Safety and quality of cystectomy and pelvic lymph node dissection after neoadjuvant durvalumab and cisplatin/gemcitabine.

OBJECTIVE: To report on the surgical safety and quality of pelvic lymph node dissection (PLND) in patients treated with radical cystectomy (RC) and PLND for muscle-invasive bladder cancer (MIBC) after neoadjuvant chemo-immunotherapy. PATIENTS AND METHODS: The Swiss Group for Clinical Cancer Research (SAKK) 06/17 was an open-label single-arm phase II trial including 61 cisplatin-fit patients with clinical stage (c)T2-T4a cN0-1 operable urothelial MIBC or upper urinary tract cancer. Patients received neoadjuvant cisplatin/gemcitabine and durvalumab followed by surgery. Prospective quality assessment of surgeries was performed via central review of intraoperative photographs. Postoperative complications were assessed using the Clavien-Dindo Classification. Data were analysed descriptively. RESULTS: A total of 50 patients received RC and PLND. All patients received neoadjuvant chemo-immunotherapy. The median (interquartile range) number of lymph nodes removed was 29 (23-38). No intraoperative complications were registered. Grade ≥III postoperative complications were reported in 12 patients (24%). Complete nodal dissection (100%) was performed at the level of the obturator fossa (bilaterally) and of the left external iliac region; in 49 patients (98%) at the internal iliac region and at the right external iliac region; in 39 (78%) and 38 (76%) patients at the right and left presacral level, respectively. CONCLUSION: This study supports the surgical safety of RC and PLND following neoadjuvant chemo-immunotherapy in patients with MIBC. The extent and completeness of protocol-defined PLND varies between patients, highlighting the need to communicate and monitor the surgical template.

[Radical cystectomy in the geriatric population. Tools for screening postoperative complications]. / Cystectomie radicale chez les patients gériatriques. Outils de dépistage des complications postopératoires.

Radical cystectomy is the gold standard for the treatment of muscle-invasive bladder cancer. Advanced age is only a relative criterion when selecting patients eligible for radical cystectomy, and to reduce post-operative complications, the management of an elderly patient requires a multidisciplinary approach. The role of the geriatrician is therefore essential, in collaboration with the urologist, to ensure appropriate follow-up. A series of preoperative screening tests should be used to identify frailer patients who are at high risk of developing complications, so that appropriate follow-up can be carried out.

La cystectomie radicale est le traitement de choix du cancer de la vessie musculo-invasif. L'âge avancé ne représente qu'un critère relatif lors de la sélection des patients éligibles à une cystectomie radicale. Afin de réduire les complications postopératoires, la prise en charge d'un patient âgé nécessite une approche multidisciplinaire. Le rôle du gériatre est donc essentiel, en collaboration avec l'urologue, afin d'assurer un suivi approprié. Une série de tests de dépistage préopératoires identifie les patients plus fragiles, présentant un risque accru de complications, et permet de réaliser un suivi adapté.

[Bladder cancer : a comprehensive follow-up for an efficient and personalized care]. / Cancer de la vessie : un suivi personnalisé pour une prise en charge efficiente.

Bladder cancer is a common cancer in the Swiss population. The heterogeneous nature of the disease requires long-term oncological monitoring, as well as metabolic and functional follow-up. Patients' quality of life must also be considered during follow-up.

Le cancer de la vessie est fréquent dans la population suisse. Son évolution étant hétérogène, cela nécessite une surveillance oncologique sur le long terme, mais également un suivi sur les plans métabolique et fonctionnel. La qualité de vie des patients doit aussi être considérée pendant le suivi.

[A Swiss Urological Society register of cystectomies to improve surgical quality]. / Un registre des cystectomies de la Société suisse d'urologie pour une meilleure qualité chirurgicale.

In the era of highly specialised medicine, the Swiss Urological Society has set up a national register from January 2019 that will prospectively record all data relating to cystectomies. Doctors will be able to use this information to compare their activities at national level, refine surgical techniques and optimise the perioperative management of cystectomy patients. This article presents the register and provides an initial assessment of cystectomy surgery activity in Switzerland over the first four years of its set up.

