Hip and knee replacement in lower limb amputees: a scoping review.

BACKGROUND: There are many consequences of lower limb amputation, including altered biomechanics of gait. It has previously been shown that these can lead to increased rates of osteoarthritis (OA). A common and successful treatment for severe OA is joint replacement. However, it is unclear whether amputees undergoing this surgery can expect the same outcomes or complication profile compared with non-amputees. Furthermore, there are key technical challenges associated with hip or knee replacement in lower limb amputees. This scoping review aimed to identify and summarise the existing evidence base. METHODS: This was a systematic scoping review performed according to PRISMA guidelines. An electronic database search of MEDLINE (PubMed), Cochrane Library, EMBASE and CINAHL was completed from the date of inception to 1st April 2023. All peer reviewed literature related to hip or knee replacement among lower limb amputees was included. RESULTS: Of the 931 records identified, 40 studies were included in this study. The available literature consisted primarily of case reports and case series, with generally low level of evidence. In total, there were 265 patients of which 195 received total hip replacement (THR), 51 received total knee replacement (TKR) and 21 received hip hemiarthroplasty. The most common reason for amputation was trauma (34.2%), and the main indication for joint replacement was OA (77.1%), occurring more frequently in the contralateral limb (66.7%). The outcomes reported varied widely between studies, with most suggesting good functional status post-operatively. A variety of technical tips were reported, primarily concerned with intra-operative control of the residual limb. CONCLUSION: There is a need for more observational studies to clearly define the association between amputation and subsequent need for joint replacement. Furthermore, comparative studies are needed to identify whether amputees can be expected to achieve similar functional outcomes after surgery, and if they are at higher risk of certain complications.

Predicting 30-day mortality after hip fracture: the G4A calibrated prognostic tool.

INTRODUCTION: Proximal femoral fracture is common with a high mortality (7% mortality at 30 days). Accurate determination of mortality risk allows better consenting, clinical management and expectation management. Our study aim was to develop a prognostic tool to predict 30-day mortality after proximal femoral fracture, among patients treated within a dedicated hip fracture unit. MATERIALS AND METHODS: We collected data from our hospital concerning 2210 patients with 2287 proximal femoral fractures. The clinical parameters of 97 patients who died within 30 days of surgery were analysed. We used logistic regression to determine if the parameters' relationship with 30-day mortality was statistically significant or not. The statistically significant parameters were used to create a prognostic model for predicting 30-day mortality. RESULTS: The 5 independent predictors of 30-day mortality were gender, age, admission source, preoperative Abbreviated Mental Test Score (AMTS) and American Society of Anesthesiologists Score (ASA). The highest risk was for males >85 years, admitted from institutional care, with low preoperative mental test score and high ASA grade. Using these predictors, we formulated the G4A score. The Hosmer-Lemeshow 'goodness of fit' test showed good concordance between observed and predicted mortality rates. CONCLUSIONS: We recommend the use of the G4A score to predict 30-day mortality after surgery for proximal femoral fracture, particularly within dedicated hip fracture units. Further research is needed to establish whether the findings of this study are applicable on a national scale.

Surgeon-Team Separation in Robotic Theaters: A Qualitative Observational and Interview Study.

BACKGROUND: The rapid uptake of robotic surgery has largely been driven by the improved technical aspects of minimally invasive surgery including improved ergonomics, wristed instruments, and 3-dimensional vision. However, little attention has been given to the effect of physical separation of the surgeon from the rest of the operating team. PURPOSE: The aim of this study was to examine in depth how this separation affected team dynamics and staff emotions. METHODS: Robotic procedures were observed in 2 tertiary hospitals, and laparoscopic/open procedures were added for comparison; field notes were taken instantaneously. One-to-one interviews with theater team members were audio recorded and transcribed verbatim. Qualitative analysis was conducted via grounded theory approach using NVIVO11. RESULTS: Twenty-nine participants (26 interviewed) were recruited to the study (11 females) and 134 (109 robotic) hours of observation were completed across gynecology, urology, and colorectal surgery.The following 3 main themes emerged with compounding factors identified: (a) communication challenge, (b) immersion versus distraction, and (c) emotional impact. Compounding factors included the following: individual and team experience, staffing levels, and the physical theater environment. CONCLUSIONS: Our emergent theory is that "surgeon-team separation in robotic theaters poses communication challenges which impacts on situational awareness and staff emotions." These can be ameliorated by staff training, increased experience, and team/procedure consistency.

