Haemospermia in the Real- Life Setting: A New High-Risk Stratification.

OBJECTIVE: To (i) identify a novel risk stratification for patients complaining of haemospermia; and, (ii) compare its predictive ability to select high-risk patients by retrospectively validating the EAU guidelines classification. METHODS: Data from 283 consecutive patients complaining of a single episode/recurrent haemospermia were retrospectively analyzed. Patients were stratified into low vs high-risk according to EAU guidelines, whose diagnostic performance was then validated. We identified a new risk stratification model based on clinical factors associated with (i) positive semen culture and (ii) prostate cancer (PCa) and bladder cancer (BC). Diagnostic accuracy of the two predictive models (EAU vs New) was assessed and decision curve analyses (DCA) tested their clinical benefit. RESULTS: Overall, 259 (91.5%) were high-risk and 24 (8.5%) low risk according to the EAU guidelines. Recurrent haemospermia was reported by 134 (47.4%) patients. 126 (44.5%) had baseline CCI score ≥ 1. At MVA logistic regression analysis, history of recurrent genito - urinary tract infections was identified as a predictor for positive semen culture (OR: 3.39, 95% CI: 1.77 - 6.57, P =.002). Likewise, baseline CCI ≥ 1 was identified as a predictor for PCa and BC (OR: 1.55, 95% CI: 1.17 - 2.04, P =.009). Sensitivity, specificity, and AUC of the EAU guidelines were 13.3%, 89.2% and 51% respectively, whereas the new model performed substantially better: 98.9%, 58% and 78% respectively. CONCLUSION: The application of the EAU guidelines risk stratification does not ensure proper identification of high-risk patients complaining of haemospermia. We propose a novel, better performing and easily implementable risk stratification tool.

Can We Rely Solely on the International Prostate Symptoms Score to Investigate Storage Symptoms in Men with Lower Urinary Tract Symptoms Associated with Benign Prostatic Enlargement? Findings from a Cross-sectional Study.

BACKGROUND: Discrepancies exist between patient-reported storage phase symptoms severity and International Prostate Symptom Score (IPSS) scores. OBJECTIVE: To investigate whether the Overactive Bladder questionnaire (OABq) can detect further storage phase lower urinary tract symptoms (LUTS) among patients complaining solely of voiding LUTS based on the IPSS questionnaire, and to address the real-life impact of voiding LUTS towards patients' quality of life (QoL). DESIGN, SETTING, AND PARTICIPANTS: Data from 233 consecutive men seeking medical help for LUTS/benign prostate enlargement for the first time were analysed. All patients completed both the OABq and the IPSS questionnaire. In order to investigate patients with predominantly voiding phase symptoms, men with storage phase symptoms at IPSS were eventually excluded from the analysis. Patients with an OABq score of ≥40 were considered as those having moderate-to-severe storage LUTS. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Descriptive statistics and linear regression models tested the associations between OABq scores, IPSS, and IPSS-QoL. RESULTS AND LIMITATIONS: OABq scores were higher in men with severe voiding symptoms than in men with mild voiding symptoms (p < 0.001). More than half of patients with predominant voiding symptoms, according to the IPSS questionnaire, depicted a pathologic OABq score. A higher rate of pathologic OABq scores was found in men with moderate/severe voiding symptoms than in those with mild scores (67.4% vs 49.6%, p < 0.001). At multivariable analysis, younger age (beta -0.1, p < 0.01), IPSS voiding subscore (beta 0.3, p < 0.001), and OABq score ≥40 (beta 1.1, p < 0.001) emerged as independent predictors of IPSS-QoL after accounting for prostate volume and flow max. CONCLUSIONS: The OABq can detect the presence of further storage phase LUTS in patients presenting solely with voiding LUTS and IPSS suggestive of voiding phase symptoms. In addition, the OABq was associated with worse patient QoL regardless of the severity of voiding symptoms. PATIENT SUMMARY: The Overactive Bladder questionnaire (OABq) is able to detect the presence of additional storage lower urinary tract symptoms (LUTS) in patients presenting solely with voiding LUTS according to the IPSS questionnaire. Moreover, the OABq is associated with worse quality of life in these patients regardless of the severity of voiding symptoms.

Patients presenting with lower urinary tract symptoms who most deserve to be investigated for primary bladder neck obstruction.

