions in urinary diversions as well as novel technologies for robotic ureteroscopy and percutaneous access. Numerous clinicians have demonstrated the safety and feasibility of using robot-assisted surgery to treat nephrolithiasis, mainly in complex renal anatomy. Further research is necessary to identify the best candidates for utilization of robotics in complex stone disease, and further technological developments will continue to further advance the use of these platforms in the treatment of nephrolithiasis.

Does Perioperative Testosterone Predict Post-Prostatectomy Genomic Risk Score?

PURPOSE: The role of endogenous testosterone in de novo prostate cancer pathogenesis in humans remains unclear. The effect of testosterone on the tumor genome is not explored. We sought to explore the correlation between perioperative testosterone level and genomic risk score in a cohort of men who underwent radical prostatectomy. MATERIALS AND METHODS: We included patients who underwent radical prostatectomy (2013-2018) and had adverse pathological features in their final surgical specimens (positive margin, and/or pT3a or higher). The outcome of interest was the genomic risk score: low (<0.45), intermediate (0.45-0.6) and high (>0.6). The associations between serum testosterone level and 188 gene expression-based signatures were examined. Secondary outcomes of interest included biochemical recurrence and receipt of secondary treatment. RESULTS: The median genomic risk score was lower in the low testosterone group compared to the intermediate and normal testosterone groups (0.38 vs 0.52 vs 0.53, respectively; p=0.049). There was no difference in biochemical recurrence-free survival between the 3 testosterone groups (p=0.9). Patients with low testosterone levels had higher odds of receiving secondary treatment (OR: 2.27; 95% CI: 1.14-4.50; p=0.02) than those with normal levels. A total of 43 (of 188) gene expression signatures were associated with testosterone level (p <0.05). In total, 33 signatures were positively associated with serum testosterone levels, including 12 signatures involved in DNA repair pathways. CONCLUSIONS: This is the first study to assess the correlation of preoperative testosterone level on the tumor transcriptome and showed no clinical correlation between pre-defined genomic risk score groups and testosterone groups. This study adds to the notion of the limited role of endogenous testosterone on the development of de novo high-risk localized prostate cancer.

External validation of genomic classifier-based risk-stratification tool to identify candidates for adjuvant radiation therapy in patients with prostate cancer.

OBJECTIVE: To externally validate a Genomic Classifier (GC) based risk-stratification nomogram identifying candidates who would benefit from adjuvant radiation (aRT) therapy after radical prostatectomy (RP). METHODS: We identified 350 patients who underwent RP, between 2013 and 2018, and had adverse pathological features (positive margin, and/or pT3a or higher) on final pathology. Genomic profile was available for all these men. The clinical recurrence-free survival was estimated using the Kaplan-Meier method. The external validity of the nomogram was tested using the concordance index (c-index), calibration plot, and decision curve analysis. RESULTS: The median follow-up of the cohort was 26.5 months. Overall, 14% of the patients received aRT. During the follow-up period, 3.4% of the patients developed metastasis. Overall 3-year metastasis-free survival was 95% (95% CI 0.92-0.98). The c-index of the nomogram was 0.84. The calibration of the model was favorable. Decision-curve analysis showed a positive net benefit for probabilities ranging between 0.01 and 0.09, with the highest difference at threshold probability around 0.05. At that threshold, the net benefit is 0.06 for the model and 0 for treating all the patients. CONCLUSION: Our report is the first to confirm the validity of this genomic-based risk-stratification tool in identifying men who might benefit from aRT after RP. As such, it can be a useful instrument to be incorporated in shared decision making on whether administration of aRT will lead to a clinically meaningful benefit. Such a model can also be useful for patients' classification in future clinical trials.

Family history in patients who would have been candidates for active surveillance.

