Preoperative Plasma Insulin-Like Growth Factor-I and Its Binding Proteins-Based Risk Stratification of Patients Treated With Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma.

INTRODUCTION: We evaluate the predictive and prognostic value of insulin-like growth factor-I (IGF-1), IGF binding protein-2 (IGFBP-2) and -3 (IGFBP-3) in patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). METHODS: This is a retrospective analysis of a multi-institutional database comprising 753 patients who underwent RNU for UTUC and had a preoperative plasma available. Logistic and Cox regression analyses were performed. The discriminative ability and clinical utility of the models was calculated using the lasso regression test, area under receiver operating characteristics curves, C-index, and decision curve analysis (DCA). RESULTS: Lower preoperative plasma levels of IGFBP-2 and -3 independently correlated with increased risks of lymph node metastasis, pT3/4 disease, nonorgan confined disease, and worse recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) (all P ≤ .004). The addition of both IGFBP-2 and -3 to a postoperative multivariable model, that included standard clinicopathologic characteristics, improved the model's concordance index by 10%, 9%, and 8% for RFS, CSS, and OS, respectively. On DCA, addition of both IGFBP-2 and -3 to base models improved their performance for RFS, CSS, and OS by a statistically and clinically significant margin. Plasma IGF-1 was not associated with any of outcomes. CONCLUSIONS: We confirmed that a lower plasma levels of IGFBP-2 and -3 both are independent and clinically significant predictors of adverse pathological features and survival outcomes in UTUC patients treated with RNU. These findings might help guide the clinical decision-making regarding perioperative systemic therapy and follow-up scheduling.

Robotic distal ureterectomy for high-risk distal ureteral urothelial carcinoma: a retrospective multicenter comparative analysis (ROBUUST 2.0 collaborative group).

BACKGROUND: The role of kidney-sparing surgery in patients with high-risk upper urinary tract urothelial carcinoma is controversial. The present study aimed to assess oncological and functional outcomes of robot-assisted distal ureterectomy in patients with high-risk distal ureteral tumors. METHODS: The ROBUUST 2.0 multicenter international (2015-2022) dataset was used for this retrospective cohort analysis. High-risk patients with distal ureteral tumors were divided based on type of surgery: robot-assisted distal ureterectomy or robot-assisted nephroureterectomy. A survival analysis was performed for local recurrence-free survival, distant metastasis-free survival, and overall survival. After adjusting for clinical features of the high-risk prognostic group, Cox proportional hazard model was plotted to evaluate significant predictors of time-to-event outcomes. RESULTS: Overall, 477 patients were retrieved, of which 58 received robot-assisted distal ureterectomy and 419 robot-assisted nephroureterectomy, respectively, with a mean (±SD) follow-up of 29.6 months (±2.6). The two groups were comparable in terms of baseline features. At survival analysis, no significant difference was observed in terms of recurrence-free survival (P=0.6), metastasis-free survival (P=0.5) and overall survival (P=0.7) between robot-assisted distal ureterectomy and robot-assisted nephroureterectomy. At Cox regression analysis, type of surgery was never a significant predictor of worse oncological outcomes. At last follow-up patients undergoing robot-assisted distal ureterectomy had significantly better postoperative renal function. CONCLUSIONS: Comparable outcomes in terms of recurrence-free survival, metastasis-free survival, and overall survival between robot-assisted distal ureterectomy and robot-assisted nephroureterectomy patients, and better postoperative renal function preservation in the former group were observed. Kidney-sparing surgery should be considered as a potential option for selected patients with high-risk distal ureteral UTUC.

Decisional and prognostic impact of diagnostic ureteroscopy in high-risk upper tract urothelial carcinoma: A multi-institutional collaborative analysis (ROBUUST collaborative group).