Dans l'ère de la médecine hautement spécialisée, la Société suisse d'urologie a mis au point dès janvier 2019 un registre national permettant de répertorier prospectivement l'ensemble des données relatives aux cystectomies. Les médecins profitent de ces renseignements pour comparer leur activité au niveau national, affiner les techniques chirurgicales et optimiser la prise en charge périopératoire des patients opérés d'une cystectomie. Cet article est consacré à la présentation du registre et offre un bilan initial de l'activité chirurgicale de cystectomie en Suisse au cours des quatre premières années de sa mise en place.

[Nutcracker syndrome: a cause of unexplained hematuria]. / Syndrome du casse-noisette : une cause d'hématurie inexpliquée.

Hematuria is frequently encountered in clinical practice. Its diagnostic spectrum is wide: urinary tract infection, lithiasis, malignant tumor and nephropathy. In the absence of one of these causes, the nutcracker syndrome must be evoked. It results from compression of the left renal vein between the abdominal aorta and the superior mesenteric artery. Knowing how to diagnose it can avoid morbid consequences (chronic renal disease, renal vein thrombosis). In addition to hematuria, its main symptoms are left lumbago, varicoceles, and orthostatic proteinuria. The clinical picture and complementary examinations (ultrasound-doppler, computed tomography angiography, magnetic resonance angiography, and phlebography) generally allow the diagnosis to be made. Treatment varies according to age and severity of symptoms.

L'hématurie est fréquemment rencontrée en pratique clinique. Son spectre diagnostique est large : infection urinaire, lithiase, tumeur maligne et néphropathie. En l'absence de l'une de ces causes, le syndrome du casse-noisette doit être évoqué. Il résulte de la compression de la veine rénale gauche entre l'aorte abdominale et l'artère mésentérique supérieure. Savoir le diagnostiquer permet d'éviter des conséquences morbides (maladie rénale chronique, thrombose veineuse rénale). Outre l'hématurie, ses principaux symptômes sont la lombalgie gauche, les varicocèles et la protéinurie orthostatique. Le tableau clinique et les examens complémentaires (échographie-doppler, angioscanner, angio-IRM et phlébographie) permettent généralement de poser le diagnostic. Le traitement varie en fonction de l'âge et de la sévérité des symptômes.

[Management of urologic cancers in elderly people†: which implications†?] / Prise en charge de cancers urologiques chez la population âgée†: quels enjeux†?

Elderly patients with urologic cancer are often undertreated because of their age. Recently, many studies showed that advanced age is not an absolute contraindication to radical surgery for bladder and prostate cancer patients. For small renal cancers, instead, active surveillance with a close follow-up may be a valid alternative to surgery because of a low risk of progression. Patients' selection remains a crucial step to define the best treatment. This article summarizes the new tendencies of urologic cancer management in elderly patients.

Les personnes âgées avec un cancer urologique sont souvent traitées de façon sous-optimale en se basant uniquement sur leur âge avancé. Récemment, plusieurs chercheurs se sont intéressés à cette classe de la population et ont montré que l'âge avancé n'est pas forcément une contre-indication à réaliser une chirurgie majeure. Cependant, l'évaluation des bénéfices et des risques est déterminante car la grande majorité des néoplasies du rein et de la prostate ont une lente évolution et un faible risque de progression, raison pour laquelle, une surveillance active avec des examens réguliers peut donc être la meilleure alternative. La sélection du patient reste une étape cruciale afin de proposer la meilleure option thérapeutique. Cet article résume les nouvelles tendances de prise de charge des 3 pathologies onco-urologiques les plus fréquentes.

[Improved rehabilitation after major urological surgery : what role for the general practitioner ?] / Réhabilitation améliorée après chirurgie urologique majeure : quel rôle pour le médecin généraliste ?

Enhanced recovery after surgery (ERAS) is a multimodal concept aiming to reduce surgical stress and prevent postoperative complications. Once adapted to urologic patients in 2013, this protocol evolves continuously and many international centers have now implemented it. This article resumes ERAS key principles for general practitioners as they can have a significant impact on patient's optimization before surgery.