We aimed to investigate clinical features potentially useful in primary bladder neck obstruction (PBNO) diagnosis in men presenting with lower urinary tract symptoms (LUTS). Data from 1229 men presenting for LUTS as their primary complaint at a single centre were retrospectively analysed. All patients underwent a comprehensive medical and physical assessment, and completed the International Prostate Symptoms Score. All patients were investigated with uroflowmetry, and trans-rectal ultrasound imaging to define prostate volume. Urodynamic evaluation was performed when the diagnosis of benign prostatic enlargement was not confirmed and the patient presented a significant chance of detrusor overactivity or underactivity. As per our internal protocol, patients < 60 years old with bothersome LUTS and > 60 years with a prostate volume (PV) < 40 mL were also investigated with urethrocystoscopy to rule out urethral stricture. Logistic regression analysis tested clinical predictors of possible PBNO. Of 1229 patients, 136 (11%) featured a clinical profile which was consistent with PBNO. Overall, these patients were younger (p < 0.0001), had lower BMI (p < 0.0001), less comorbidities (p = 0.004) and lower PSA values (p < 0.0001), but worse IPSS scores (p = 0.01) and lower PV values (p < 0.0001) compared to patients with other-aetiology LUTS. At multivariable analysis, younger age (OR 0.90; p = 0.003) and higher IPSS scores (OR 1.12; p = 0.01) were more likely to be associated with this subset of patients, after accounting for other clinical variables. One out of ten young/middle-aged men presenting for LUTS may be affected from PBNO. Younger patients with more severe LUTS systematically deserve an extensive assessment to rule out PBNO, thus including urethrocystoscopy and urodynamics with voiding-cysto-urethrogram.

Trends in reported male sexual dysfunction over the past decade: an evolving landscape.

We investigated changes in patterns of reported male SDs at a single academic centre over a 10-year time frame. Comprehensive data of 2013 patients consecutively assessed for the first time by a single Sexual Medicine expert between 2006 and 2019 has been analysed. All patients were assessed with a thorough sexual and medical history. Primary reason for seeking medical help at first assessment was recorded for all patients and categorized as: erectile dysfunction (ED), premature ejaculation (PE), low/reduced sexual desire/interest (LSD/I), Peyronie's disease (PD), and other SDs. Linear and logistic regression models tested the association between different reasons for seeking medical help and the time at first evaluation. Local polynomial regression model explored the probability of reporting different SDs over the analysed time frame. Median (IQR) age at first clinical assessment was 50 (38-61) years. Overall, most patients were assessed for ED (824; 41%), followed by PD (369; 18%), PE (322; 16%), LSD/I (204; 10%) and other SDs (294; 15%). Significant changes in terms of reported SD over the analysed time frame were observed. The likelihood of assessing patients for ED significantly increased up to 2013, with a decrease in the past 5 years (p < 0.001). PE assessment at presentation linearly decreased over time (OR: 0.94; 95% CI: 0.91-0.96; p < 0.001). Patients assessed during the past few years were more likely to report PD (OR: 1.20; 95% CI: 1.15-1.25; p < 0.001) and LSD/I (OR: 1.21; 95% CI: 1.16-1.26; p < 0.001), with a linear increase over the evaluated time frame. Likewise, patients were also more likely to report other SDs (Coeff: 1.06; 95% CI: 1.02-1.10; p = 0.004), with a linear increase over time. These results may reflect real changes in SD incidence, increased public awareness towards different SDs and the possible impact of novel treatments available on the market throughout the same time frame.

Is It Compulsory to Investigate for Erectile Dysfunction in Patients Presenting for Low Urinary Tract Symptoms?

BACKGROUND: Current European Association of Urology guidelines suggest investigation of erectile dysfunction (ED) among patients with lower urinary tract symptoms (LUTS) whenever there is a clinical suspicion. OBJECTIVE: To assess factors predictive of ED, which may drive the need for a clinical assessment in men only presenting for LUTS. DESIGN, SETTING, AND PARTICIPANTS: Data from 914 men presenting for LUTS at a single-center outpatient clinic and without a previous diagnosis of ED were analyzed. INTERVENTION: All patients completed the International Prostatic Symptom Score (IPSS) and the International Index of Erectile Function-erectile function (IIEF-EF) questionnaires. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Logistic regression analyses tested potential predictors of ED and severe ED. The accuracy of the predictive models was assessed, and decision curve analyses (DCAs) tested their clinical benefit. RESULTS AND LIMITATIONS: The median baseline IPSS score was 12 (7-19). IIEF-EF scores suggestive of unreported ED were observed in 503 (55%) patients; of all, 251 (27%) men showed severe ED. At logistic regression analysis, age (odds ratio [OR]: 1.04; p<0.001), IPSS score (OR: 1.04; p<0.001), diabetes mellitus (OR: 2.37; p=0.02), and smoking history (OR 1.36; p=0.03) were associated with unreported ED, after accounting for body mass index, hypertension, other cardiovascular diseases, and dyslipidemia. The same factors were associated with severe ED (all p≤0.03). The predictive model including these variables showed good accuracy for predicting ED (areas under the curve 0.69 and 0.72, respectively). However, DCAs showed no greater clinical benefit regarding identifying which patients should actually be screened for ED using these variables versus screening all patients with LUTS. Conversely, the net clinical benefit of the tested model was higher when predicting severe ED. As a limitation, we could not check prospectively the clinical impact of detecting ED in LUTS patients. CONCLUSIONS: Given the importance of ED in terms of overall men's health, segregating patients to be investigated or not for ED according to the traditional risk factors did not emerge more clinically useful than screening all patients presenting for LUTS. PATIENT SUMMARY: Lower urinary tract symptoms (LUTS) are frequently associated with erectile dysfunction (ED). Patients presenting for LUTS only in the everyday clinical practice should always be screened for ED and managed accordingly.