BACKGROUND: Diagnostic ureteroscopy (URS) with or without biopsy remains a subject of contention in the management of upper tract urothelial carcinoma (UTUC), with varying recommendations across different guidelines. The study aims to analyse the decision-making and prognostic role of diagnostic ureteroscopy (URS) in high-risk UTUC patients undergoing curative surgery. MATERIALS AND METHODS: In this retrospective multi-institutional analysis of high-risk UTUC patients from the ROBUUST dataset, a comparison between patients who received or not preoperative URS and biopsy before curative surgery was carried out. Logistic regression analysis evaluated differences between patients receiving URS and its impact on treatment strategy. Survival analysis included 5-year recurrence-free survival (RFS), metastasis-free survival (MFS), cancer-specific survival (CSS) and overall survival (OS). After adjusting for high-risk prognostic group features, Cox proportional hazard model estimated significant predictors of time-to-event outcomes. RESULTS: Overall, 1,912 patients were included, 1,035 with preoperative URS and biopsy and 877 without. Median follow-up: 24 months. Robot-assisted radical nephroureterectomy was the most common procedure (55.1%), in both subgroups. The 5-year OS (P = 0.04) and CSS (P < 0.001) were significantly higher for patients undergoing URS. The 5-year RFS (P = 0.6), and MFS (P = 0.3) were comparable between the 2 groups. Preoperative URS and biopsy were neither a significant predictor of worse oncological outcomes nor of a specific treatment modality. CONCLUSIONS: The advantage in terms of OS and CSS in patients undergoing preoperative URS could derive from a better selection of candidates for curative treatment. The treatment strategy is likely more influenced by tumor features than by URS findings.

Transurethral Incisions for Bladder Neck Contracture: Comparable Results without Intralesional Injections.

To present our 12-year experience using an endoscopic approach to manage bladder neck contracture (BNC) without adjunctive intralesional agents and compare it to published series not incorporating them, we retrospectively reviewed 123 patients treated for BNC from 2008 to 2020. All underwent 24 Fr balloon dilation followed by transurethral incision of BNC (TUIBNC) with deep incisions at 3 and 9 o'clock using a Collins knife without the use of intralesional injections. Success was defined as a patent bladder neck and 16 Fr cystoscope passage into the bladder two months later. Most with recurrent BNC underwent repeat TUIBNC. Success rates, demographics, and BNC characteristics were analyzed. The etiology of BNC in our cohort was most commonly radical prostatectomy with or without radiation (36/123, 29.3%, 40/123, 32.5%). Some had BNC treatment prior to referral (30/123, 24.4%). At 12-month follow-up, bladder neck patency was observed in 101/123 (82.1%) after one TUIBNC. An additional 15 patients (116/123, 94.3%) had success after two TUIBNCs. On univariate and multivariate analyses, ≥2 endoscopic treatments was the only factor associated with failure. TUIBNC via balloon dilation and deep bilateral incisions without the use of adjunctive intralesional injections has a high patency rate. History of two or more prior endoscopic procedures is associated with failure.

Pathologic fracture in metastatic kidney cancer: Identifying widening disparities and opportunity for quality improvement.

BACKGROUND: Management and palliation of pathologic fracture (PFx) secondary to metastatic prostate (mCaP) and renal cancer (mRCa) is hospital resource intensive. Using a national all-payer database, we assessed the burden of PFx secondary to mCaP and mRCa nationwide. Admission rates, mortality, surgical fixation rates, and risk factors for high-cost admissions for pathologic fractures were assessed METHODS: National Inpatient Sample was queried from 2013 to 2015 for mCaP and mRCa admissions. Hospitalization costs of PFx was assessed over time by cancer type. Hospitalization outcomes were stratified by cancer type. Multivariable logistic regression models were constructed to examine predictors of high-cost admission for PFx (>75th percentile). RESULTS: From 2013 to 2015, there were 21,466 and 6,334 admissions for mCaP and mRCa with bone metastasis, respectively. Proportion of admissions for PFx was greater in mRCa than mCaP (15.9% vs. 7.2%, P < 0.01). PFx secondary to mRCa was associated with longer length of stay, hospitalization cost, and greater rate of surgical fixation. Costs of admission for PFx increased by $4,005 dollars from 2013 to 2015 for mRCa (P = 0.03), but did not increase for mCaP (P = 0.5). On multivariable analysis, mRCa was associated with greater odds of PFx (OR:2.12, P < 0.01), and high-cost hospitalization for mRCa associated PFx (OR:1.37, P = 0.02). CONCLUSIONS: PFx secondary to mRCa represents a significant health care burden. mRCa was associated with greater odds of PFx compared to mCaP, as well as greater inpatient morbidity and cost. Formalized guidelines on screening and management of bone lesions in mRCa may be needed to mitigate this under-recognized health care burden.