Le protocole de réhabilitation améliorée après chirurgie est un concept de prise en charge multimodale visant à anticiper puis gérer de manière optimale le stress chirurgical inhérent à toute intervention. Adapté depuis 2013 à l'urologie, il évolue régulièrement et les centres internationaux qui appliquent ses principes sont toujours plus nombreux. Avant une chirurgie majeure, il existe un potentiel d'optimisation d'un patient auquel le généraliste peut participer activement. Cet article résume à l'attention d'un médecin généraliste les principaux points constituant cette démarche.

[Ambulatory surgery in urology]. / Chirurgie ambulatoire en urologie : il est temps d'en parler.

The volume of ambulatory surgery in urology increases every year. Successful ambulatory care is defined by low hospital (re)admission rates, insuring optimal oncologic and functional outcomes. New medical techniques such as minimally invasive surgical approaches and less side effects of anesthesia have helped the development of ambulatory surgery. Additionally, it is essential to lower the burden of healthcare systems financially, without compromising quality of care. Ambulatory surgery needs a multidisciplinary team involvement, where the general practitioner has a key role.

La pratique ambulatoire en urologie augmente chaque année. Les avancées médicochirurgicales ont permis de diminuer les gestes invasifs et les effets secondaires des anesthésiques. Sur le plan financier, il est essentiel de contrôler les dépenses de santé publique, tout en maintenant comme premier objectif la sécurité du patient. Les critères de succès d'une prise en charge ambulatoire se mesurent au faible taux d'hospitalisation et de réadmission, sans compromission quant aux résultats de la chirurgie. La prise en charge ambulatoire exige une équipe pluridisciplinaire et le médecin traitant joue un rôle essentiel dans l'itinéraire clinique de son patient.

Role of survivin expression in predicting biochemical recurrence after radical prostatectomy: a multi-institutional study.

OBJECTIVE: To assess the association of survivin expression with clinicopathological features and biochemical recurrence (BCR) after radical prostatectomy (RP) in a large multi-institutional cohort. METHODS: Survivin expression was evaluated by immunohistochemistry on a tissue microarray of RP cores from 3 117 patients. Survivin expression was considered altered when at least 10% of the tumour cells stained positive. The association of altered survivin expression with BCR was evaluated using Cox proportional hazards regression models. RESULTS: Survivin expression was altered in 1 330 patients (42.6%). Altered expression was associated with higher Gleason score on RP (P = 0.001), extracapsular extension (P = 0.019), seminal vesicle invasion (P < 0.001) and lymph node metastases (P = 0.009). The median (interquartile range) follow-up was 38 (21-66) months. Patients with altered survivin expression had a shorter BCR-free survival time than those with normal expression (5-year BCR-free survival estimates: 74.7 vs 79.0%; P = 0.008). Altered survivin expression did not retain its prognostic value, however, after adjustment for the effect of established clinicopathological factors (P = 0.73). Subgroup analyses also showed no independent prognostic value of survivin. CONCLUSIONS: Survivin expression is commonly altered in patients undergoing RP. Altered survivin expression is associated with the clinicopathological features of biologically and clinically aggressive PCa. Survivin expression was associated with BCR only in univariable analysis, limiting its value in daily clinical decision-making.

Promising role of preoperative neutrophil-to-lymphocyte ratio in patients treated with radical nephroureterectomy.

OBJECTIVE: Several retrospective studies with small cohorts reported neutrophil-to-lymphocyte ratio (NLR) as a prognostic marker in upper tract urothelial carcinoma (UTUC) following radical nephroureterectomy (RNU). We aimed at validating the predictive and prognostic role of NLR in a large multi-institutional cohort. METHODS: Preoperative NLR was assessed in a multi-institutional cohort of 2477 patients with UTUC treated with RNU. Altered NLR was defined by a ratio >2.7. Logistic regression analyses were performed to assess the association between NLR and lymph node metastasis, muscle-invasive and non-organ-confined disease. The association of altered NLR with recurrence-free survival (RFS) and cancer-specific survival (CSS) was evaluated using Cox proportional hazards regression models. RESULTS: Altered NLR was observed in 1428 (62.8 %) patients and associated with more advanced pathological tumor stage, lymph node metastasis, lymphovascular invasion, tumor necrosis and sessile tumor architecture. In a preoperative model that included age, gender, tumor location and architecture, NLR was an independent predictive factor for the presence of lymph node metastasis, muscle-invasive and non-organ-confined disease (p < 0.001). Within a median follow-up of 40 months (IQR 20-76 months), 548 (24.1 %) patients experienced disease recurrence and 453 patients (19.9 %) died from their cancer. Compared to patients with normal NLR, those with altered NLR had worse RFS (0.003) and CSS (p = 0.002). In multivariable analyses that adjusted for the effects of standard clinicopathologic features, altered NLR did not retain an independent value. In the subgroup of patients treated with lymphadenectomy in addition to RNU, NLR was independently associated with CSS (p = 0.03). CONCLUSION: In UTUC, preoperative NLR is associated with adverse clinicopathologic features and independently predicts features of biologically and clinically aggressive UTUC such as lymph node metastasis, muscle-invasive or non-organ-confined status. NLR may help better risk stratify patients with regard to lymphadenectomy and conservative therapy.