Perioperative and oncologic outcomes of open radical nephrectomy and inferior vena cava thrombectomy with liver mobilization and Pringle maneuver for Mayo III level tumor thrombus: single institution experience.

BACKGROUND: Scarce data are available regarding the technique and outcomes for patients with RCC and Mayo III caval thrombi. The aim of this study was to report surgical and oncological outcomes of RCC patients with Mayo III thrombi treated with radical nephrectomy and thrombectomy after liver mobilization (LM) and Pringle maneuver (PM). METHODS: Retrospective analysis of surgical technique, outcomes and cancer control in 19 patients undergoing LM and PM in a single tertiary care institution were analyzed. RESULTS: Overall, 78% of the patients had performance status ECOG 1 and 58% had a Comorbidity Index >2. Median surgical time was 305 minutes (IQR 264-440). Intraoperative complications were reported for 39% of patients and postoperative complications for 58% (only grade 1 and 2). Intensive Care Unit support was necessary in 16% of the cases. Median length of hospital stay was 9 days (IQR: 7-11). Thirty- and 90-day mortality were 5% and 15%. Two-year overall survival and cancer-specific survival were 60% and 62%, respectively. CONCLUSIONS: We reported surgical techniques, intra- and perioperative complications and follow-up in the largest cohort of RCC patients requiring LM and PM.

Pathological High-risk Renal Cell Carcinoma: Trends in Clinical Characteristics Over 25 Years.

BACKGROUND/AIM: The incidence of renal cell carcinoma (RCC) has been increasing mainly due to the increase in the incidental detection of small renal masses. The aim of this study was to verify whether the trend towards early diagnosis changed the clinical characteristics of pathologically-defined high-risk RCC patients over the last decades. PATIENTS AND METHODS: A total of 741 patients with pathologically-confirmed high-risk RCC (pT1-4, and/or pN1 and/or Fuhrman grade 3-4 and/or all M1 patients) treated with radical (RN) or partial nephrectomy (PN) at a single tertiary referral center between 1987 and 2011 were included in the study. The temporal trends of pre-operative clinical and tumor characteristics were assessed relying on the lowess smoother weighted function with corresponding 95% confidence interval. Estimated annual percentage changes (EAPC) were evaluated using a log linear regression model. RESULTS: The median age of patients increased from 57.5 to 67.3 years between 1987 and 2011 (EAPC 4.9%, p=0.002). Body mass index and gender rates remained stable during the study period. A constant trend towards patients with one or more comorbidity was observed. Moreover, the proportion of asymptomatic patients at diagnosis and of clinical T1 increased by 41.1 and 19.8%, respectively (all p≤0.007). The clinical tumor size dropped from 8.4 to 6.2 cm (EAPC -1.2%, p=0.001). This trend was accompanied by a clinically-relevant increase by 15.3% in the rate of patients without clinical metastases (p=0.07). Conversely, the rate of clinical lymphadenopathies remained stable over time. Finally, the rate of PNs performed increased by 23.3% (p<0.001). CONCLUSION: Over the years, pathologically-confirmed high-risk RCC patients are older, mostly asymptomatic, with smaller cancers, with a higher rate of tumors localized to the kidney and with a decreased rate of metastatic disease at diagnosis. These trends can explain the increasing number of PNs performed despite the presence of a high-risk cancer profile.

Anti-Mullerian Hormone-to-Testosterone Ratio is Predictive of Positive Sperm Retrieval in Men with Idiopathic Non-Obstructive Azoospermia.