A Single Center Evaluation of the Diagnostic Accuracy of Multiparametric Magnetic Resonance Imaging against Transperineal Prostate Mapping Biopsy: An Analysis of Men with Benign Histology and Insignificant Cancer following Transrectal Ultrasound Biopsy.

PURPOSE: In this study we evaluated the diagnostic performance of transrectal ultrasound guided biopsy and multiparametric magnetic resonance imaging to detect prostate cancer against transperineal prostate mapping biopsy as the reference test. MATERIALS AND METHODS: Transrectal ultrasound guided biopsy, multiparametric magnetic resonance imaging and transperineal prostate mapping biopsy were performed in 426 patients between April 2012 and January 2016. Patients initially underwent systematic 12 core transrectal ultrasound guided biopsy followed 3 months later by 1.5 Tesla, high resolution T2, diffusion-weighted, dynamic contrast enhanced multiparametric magnetic resonance imaging. Two specialist uroradiologists blinded to the results of transperineal prostate mapping biopsy allocated a PI-RADS™ (Prostate Imaging-Reporting and Data System) score to each multiparametric magnetic resonance imaging study. Transperineal prostate mapping biopsy with 5 mm interval sampling, which was performed within 6 months of multiparametric magnetic resonance imaging, served as the reference test. RESULTS: Transrectal ultrasound guided biopsy identified 247 of 426 patients with prostate cancer and 179 of 426 with benign histology. Transperineal prostate mapping biopsy detected prostate cancer in 321 of 426 patients. On transperineal prostate mapping biopsy 94 of 179 patients with benign transrectal ultrasound guided biopsy had prostate cancer and 95 of 247 with prostate cancer on transrectal ultrasound guided biopsy were identified with cancer of higher grade. Using a multiparametric magnetic resonance imaging PI-RADS score of 3 or greater to detect significant prostate cancer, defined as any core containing Gleason 4 + 3 or greater prostate cancer on transperineal prostate mapping biopsy, the ROC AUC was 0.754 (95% CI 0.677-0.819) with 87.0% sensitivity (95% CI 77.3-97.0), 55.3% specificity (95% CI 50.2-60.4) and 97.1% negative predictive value (95% CI 94.8-99.4). CONCLUSIONS: Multiparametric magnetic resonance imaging is a more accurate diagnostic test than transrectal ultrasound guided biopsy. However, a significant proportion of ISUP (International Society of Urological Pathology) Grade Group 2 prostate cancer remained undetected following multiparametric magnetic resonance imaging. Although multiparametric magnetic resonance imaging could avoid unnecessary biopsy in many patients with ISUP Grade Group 3 or greater prostate cancer, at less stringent definitions of significant cancer a substantial proportion of prostate cancer would remain undetected after multiparametric magnetic resonance imaging.

Initial experience of an algorithm-based protocol for the community follow-up of men with prostate cancer.