[Immunotherapy : a revolution in the management of urothelial bladder cancer ?] / Immunothérapie : une révolution dans la prise en charge du cancer de la vessie ?

The treatment of urothelial bladder cancer has changed very little in recent years, with high rates of disease recurrence and progression, even in low aggressive urothelial bladder cancer. Immunotherapy has already proven its effectiveness as a treatment for several types of cancer and has been used in high-grade non-muscle-invasive bladder cancer for decades. Recent findings on immune checkpoints inhibitors have opened up a new chapter for treatment of bladder cancer, offering interesting therapeutic perspectives that could revolutionize the management.

Le traitement du cancer de la vessie a très peu évolué depuis plusieurs années avec des taux de récidives et de progression élevés, même dans les tumeurs peu invasives. L'immunothérapie a déjà fait ses preuves comme traitement de plusieurs types de cancer et est utilisée dans le cancer de la vessie non musculo-invasif de haut grade depuis des décennies. Les récentes découvertes sur les inhibiteurs de points de contrôle immunitaire (checkpoints inhibitors) ouvrent tout un nouveau chapitre sur le traitement des différents stades du cancer de la vessie, y compris les tumeurs musculo-invasives et métastatiques, offrant des perspectives thérapeutiques, capables de révolutionner la prise en charge.

[Local treatment in oligometastatic urological malignancies : evidence of wishful thinking ?] / Ablation du cancer primaire dans les néoplasies urologiques oligométastatiques : évidence ou vœux pieux ?

In the past, it was generally considered that the window of curability had been missed in metastatic solid cancers. At present, novel evidence suggests that oligometastatic cancer might be amenable to a multimodal curative treatment, including ablation of the primary tumour. In this article, we summarise the indications, the controversies and future perspectives of local treatment in oligometastatic urological malignancies.

Dans le passé, on considérait le plus souvent que la fenêtre de curabilité dans les cancers solides à un stade métastatique avait été manquée. De nouvelles évidences suggèrent à présent que la maladie à un stade oligométastatique est accessible, dans certains cas, à un traitement multimodal curatif, incluant l'ablation de la tumeur primaire. Dans cet article, nous résumons les indications, les controverses ainsi que les perspectives futures du traitement local dans les cancers oligométastatiques urologiques.

Association of human telomerase reverse transcriptase gene polymorphisms, serum levels, and telomere length with renal cell carcinoma risk and pathology.

Human telomerase reverse transcriptase (hTERT) is the catalytic subunit of the human telomerase and plays a key role in telomere restitution and gene regulation. Evidence suggests that hTERT is linked with the risk and progression of several malignancies, but there are no comprehensive data in renal cell carcinoma (RCC). In this case-control study, we assessed seven polymorphic hTERT gene variants (MNS16A, rs2736100, rs2736098, rs7726159, rs2853677, rs13172201, and rs10069690), hTERT serum levels, and the telomere length of 663 individuals, including 243 with clear cell RCC and 420 age- and gender-matched healthy controls. The SL and SS genotypes of MNS16A were associated with a decreased risk for RCC on the multivariable logistic regression analysis (SL-OR 0.72, SS-OR 0.37, P < 0.001). The GG genotype of rs2736098 was associated with a decreased risk for RCC compared with AA (OR 0.18, P < 0.001). Both telomere length and hTERT serum levels increased with every G allele in rs2736098 (P = 0.008). Pretherapeutic hTERT serum levels were higher in patients with advanced tumor stages (P = 0.037) and distant metastases (P = 0.006). Rs2736100, rs7726159, rs2853677, rs13172201, and rs10069690 were not linked with RCC risk, and none of the polymorphisms was associated with RCC pathology. In conclusion, the polymorphic number of tandem repeats in hTERT (MNS16A) and rs2736098 may be linked with the risk for RCC. Rs2736098 may have an important role in telomere length restitution and serum hTERT levels may represent a novel biomarker for RCC. © 2015 Wiley Periodicals, Inc.

