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Artificial intelligence (AI) aims at simulating, or approximating, human intelligence in machines with the goal of reproducing, replacing or even improving brain tasks of perception, reasoning, and learning. For example, we have seen AI/ML models treating the ordinal variable Gleason Score as a continuous variable or age as any number between zero and infinity. And do the AI/ML models improve predictions above and beyond current standard of care and models based on already known predictors of the outcome?. [Extracted from the article]

Objectives: To determine if management of ureteric stones in the UK changed during the coronavirus disease 2019 (COVID‐19) pandemic and whether this affected patient outcomes. Patients and methods: We conducted a multicentre retrospective study of adults with computed tomography‐confirmed ureteric stone disease at 39 UK hospitals during a pre‐pandemic period (23/3/2019–22/6/2019) and a period during the pandemic (the 3‐month period after the first severe acute respiratory syndrome coronavirus‐2 case at individual sites). The primary outcome was success of primary treatment modality, defined as no further treatment required for the index ureteric stone. Our study protocol was published prior to data collection. Results: A total of 3735 patients were included (pre‐pandemic 1956 patients; pandemic 1779 patients). Stone size was similar between groups (P > 0.05). During the pandemic, patients had lower hospital admission rates (pre‐pandemic 54.0% vs pandemic 46.5%, P < 0.001), shorter mean length of stay (4.1 vs 3.3 days, P = 0.02), and higher rates of use of medical expulsive therapy (17.4% vs 25.4%, P < 0.001). In patients who received interventional management (pre‐pandemic 787 vs pandemic 685), rates of extracorporeal shockwave lithotripsy (22.7% vs 34.1%, P < 0.001) and nephrostomy were higher (7.1% vs 10.5%, P = 0.03); and rates of ureteroscopy (57.2% vs 47.5%, P < 0.001), stent insertion (68.4% vs 54.6%, P < 0.001), and general anaesthetic (92.2% vs 76.2%, P < 0.001) were lower. There was no difference in success of primary treatment modality between patient cohorts (pre‐pandemic 73.8% vs pandemic 76.1%, P = 0.11), nor when patients were stratified by treatment modality or stone size. Rates of operative complications, 30‐day mortality, and re‐admission and renal function at 6 months did not differ between the data collection periods. Conclusions: During the COVID‐19 pandemic, there were lower admission rates and fewer invasive procedures performed. Despite this, there were no differences in treatment success or outcomes. Our findings indicate that clinicians can safely adopt management strategies developed during the pandemic to treat more patients conservatively and in the community. [ABSTRACT FROM AUTHOR]

Objective: To systematically identify and compare the performance of prognostic models providing estimates of survival or recurrence of localized renal cell cancer (RCC) in patients treated with surgery with curative intent. Materials and Methods: We performed a systematic review (PROSPERO CRD42019162349). We searched Medline, EMBASE and the Cochrane Library from 1 January 2000 to 12 December 2019 to identify studies reporting the performance of one or more prognostic model(s) that predict recurrence‐free survival (RFS), cancer‐specific survival (CSS) or overall survival (OS) in patients who have undergone surgical resection for localized RCC. For each outcome we summarized the discrimination of each model using the C‐statistic and performed multivariate random‐effects meta‐analysis of the logit transformed C‐statistic to rank the models. Results: Of a total of 13 549 articles, 57 included data on the performance of 22 models in external populations. C‐statistics ranged from 0.59 to 0.90. Several risk models were assessed in two or more external populations and had similarly high discriminative performance. For RFS, these were the Sorbellini, Karakiewicz, Leibovich and Kattan models, with the UCLA Integrated Staging System model also having similar performance in European/US populations. All had C‐statistics ≥0.75 in at least half of the validations. For CSS, they the models with the highest discriminative performance in two or more external validation studies were the Zisman, Stage, Size, Grade and Necrosis (SSIGN), Karakiewicz, Leibovich and Sorbellini models (C‐statistic ≥0.80 in at least half of the validations), and for OS they were the Leibovich, Karakiewicz, Sorbellini and SSIGN models. For all outcomes, the models based on clinical features at presentation alone (Cindolo and Yaycioglu) had consistently lower discrimination. Estimates of model calibration were only infrequently included but most underestimated survival. Conclusion: Several models had good discriminative ability, with there being no single 'best' model. The choice from these models for each setting should be informed by both the comparative performance and availability of factors included in the models. All would need recalibration if used to provide absolute survival estimates. [ABSTRACT FROM AUTHOR]

