Circadian Rhythms in Anticancer Immunity: Mechanisms and Treatment Opportunities.

Circadian rhythms of approximately 24 h have emerged as important modulators of the immune system. These oscillations are important for mounting short-term, innate immune responses, but surprisingly also long-term, adaptive immune responses. Recent data indicate that they play a central role in antitumor immunity, in both mice and humans. In this review, we discuss the evolving literature on circadian antitumor immune responses and the underlying mechanisms that control them. We further provide an overview of circadian treatment regimens-chrono-immunotherapies-that harness time-of-day differences in immunity for optimal efficacy. Our aim is to provide an overview for researchers and clinicians alike, for a better understanding of the circadian immune system and how to best harness it for chronotherapeutic interventions. This knowledge is important for a better understanding of immune responses per se and could revolutionize the way we approach the treatment of cancer and a range of other diseases, ultimately improving clinical practice.

Circadian tumor infiltration and function of CD8+ T cells dictate immunotherapy efficacy.

The quality and quantity of tumor-infiltrating lymphocytes, particularly CD8+ T cells, are important parameters for the control of tumor growth and response to immunotherapy. Here, we show in murine and human cancers that these parameters exhibit circadian oscillations, driven by both the endogenous circadian clock of leukocytes and rhythmic leukocyte infiltration, which depends on the circadian clock of endothelial cells in the tumor microenvironment. To harness these rhythms therapeutically, we demonstrate that efficacy of chimeric antigen receptor T cell therapy and immune checkpoint blockade can be improved by adjusting the time of treatment during the day. Furthermore, time-of-day-dependent T cell signatures in murine tumor models predict overall survival in patients with melanoma and correlate with response to anti-PD-1 therapy. Our data demonstrate the functional significance of circadian dynamics in the tumor microenvironment and suggest the importance of leveraging these features for improving future clinical trial design and patient care.

Telemedicine in urologic oncology care: Will telemedicine exacerbate disparities?

INTRODUCTION: Disparities in prostate, bladder, and kidney cancer outcomes are associated with access to care. Telemedicine can improve access but may be underutilized by certain patient populations. Our objective was to determine if the patient populations who suffer worse oncologic outcomes are the same as those who are less likely to use telemedicine. METHODS: Using an institutional database, we identified all prostate, bladder and kidney cancer encounters from March 14, 2020 to October 31, 2021 (n = 15,623; n = 4, 14; n = 3,830). Telemedicine was used in 13%, 8%, and 12% of these encounters, respectively. We performed random effects modeling analysis to examine patient and provider characteristics associated with telemedicine use. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were reported as measures of association. RESULTS: Among prostate, bladder, and kidney cancer patients, Black patients had lower odds of a telemedicine encounter (OR 0.51, 95% CI 0.37-0.69; OR 0.22, 95% CI 0.07-0.70; OR 0.46, 95% CI 0.24-0.86), and patients residing in small and isolated small rural towns areas had higher odds of a telemedicine encounter (OR 1.44, 95% CI 1.09-1.91; OR 2.12, 95% CI 1.14-3.94; OR 1.89, 95% CI 1.12-3.19). Compared to providers in practice ≤5 years, providers in practice for 6 to 15 years had significantly higher odds of a telemedicine encounter for prostate and bladder cancer patients (OR 4.10, 95% CI 1.4511.58; OR 3.42, 95% CI 1.09-10.77). CONCLUSION: The lower rates of telemedicine use among Black patients could exacerbate pre-existing disparities in prostate, bladder, and kidney cancer outcomes.

A Multipronged Intervention to Reduce Readmissions and Readmission Intensity After Radical Cystectomy.