Safety and Feasibility of Telehealth Only Preoperative Evaluation Before Minimally Invasive Robotic Urologic Surgery.

Purpose: Telehealth utilization has increased dramatically over the past few years due to improvement in technology and the COVID-19 pandemic. To date, no study has examined whether a telehealth visit alone for preoperative evaluation is safe and sufficient before surgery. We examined the safety and feasibility of preoperative telehealth visits alone before minimally invasive urologic surgery. Materials and Methods: Single institution retrospective review of robotic prostate, kidney, and cystectomy procedures between April and December 2020. Cases were dichotomized into those who underwent preoperative evaluation by telehealth only vs traditional in-person visits. Outcomes included complications, blood loss, conversion to open surgery rates, and operative times. We assessed efficiency of care by measuring time from preoperative visit to surgery. Results: Three hundred fourteen patients were included in the study, with 14% of cases (n = 45) being performed after a preoperative telehealth visit. The majority of cases included in analysis were robotic surgeries of the prostate (56.1% of all cases, n = 176) and the kidney (35.0% of all cases, n = 110). Patients seen via telehealth alone preoperatively had no significant differences in any grade of complications, perioperative outcomes, blood loss, operative time, and length of stay. There was no difference in change in anticipated procedure between the groups, and there was no case of conversion to open surgery in the telehealth only group. Time from preoperative visit to surgery was significantly shorter for the telehealth group by 13 days. Conclusions: Our study is the first to analyze the safety of telehealth only preoperative visits before minimally invasive urologic surgery. We found no difference in perioperative outcomes including conversion to open surgery or change in planned procedure. Furthermore, telehealth preoperative visits appeared to facilitate shorter time to surgery. This study has important implications for expediting patient care and medicolegal considerations.

Progress in the development of tissue-based biomarkers for urothelial cancer.

INTRODUCTION: As the understanding of molecular mechanisms of bladder cancer advances, molecularly-guided precision medicine becomes increasingly relevant. Biomarkers play a critical role in this setting, predicting treatment response and identifying candidates for targeted therapies. AREAS COVERED: Current literature on biomarkers in their role in disease prognosis and response to neoadjuvant and adjuvant therapies. In non-muscle invasive bladder cancer, particular focus is on markers of disease progression, and response to intravesical therapy. In muscle invasive and advanced bladder cancer, particular emphasis is on markers associated with neoadjuvant chemotherapy, as well as systemic immunotherapy. We discuss current shortcomings and pitfalls in contemporary markers, and future avenues of prospective research. EXPERT OPINION: The focus on biomarkers has moved from immunohistochemical analysis and tumor-related phenotypic changes to examining genetic alterations. Single marker analysis has been shown to be insufficient in predicting both disease course and response to therapy, and studies have shifted toward examining marker combinations and genetic classifiers. Ultimately, significant progress in implementing biomarkers into clinical guidelines remains elusive, largely due to lack of prospective studies in well-defined patient cohorts and with clinically meaningful endpoints. Until then, despite their promising value, tissue markers should be limited to experimental settings and clinical trials.

Periurethral Abscess Following Urethral Reconstruction: Clinical Features and Prognosis.