Presurgical axitinib therapy increases fibrotic reactions within tumor thrombus in renal cell carcinoma with thrombus extending to the inferior vena cava. Keywords: neoadjuvant; thrombus; systemic treatment; tyrosine kinase inhibitor; cava thrombus EN neoadjuvant thrombus systemic treatment tyrosine kinase inhibitor cava thrombus 566 568 3 04/25/23 20230501 NES 230501 Abbreviations GRADE Grading of recommendations assessment, development and evaluation IO immunotherapies IVC inferior vena cava TKI tyrosine kinase inhibitor VTT venous tumour thrombus Renal cell carcinoma (RCC) with venous tumour thrombus (VTT) extension into the inferior vena cava (IVC) occurs in about 4%-15% of cases [[1]]. Neoadjuvant, thrombus, systemic treatment, tyrosine kinase inhibitor, cava thrombus. [Extracted from the article]

Objective: To investigate whether pT1 renal cell carcinoma (RCC) should be followed differently after partial (PN) or radical nephrectomy (RN) based on a retrospective analysis of a multicentre database (RECUR). Subjects: A retrospective study was conducted in 3380 patients treated for nonmetastatic RCC between January 2006 and December 2011 across 15 centres from 10 countries, as part of the RECUR database project. For patients with pT1 clear‐cell RCC, patterns of recurrence were compared between RN and PN according to recurrence site. Univariate and multivariate models were used to evaluate the association between surgical approach and recurrence‐free survival (RFS) and cancer‐specific mortality (CSM). Results: From the database 1995 patients were identified as low‐risk patients (pT1, pN0, pNx), of whom 1055 (52.9%) underwent PN. On multivariate analysis, features associated with worse RFS included tumour size (hazard ratio [HR] 1.32, 95% confidence interval [CI] 1.14–1.39; P < 0.001), nuclear grade (HR 2.31, 95% CI 1.73–3.08; P < 0.001), tumour necrosis (HR 1.5, 95% CI 1.03–2.3; P = 0.037), vascular invasion (HR 2.4, 95% CI 1.3–4.4; P = 0.005) and positive surgical margins (HR 4.4, 95% CI 2.3–8.5; P < 0.001). Kaplan–Meier analysis of CSM revealed that the survival of patients with recurrence after PN was significantly better than those with recurrence after RN (P = 0.02). While the above‐mentioned risk factors were associated with prognosis, type of surgery alone was not an independent prognostic variable for RFS nor CSM. Limitations include the retrospective nature of the study. Conclusion: Our results showed that follow‐up protocols should not rely solely on stage and type of primary surgery. An optimized regimen should also include validated risk factors rather than type of surgery alone to select the best imaging method and to avoid unnecessary imaging. A follow‐up of more than 3 years should be considered in patients with pT1 tumours after RN. A novel follow‐up strategy is proposed. [ABSTRACT FROM AUTHOR]