OBJECTIVE: To evaluate the implementation of a novel algorithm-based discharge programme for the community follow-up of men with prostate cancer. PATIENTS AND METHODS: Men with prostate cancer considered suitable for discharge were identified from consultant-led and clinical nurse-specialist telephone clinics at Nottingham University Hospitals National Health Service Trust. Patients were discharged on to one of four discharge pathways: watchful waiting, androgen-deprivation therapy (ADT), post-prostatectomy, and post-radiotherapy. Primary care providers were asked to adhere to specific surveillance measures and refer patients back to secondary care after breach of pre-defined prostate-specific antigen (PSA) level threshold criteria. Reasons for non-compliance, re-referral, and cause of death were determined for all discharged men. RESULTS: In all, 573 men were discharged across all four pathways; 169 on the watchful-waiting pathway, 229 on the ADT pathway, 95 on the post-prostatectomy pathway, and 80 on the post-radiotherapy pathway. All patients had ≥12 months of follow-up. In all, 48 of 54 (88.9%) men were re-referred promptly after a PSA-threshold breach. Of the remaining six patients there were three refusals, one unrelated death before referral, and two late referrals at 4 months. Three patients were lost to follow-up due to database non-registration and were subsequently recalled, none of whom had a PSA-threshold breach. There were three unexpected deaths attributed to prostate cancer: two were community deaths with no biochemical or clinical evidence of prostate cancer progression, while one was due to a likely progressive PSA non-secreting tumour. CONCLUSION: Initial results suggest the algorithm-based protocol is a viable, effective, and oncologically safe method for the controlled discharge of men from secondary to primary care. Longer-term follow-up, patient satisfaction and cost-effectiveness data are required to assess the true impact of the initiative.

Prognostic value of prior history of urothelial carcinoma of the bladder in patients with upper urinary tract urothelial carcinoma: results from a retrospective multicenter study.

BACKGROUND: Patients with urothelial carcinoma (UC) often develop multifocal metachronous tumors throughout the genitourinary tract. In the present study, we evaluated the prognostic value of prior history of UC of the bladder (UCB) in patients with upper tract urothelial carcinoma (UTUC) in an international multi-institutional cohort. PATIENTS AND METHODS: Data from 785 patients who underwent radical nephroureterectomy (RNU) with ipsilateral bladder cuff resection at nine academic institutions in Europe and the USA between 1987 and 2008 were reviewed. Log-rank tests and Cox proportional hazards regression models were used for univariable and multivariable analyses. RESULTS: The median follow-up of the whole cohort was 34 months (interquartile range 15-66 months). Five hundred and fifty-eight (72 %) patients had no UCB before the diagnosis of UTUC; a prior history of non-muscle-invasive and muscle-invasive UCB before the UTUC was found in 179 (23 %) and 36 (5 %), respectively. History of UCB before RNU was an independent predictor of both recurrence-free survival (p = 0.012; no UCB vs. non-muscle-invasive UCB: hazard ratio (HR) 1.4, p = 0.082; no UCB vs. muscle-invasive UCB: HR 2.1, p = 0.007) and cancer-specific survival (p = 0.008; no UCB vs. non-muscle-invasive UCB: HR 1.2, p = 0.279; no UCB vs. muscle-invasive UCB: HR 2.3, p = 0.008) on multivariable Cox regression analyses that included age, gender, surgical type, stage, grade, presence of concomitant carcinoma in situ, presence of lymphovascular invasion, and lymph node status. CONCLUSIONS: Prior history of muscle-invasive UCB was significantly associated with an increased risk of disease recurrence and cancer-specific death in patients with UTUC.

Disease-free survival as a surrogate for overall survival in upper tract urothelial carcinoma.

OBJECTIVES: The primary endpoint in trials of perioperative systemic therapy for urothelial carcinoma is 5-year overall survival (OS). A shorter-term endpoint could significantly speed the translation of advances into practice. We hypothesized that disease-free survival (DFS) could be a surrogate endpoint for OS in upper tract urothelial carcinoma (UTUC) patients treated with radical nephroureterectomy (RNU). PATIENTS AND METHODS: The study included 2,492 patients treated with RNU with curative intent for UTUC. RESULTS: 2/3-year DFS estimates were 78/73 %, and the 5-year OS estimate was 64 %. The overall agreements between 2- and 3-year DFS with 5-year OS were 85 and 87 %, respectively. Agreements were similar when analyzed in subgroups stratified by pathological stages, lymph node status, and adjuvant chemotherapy. The kappa statistic was 0.59 (95 % CI 0.55-0.63) for 2-year DFS/5-year OS and 0.64 (95 % CI 0.61-0.68) for 3-year DFS/5-year OS, indicating moderate reliability. The hazard ratio for DFS as a time-dependent variable for predicting OS was 11.5 (95 % CI 9.1-14.4), indicating a strong relationship between DFS and OS. CONCLUSIONS: In patients treated with RNU for UTUC, DFS and OS are highly correlated, regardless of tumor stage and adjuvant chemotherapy. While significant differences in DFS, assessed at 2 and 3 years, are highly likely to persist in OS at 5 years, marginal DFS advantages may not translate into OS benefit. External validation is necessary before accepting DFS as an appropriate surrogate endpoint for clinical trials investigating advanced UTUC patients.