INTRODUCTION It is unknown whether a family history of prostate cancer confers additional risk among men who are candidates for active surveillance (AS). MATERIALS AND METHODS: Using a prospectively maintained database of men who underwent radical prostatectomy (RP) (2010- 2018), candidates for AS were identified according to the expanded criteria. Pathological upgrading was defined as a pathologic Gleason score (pGS) of 3+4 or higher for patients with a biopsy GS of 3+3 and a pGS of 4+3 or higher for patients with a biopsy GS of 3+4. Major upgrading was defined as a pGS of 4+4 or higher. The ₓ2 test was used for comparisons. RESULTS: Of 1,320 men who were candidates for AS, 288 (21.8%) had a family history of prostate cancer. There were no differences in terms of the age, number of positive cores, or number of patients with a GS of 7 between the two groups. Pathological upgrading was observed in 61.1% of the total cohort, with no difference observed between the two groups (60.7% versus 62.5%; p = 0.5). CONCLUSION: In men who are eligible for AS according to the expanded criteria, a family history of prostate cancer does not appear to be associated with adverse pathology at RP.

Application of TAP Block in Laparoscopic Urological Surgery: Current Status and Future Directions.

PURPOSE OF REVIEW: Amid the opioid crisis, postoperative pain management is a major challenge for practitioners. Recent pain management guidelines emphasize the importance of using regional anesthesia as part of opioid-sparing multimodal analgesia. This report aims to review recent evidence regarding the utilization of transversus abdominis plane (TAP) block in minimally invasive urologic surgery. RECENT FINDINGS: TAP block has been shown to improve early and late pain at rest, and to reduce opioid consumption after minimally invasive surgery. These benefits have indirectly reduced the incidence of postoperative delirium, pneumonia, urinary retention, and falls. Compared to epidural analgesia, TAP block provides similar pain control, has a lower incidence of hypotension, and is associated with a shorter length of stay. Few studies focus specifically on the outcomes of TAP block in minimally invasive urologic surgery. TAP block decreases postoperative pain and reduces opioid consumption without increasing complications. TAP block should be integrated as an indispensable component in enhanced recovery after surgery protocols.

Ki-67 expression predicts biochemical recurrence after radical prostatectomy in the setting of positive surgical margins.

BACKGROUND: Positive surgical margin (PSM) is a predictor of biochemical recurrence (BCR) following radical prostatectomy (RP). Attempts to stratify PSM based on linear length, Gleason score, location and number have failed to add to predictive models using margin status alone. We evaluated the prognostic significance of Ki-67 expression in this setting. METHODS: Immunohistochemical staining for Ki-67 was done on prostatectomy specimens from 117 patients who had a PSM. Ki67 expression was measured at the margin and in the index lesion. Patients were dichotomized based on Ki-67 expression into three groups. Group 1 with no Ki-67 expression, Group 2 with Ki-67 ≤ 2%, and Group 3 with Ki-67 ≥ 3%. To eliminate the impact of the adjuvant treatment (AT) on the outcome, data were analyzed by the Cox proportional hazards in which AT was Considered as a time-dependent covariate. RESULTS: The discordance rate of Ki-67 expression between matched index lesion and margin specimens was 44/117 (37.6%). There was a trend for higher risk of BCR (HR:2.06, (0.97-4.43), P = 0.06) in patients expressing high Ki67 at the surgical margin although this was not statistically significant. However High Ki-67 expression in the index lesion was an independent predictive factor for BCR in this subset of patients. (HR:4, (1.64-9.80), P = 0.002). CONCLUSION: High Ki67 expression in the index prostate cancer lesion is an independent predictor of BCR in patients with positive surgical margin following radical prostatectomy. Our findings need to be validated in a larger cohort.

Incidence of sepsis following transrectal ultrasound guided prostate biopsy at a tertiary-care medical center in Lebanon.