OBJECTIVE: To develop a multipronged, evidence-based protocol to reduce readmission risk and readmission intensity, as represented by the duration of the index readmission, after radical cystectomy. MATERIALS AND METHODS: A per-protocol study was performed. The protocol included preoperative nutritional supplementation, early stent removal, and a follow-up phone call within 4-5days of discharge. The preprotocol period was from February 1, 2020 to July 31, 2021 and the postprotocol period was from December 1, 2020 to November 31, 2021. Using multivariate regression models, we compared outcomes among patients treated with radical cystectomy before and after protocol initiation. RESULTS: We identified 70 preprotocol patients and 126 postprotocol patients. After adjusting for age, sex, BMI, and frailty score, there was a significant reduction in 90-day readmission intensity (7 vs 5days; P = .048) among postprotocol patients. CONCLUSION: After implementation of an evidence-based protocol for patients undergoing radical 90-day readmission intensity decreased significantly. This protocol may move the needle forward on reducing readmissions, but a larger randomized trial is needed.

Utilizing a Questionnaire to Implement a Risk-based Antibiotic Prophylaxis Protocol for Transrectal Prostate Biopsy.

OBJECTIVE: To develop and evaluate a risk-based antibiotic prophylaxis protocol for patients undergoing transrectal prostate biopsy. METHODS: We created a risk-based protocol for antibiotic prophylaxis before transrectal prostate biopsy. Patients were screened for infection risk-factors with a self-administered questionnaire. The protocol was implemented from January 1, 2020 to March 31, 2020. We compared patient risk-factors, antibiotic regimens, and 30-day infection rates for patients undergoing transrectal prostate biopsies during the intervention and for a 3-month period before the intervention. RESULTS: There were 116 prostate biopsies in the preintervention group and 104 in the intervention group. Although there was no significant difference in the number of high-risk patients between the 2 groups (48% vs 55%; P = .33), the percentage of patients treated with augmented prophylaxis decreased from 74% to 45% (P = 0.03). The duration of antibiotic administration and the median number of doses prescribed also decreased significantly. Despite significant decreases in antibiotic use, there were no differences in infection rates (5% vs 5%; P = .90) or sepsis rates (1% vs 2%; P = .60). CONCLUSION: We developed a risk-based protocol for prophylactic antibiotics before prostate biopsy. The protocol was associated with less antibiotic use but did not lead to an increase in infectious complications.

Large Variations in the Prices of Urologic Procedures at Academic Medical Centers 1 Year After Implementation of the Price Transparency Final Rule.

Importance: Patients with urologic diseases often experience financial toxicity, defined as high levels of financial burden and concern, after receiving care. The Price Transparency Final Rule, which requires hospitals to disclose both the commercial and cash prices for at least 300 services, was implemented to facilitate price shopping, decrease price dispersion, and lower health care costs. Objective: To evaluate compliance with the Price Transparency Final Rule and to quantify variations in the price of urologic procedures among academic hospitals and by insurance class. Design, Setting, and Participants: This was a cross-sectional study that determined the prices of 5 common urologic procedures among academic medical centers and by insurance class. Prices were obtained from the Turquoise Health Database on March 24, 2022. Academic hospitals were identified from the Association of American Medical Colleges website. The 5 most common urologic procedures were cystourethroscopy, prostate biopsy, laparoscopic radical prostatectomy, transurethral resection of the prostate, and ureteroscopy with laser lithotripsy. Using the corresponding Current Procedural Terminology codes, the Turquoise Health Database was queried to identify the cash price, Medicare price, Medicaid price, and commercial insurance price for these procedures. Exposures: The Price Transparency Final Rule, which went into effect January 1, 2021. Main Outcomes and Measures: Variability in procedure price among academic medical centers and by insurance class (Medicare, Medicaid, commercial, and cash price). Results: Of 153 hospitals, only 20 (13%) listed a commercial price for all 5 procedures. The commercial price was reported most often for cystourethroscopy (86 hospitals [56%]) and least often for laparoscopic radical prostatectomy (45 hospitals [29%]). The cash price was lower than the Medicare, Medicaid, and commercial price at 24 hospitals (16%). Prices varied substantially across hospitals for all 5 procedures. There were significant variations in the prices of cystoscopy (χ23 = 85.9; P = .001), prostate biopsy (χ23 = 64.6; P = .001), prostatectomy (χ23 = 24.4; P = .001), transurethral resection of the prostate (χ23 = 51.3; P = .001), and ureteroscopy with laser lithotripsy (χ23 = 63.0; P = .001) by insurance type. Conclusions and Relevance: These findings suggest that, more than 1 year after the implementation of the Price Transparency Final Rule, there are still large variations in the prices of urologic procedures among academic hospitals and by insurance class. Currently, in certain situations, health care costs could be reduced if patients paid out of pocket. The Centers for Medicare & Medicaid Services may improve price transparency by better enforcing penalties for noncompliance, increasing penalties, and ensuring that hospitals report prices in a way that is easy for patients to access and understand.