Prediction of cancer specific survival after radical nephroureterectomy for upper tract urothelial carcinoma: development of an optimized postoperative nomogram using decision curve analysis.

PURPOSE: We conceived and proposed a unique and optimized nomogram to predict cancer specific survival after radical nephroureterectomy in patients with upper tract urothelial carcinoma by merging the 2 largest multicenter data sets reported in this population. MATERIALS AND METHODS: The international and the French national collaborative groups on upper tract urothelial carcinoma pooled data on 3,387 patients treated with radical nephroureterectomy for whom full data for nomogram development were available. The merged study population was randomly split into the development cohort (2,371) and the external validation cohort (1,016). Cox regressions were used for univariable and multivariable analyses, and to build different models. The ultimate reduced nomogram was assessed using Harrell's concordance index (c-index) and decision curve analysis. RESULTS: Of the 2,371 patients in the nomogram development cohort 510 (21.5%) died of upper tract urothelial carcinoma during followup. The actuarial cancer specific survival probability at 5 years was 73.7% (95% CI 71.9-75.6). Decision curve analysis revealed that the use of the best model was associated with benefit gains relative to the prediction of cancer specific survival. The optimized nomogram included only 5 variables associated with cancer specific survival on multivariable analysis, those of age (p = 0.001), T stage (p <0.001), N stage (p = 0.001), architecture (p = 0.02) and lymphovascular invasion (p = 0.001). The discriminative accuracy of the nomogram was 0.8 (95% CI 0.77-0.86). CONCLUSIONS: Using standard pathological features obtained from the largest data set of upper tract urothelial carcinomas worldwide, we devised and validated an accurate and ultimate nomogram, superior to any single clinical variable, for predicting cancer specific survival after radical nephroureterectomy.

International validation of the prognostic value of subclassification for AJCC stage pT3 upper tract urothelial carcinoma of the renal pelvis.

UNLABELLED: What's known on the subject? and What does the study add? Tumour stage is a powerful predictor of clinical outcomes and the most important factor driving clinical decision-making after radical nephroureterectomy (RNU) in upper tract urothelial carcinoma (UTUC). It has been suggested that renal pelvic pT3 subclassification into microscopic infiltration of the renal parenchyma (pT3a) versus macroscopic infiltration or invasion of peripelvic adipose tissue (pT3b) has strong prognostic value. This is an external validation study of the prognostic value of pT3 subclassification of renal pelvic UTUC in a large international cohort of patients treated with RNU. pT3b UTUC is associated with features of aggressive tumour biology, disease recurrence and cancer-specific mortality. However, pT3 subclassification is not an independent predictor of clinical outcomes. OBJECTIVE: To externally validate the prognostic value of subclassification of pT3 renal pelvic upper tract urothelial carcinoma (UTUC) in a large international cohort of patients treated with radical nephroureterectomy (RNU). PATIENTS AND METHODS: The RNU specimens with pT3 UTUC of the renal pelvis from 284 patients at 11 centres located in Asia, North America and Europe were retrospectively evaluated. All specimens were reviewed by genitourinary pathologists at each institution. Tumours were categorized as pT3a (microscopic infiltration of the renal parenchyma) or pT3b (macroscopic infiltration of the renal parenchyma and/or infiltration of peripelvic adipose tissue). RESULTS: Overall, 148 (52%) tumours were classified as pT3a and 136 (48%) as pT3b. Patients with pT3b disease were more likely to have high-grade tumours and sessile tumour architecture (all P ≤ 0.02). Patients with pT3b tumours were at increased risk of disease recurrence (5-year estimates: 55% versus 42%, P = 0.012) and cancer-specific mortality (CSM) (5-year estimates: 48% versus 40%, P = 0.04). Lymph node status, tumour architecture and tumour grade were independently associated with disease recurrence, whereas lymph node status, tumour architecture and lymphovascular invasion were independently associated with CSM. Subclassification of pT3 tumours was not associated with recurrence or CSM in multivariable analyses. CONCLUSION: Patients with pT3b UTUC were more likely to have tumours with aggressive pathological features and were at higher risk of disease recurrence and CSM after RNU compared with patients with pT3a disease. However, the pT3 subclassification did not remain an independent predictor of disease recurrence or CSM after controlling for tumour grade, lymph node status, tumour architecture and lymphovascular invasion.