Dynamic Prognostication Using Conditional Recurrence and Progression Estimates for Patients with Nonmuscle Invasive Bladder Cancer.

PURPOSE: Conditional estimates provide a dynamic prediction of outcomes but to our knowledge there are no data on nonmuscle invasive bladder cancer. We assessed changes in conditional recurrence and progression rates after transurethral resection of the bladder and explored the prognostic impact of established factors and risk groups with time. MATERIALS AND METHODS: We retrospectively analyzed data on 1,292 consecutive patients with newly diagnosed Ta/T1 bladder cancer who underwent transurethral resection of the bladder. Study end points were time to first recurrence and time to progression. RESULTS: The 2-year recurrence rate at baseline was 36%, which improved as a function of the time that patients were free of disease recurrence. After 6, 12, 24, 36 and 48 months the 2-year conditional recurrence rate improved to 31% (14% improvement vs baseline), 22% (39% improvement), 16% (56% improvement), 13% (64% improvement) and 11% (69% improvement), respectively. Comparably, conditional progression rates improved with increasing followup, although relative differences were less distinct. The prognostic impact of established factors and nonmuscle invasive bladder cancer risk groups progressively decreased with time and finally disappeared. However, bacillus Calmette-Guérin had a protective effect on progression even after 3 years. We provide tables with dynamic prognostic information at all analyzed time points. CONCLUSIONS: In patients with primary Ta/T1 bladder cancer recurrence and progression rates improve with time. The prognostic impact of established factors and risk groups decreases and finally disappears. The effect of bacillus Calmette-Guérin on progression is long-lasting. Conditional outcome estimates may improve patient counseling and individualize surveillance planning.

Oncologic Outcomes of Kidney Sparing Surgery versus Radical Nephroureterectomy for the Elective Treatment of Clinically Organ Confined Upper Tract Urothelial Carcinoma of the Distal Ureter.

PURPOSE: We compared the oncologic outcomes of radical nephroureterectomy, distal ureterectomy and endoscopic surgery for elective treatment of clinically organ confined upper tract urothelial carcinoma of the distal ureter. MATERIALS AND METHODS: From a multi-institutional collaborative database we identified 304 patients with unifocal, clinically organ confined urothelial carcinoma of the distal ureter and bilateral functional kidneys. Rates of overall, cancer specific, local recurrence-free and intravesical recurrence-free survival according to surgery type were compared using Kaplan-Meier statistics. Univariable and multivariable Cox regression analyses were performed to assess the adjusted outcomes of radical nephroureterectomy, distal ureterectomy and endoscopic surgery. RESULTS: Overall 128 (42.1%), 134 (44.1%) and 42 patients (13.8%) were treated with radical nephroureterectomy, distal ureterectomy and endoscopic surgery, respectively. Although rates of overall, cancer specific and intravesical recurrence-free survival were equivalent among the 3 surgical procedures, 5-year local recurrence-free survival was lower for endoscopic surgery (35.7%) than for nephroureterectomy (95.0%, p <0.001) or ureterectomy (85.5%, p = 0.01) with no significant difference between nephroureterectomy and distal ureterectomy. On multivariable analyses only endoscopic surgery was an independent predictor of decreased local recurrence-free survival compared to nephroureterectomy (HR 1.27, p = 0.001) or distal ureterectomy (HR 1.14, p = 0.01). Distal ureterectomy and endoscopic surgery did not significantly correlate to cancer specific or intravesical recurrence-free survival. However, when adjustment was made for ASA(®) (American Society of Anesthesiologists(®)) score, distal ureterectomy (HR 0.80, p = 0.01) and endoscopic surgery (HR 0.84, p = 0.02) were independent predictors of increased overall survival, although no significant difference was found between them. CONCLUSIONS: Because of better oncologic outcomes, distal ureterectomy could be considered the elective first line treatment of clinically organ confined urothelial carcinoma of the distal ureter.