BACKGROUND: Urosepsis is a rare but life-threatening complication following transrectal ultrasound (TRUS) guided needle prostate biopsy. Despite the technological and pharmacological improvements, the problem of bacterial urosepsis after prostate biopsy remains. A strategy for preventing urosepsis following TRUS prostate biopsy in áreas with high prevalence of resistant strains or patients presenting risk factors is lacking. OBJECTIVES: The aim of this study was to assess the prevalence of urosepsis, as well its predictors, following TRUS guided needle biopsy of the prostate in a tertiary care medical center in Lebanon. MATERIALS AND METHODS: We carried out a retrospective study on all patients who underwent TRUS prostate biopsy at the American University of Beirut Medical Center between January 1, 2011 and June 31, 2013. Patients' hospital charts were reviewed. Data collected included demographic information, pre-procedure disease specific information, as well as post-procedure information. Predictors of urosepsis following TRUS were assessed. RESULTS: In total, 265 patients were included in this study, where the prevalence of urosepsis following TRUS prostate biopsy was found to be 9.4%. The significant independente predictors of urosepsis were found to be: age with an OR=0.93 (95% CI: 0.88-1.00, p-value=0.03), and hypertension comorbidity with an OR=3.25 (95% CI: 1.19-8.85, p-value=0.02). CONCLUSION: We found a high prevalence of urosepsis among patients who have undergone TRUS prostate biopsy, and identified two significant risk factors. The results of this study highlight the importance of implementing strategies for prevention of urosepsis following TRUS prostate biopsy.

Partial nephrectomy for metastatic renal cell carcinoma: Where do we stand?

Nephron-sparing surgery (NSS) for renal cell carcinoma (RCC) offers comparable oncologic results, but a lower risk of chronic kidney disease, when compared with radical nephrectomy. However, there are limited data in the literature examining the safety of NSS in the setting of metastatic RCC. To evaluate the feasibility of NSS and impact on cancer-specific survival (CSS) in patients with metastatic disease, we performed a systematic review of the literature. There is ample evidence that NSS is feasible in metastatic RCC, with comparable results in terms of CSS compared with radical cytoreductive nephrectomy.

Preoperative lymphocyte-to-monocyte ratio predicts clinical outcome in patients undergoing radical cystectomy for transitional cell carcinoma of the bladder: a retrospective analysis.

BACKGROUND: Inflammation is a critical component of tumorigenesis, and many cancers arise from sites of infection, chronic irritation, and inflammation. Inflammatory cytokines triggered by tumors alter hematologic components, including neutrophil, lymphocyte, and monocyte counts. The neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios have been shown to be valuable prognostic markers in various types of cancers, including bladder cancer. Risk stratification based on clinicopathologic data is insufficient to support treatment-related choices in patients with bladder cancer. Novel prognostic markers are therefore needed. An elevated pretreatment lymphocyte-to-monocyte ratio (LMR) is reportedly associated with improved overall survival (OS) and a longer time to treatment recurrence (TTR) in some types of cancers. However, these data are lacking in patients with bladder cancer. The aim of the present study was to investigate the effect of the preoperative LMR on OS and TTR in a cohort of patients with bladder cancer. METHODS: Sixty-eight patients with transitional cell carcinoma of the bladder were included in this retrospective analysis. The associations between a high and low LMR with OS and TTR were analyzed using Kaplan-Meier curves and compared by the log-rank test. RESULTS: In our study cohort, an elevated preoperative LMR was significantly associated with an increased TTR (P = 0.001) and OS (P = 0.020). Patients with an LMR of ≤2.87 showed a median TTR of 2.0 years (95% CI, 0.27-3.73), whereas patients with an LMR of >2.87 had a median TTR of 11.1 years (95% CI, 2.31-19.88) (P = 0.001). Patients with an LMR of ≤2.81 showed a median OS of 2.7 years (95% CI, 0.63-4.70), whereas patients with an LMR of >2.81 had a median OS of 6.0 years (95% CI, 3.60-8.40) (P = 0.020). The clinical stage at diagnosis was the only clinicopathologic feature associated with the LMR, while tumor invasion depth showed borderline significance. CONCLUSIONS: The LMR is an easily measured and inexpensive prognostic marker that was significantly correlated with OS and TTR in the present retrospective analysis. However, because of the small sample size in this study, larger multicenter, prospective studies are needed.

Bibliometric analysis of focal therapy in prostate cancer research.