Predicting clinical outcomes after radical nephroureterectomy for upper tract urothelial carcinoma.

BACKGROUND: Novel prognostic factors for patients after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) have recently been described. OBJECTIVE: We tested the prognostic value of pathologic characteristics and developed models to predict the individual probabilities of recurrence-free survival (RFS) and cancer-specific survival (CSS) after RNU. DESIGN, SETTING, AND PARTICIPANTS: Our study included 2244 patients treated with RNU without neoadjuvant or adjuvant therapy at 23 international institutions. Tumor characteristics included T classification, grade, lymph node status, lymphovascular invasion, tumor architecture, location, and concomitant carcinoma in situ (CIS). The cohort was randomly split for development (12 centers, n=1273) and external validation (11 centers, n=971). INTERVENTIONS: All patients underwent RNU. MEASUREMENTS: Univariable and multivariable models addressed RFS, CSS, and comparison of discrimination and calibration with American Joint Committee on Cancer (AJCC) stage grouping. RESULTS AND LIMITATIONS: At a median follow-up of 45 mo, 501 patients (22.3%) experienced disease recurrence and 418 patients (18.6%) died of UTUC. On multivariable analysis, T classification (p for trend <0.001), lymph node metastasis (hazard ratio [HR]: 1.98; p=0.002), lymphovascular invasion (HR: 1.66; p<0.001), sessile tumor architecture (HR: 1.76; p<0.001), and concomitant CIS (HR: 1.33; p=0.035) were associated with disease recurrence. Similarly, T classification (p for trend<0.001), lymph node metastasis (HR: 2.23; p=0.001), lymphovascular invasion (HR: 1.81; p<0.001), and sessile tumor architecture (HR: 1.72; p=0.001) were independently associated with cancer-specific mortality. Our models achieved 76.8% and 81.5% accuracy for predicting RFS and CSS, respectively. In contrast to these well-calibrated models, stratification based upon AJCC stage grouping resulted in a large degree of heterogeneity and did not improve discrimination. CONCLUSIONS: Using standard pathologic features, we developed highly accurate prognostic models for the prediction of RFS and CSS after RNU for UTUC. These models offer improvements in calibration over AJCC stage grouping and can be used for individualized patient counseling, follow-up scheduling, risk stratification for adjuvant therapies, and inclusion criteria for clinical trials.

Prognostic role of ECOG performance status in patients with urothelial carcinoma of the upper urinary tract: an international study.