OBJECTIVE: To evaluate the clinical and prognostic details of periurethral abscess (PUA) formation following urethroplasty (UP). METHODS: A retrospective review was performed to identify men who developed PUA after UP between 2007 and 2019 at a single tertiary care referral center. Patient demographics, stricture characteristics, and UP technique were recorded. Outcomes included time to PUA, presenting symptoms, wound cultures, imaging, and ultimate management. Comparative analysis between PUA and non-PUA patients was performed using Fisher's Exact test and Student's t-test. RESULTS: Among 1499 UP cases, 9 (0.6%) developed PUA. Mean stricture length was 4.6 cm with most located in the bulbar urethra (5/9, 56%), while 4/9 (44%) had undergone prior UP. PUA rates were 7/288 (2.4%) and 2/815 (0.3%) for substitution and anastomotic UP respectively. Voiding cystourethrogram (VCUG) demonstrated extravasation in 67% (4/6) of available UP cases imaged. Subsequent VCUG confirmed leak improvement or resolution in all cases. Wound cultures were frequently polymicrobial (4/6, 67%). Management included antibiotics with (6/9) and without (3/9) incision and drainage (I/D). Urinary drainage was performed in 5 patients using suprapubic tube (3/5) and foley placement (2/5). PUA resolution was observed in all patients while stricture symptom recurrence was observed in 2/9 (22%) patients with mean time to recurrence of 15 months. Overall mean follow-up time was 22 months. CONCLUSION: PUA is a rare complication of UP that may be more common in setting of postoperative urine leak. PUA is safely managed with I/D, urethral rest, and antibiotics, with low risk of recurrent stricture formation thereafter.

Restoration of Continence after Prostatectomy is Associated With Weight Loss: A Pilot Study.

OBJECTIVES: To examine association between post-prostatectomy incontinence (PPI) severity and weight changes before and after restoration of continence via artificial urinary sphincter (AUS). METHODS: Single surgeon, retrospective review of urologic prosthetic surgery (UPS) after radical prostatectomy (RP). A cohort of post-RP inflatable penile prosthesis (IPP) patients served as a surgical control. Body Mass Index (BMI) and total body weight were assessed pre and post-UPS. Multivariable linear regression was utilized to assess BMI changes post-UPS. RESULTS: 187 AUS and 63 IPP patients met selection criteria. Greater PPI severity was associated with faster BMI gain after RP (coeff. 0.14 kg/m2, P = 0.03, per pad used) and magnitude of incontinence improvement (mean reduction in daily pad use) after AUS insertion was associated with greater BMI reduction at 12 months post-UPS (coeff. - 0.13 kg/m2, P = 0.04). On multivariable regression, AUS insertion was associated with a decrease in BMI by - 2.83 kg/m2 12 months post-UPS (P = 0.02). Twelve months post-UPS, men with AUS exhibited a mean BMI reduction of -1.0 kg/m2 compared to a mean BMI increase in the IPP cohort of 0.4 kg/m2 (P < 0.01). Compared to IPP, AUS patients experienced absolute body weight reduction by 6 kg [Median(IQR): 90.4 (80.3-100.1) vs 96.4 (87.1-108.8) kg, P = 0.03], with nearly one-third having clinically significant weight loss (>5% body weight) at 12 months post-UPS (31.8% vs 8.3%, P < 0.01). CONCLUSION: Severe PPI appears to be associated with weight gain and correction of PPI via AUS insertion with weight loss.

Male stress urinary incontinence is often underreported.

INTRODUCTION Patient-reported pads per day use is a widely used metric in grading the severity of stress urinary incontinence and guiding surgical decision-making, particularly in mild-to-moderate cases. We sought to compare patient-reported stress urinary incontinence severity by pads per day with objective findings on standing cough test. We hypothesize that patient-reported pads per day often underestimates stress urinary incontinence severity. MATERIALS AND METHODS: We retrospectively reviewed our male stress urinary incontinence surgical database and identified 299 patients with self-reported mild-to-moderate stress urinary incontinence who were evaluated with standing cough test prior to surgical intervention between 2007 and 2019. Patients were evaluated with the Male Stress Incontinence Grading Scale for urinary leakage during a standing cough test. This test has been shown to reliably and accurately predict surgical success. Binary logistic regression analysis was used to identify parameters associated with stress urinary incontinence upgrading in a multivariable model. RESULTS: Among 299 patients with reported mild-to-moderate stress urinary incontinence, 101 (34%) were upgraded to severe stress urinary incontinence by standing cough test. Prior stress urinary incontinence surgery (OR 4.1, 95% CI 2.0-8.0, p < 0.0001) and radiation (OR 3.2, 95% CI 1.7-5.7, p < 0.0001) were significantly associated with Male Stress Incontinence Grading Scale upgrading in multivariable analysis. CONCLUSIONS: Roughly one-third of men who report mild-to-moderate stress urinary incontinence actually have severe incontinence observed on physical examination. All men being evaluated for stress urinary incontinence should undergo standing cough test to accurately grade incontinence severity and guide surgical management.