Discovery of a small molecule that selectively destabilizes Cryptochrome 1 and enhances life span in p53 knockout mice.

Cryptochromes are negative transcriptional regulators of the circadian clock in mammals. It is not clear how reducing the level of endogenous CRY1 in mammals will affect circadian rhythm and the relation of such a decrease with apoptosis. Here, we discovered a molecule (M47) that destabilizes Cryptochrome 1 (CRY1) both in vitro and in vivo. The M47 selectively enhanced the degradation rate of CRY1 by increasing its ubiquitination and resulted in increasing the circadian period length of U2OS Bmal1-dLuc cells. In addition, subcellular fractionation studies from mice liver indicated that M47 increased degradation of the CRY1 in the nucleus. Furthermore, M47-mediated CRY1 reduction enhanced oxaliplatin-induced apoptosis in Ras-transformed p53 null fibroblast cells. Systemic repetitive administration of M47 increased the median lifespan of p53-/- mice by ~25%. Collectively our data suggest that M47 is a promising molecule to treat forms of cancer depending on the p53 mutation.

Comparison of AUA and phoenix definitions of biochemical failure following permanent brachytherapy for prostate cancer.

PURPOSE: To compare biochemical recurrence free survival (BCRFS) and cancer-specific survival (CSS) after brachytherapy using the AUA and the Phoenix definitions. METHODS AND MATERIALS: 2634 men with T1-T4N0M0 prostate cancer were treated with brachytherapy with or without neoadjuvant hormonal therapy or external beam radiation therapy. Five, 10, and 15- year BCRFS and CSS were estimated with Kaplan-Meier estimates with log rank. Multivariate analysis of survival was performed with Cox regression analysis. RESULTS: Median age was 66, follow-up was 8.6 years, and prostate specific antigen was 6.9. Overall, 11.1% (n = 293) of patients experienced Phoenix BCR and 17.48% (n = 457) experienced AUA BCR. The rates of AUA BCR and Phoenix BCR were significantly different at 5 and 10-years but not at 15 years. Patients treated with BED ≤ 200 Gy were more likely to experience AUA BCR (22.5% vs. 12.4%, OR 1.44, p < 0.001) and Phoenix BCR (14.3% and 8.3%, OR 1.37, p < 0.001) than patients treated with a BED > 200 Gy. CONCLUSIONS: Compared to the Phoenix definition, the AUA definition of BCR after brachytherapy is associated with significantly worse BCRFS for the first 15 years after treatment. Receiving a BED > 200, which cannot be achieved without the addition of brachytherapy, is associated with better BCRFS and CSS. Our findings reaffirm the importance of dose in the management of prostate cancer.

Autoimmune encephalitis and paraneoplastic syndromes in Turkey: a multi-centre study.