OBJECTIVE: To evaluate the prognostic role of ECOG Performance status (ECOG-PS) in a large multi-institutional international cohort of patients treated with radical nephroureterectomy for upper tract urothelial carcinoma. MATERIALS AND METHODS: Data of 427 patients treated with radical nephroureterectomy at five international institutions in Asia, Europe and Northern America were collected retrospectively from 1987 to 2008. Logistic and Cox regression models were used for univariable and multivariable analyses. RESULTS: ECOG-PS was 0 in 272 of 427 (64%) patients. The median follow-up of the whole cohort was 32 months. The five-year recurrence-free (RFS), cancer-specific (CSS) and overall (OS) survival estimates were 71.7%, 74.9% and 68.5%, respectively, in patients with ECOG-PS 0 compared with 60.1%, 67.8%, and 51.4% respectively, in patients with ECOG-PS ≥1 (P value 0.08 for RFS, 0.43 for CSS, and <0.001 for OS, respectively). On multivariable Cox regression analyses, ECOG-PS was not an independent predictor of either RFS (hazard ratio 1.4; P = 0.107) or CSS (hazard ratio 1.2; P = 0.426) but was an independent predictor of OS (hazard ratio 1.5; P = 0.03). CONCLUSIONS: In this large multicentre international study, ECOG-PS was not significantly associated with RFS and CSS. Conversely we find a strong association with survival 1-month after surgery and OS. Further research is needed to ascertain the additive prognostic role of ECOG-PS in well-designed prospective multicentre studies.

The impact of tumor multifocality on outcomes in patients treated with radical nephroureterectomy.

BACKGROUND: The prognostic impact of multifocal upper-tract urothelial carcinoma (UTUC) is poorly understood. OBJECTIVE: To investigate the association between tumor multifocality and clinicopathologic features and outcomes of UTUC in patients managed by radical nephroureterectomy (RNU). DESIGN, SETTING, AND PARTICIPANTS: The study included 2492 patients treated with either open or laparoscopic RNU. Tumor and patient characteristics included tumor stage, tumor grade, lymph node status, lymphovascular invasion (LVI), tumor architecture, tumor location, unifocal or multifocal disease, gender, age, history of bladder cancer (BCa), Eastern Cooperative Oncology Group (ECOG) performance status (PS), and adjuvant chemotherapy. tumor multifocality of UTUC was defined as the synchronous presence of multiple tumors in the renal pelvis or ureter. INTERVENTION: All patients were treated with either open or laparoscopic RNU. MEASUREMENTS: Univariable and multivariable models tested the effect of tumor multifocality on disease progression and cancer-specific mortality. RESULTS AND LIMITATIONS: Five hundred ninety patients (23.7%) had tumor multifocality at the time of RNU. The median follow-up was 45 mo (interquartile range [IQR]: 0-101). Tumor multifocality was significantly associated with a history of previous BCa (p=0.032), lymph node involvement (p=0.036), tumor location in the ureter (p=0.003), higher tumor stage (p<0.001), higher tumor grade (p<0.001), sessile tumor architecture (p=0.003), and LVI (p=0.001). In organ-confined patients, tumor multifocality was an independent predictor of both disease progression (hazard ratio [HR]: 1.43; p=0.019) and cancer-specific mortality (HR: 1.46; p=0.027). When assessed in all patients, tumor multifocality was associated with both disease progression and cancer-specific mortality in univariable (p=0.005 and p=0.006, respectively) but not in multivariable analyses (p=0.468 and p=0.798, respectively). The main limitation is the retrospective design of the study. CONCLUSIONS: Tumor multifocality is an independent prognosticator of disease progression and cancer-specific mortality in patients with organ-confined UTUC treated with RNU. Multifocal organ-confined patients with UTUC may need closer follow-up. Integration of tumor multifocality with other factors may help identify those patients who would benefit from multimodal therapy.

Focal therapy for localised prostate cancer: are we asking the correct research questions?

The goals of focal therapy are laudable, namely reducing morbidity of treatment while ensuring at least equivalent oncological outcomes when compared with established interventions for localised prostate cancer, e.g. RP and external beam radiotherapy. While progress has been made towards better identifying the index lesion in these patients, there is much yet to be done to establish the validity of the index lesion theory as the metastatic focus and to establish that current targeting and ablative platforms are adequate to deliver the goals outlined above. The correct research questions have not yet been asked to establish either of these key principles underpinning focal therapy for localised prostate cancer.