The lack of clinically-reliable biomarkers makes impossible to predict sperm retrieval outcomes at testicular sperm extraction (TESE) in men with non-obstructive azoospermia (NOA), resulting in up to 50% of unnecessary surgical interventions. Clinical data, hormonal profile and histological classification of testis parenchyma from 47 white-Caucasian idiopathic NOA (iNOA) men submitted to microdissection TESE (microTESE) were analyzed. Logistic regression analyses tested potential clinical predictors of positive sperm retrieval. The predictive accuracy of all variables was evaluated using the receiver operating characteristic-derived area under the curve, and the clinical net benefit estimated by a decision-curve analysis (DCA). Overall, 23 (49%) and 24 (51%) patients were classified as positive and negative sperm retrievals at microTESE. While circulating hormones associated to a condition of primary hypogonadism did not predict sperm retrieval, levels of anti-Mullerian hormone (AMH) and the ratio AMH-to-total Testosterone (AMH/tT) achieved independent predictor status for sperm retrieval at microTESE, with a predictive accuracy of 93% and 95%. Using cutoff values of <4.62 ng/ml for AMH and <1.02 for AMH/tT, positive sperm retrieval was predicted in all individuals, with 19 men out of 47 potentially spared from surgery. DCA findings demonstrated clinical net benefit using AMH and AMH/tT for patient selection at microTESE.

Nephron-sparing techniques independently decrease the risk of cardiovascular events relative to radical nephrectomy in patients with a T1a-T1b renal mass and normal preoperative renal function.

BACKGROUND: Some reports have suggested that nephron-sparing surgery (NSS) may protect against cardiovascular events (CVe) when compared with radical nephrectomy (RN). However, previous studies did not adjust the results for potential selection bias secondary to baseline cardiovascular risk. OBJECTIVE: To test the effect of treatment type (NSS vs RN) on the risk of developing CVe after accounting for individual cardiovascular risk. DESIGN, SETTING, AND PARTICIPANTS: A multi-institutional collaboration including 1331 patients with a clinical T1a-T1b N0 M0 renal mass and normal renal function before surgery (defined as an estimated glomerular filtration rate≥60 ml/min/1.73 m2). INTERVENTION: RN (n=462, 34.7%) or NSS (n=869, 65.3%) between 1987 and 2013. OUTCOME MEASUREMENT AND STATISTICAL ANALYSES: CVe was defined as onset during the follow-up period of coronary artery disease, cardiomyopathy, hypertension, vasculopathy, heart failure, dysrhythmias, or cerebrovascular disease not known before surgery. Cox regression analyses were performed. To adjust for inherent baseline differences among patients, we performed multivariate analyses adjusting for all available characteristics depicting the overall and cardiovascular-specific profile of the patients. RESULTS AND LIMITATIONS: When stratifying for treatment type, the proportion of patients who experienced CVe at 1, 5, and 10 yr was 5.5%, 9.9%, and 20.2% for NSS patients compared to 8.7%, 15.6%, and 25.9%, respectively, for RN patients (p=0.001). In multivariate analyses, patients who underwent NSS showed a significantly lower risk of developing CVe compared with their RN counterparts (hazard ratio 0.57, 95% confidence interval 0.34-0.96; p=0.03) after accounting for clinical characteristics and cardiovascular profile. Limitations include the retrospective design of the study because other potential confounders may exist. CONCLUSIONS: The risk of CVe after renal surgery is not negligible. Patients treated with NSS have roughly half the risk of developing CVe relative to their RN counterparts. After accounting for clinical characteristics, comorbidities, and cardiovascular risk at diagnosis, NSS independently decreases the risk of CVe relative to RN. PATIENT SUMMARY: The risk of having a cardiovascular event after renal surgery decreases if a portion of the affected kidney is spared.

Impact of synchronous metastasis distribution on cancer specific survival in renal cell carcinoma after radical nephrectomy with tumor thrombectomy.