Prognostic value of Caveolin-1 in patients treated with radical prostatectomy: a multicentric validation study.

OBJECTIVE: To validate Caveolin-1 as an independent prognostic marker of biochemical recurrence (BCR) in a large multi-institutional cohort of patients with prostate cancer treated with radical prostatectomy (RP). PATIENTS AND METHODS: Caveolin-1 expression was evaluated by immunochemistry on a tissue microarray in 3 117 patients treated with RP for prostate cancer at five institutions. Univariable and multivariable Cox proportional hazards regression models assessed the association of Caveolin-1 status with BCR. Harrell's c-index quantified prognostic accuracy. RESULTS: Caveolin-1 was overexpressed in 644 (20.6%) patients and was associated with higher pathological Gleason sum (P = 0.002) and lymph node metastases (P = 0.05). Within a median (interquartile range) follow-up of 38 (21-66) months, 617 (19.8%) patients experienced BCR. Patients with overexpression of Caveolin-1 had worse BCR-free survival than those with normal expression (log-rank test, P = 0.004). Caveolin-1 was an independent predictor of BCR in multivariable analyses that adjusted for the effects of standard clinicopathological features (hazard ratio 1.21, P = 0.037). Addition of Caveolin-1 in a model for prediction of BCR based on these standard prognosticators did not significantly improve the predictive accuracy of the model. In subgroup analyses, Caveolin-1 was associated with BCR in patients with favourable pathological features (pT2pN0 and Gleason score = 6; P = 0.021). CONCLUSIONS: We confirmed that overexpression of Caveolin-1 is associated with adverse pathological features in prostate cancer and independently predicts BCR after RP, especially in patients with favourable pathological features. However, it did not add prognostically relevant information to established predictors of BCR, limiting its use in clinical practice.

Impact of smoking status on survival after cytoreductive nephrectomy for metastatic renal cell carcinoma.

OBJECTIVE: To assess the association of smoking status with standard clinicopathological features and overall survival (OS) in a large multi-institutional cohort of patients with metastatic renal cell carcinoma (mRCC) treated with cytoreductive nephrectomy (CNT). METHODS: A total of 613 patients with mRCC treated with CNT in US and Europe institutions between 1990 and 2013 were included. Smoking history comprised smoking status, smoking duration in years, number of cigarettes per day and years since smoking cessation. Cumulative smoking exposure was categorized as light short term, heavy long term and moderate. Association between smoking history and OS was assessed by Cox regression logistic analysis. RESULTS: One hundred and seventy-one patients (27.9 %) never smoked, 193 (31.5 %) were former smokers and 249 (40.6 %) were current smokers. Smoking status was associated with a higher number of metastases (p < 0.001) and an abnormal preoperative corrected calcium level (p = 0.01). Median follow-up was 16 (IQR 7-24) months. Current smokers had a shorter OS than never and former smokers (log rank, p = 0.004). Smoking status was significantly associated with OS in univariable analysis (HR 1.45; 95 % CI 1.16-1.82; p < 0.001), and in multivariable analysis that adjusted for established prognostic factors (HR 1.46; 95 % CI 1.16-1.84; p = 0.002). Daily consumption of more than 20 cigarettes, more than 20 years of smoking exposure and heavy long exposure were all independent prognosticators of worse OS. CONCLUSIONS: Current smoking and a higher cumulative smoking exposure are associated with a higher risk of death in patients with mRCC treated with CNT. Even at this stage, smoking negatively affects kidney cancer outcomes.

Prognostic role of ERCC1 protein expression in upper tract urothelial carcinoma following radical nephroureterectomy with curative intent.