Impact of tumour location versus multifocality in patients with upper tract urothelial carcinoma treated with nephroureterectomy and bladder cuff excision: a homogeneous series without perioperative chemotherapy.

UNLABELLED: It is well established that upper tract urothelial carcinoma is a rare cancer with an aggressive course. Currently, radical nephroureterectomy with bladder cuff excision remains the standard of care in the treatment of these tumours. Previous studies demonstrate that stage, grade and lymphovascular invasion have prognostic significance on recurrence and outcome whereas the prognostic impact of tumour location remains unclear. This study provides an accurate analysis of the impact of tumour location and multifocality on prognosis in patients with upper tract urothelial carcinoma following nephroureterectomy with bladder cuff excision. Ureteral tumour location, particularly when associated with multifocal disease in the renal pelvis, is significantly associated with an increased risk of disease recurrence and cancer-specific death after surgery. OBJECTIVE: To examine the significance of ureteral and renal pelvic location of upper tract urothelial carcinoma in a large multi-institutional study. MATERIALS AND METHODS: We collected and pooled a database of 637 patients with upper tract urothelial carcinoma who underwent radical nephroureterectomy and bladder cuff excision in nine international academic centres. Univariate and multivariate models examined the effect of tumour location on recurrence-free survival (RFS) and cancer-specific survival (CSS) rates. Collected variables included age, gender, race, presence of lymphovascular invasion, concomitant carcinoma in situ, pathological stage, lymph node dissection and type of surgery (open vs laparoscopic). RESULTS: Anatomically, 34% of tumours were ureteral, 59% were renal pelvic and 7% were multifocal. Median follow-up for patients alive was 42 months (interquartile range: 19-76). Race, type of surgery, pathological stage and presence of lymphovascular invasion were significantly different across the three subgroups of patients (all P values <0.05). Age, gender, grade, presence of concomitant carcinoma in situ and follow-up duration were similar among the three subgroups. On multivariable Cox regression analyses, ureteral tumour location was an independent predictor of worse RFS (hazard ratio 2.1, P = 0.006) and CSS (hazard ratio 2.0, P = 0.027). When associated with renal pelvic disease, ureteral location was an even stronger independent predictor of worse RFS (hazard ratio 4.6, P < 0.001) and CSS (hazard ratio 4.0, P < 0.001). CONCLUSION: Ureteral tumour location, particularly in association with multifocal disease in the renal pelvis, is an independent prognostic factor for higher disease recurrence and cancer-specific mortality.

No overt influence of lymphadenectomy on cancer-specific survival in organ-confined versus locally advanced upper urinary tract urothelial carcinoma undergoing radical nephroureterectomy: a retrospective international, multi-institutional study.

PURPOSE: Lymph node dissection (LND) is not routinely performed during radical nephroureterectomy (RNU) in upper tract urothelial carcinomas (UTUC), and its clinical relevance is unclear. The purpose of the present study was to evaluate the impact of LND on clinical outcomes in a large multicenter series of RNU for UTUC. METHODS: Detailed data on 785 patients subject to RNU were provided by nine international academic centers. The choice to perform lymphadenectomy was determined by the treating surgeon. All pathology slides were evaluated by dedicated genitourinary pathologists. Univariable and multivariable Cox regression models evaluated the association of nodal status with recurrence-free (RFS) and cancer-specific (CSS) survival. RESULTS: One hundred and ninety patients had LND. Pathological N stage was pN0 in 17%, pNx in 76%, and pN+ in 7%. The median follow-up period of the entire cohort was 34 months (interquartile range [IQR]: 15-65 months). Overall, five-year RFS and CSS estimates were 72.2 and 76%, respectively. In multivariable Cox regression analyses, pN0/pNx substaging was not an independent predictor of either RFS (hazard ratio [HR]: 1.1; P = 0.631) or CSS (HR: 1.3; P = 0.223). Similar results were obtained in a subgroup analysis limited to patients with organ-confined disease (HR: 0.9; P = 0.907 for RFS; HR: 0.4; P = 0.419 for CSS). Conversely, in patients with locally advanced disease, patients with pN0 disease have significantly better cancer-related outcomes (HR: 0.3; P < 0.001 for RFS; HR: 0.3; P < 0.001 for CSS). CONCLUSION: The present series suggests pNx is more significantly associated with a worse prognosis than pN0, but only in patients with locally advanced UTUC.