Perioperative outcomes and cost of robotic vs open simple prostatectomy in the modern robotic era: results from the National Inpatient Sample.

OBJECTIVES: To perform a comparative analysis of perioperative outcomes and hospitalisation cost between open (OSP) and robot-assisted simple prostatectomy (RASP) for treatment of benign prostatic hyperplasia (BPH) using the National Inpatient Sample (NIS) in the contemporary robotic era. MATERIALS AND METHODS: The NIS was queried for cases of OSP and RASP for the treatment of BPH between 2013 and 2016. Perioperative complications, unadjusted hospital cost and length of stay (LOS) were compared between RASP and OSP. Smoothed linear regression curves comparing hospitalisation cost by increasing LOS was stratified by surgical approach to identify point of cost equivalency between RASP and OSP. Multivariable linear regression analysis was used to construct a hospitalisation cost model to examine the contribution of the robotic approach and LOS to hospitalisation cost. RESULTS: The total analytical cohort included 2551 OSP and 704 RASP procedures. Patients undergoing RASP were younger, at a median (interquartile range [IQR]) age of 68 (63-73) vs 71 (65-77) years, and with less comorbidity (76.8% vs 86.5%, P < 0.01). RASP was associated with fewer total complications (11.1% vs 29.2%, P < 0.01) and a greater likelihood of routine discharge to home rather than another facility (88.9% vs 76.7%, P < 0.01). While LOS was shorter with RASP (median [IQR], 2 [1-3] vs 4 [3-6] days, P < 0.01), total unadjusted hospitalisation cost (in United States dollars) was greater (median [IQR], $10 855 [$7965-$15 675] vs $13 467 [$10 572-$17 722], P < 0.01). Presence of any complication increased both LOS and hospitalisation cost (P < 0.01). Linear regression modelling determined the point of cost equivalence between RASP staying a median of 2 days was an OSP case staying between 5 and 6 days. On multivariable regression analysis, the robotic approach contributed an additional $6175 (P < 0.01) to the cost model, whereas each additional day of hospitalisation contributed $1687 (P < 0.01), suggesting LOS would need to be 3-4 days shorter with RASP to offset surgical costs of the robot. CONCLUSIONS: While RASP appears to have significantly better perioperative complication rates with shorter LOS and likely discharge to home, total hospitalisation cost remained greater, likely related to upfront operative costs. While this retrospective study is limited by selection bias for patients undergoing RASP, the benefits of improved convalescence, discharge to home, and lower rate of perioperative complications appear to justify performance of RASP in an experienced pelvic robotic centre despite relatively greater hospitalisation cost if referral to an experienced holmium laser enucleation of the prostate centre is not feasible.

Population-based analysis of cost and peri-operative outcomes between open and robotic primary retroperitoneal lymph node dissection for germ cell tumors.

PURPOSE: To compare perioperative outcomes and perform the first cost analysis between open retroperitoneal lymph node dissection (O-RPLND) and Robotic-RPLND (R-RPLND) using a national all-payer inpatient care database. METHODS: Nationwide Inpatient Sample (NIS) was queried between 2013-2016 for primary RPLND and germ cell tumor. We compared cost, length of stay (LOS), and complications between O-RPLND and R-RPLND. Linear regression plots identified point of cost equivalence between R-RPLND and O-RPLND. A multivariable linear regression model was generated to analyze predictors of cost. RESULTS: 44 cases of R-RPLND and 319 cases of O-RPLND were identified. R-RPLND was associated with lower rate of complications (0% vs. 16.6%, p < 0.01) and shorter LOS [Median (IQR): 1.5 (1-3) days vs. 4 (3-6) days, p < 0.01]. Rates of ileus, genitourinary complications, and transfusions were lower with R-RPLND, but did not reach significance. On multivariable analysis, robotic approach independently contributed $4457, while each day of hospitalization contributed to an additional $2,431 to the overall model of cost. Linear regression plots determined point of cost equivalence between an R-RPLND staying a mean of 2 days was 4-5 days for O-RPLND, supporting the multivariable analysis. Total hospitalization cost was equivalent between R-RPLND and O-RPLND [Median (IQR): $15,681($12,735-$21,596) vs $16,718($11,799-$24,403), p = 0.48]-suggesting that the cost equivalency of R-RPLND is, at least in part, attributable to shorter LOS. CONCLUSION: While O-RPLND remains the gold standard and this study is limited by selection bias of a robotic approach to RPLND, our findings suggest primary R-RPLND may represent a cost-equivalent option with decreased hospital LOS in select cases.