Objective: To evaluate intermediate‐ and long‐term oncological outcomes of active surveillance (AS) for localized renal masses (LRMs). Methods: This systematic literature review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses statement and registered on PROSPERO (CRD42021230416). Studies on AS for LRMs with at least 3 years' follow‐up were eligible. Two review authors independently screened the literature, extracted data, and assessed risk of bias. The primary outcomes were metastasis rate, renal cell carcinoma (RCC)‐specific mortality (RCC‐SM) and all‐cause mortality (ACM). Pooled estimates were obtained from random‐effects models. Subgroup analyses were performed for small renal masses (SRMs; ≤4 cm) and non‐SRMs (>4 cm). Results: We analysed 18 unique cohorts comprising 2066 patients. The pooled initial maximum tumour size was 2.8 cm (95% confidence interval [CI] 2.7–3.0) and the percutaneous biopsy rate was 28%. The pooled mean annual growth rate was 2.8 mm (95% CI 2.1–3.4). Within a pooled mean follow‐up of 53 months, 2.1% (95% CI 1.0–3.6) of patients developed metastatic disease, 1.0% (95% CI 0.3–2.1) died from RCC and 22.6% (95% CI 15.8–30.2) died from any cause. For patients with SRMs (nine studies, n = 987), the pooled metastasis rate was 1.8% (95% CI 0.5–3.7), RCC‐SM was 0.6% (95% CI 0–2.1), and ACM was 28.5% (95% CI 17.4–41.4). Across five studies reporting on outcomes of 239 patients with non‐SRMs, the pooled metastasis rate was 5.1% (95% CI 0–17.3), RCC‐SM was 2.1% (95% CI 0–8.9) and ACM was 29.1% (95% CI 13.6–47.3). This review is limited by non‐standardized inclusion criteria, definitions and follow‐up, data heterogeneity, limited patient numbers in sub‐analyses and absence of high‐quality studies. Conclusions: Active surveillance is a safe intermediate‐ and long‐term management option for well‐selected patients with LRMs, especially those with SRMs. Limited data are available for non‐SRMs, but current evidence would support further evaluation of this approach in selected patients. It is not possible to draw definitive conclusions until more high‐quality data become available. [ABSTRACT FROM AUTHOR]

Objectives: To externally validate a nomogram recently proposed by Larcher et al. (BJU Int. 2017; 120: 490) and to develop a simplified model with comparable accuracy to guide on the need for staging chest computed tomography (CT) for patients with new renal masses. Patients and Methods: We analysed the data of 1082 consecutive patients with unilateral enhancing renal masses referred to urology multidisciplinary team meetings at two centres between 2011 and 2017. All patients underwent a staging chest CT at diagnosis. We fitted multivariable logistic regression models and tested the Larcher model performance using area under the receiver‐operating curve (AUC), calibration and decision curve analysis. Results: Forty‐two patients (3.9%) had a positive chest CT. The Larcher nomogram had an AUC of 83.8% (95% confidence interval [CI] 77.1–90.6), but was only moderately well calibrated (calibration‐in‐the‐large = −0.61, slope = 0.82). Specifically, the nomogram overestimated the risk of positive chest CT, and the magnitude of miscalibration increased with increasing predicted risks. Using a stepwise backward approach, a new model was developed including tumour size, nodal stage and systemic symptoms. Compared with the Larcher model, the new model had a similar AUC (82.7% [95% CI 75.5–90.0]), but improved calibration and clinical net benefit. The predicted risk of positive chest CT was <1% in the low‐risk group and 1.9–79.9% in the high‐risk group. Conclusion: The Larcher nomogram is an accurate prediction tool that was moderately well calibrated with our dataset. However, our simplified model has similar accuracy and uses more objective variables available from referral, so may be easier to incorporate into clinical practice. The low‐risk group from our model (tumour size ≤4 cm and no systemic symptoms) had a risk of positive chest CT <1%, suggesting these patients may forego chest CT. [ABSTRACT FROM AUTHOR]

Objective: To summarize the available evidence on renorrhaphy techniques and to assess their impact on peri‐operative outcomes after minimally invasive partial nephrectomy (MIPN). Materials and Methods: A systematic review of the literature was performed in January 2018 without time restrictions, using MEDLINE, Cochrane and Web of Science databases according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses statement recommendations. Studies providing sufficient details on renorrhaphy techniques during laparoscopic or robot‐assisted partial nephrectomy and comparative studies focused on peri‐operative outcomes were included in qualitative and quantitative analyses, respectively. Results: Overall, 67 and 19 studies were included in the qualitative and quantitative analyses, respectively. The overall quality of evidence was low. Specific tumour features (i.e. size, hilar location, anatomical complexity, nearness to renal sinus and/or urinary collecting system), surgeon's experience, robot‐assisted technology, as well as the aim of reducing warm ischaemia time and the amount of devascularized renal parenchyma preserved represented the key factors driving the evolution of the renorrhaphy techniques during MIPN over the past decade. Quantitative synthesis showed that running suture was associated with shorter operating and ischaemia time, and lower postoperative complication and transfusion rates than interrupted suture. Barbed suture had lower operating and ischaemia time and less blood loss than non‐barbed suture. The single‐layer suture technique was associated with shorter operating and ischaemia time than the double‐layer technique. No comparisons were possible concerning renal functional outcomes because of non‐homogeneous data reporting. Conclusions: Renorrhaphy techniques significantly evolved over the years, improving outcomes. Running suture, particularly using barbed wires, shortened the operating and ischaemia times. A further advantage could derive from avoiding a double‐layer suture. [ABSTRACT FROM AUTHOR]