PURPOSE: Metastatic renal cell carcinoma can be clinically diverse in terms of the pattern of metastatic disease and response to treatment. We studied the impact of metastasis and location on cancer specific survival. MATERIALS AND METHODS: The records of 2,017 patients with renal cell cancer and tumor thrombus who underwent radical nephrectomy and tumor thrombectomy from 1971 to 2012 at 22 centers in the United States and Europe were analyzed. Number and location of synchronous metastases were compared with respect to patient cancer specific survival. Multivariable Cox regression models were used to quantify the impact of covariates. RESULTS: Lymph node metastasis (155) or distant metastasis (725) was present in 880 (44%) patients. Of the patients with distant disease 385 (53%) had an isolated metastasis. The 5-year cancer specific survival was 51.3% (95% CI 48.6-53.9) for the entire group. On univariable analysis patients with isolated lymph node metastasis had a significantly worse cancer specific survival than those with a solitary distant metastasis. The location of distant metastasis did not have any significant effect on cancer specific survival. On multivariable analysis the presence of lymph node metastasis, isolated distant metastasis and multiple distant metastases were independently associated with cancer specific survival. Moreover higher tumor thrombus level, papillary histology and the use of postoperative systemic therapy were independently associated with worse cancer specific survival. CONCLUSIONS: In our multi-institutional series of patients with renal cell cancer who underwent radical nephrectomy and tumor thrombectomy, almost half of the patients had synchronous lymph node or distant organ metastasis. Survival was superior in patients with solitary distant metastasis compared to isolated lymph node disease.

Awareness and knowledge of human papillomavirus-related diseases are still dramatically insufficient in the era of high-coverage vaccination programs.

PURPOSE: Assess knowledge and awareness concerning human papillomavirus (HPV) infection, HPV-associated diseases, and the existence of a specific vaccine among non-HPV-screened Caucasian-European adults after the market introduction of HPV vaccines. METHODS: A cohort of 934 consecutive patients seeking their first medical help for uroandrologic purposes anonymously completed a 17-item questionnaire related to HPV. Data were compared with those of an age-comparable cohort of nurses (controls; n = 172). RESULTS: Knowledge and awareness of HPV infection were reported in 564 (51%) and 735 (66.5%) participants, respectively. Overall, 51.3% participants were informed that HPV is sexually transmitted, but most reported not being aware that HPV infection can be associated with anogenital warts (61.7%), female genitalia (46.6%), penile (58.5%), and oropharyngeal cancer (79.7%). Only 36.5% of the participants were informed regarding the existence of a specific vaccine. HPV knowledge was retrieved through the media and/or the Internet, at school, doctors, and relatives or friends in 395 (35.7%), 155 (14%), 97 (8.8%), and 88 (8.0%) participants, respectively. Multivariable analyses showed that female gender [odds ratio (OR) 3.08; p < 0.001; 95% confidence interval 2.18-4.35] and educational status [high school diploma versus primary-secondary (OR 1.61; p = 0.03; 1.04-2.51); university degree versus primary-secondary (OR 2.89; p < 0.001; 1.83-4.57)] were significantly associated with awareness of HPV. CONCLUSIONS: Only approximately half of the participants reported knowing what HPV infection is, even after the approval and market introduction of the HPV vaccine. Awareness about the existence and availability of a HPV vaccine was even lower.

Extent of lymph node dissection at nephrectomy affects cancer-specific survival and metastatic progression in specific sub-categories of patients with renal cell carcinoma (RCC).

OBJECTIVE: To test whether the number of lymph nodes removed affects cancer-specific survival (CSS) or metastatic progression-free survival (MPFS) in different renal cell carcinoma (RCC) scenarios. METHODS: We used Cox regression analyses to analyse the effect of the number of lymph nodes removed on CSS and MPFS in 1983 patients with RCC treated with nephrectomy. To adjust for possible clinical and surgical selection bias, analyses were further adjusted for number of positive nodes, presence of metastases, age, performance status, T stage, tumour size and grade. RESULTS: The prevalence of lymph node invasion was 6.1%. The mean follow-up period was 83.3 months. Multivariable analyses showed that the number of nodes removed had an independent, protective effect on CSS in patients with pT2a-pT2b or pT3c-pT4 RCC (hazard ratio [HR] 0.91, P = 0.008 and HR 0.89, P < 0.001, respectively), in patients with bulky tumours (tumour size >10 cm, HR 0.97, P = 0.03) or when sarcomatoid features were found (HR 0.81, P = 0.006). The removal of each additional lymph node was associated with a 3-19% increase in CSS. When considering MPFS as an endpoint, the number of nodes removed had an independent, protective effect in the same patient categories. CONCLUSIONS: When clinically indicated, the number of nodes removed affects CSS and MPFS in specific sub-categories of patients with RCC.

Lessons learned from the International Renal Cell Carcinoma-Venous Thrombus Consortium (IRCC-VTC).