Explantation of High Submuscular Reservoirs: Safety and Practical Considerations.

BACKGROUND: Over the past decade, high submuscular (HSM) placement of inflatable penile prosthesis (IPP) reservoirs has emerged as a viable alternative to space of Retzius (SOR) placement; however, data comparing the feasibility and complications of HSM vs SOR reservoir removal do not presently exist. AIM: To present a comparison of the safety, feasibility, and ease of removal of HSM vs SOR reservoirs in a tertiary care, university-based, high-volume prosthetic urology practice. METHODS: Data were retrospectively collected on patients who underwent IPP reservoir removal between January 2011 and June 2020. Cases were separated into 2 cohorts based on reservoir location. Statistical analysis was performed using Fisher's exact and Chi-squared tests for categorical variables and Student's t-test for continuous variables. Timing from IPP insertion to explant was compared between the HSM and SOR groups using the Mann-Whitney U test. OUTCOMES: Time from IPP insertion to explant, operative time, intraoperative and postoperative complications, and need for a counter incision were compared between the HSM and SOR groups. RESULTS: Between January 2011 and June 2020, 106 (73 HSM, 33 SOR) patients underwent IPP removal or replacement by a single surgeon at our institution. Average time from IPP insertion to removal was 43.6 months (24.2 HSM, 52.7 SOR, P = .07)-reservoir removal occurred at the time of device explant in 70 of 106 (66%) cases. More HSM reservoirs were explanted at the time of IPP removal compared with the SOR cohort (54 of 73, 74% HSM vs 16 of 33, 48.5% SOR, P = .01). Similar rates of complications were noted between the HSM and SOR groups (1.9% vs 6.3%, P = .35). There was no significant difference in need for counter incision between the 2 groups (24 [42%] HSM vs 4 [25%] SOR, P = .16) or in average operative times (76.5 ± 38.3 minutes HSM vs 68.1 ± 34.3 minutes SOR, P = .52). CLINICAL IMPLICATIONS: Our experience with explanting HSM reservoirs supports the safety and ease of their removal. STRENGTHS AND LIMITATIONS: Although the absolute cohort size is relatively low, this study reflects one of the largest single-institution experiences examining penile implant reservoir removal. In addition, reservoir location was not randomized but was instead determined by which patients presented with complications necessitating reservoir removal during the study period. CONCLUSIONS: HSM reservoir removal has comparable perioperative complication rates and operative times when compared with SOR reservoir removal. Kavoussi M, Bhanvadia RR, VanDyke ME, et al. Explantation of High Submuscular Reservoirs: Safety and Practical Considerations. J Sex Med 2020;17:2488-2494.

MEIS-mediated suppression of human prostate cancer growth and metastasis through HOXB13-dependent regulation of proteoglycans.

The molecular roles of HOX transcriptional activity in human prostate epithelial cells remain unclear, impeding the implementation of new treatment strategies for cancer prevention and therapy. MEIS proteins are transcription factors that bind and direct HOX protein activity. MEIS proteins are putative tumor suppressors that are frequently silenced in aggressive forms of prostate cancer. Here we show that MEIS1 expression is sufficient to decrease proliferation and metastasis of prostate cancer cells in vitro and in vivo murine xenograft models. HOXB13 deletion demonstrates that the tumor-suppressive activity of MEIS1 is dependent on HOXB13. Integration of ChIP-seq and RNA-seq data revealed direct and HOXB13-dependent regulation of proteoglycans including decorin (DCN) as a mechanism of MEIS1-driven tumor suppression. These results define and underscore the importance of MEIS1-HOXB13 transcriptional regulation in suppressing prostate cancer progression and provide a mechanistic framework for the investigation of HOXB13 mutants and oncogenic cofactors when MEIS1/2 are silenced.