BACKGROUND: Autoimmune encephalitis (AIE) and paraneoplastic syndromes (PNS) are both rare groups of neurological diseases that are difficult to diagnose. AIM: We aimed to determine the common and distinct aspects of these two aetiologies of encephalitis as well as the characteristics of our patient group. METHODS: We respectively analysed the records of the patients including symptoms, demographic features, neurological examination, cranial-magnetic-resonance-imaging (MRI), electroencephalography (EEG) findings, cerebrospinal fluid results (CSF) findings. Autoimmune/paraneoplastic autoantibodies in blood and/or CSF were all documented. RESULTS: Forty-six patients fulfilled the diagnostic criteria. Thirty-eight of them were diagnosed with AIE, and 8 of them were diagnosed with PNS. The PNS group had higher nonconvulsive status epilepticus than the AIE (2/8 vs 0/38; p=0.027). PNS patients were diagnosed with a malignancy in their follow-ups more than those in the AIE group [4/38 vs 8/8] (p<0.001). When the symptoms of antibody-positive and negative patients were compared in the AIE group, the rates of consciousness/memory problems (13/15 vs 11/23; p=0.020) and speech impairment (8/15 vs 2/23; p=0.004) were significantly higher in patients without antibodies (n: 15) than in antibody-positive patients (n: 23). In antibody-negative groups, the rates of memory problems in neurological examination (13/15 vs 12/23 p=0.028) and temporal findings on electroencephalography were more prominent than antibody-positive groups (1/23 vs 5/15; p=0.027). The number of patients with cerebellar signs was higher in antibody-positive patients (6/23 vs 0/15; p=0.038). CONCLUSION: Although the positivity of autoantibodies is critical in the diagnosis of AIE and PNS, even minor differences in clinical and laboratory findings of patients are helpful in the diagnosis, especially in the autoantibody-negative patients. Comparing the data with other population studies has shown that several inherited and environmental factors may contribute to the pathophysiology of AIE and PNS, as well as clinical and laboratory differences.

Large Variation in International Prescribing Rates of Opioids After Robotic Prostatectomy.

OBJECTIVE: To compare international opioid prescribing patterns for patients undergoing robotic assisted laparoscopic prostatectomy. To our knowledge, this is the first study to assess international opioid prescribing trends among urologists. METHODS: An anonymous Web-based survey assessing the frequency and quantity of opioid prescriptions for robotic assisted laparoscopic prostatectomy was designed using Qualtrics software. The survey was distributed to urologists internationally via Twitter and email in early 2021. Prescribing patterns were analyzed based on country of practice in three groups: United States, Canada, and all other countries. RESULTS: 160 participants from 26 countries completed the survey including the United States (51%), Greece (19%), Canada (9%), Israel (3.1%). The percentage of providers prescribing post-discharge opioids significantly differed between Canada, the United States, and other countries (86%, 63%, and 11%, respectively, P <.0001). There was a significant difference between years of experience in those who provide opioids compared to those who do not (8 years vs 5 years, P = .0004). The average morphine milligram equivalents (MME) provided in those who did prescribe opioids was greatest in the United States but was not significantly different between groups (mean MME: United States 58 mg, Canada 46 mg, all others 54 mg; P = .63). Attending physicians prescribed more MME than trainees (residents, fellows) on average (attending mean MME = 75 mg, trainee mean MME = 40 mg, P = .017). CONCLUSION: Opioid prescriptions after robotic assisted prostatectomy are common in North America and used sparingly in the rest of the world.

Robotic assisted radical cystectomy versus open radical cystectomy: a review of what we do and don't know.

Radical cystectomy (RC) is the gold standard treatment for muscle-invasive and high-risk, noninvasive bladder cancer. Since 2003, robot-assisted radical cystectomy (RARC) has been gaining popularity. Metanalyses show that the primary advantage of RARC is less blood loss and the primary advantage of open radical cystectomy (ORC) is shorter operative times. There do not appear to be significant differences in complications, cancer-related outcomes or survival between the two approaches. Cost analyses comparing RARC and ORC are complicated by the often-ill-defined distinction between the cost to the hospital versus the cost to payors. However, it is likely that for both hospitals and payors, RARC is cost effective at high-volume centers. It is feasible that in the future, increased experience with RARC will lead to improved outcomes and justify the use of RARC over ORC.

Implementation of a nonopioid protocol following robot-assisted radical cystectomy with intracorporeal urinary diversion.