Renal cell carcinoma (RCC) extension into the renal vein or the inferior vena cava occurs in 4%-10% of all kidney cancer cases. This entity shows a wide range of different clinical and surgical scenarios, making natural history and oncological outcomes variable and poorly characterized. Infrequency and variability make it necessary to share the experience from different institutions to properly analyze surgical outcomes in this setting. The International Renal Cell Carcinoma-Venous Tumor Thrombus Consortium was created to answer the questions generated by competing results from different retrospective studies in RCC with venous extension on current controversial topics. The aim of this article is to summarize the experience gained from the analysis of the world's largest cohort of patients in this unique setting to date.

The key role of time in predicting progression-free survival in patients with renal cell carcinoma treated with partial or radical nephrectomy: conditional survival analysis.

INTRODUCTION: In surgically treated patients with renal cell carcinoma (RCC), the progression-free survival (PFS) rate may significantly change according to the progression-free postoperative period. To test this hypothesis, we set to evaluate the conditional PFS rate in surgically treated patients with RCC. METHODS: We evaluated 1,454 patients with RCC, surgically treated between 1987 and 2010, at a single institution. Cumulative survival estimates were used to generate conditional PFS rates. Separate Cox regression models were fitted to predict clinical-progression risk in patients who were progression free from 1 to 10 years after surgery. RESULTS: During the immediate postoperative period, the 5-year PFS rate was 88%, and it increased to 92%, 94%, and 97% in patients who remained progression free at, respectively, 1, 5, and 10 years after surgery. At multivariable analyses, where patients with stage I disease were considered as a reference, the highest clinical-progression risk was observed at the eighth postoperative year in patients with stage II disease (hazard ratio [HR]: 2.9) and during the immediate postoperative period in patients with stage III to IV disease (HR: 5.5). In comparison with patients with grade I disease, the highest clinical-progression risk was observed at the fourth (as well as eighth) postoperative year in patients with grade II disease (HR: 5.7), sixth postoperative year in patients with grade III disease (HR: 7.2), and during the immediate postoperative period in patients with grade IV disease (HR: 8.5). CONCLUSIONS: The postoperative progression-free period has an important effect on the subsequent clinical-progression risk. This aspect should be considered along with tumor characteristics to plan the most cost-effective follow-up scheme for surgically treated patients with RCC.

Impact of histologic subtype on cancer-specific survival in patients with renal cell carcinoma and tumor thrombus.

BACKGROUND: Although different prognostic factors for patients with renal cell carcinoma (RCC) and vena cava tumor thrombus (TT) have been studied, the prognostic value of histologic subtype in these patients remains unclear. OBJECTIVE: We analyzed the impact of histologic subtype on cancer-specific survival (CSS). DESIGN, SETTINGS, AND PARTICIPANTS: We retrospectively analyzed the records of 1774 patients with RCC and TT who underwent radical nephrectomy and tumor thrombectomy from 1971 to 2012 at 22 US and European centers. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable ordered logistic and Cox regression models were used to quantify the impact of tumor histology on CSS. RESULTS AND LIMITATIONS: Overall 5-yr CSS was 53.4% (confidence interval [CI], 50.5-56.2) in the entire group. TT level (according to the Mayo classification of macroscopic venous invasion in RCC) was I in 38.5% of patients, II in 30.6%, III in 17.3%, and IV in 13.5%. Histologic subtypes were clear cell renal cell carcinoma (cRCC) in 89.9% of patients, papillary renal cell carcinoma (pRCC) in 8.5%, and chromophobe RCC in 1.6%. In univariable analysis, pRCC was associated with a significantly worse CSS (p<0.001) compared with cRCC. In multivariable analysis, the presence of pRCC was independently associated with CSS (hazard ratio: 1.62; CI, 1.01-2.61; p<0.05). Higher TT level, positive lymph node status, distant metastasis, and fat invasion were also independently associated with CSS. CONCLUSIONS: In our multi-institutional series, we found that patients with pRCC and vena cava TT who underwent radical nephrectomy and tumor thrombectomy had significantly worse cancer-specific outcomes when compared with patients with other histologic subtypes of RCC. We confirmed that higher TT level and fat invasion were independently associated with reduced CSS.

When to perform lymph node dissection in patients with renal cell carcinoma: a novel approach to the preoperative assessment of risk of lymph node invasion at surgery and of lymph node progression during follow-up.