Racial differences in the outcome of patients with urothelial carcinoma of the upper urinary tract: an international study.

OBJECTIVE: •To assess the impact of differences in ethnicity on clinico-pathological characteristics and outcomes of patients with upper urinary tract urothelial carcinoma (UTUC) in a large multi-center series of patients treated with radical nephroureterectomy (RNU). MATERIALS AND METHODS: •We retrospectively collected the data of 2163 patients treated with RNU at 20 academic centres in America, Asia, and Europe. •Univariable and multivariable Cox regression models addressed recurrence-free survival (RFS) and cancer-specific survival (CSS). RESULTS: •In all, 1794 (83%) patients were Caucasian and 369 (17%) were Japanese. All the main clinical and pathological features were significantly different between the two ethnicities. •The median follow-up of the whole cohort was 36 months. At last follow-up, 554 patients (26%) developed disease recurrence and 461 (21%) were dead from UTUC. •The 5-year RFS and CSS estimates were 71.5% and 74.2%, respectively, for Caucasian patients compared with 68.8% and 75.4%, respectively, for Japanese patients. •On univariable Cox regression analyses, ethnicity was not significantly associated with either RFS (P= 0.231) or CSS (P= 0.752). •On multivariable Cox regression analyses that adjusted for the effects of age, gender, surgical type, T stage, grade, tumour architecture, presence of concomitant carcinoma in situ, lymphovascular invasion, tumour necrosis, and lymph node status, ethnicity was not associated with either RFS (hazard ratio [HR] 1.1; P= 0.447) or CSS (HR 1.0; P= 0.908). CONCLUSIONS: •There were major differences in the clinico-pathological characteristics of Caucasian and Japanese patients. •However, RFS and CSS probabilities were not affected by ethnicity and race was not an independent predictor of either recurrence or cancer-related death.

Chronological age is not an independent predictor of clinical outcomes after radical nephroureterectomy.

PURPOSE: Higher chronological age has been suggested to confer worse prognosis in patients with upper tract urothelial carcinoma (UTUC). The aim of the current study was to test this hypothesis in a large multicenter external validation cohort of patients treated with radical nephroureterectomy (RNU) while controlling for patient performance status. MATERIALS AND METHODS: We retrospectively reviewed the data from 1,169 patients treated with RNU for UTUC. Age at RNU was analyzed both as a continuous and categorical variable (<50 years, n = 66; 50-59.9 years, n = 185; 60-69.9 years, n = 367; 70-79.9 years, n = 419; ≥80 years, n = 132). Median follow-up was 37 months. RESULTS: Actuarial recurrence-free, cancer-specific, and all-cause survival estimates at 5 years after RNU were 69, 73, and 61%, respectively. Advanced age was associated with female gender, higher ECOG status, higher ASA score, and a lower probability of receiving adjuvant chemotherapy (all P values ≤ 0.02). In multivariable analyses, advanced age was associated with decreased recurrence-free (P = 0.021), cancer-specific (P = 0.002), and all-cause survival (P < 0.001) after controlling for the effects of gender, tumor location, number of lymph nodes removed, tumor grade, stage, architecture, necrosis, and lymphovascular invasion. After addition of ECOG status, age remained an independent predictor of only all-cause mortality (P > 0.001). CONCLUSIONS: We confirmed that advanced patient age at the time of RNU is associated with worse clinical outcomes after surgery. However, ECOG performance status abrogated the association. Furthermore, a large proportion of elderly patients were cured with RNU. This suggests that chronological age alone is an inadequate indicator criterion to predict response of older UTUC patients to RNU.