BACKGROUND: Excision repair cross-complementing 1 (ERCC1) has been associated with outcomes of urothelial carcinoma of the bladder, but was not yet studied in upper tract urothelial carcinoma (UTUC). The aim of this study was to assess the prognostic role of ERCC1 expression in a large international cohort of UTUC patients. METHODS: Immunohistochemical ERCC1 expression was evaluated in 716 UTUC patients who underwent radical nephroureterectomy with curative intent. ERCC1 was considered positive when the H-score was >1.0. Associations with overall survival and cancer-specific survival were assessed using univariable and multivariable Cox models. RESULTS: ERCC1 was expressed in 303 tumors (42.3 %) and linked with the presence of tumor necrosis (16.2 vs. 10.4 %, p = 0.023), but not with any other clinical or pathological variable. ERCC1 status did not predict cancer-specific survival and overall survival on both univariable (p = 0.70 and 0.32, respectively) and multivariable analyses (p = 0.48 and 0.33, respectively). CONCLUSIONS: ERCC1 is expressed in a significant proportion of UTUC and is linked with tumor necrosis, but its expression appears not to be associated with prognosis following radical nephroureterectomy.

Preoperative serum cholesterol is an independent prognostic factor for patients with renal cell carcinoma (RCC).

OBJECTIVE: To assess the prognostic role of preoperative serum cholesterol in patients with renal cell carcinoma (RCC), as increasing evidence suggests that alterations in the lipid profile are associated with the development, progression and prognosis of various cancers. PATIENTS AND METHODS: We analysed 867 patients, who underwent radical or partial nephrectomy for RCC between 2002 and 2012. Preoperative total cholesterol levels were determined in serum using colorimetric analysis (CHOD-PAP method). The association with cancer-specific survival (CSS) was assessed with Cox models. Discrimination was quantified with the C-index. The median follow-up was 52 months. RESULTS: The median (interquartile range) serum cholesterol was 195 (166-232) mg/dL. Decreasing serum cholesterol was associated with more advanced T, N and M stages (P < 0.001), higher grades (P = 0.001) and presence of tumour necrosis (P = 0.002). Continuously coded cholesterol was associated with CSS in both univariable (hazard ratio [HR] 0.87, P < 0.001) and multivariable analyses (HR 0.93, P = 0.001). The discrimination of a multivariable base model increased significantly from 88.3% to 89.2% following inclusion of cholesterol (P = 0.006). In patients with clinically localised disease (T1-3N0/+M0), cholesterol remained associated with CSS in multivariable analysis (HR 0.90, P = 0.002) and increased the discrimination from 74.6% to 76.9% (P = 0.002). CONCLUSIONS: Preoperative serum cholesterol is an independent prognostic factor for patients with RCC, with lower levels being associated with worse survival. Its use increases the discrimination of established prognostic factors. As cholesterol is a broadly available routine marker, its use may provide a meaningful adjunct in clinical practice. The biological rationale underlying this association remains to be clarified.

Adjuvant cisplatin-based combined chemotherapy for lymph node (LN)-positive urothelial carcinoma of the bladder (UCB) after radical cystectomy (RC): a retrospective international study of >1500 patients.

OBJECTIVE: To compare outcomes of patients with lymph node (LN)-positive urothelial carcinoma of the bladder (UCB) treated with or without cisplatin-based combined adjuvant chemotherapy (AC) after radical cystectomy (RC). PATIENTS AND METHODS: We retrospectively analysed 1523 patients with LN-positive UCB, who underwent RC with bilateral pelvic LN dissection. All patients had no evidence of disease after RC. AC was administered within 3 months. Competing-risks models were applied to compare UCB-related mortality. RESULTS: Of the 1523 patients, 874 (57.4%) received AC. The cumulative 1-, 2- and 5-year UCB-related mortality rates for all patients were 16%, 36% and 56%, respectively. Administration of AC was associated with an 18% relative reduction in the risk of UCB-related death (subhazard ratio 0.82, P = 0.005). The absolute reduction in mortality was 3.5% at 5 years. The positive effect of AC was detectable in patients aged ≤70 years, in women, in pT3-4 disease, and in those with a higher LN density and lymphovascular invasion. This study is limited by its retrospective and non-randomised design, selection bias, the absence of central pathological review and lack in standardisation of LN dissection and cisplatin-based protocols. CONCLUSION: AC seems to reduce UCB-related mortality in patients with LN-positive UCB after RC. Younger patients, women and those with high-risk features such as pT3-4 disease, a higher LN density and lymphovascular invasion appear to benefit most. Appropriately powered prospective randomised trials are necessary to confirm these findings.