OBJECTIVE: To identify preoperatively patients who might benefit from lymph node dissection (LND). PATIENTS AND METHODS: We assessed lymph node invasion (LNI) at final pathology and lymph node (LN) progression during the follow-up for 1983 patients with RCC, treated with either partial or radical nephrectomy. LN progression was defined as the onset of a new clinically detected lymphadenopathy (>10 mm) in the retroperitoneal lymphatic area. Logistic regression analyses were used to assess the effect of each potential clinical predictor (age, body mass index, tumour side, symptoms, performance status, clinical tumour size, clinical tumour-node-metastasis stage, and albumin, calcium, creatinine, haemoglobin and platelet levels) on the outcome of interest. The most parsimonious multivariable predictive model was developed, and discrimination, calibration and net benefit were calculated. RESULTS: The prevalence of LNI was 6.1% (120/1983 patients) and during the follow-up period, 82 patients (4.1%) experienced LN progression. On multivariable analyses, the most informative independent predictors were tumour stage (cT3-4 vs cT1-2, odds ratio [OR] 1.52, P = 0.05), clinical nodal status [cN1 vs cN0, OR 7.09, P < 0.001], metastases at diagnosis (OR 3.04, P < 0.001) and clinical tumour size (OR 1.14, P < 0.001). The accuracy of the multivariable model was found to be 86.9%, with excellent calibration and net benefit at decision-curve analyses. CONCLUSIONS: By relying on a unique approach, combining the risk of harbouring LNI and/or LN progression during the follow-up period, we have provided the first clinical presurgery model predicting the need for LND.

Effect of number and location of distant metastases on renal cell carcinoma mortality in candidates for cytoreductive nephrectomy: implications for multimodal therapy.

OBJECTIVE: To test whether the combination of number and location of distant metastases affects cancer-specific survival in patients with metastatic renal cell carcinoma. METHODS: Overall, 242 metastatic renal cell carcinoma patients with synchronous metastases at diagnosis underwent cytoreductive nephrectomy at a single institution. Combinations of number and location of distant metastases were coded as: single metastasis and single organ affected, multiple metastases and single organ affected, single metastasis for each of the multiple organs affected, and multiple metastases for each of the multiple organs affected. Covariates included age, symptoms, performance status, American Society of Anesthesiologists score, hemoglobin, lactate dehydrogenase, tumor size, Fuhrman grade, T stage, lymph node status, necrosis, sarcomatoid features and metastasectomy at the time of nephrectomy. RESULTS: The median survival was 34.7 versus 32.3 versus 29.6 versus 8.5 months for single metastasis and single organ affected, multiple metastases and single organ affected single metastasis for each of the multiple organs affected, and multiple metastases for each of the multiple organs affected patients, respectively. At multivariable analyses, the combination of number and location of distant metastases resulted in one of the most informative and independent predictors of cancer-specific survival in metastatic renal cell carcinoma patients. The lung was the location with the highest rate of single organ affected (50.3% vs 35.1% in other sites; P < 0.001). Considering only patients with a single metastasis, no statistically significantly different cancer-specific survival rates were recorded (P > 0.3) among different metastatic organs. CONCLUSIONS: Among metastatic renal cell carcinoma patients undergoing cytoreductive nephrectomy, the combination of the number and location of distant metastases is a major independent predictor of cancer-specific survival. Patients with multiple organs affected by multifocal disease are more likely to have poorer survival.

Staging lymphadenectomy in renal cell carcinoma must be extended: a sensitivity curve analysis.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: In renal cell carcinoma the role of lymphadenectomy (LND) is still controversial. Moreover, no firm consensus exists regarding the minimum number of lymph nodes that should be removed to obtain a satisfactory staging LND at the time of surgery. Our findings demonstrate that, when clinically indicated, staging LND in renal cell carcinoma should be extended. The removal of 15 lymph nodes might represent the lowest threshold to define a staging LND as adequate. More extended LND should be pursued if unfavourable clinical and pathological characteristics are evident at diagnosis and/or during surgery. OBJECTIVE: To investigate the staging of lymphadenectomy in renal cell carcinoma. No convincing data exist regarding the minimum number of lymph nodes that should be removed at the time of nephrectomy to ensure an accurate staging. METHODS: Between 1987 and 2011, 850 patients with renal cell carcinoma underwent either partial or radical nephrectomy plus lymph node dissection (LND) at a single tertiary care institution (Tany N0-1Many ). Receiver operating characteristic curve coordinates were used to graph the probability of finding lymph node invasion according to the number of removed lymph nodes. Assuming that the likelihood of finding lymph node invasion according to the number of lymph nodes removed may be affected by patient characteristics, analyses were further stratified for clinical and pathological characteristics. RESULTS: The rate of lymph node metastases strongly correlated with the clinical and pathological characteristics of the patients. Fifteen lymph nodes need to be removed to achieve a 90% probability of detecting at least one metastatic lymph node. Only slight differences were recorded after stratification for clinical nodal status, the presence of metastases at diagnosis and pathological T stage. Finally, 13, 16 and 21 lymph nodes need to be removed to achieve a 90% probability of detecting lymph node invasion, if present, in the low risk (score 0-1), intermediate risk (score 2-3) and high risk (score 4-5) Mayo Clinic classification, respectively. CONCLUSION: The removal of 15 lymph nodes represents the lowest threshold for considering a staging LND as adequate. More extended LND should be pursued if unfavourable clinical and pathological characteristics are evident at diagnosis and/or during surgery.