Introduction: The use of focal therapies for prostate cancer (PCa) has soared, as it controls disease and is associated with minimal side effects. Bibliometric analysis examines the global research landscape on any topic to identify gaps in the research and areas for improvement and prioritize future research efforts. This study aims to examine the research outputs and trends and collaboration landscape in the field of focal therapy for PCa on a global scale. Methods: We searched Medline, PubMed and Scopus for peer-reviewed publications on our research topic using controlled keywords. Search results were limited to the period between 1980 and 2022, screened for duplicates and then included in our study based on prespecified eligibility criteria. The Bibliometrix Package was used for comprehensive science mapping analysis of co-authorship, co-citation and co-occurrence analysis of countries, institutions, authors, references and keywords in this field. Results: This analysis included 2578 research articles. The annual scientific production increased from one article in 1982 to 143 in 2022 (13.21%). The average citation per year was incrementally increasing, and these documents were cited around 32.52 times. The documents included in this analysis were published in 633 sources. The international collaboration index was 22.7. In total, 6280 author keywords were identified. The most used keywords were 'prostate cancer', 'focal therapy', 'prostate' and 'photodynamic therapy'. Conclusion: This bibliometric analysis has provided a comprehensive review of focal therapy in PCa research, highlighting both the significant growth in the field and the existing gaps that require further exploration. The study points to the need for more diverse international collaboration and exploration of various treatment modalities within the context of focal therapy.

Cerebral and Muscular Metastases From Prostate Adenocarcinoma Initially Depicted by 177 Lu-PSMA SPECT/CT.

ABSTRACT: Cerebral and muscular metastases from prostatic adenocarcinoma occur rarely. Patients who develop such metastatic pattern exhibit noticeable symptoms. Herein, we present a 68-year-old man diagnosed with metastatic castrate-resistant prostate cancer. The patient received multiple 177 Lu-PSMA cycles. After the last cycle, a posttreatment SPECT/CT suggested disease progression with uncommon metastatic pattern in the right temporal brain lobe and muscles. 68 Ga-PSMA PET/CT and brain MRI confirmed these findings. Surprisingly, the patient remained asymptomatic up until the conclusion of the follow-up, which lasted for 3 months. This case emphasizes the importance of posttreatment scintigraphic imaging when other biomarkers are inconclusive.

Regional versus general anaesthesia in percutaneous nephrolithotomy: a systematic review and meta-analysis.

Introduction: Several studies have compared the safety and effectiveness of general and regional anaesthesia in percutaneous nephrolithotomy (PCNL). This study aimed to compare the perioperative and postoperative outcomes of general anaesthesia and regional anaesthesia for patients undergoing PCNL. Material and methods: For relevant articles, three electronic databases, including PubMed, Scopus, and Web of Science, were searched from their inception until March 2023. A meta-analysis has been reported in line with PRISMA 2020 and AMSTAR Guidelines. The risk ratio (RR) and mean difference (MD) were applied for the comparison of dichotomous and continuous variables with 95% confidence intervals (CI). Results: The final cohort analysis, comprised 3871 cases of PCNL, (2154 regional anaesthesia and 1717 general anaesthesia). Compared to general anaesthesia, the regional anaesthesia group had a significantly shorter length of stay (MD = -0.34 days, 95% CI -0.56 to -0.12, p = 0.002), lower postoperative nausea and vomiting rates (RR = 0.16, 95% CI 0.03 to 0.80, p = 0.026), lower complications grade III-V rates (RR = 0.68, 95% CI 0.53 to 0.88, p = 0.004), and lower postoperative visual analogue pain score (VAS) at 1 hour (MD = -3.5, 95% CI -4.1 to -2.9, p <0.001). There were no significant differences in other outcomes between the two groups. Conclusions: Our results show that PCNL under regional anaesthesia is safe and feasible, with comparable results to those done under general anaesthesia. While patient selection is important, counselling and decision-making for these procedures must go hand in hand to achieve the best clinical outcome.