PURPOSE: The implementation of robot-assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) for management of patients with muscle-invasive or high-risk noninvasive bladder cancer has increased in utilization over the last decade. Here, we seek to describe institutional opioid prescription and utilization patterns following implementation of a nonopioid (NOP) perioperative pain management protocol in patients who received RARC with ICUD. MATERIALS AND METHODS: The records of all patients who underwent RARC that utilized a NOP perioperative pain management protocol at a single academic institution from 2016 to 2020 were retrospectively reviewed. Descriptive statistical analyses were performed. For comparison, we included 74 consecutive patients who received the same NOP protocol with extracorporeal urinary diversion (ECUD). RESULTS: A total of 116 patients who received ICUD were included in our analysis. The median operation time for the ICUD group was 305 minutes (interquartile range [IQR]: 262-352). 12.1% (n = 14) of patients who underwent ICUD required narcotics during inpatient hospitalization. For these patients, the median morphine milligram equivalent requirement was 52.0 (IQR: 7.62-157). Additionally, only 12.1% (n = 14) of patients were prescribed opioids postoperatively at discharge. We identified that within 6 months of surgery only 5 (4.3%) patients required a second narcotic prescription. Furthermore, of patients who did not use mu-opioid blockers, a minority experienced postoperative ileus (15.7%, n = 16). 30- and 90-day all Clavien complication rates for patients were 44.8% (n = 52) and 49.1% (n = 57), respectively. Nineteen (16.4%) patients were readmitted within 30 days of discharge, of which none were pain related. When compared to ECUD, patients who received ICUD experienced similar complication and readmission rates. CONCLUSIONS: The implementation of a NOP protocol for patients undergoing RARC with ICUD allows for both decreased postoperative narcotic use and reduced need for narcotic prescriptions at discharge with acceptable complication and readmission rates.

Genetic Differences Between Bladder and Upper Urinary Tract Carcinoma: Implications for Therapy.

CONTEXT: Bladder urothelial carcinoma (BUC) and upper tract urothelial carcinoma (UTUC) have genetic differences, which may influence therapy. OBJECTIVE: The aim of the current review was to summarize the current genetic understanding of upper tract and BUC. EVIDENCE ACQUISITION: PubMed, Cochrane, and Web of Science online databases were searched systematically up to February 2020, using the following keywords: urothelial carcinomas, upper urinary tract, renal pelvis, ureter, bladder cancer, and genetics. EVIDENCE SYNTHESIS: UTUC and BUC share mutations in similar genes, such as FGFR3, TP53, and HRAS, and epigenetic genes, such as KDM6A and KMT2A-C, but at varying frequencies. Furthermore, subtyping of UTUC and BUC has identified similar expression subtypes, but UTUC is more often luminal with more T-cell depletion. Clonal studies indicate that BUC after UTUC is also likely luminal, while UTUC after BUC is often basal. CONCLUSIONS: UTUC and BUC share many genomic alterations, but at different frequencies, which recapitulate with their metachronous recurrences. These differences likely contribute to the behavior of these two cancers and imply that they and their metachronous recurrences should be treated as two related yet distinct entities. PATIENT SUMMARY: Urothelial carcinoma of the bladder has distinct genomic features, which are different from distinct genomic features of urothelial carcinoma of the renal pelvis and/or ureter. These features can be used for tailored treatment options specific to tumors of different locations.

Gender Differences in Incidence, Diagnosis, Treatments, and Outcomes in Clinically Localized Bladder and Renal Cancer.

OBJECTIVE: To review differences in bladder and renal cell cancer (RCC) incidence, diagnosis, treatment, and outcomes between men and women, and to summarize the evidence that explains these differences. METHODS: A review of the current literature was performed using PubMed and Google Scholar. RESULTS: The incidence of bladder cancer and RCC is higher in men. Historically higher smoking rates among men explain some but not all of the difference in incidence. Hormonal and genetic factors also contribute. In bladder cancer, the androgen receptor and estrogen receptor beta have been associated with gender and tumor characteristics. In RCC the relationships are less well defined. In both bladder cancer and RCC, differences in gene mutation patterns among men and women, particularly among genes located on the X-chromosome, have also been identified. Differences in the work-up and treatment of men and women with bladder cancer and RCC also contribute to gender disparities. CONCLUSION: Research to better delineate how the hormonal axis and genetics contribute to disparities in bladder cancer and RCC incidence and outcomes will allow for more individualized medicine. Appreciation of barriers to diagnosis and treatment will identify opportunities to improve patient care.