The extent of lymphadenectomy does affect cancer specific survival in pathologically confirmed T4 renal cell carcinoma.

BACKGROUND: Controversies exist regarding the effect of lymphadenectomy (LND) in renal cell carcinoma (RCC). We hypothesized that patients with locally advanced cancer invading beyond Gerota's fascia (pT4 Nany Many RCC) might benefit from an extended LND not only for staging but also for survival purposes. MATERIALS AND METHODS: Clinical and pathologic data were prospectively gathered in 1.847 patients treated at a single Academic Center, between 1987 and 2011. Only patients with pT4 RCC (TNM 2009, n=44, 2.4%) were included. Univariable (UVA) and multivariable (MVA) Cox regression analyses targeted the association between the number of lymph nodes removed and cancer specific mortality (CSM). Analyses were adjusted for age, Fuhrman grade, symptoms at presentation, metastases at diagnosis, ECOG performance status, tumor size, number of positive nodes, and presence of necrosis or sarcomatoid features. RESULTS: Mean number of nodes removed was 11.8 (median 8, range 1-37). Mean number of positive nodes was 4.8 (median 2, range 0-36). Cancer-specific survival rates at 1, 2 and 3 years of follow-up were 39.3%, 25.0% and 8.6%, respectively. When stratified for nodal status, cancer-specific survival rates at 1, 2 and 3 years of follow-up were 65.0, 36.1, and 9.0% vs. 13.3, 13.0, and 6.7%, for pN0 vs. pN+ cases, respectively (p=0.004). At MVA, after adjusting for all the possible confounders, the number of positive nodes resulted independently associated with CSM (HR 1.25, p=0.001). Interestingly, at MVA, the number of nodes removed achieved the independent predictor status, as well (HR 0.84, p=0.007) showing a protective effect on survival. The risk of dying increased of 16% every positive node found (p<0.001), and decreased of 8% every node removed (p=0.02) (Table II). CONCLUSIONS: A more extended retroperitoneal lymphadenectomy at the time of nephrectomy statistically significantly decreased CSM in pT4 cases.

Impact of venous tumour thrombus consistency (solid vs friable) on cancer-specific survival in patients with renal cell carcinoma.

BACKGROUND: To our knowledge, the impact of venous tumour thrombus (VTT) consistency in patients affected by renal cell carcinoma (RCC) has never been addressed. OBJECTIVE: To analyse the effect of VTT consistency on cancer-specific survival (CSS). DESIGN, SETTING, AND PARTICIPANTS: We retrospectively analysed 174 consecutive patients with RCC and renal vein or inferior vena cava (IVC) VTT who underwent surgical treatment between 1989 and 2007 at our institute. INTERVENTION: All patients underwent radical nephrectomy and thrombectomy. MEASUREMENTS: Pathologic specimens were reviewed by a single uropathologist. In addition to traditional pathologic features, the morphologic aspect of the tumour thrombus was evaluated to distinguish solid from friable patterns. The prognostic role of thrombus consistency (solid vs friable) on CSS was assessed by means of Cox regression models. RESULTS AND LIMITATIONS: The VTT was solid in 107 patients (61.5%) and friable in 67 patients (38.5%). The presence of a friable VTT increased the risk of having synchronous nodal or distant metastases, higher tumour grade, higher pathologic stage, and simultaneous perinephric fat invasion (all p < 0.05). The median follow-up was 24 mo. The median CSS was 33 mo; the median CSS was 8 mo in patients with a friable VTT and 55 mo in patients with a solid VTT (p < 0.001). On multivariable analyses, the presence of a friable VTT was an independent predictor of CSS (p = 0.02). The power of our conclusion may be somewhat limited by the relatively small study population and the retrospective nature of the study. CONCLUSIONS: In patients with RCC and VTT, the presence of a friable thrombus is an independent predictor of CSS. If our finding is confirmed by further studies, the consistency of the tumour thrombus should be introduced into routine pathologic reports to provide better patient risk stratification.