Decisions regarding the treatment of patients with early-stage prostate cancer are often based on the risk that the cancer could grow and spread quickly. However, it is not always straightforward to predict how the cancer will behave. Studies from 2017 and 2018 found that samples of less aggressive prostate cancer have higher levels of a group of proteins called MEIS proteins. MEIS proteins help control the production of numerous other proteins, which could affect the behavior of prostate cancer cells in many ways. VanOpstall et al. ­ including some of the researchers that performed the 2017 and 2018 studies ­ have investigated how MEIS proteins affect prostate cancer. When prostate cancer cells are implanted into mice, they result in tumors. VanOpstall et al. found that tumors that produced MEIS proteins grew more slowly. Next, MEIS proteins were extracted from the prostate cancer cells and were found to interact with another protein called HOXB13, which regulates the activity of numerous genes. When the cells were genetically modified to prevent HOXB13 being produced, the protective effect of MEIS proteins was lost. MEIS proteins work with HOXB13 to regulate the production of several other proteins, in particular a protein called Decorin that can suppress tumors. When MEIS proteins and HOXB13 are present, the cell produces more Decorin and the tumors grow more slowly and are less likely to spread. VanOpstall et al. found that blocking Decorin production rendered MEIS proteins less able to slow the spread of prostate cancer. These results suggest that MEIS proteins and HOXB13 are needed to stop tumors from growing and spreading, and some of this ability is by prompting production of Decorin. This study explains how MEIS proteins can reduce prostate cancer growth, providing greater confidence in using them to determine whether aggressive treatment is needed. A greater understanding of this pathway for tumor suppression could also provide an opportunity for developing anti-cancer drugs.

Lymph node count impacts survival following post-chemotherapy retroperitoneal lymphadenectomy for non-seminomatous testicular cancer: a population-based analysis.

OBJECTIVE: To evaluate the prognostic significance of lymph node count (LNC) at post-chemotherapy retroperitoneal lymphadenectomy (PC-RPLND) in metastatic non-seminomatous germ cell tumour (NSGCT) using the Surveillance, Epidemiology, and End Results (SEER) database and National Cancer Database (NCDB). PATIENTS AND METHODS: SEER (2000-2013, n = 572) and NCDB (2004-2013, n = 731) identified patients undergoing PC-RPLND for Stage II and III NSGCT. Correlation between linear or categorial variables and LNC was conducted using Spearman's rank correlation or Kruskal-Wallis test by ranks. Patients were stratified by ≤20, 21-40, and >40 LNs for Kaplan-Meier analysis. Cox proportional hazards models evaluated the association of LNC at PC-RPLND with overall mortality (OM) in the NCDB and cancer-specific mortality (CSM) in the SEER database. The relationship between LNC and OM or CSM was also modelled as a non-linear function to determine a threshold for survival benefit. RESULTS: Amongst all patients, the median (interquartile range) LNC was 17 (3-26) LNs in the NCDB, and 18 (6-31) LNs in the SEER database. More recent diagnosis year, higher hospital volume, higher median income, private insurance status, and positive LNC were associated with greater total LNC in one or both databases (P < 0.05). On Kaplan-Meier analysis, >40 LNs was associated with 5-year cancer-specific survival (CSS) of 99% and overall survival (OS) of 96%, whereas ≤20 LNs had a 5-year CSS of 91% and OS of 78% (CSS, P = 0.04; OS, P < 0.01). Risk-adjusted Cox model showed increasing LNC (per node) was inversely associated with OM (hazard ratio [HR] 0.96, 95% confidence interval [CI], 0.94-0.98; P < 0.01) and CSM (HR 0.96, 95% CI, 0.94-0.99; P = 0.01). Non-linear modelling showed the greatest benefit in OM at between 10 and 20 LNs, but continued survival benefit for OM and CSM beyond 20 LNs. CONCLUSIONS: Greater LNC during PC-RPLND appears to be associated with improved CSS and OS in NSGCT. Our data support the role of thorough RPLND for post-chemotherapy metastatic NSGCT.