Can anesthetics affect bladder cancer recurrence? Total intravenous versus volatile anesthesia in patients undergoing robot-assisted radical cystectomy: A single institution retrospective analysis.

BACKGROUND: Radical cystectomy is standard of care and part of a multidisciplinary approach for long-term survival in patients with muscle-invasive bladder cancer (MIBC) or high-grade non-MIBC. Recent data have suggested that anesthetic technique can affect long-term survival and recurrence in patients undergoing cancer related surgery. METHODS: The records of all patients who underwent robot-assisted radical cystectomy for high-risk non-MIBC or MIBC at a single academic institution from 2014 to 2020 were retrospectively reviewed. Patients were grouped according to whether they received total intravenous (TIVA) or volatile inhalation anesthesia (VIA). Univariable and multivariable cox proportional hazards models were used to compare hazard ratios for distant recurrence. Kaplan-Meier recurrence-free survival curves were constructed from the date of surgery to recurrence. RESULTS: A total of 231 patients were included, of which 126 (55%) received TIVA and 105 (45%) received VIA. Distant recurrence occurred in 8.7% and 26.7% of patients who received TIVA and VIA, respectively (P < 0.001). Kaplan-Meier analysis demonstrated significant improvement in distant recurrence-free survival with TIVA (log-rank P < 0.001). Multivariable analysis revealed a significant increase in recurrence risk with VIA (HR: 3.4, 95%CI: 1.5-7.7, P < 0.01) and increasing tumor pathological stage (pT2, pT3, pT4, all P < 0.05). CONCLUSIONS: The use of volatile inhalation anesthetics during robot-assisted radical cystectomy may be associated with an increased risk of distant recurrence. Further studies will be necessary to validate these findings.

The effect of tumor location on overall survival for pT2-4 bladder and upper tract urothelial carcinoma following radical surgery.

INTRODUCTION: Historically, staging and treatment for upper tract urothelial carcinoma were extrapolated from bladder urothelial carcinoma literature. However, embryological, genetic, and anatomical differences exist between them. We sought to explore the relationship between location of urothelial cancer and overall survival (OS). METHODS: Data was culled from the National Cancer Database from 2004-2015. Patients with pT2-pT4 treated with definitive surgery were included; those with metastatic disease or who received neoadjuvant or adjuvant treatment were excluded. Patients were stratified by tumor location and pathological stage. The primary outcome was OS. Secondary outcomes were predictors of mortality in each pT stage stratum. RESULTS: A total of 11 330 patients with bladder, 954 patients with ureteral, and 1943 patients with renal pelvis urothelial carcinoma were analyzed. Mean followup was 43.3, 39.4, and 41.4 months for bladder, ureteral, and renal pelvis, respectively. On univariable analysis, ureteral pT2 was associated with worse OS compared to both bladder (61.3 vs. 80.4 months, p=0.007) and renal pelvis (61.3 vs. 80.5 months, p=0.014). Renal pelvis pT3 was associated with improved OS compared to both bladder (42.5 vs. 28.6 months, p=0.003) and ureteral (42.5 vs. 25.7 months, p<0.001). Renal pelvis pT4 had decreased survival compared to bladder (11.4 vs. 17.7 months, p<0.001). On multivariable Cox regression, only renal pelvis pT3 was associated with a 20% decreased risk of mortality compared to bladder pT3 (hazard ratio 0.80, 95% confidence interval 0.72-0.88, p<0.001). CONCLUSIONS: Renal pelvis pT3 is associated with lower mortality. Mutational and embryological differences may play a role in this disparity.

Harnessing Natural Killer Cell Function for Genitourinary Cancers.

Natural killer (NK) cells are potently cytolytic innate lymphocytes involved in the immune surveillance of tumors and virally infected cells. Although much progress has been made in manipulating the ability of T cells to recognize and eliminate tumors, a comprehensive understanding of NK-cell infiltration into solid tumors, and their amenability to immunomodulation, remains incomplete. This article discusses recent studies showing that urologic tumors are infiltrated by NK cells and that these NK cells are often dysfunctional, but that strategies interfering with inhibitory axes have significant potential to alleviate this dysfunction.

Robotic-Assisted Partial Nephrectomy and Adrenalectomy: Case of a Pheochromocytoma Invading into Renal Parenchyma.

Although upper pole renal masses and adrenal masses can usually be distinguished on cross-sectional imaging, large masses can obscure the boundaries between the kidney and adrenal gland. We describe a unique case of an adrenal pheochromocytoma in a 42-year-old female who was referred for robotic partial nephrectomy. During the procedure, the patient developed severe hypertension. The case was aborted, and the workup revealed pheochromocytoma. After appropriate pretreatment, the patient underwent a successful robotic adrenalectomy and partial nephrectomy. Therefore, we recommend screening patients with hypertension and large upper pole masses for pheochromocytoma to better direct preoperative management.

Robotic partial nephrectomy: The current status.

INTRODUCTION: Since its introduction, robotic partial nephrectomy (RPN) has become increasingly popular, in part as a result of several advances in technique. The purpose of this paper is to review these techniques as well as the perioperative, functional, and oncologic outcomes after RPN and compare these outcomes to those after laparoscopic partial nephrectomy (LPN) and open partial nephrectomy (OPN). METHODS: A literature review was performed to identify papers and meta-analyses that compared outcomes after RPN to OPN or LPN. All meta-analyses were included in this review. RESULTS: Technical advances that have contributed to improved outcomes after RPN include the first-assistant sparing technique, the sliding clip technique, early unclamping, and selective arterial clamping. All five meta-analyses that compared LPN to RPN found that RPN was associated with a shorter warm ischemia time (WIT), but that there were no differences in estimated blood loss (EBL) or operative times. Those meta-analyses that compared intraoperative and postoperative complications, conversion to open or radical nephrectomy, length of stay (LOS), and postoperative estimated glomerular filtration rate (eGFR) either found no difference or favored RPN. Four meta-analyses compared RPN to OPN. All four found that EBL, LOS, and postoperative complications favor RPN. There were no significant differences in intraoperative complications, conversion to radical nephrectomy, or positive surgical margin rates. One meta-analysis found that eGFR was better after RPN. Operative time and WIT generally favored OPN. CONCLUSIONS: Several techniques have been described to improve outcomes after RPN. We believe that the literature shows that RPN is as good if not better than both LPN and OPN and has become the preferred surgical approach.

Development of a model to predict prostate cancer at the apex (PCAP model) in patients undergoing robot-assisted radical prostatectomy.

PURPOSE: To develop a model based on preoperative variables to predict apical prostate cancer. METHODS: We performed a retrospective analysis of 459 patients who underwent a robotic assisted radical prostatectomy (RALP) between January 2016 and September 2017. All patients had a preoperative biopsy and mpMRI of the prostate. Significant apical pathology (SAP) was defined as those patients who had a dominant nodule at the apex with a Gleason score > 6 and/or ECE at the apex. Binary logistic regression analyses were adopted to predict SAP. Variables included in the model were PSA, apical lesions prostate imaging reporting and data system (PI-RADS) score and apical biopsy Gleason score. The area under the curve (AUC) of the model was computed. RESULTS: A total of 121 (43.2%) patients had SAP. On univariable analysis, all apex-specific variables investigated emerged as predictors of SAP (all p < 0.05). On multivariable analysis PSA and apical PI-RADS score > 3 (all p < 0.05) emerged as significant predictors of SAP. The AUC of the model was 0.722. CONCLUSION: Patients with PI-RADS 3, 4 or 5 lesions at the apex were three times as more likely to have true SAP compared to those who have PI-RADS < 3 or negative mpMRI prior to undergoing RALP.