Objective: To validate microvascular (MVI) and lymphovascular (LVI) invasion as prognostic factors in patients with renal cell carcinoma (RCC). Patients and Methods: Data of patients with RCC who underwent radical or nephron‐sparing surgery were prospectively collected from three academic centres. The occurrence of MVI and LVI was determined with standard staining protocols by experienced pathologists at the time of diagnosis. The association of MVI and LVI with clinicopathological data, metastatic spread, and cancer‐specific survival (CSS) were evaluated with Fisher's exact tests, binary logistic regression analyses, and univariable and multivariable Cox proportional hazard regression models. Results: MVI was present in 201 of 747 patients (26.9%) and was associated with advanced Tumour‐Node‐Metastasis (TNM) stages, high Fuhrman grades, and sarcomatoid features (all P < 0.001). MVI was associated with a higher rate of metastatic spread. LVI was present in 32 of 573 patients (5.5%) and was associated with advanced TNM stages, high Fuhrman grade, and sarcomatoid features (all P < 0.001). Two‐thirds of LVI‐positive patients died (P < 0.001). Both LVI and MVI were significantly associated with CSS in all patients, clear cell RCC (ccRCC), and localised RCC in univariable analysis (all P < 0.001). On multivariable analysis, presence of MVI was identified as an independent prognostic factor (hazard ratio 2.09; P = 0.001). Moreover, MVI [odds ratio (OR) 2.7; P = 0.001] and not macrovascular invasion (P = 0.895) was an independent predictor of sychronuous metastatic spread. LVI was the strongest factor associated with sychronous metastatic spread (OR 4.73, 95% confidence interval 1.84–12.14; P = 0.001) in all patients and in the subgroup of patients with ccRCC (P = 0.001). Conclusions: The present study validated LVI and MVI as prognostic factors for poor outcome in RCC. These findings endorse an evaluation of both variables in the clinical routine setting to facilitate survival prognostication in follow‐up protocols and for assignment to adjuvant treatment trials. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives To construct a nomogram based on preoperative variables to better predict the likelihood of complications occurring within 30 days of radical nephroureterectomy ( RNU). Patients and Methods The charts of 731 patients undergoing RNU at eight academic medical centres between 2002 and 2014 were reviewed. Preoperative clinical, demographic and comorbidity indices were collected. Complications occurring within 30 days of surgery were graded using the modified Clavien-Dindo scale. Multivariate logistic regression determined the association between preoperative variables and post- RNU complications. A nomogram was created from the reduced multivariate model with internal validation using the bootstrapping technique with 200 repetitions. Results A total of 408 men and 323 women with a median age of 70 years and a body mass index of 27 kg/m2 were included. A total of 75% of the cohort was white, 18% had an Eastern Cooperative Oncology Group ( ECOG) performance status ≥2, 20% had a Charlson comorbidity index ( CCI) score >5 and 50% had baseline chronic kidney disease ( CKD) ≥ stage III. Overall, 279 patients (38%) experienced a complication, including 61 events (22%) with Clavien grade ≥ III. A multivariate model identified five variables associated with complications, including patient age, race, ECOG performance status, CKD stage and CCI score. A preoperative nomogram incorporating these risk factors was constructed with an area under curve of 72.2%. Conclusions Using standard preoperative variables from this multi-institutional RNU experience, we constructed and validated a nomogram for predicting peri-operative complications after RNU. Such information may permit more accurate risk stratification on an individual cases basis before major surgery. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 ( T1-3 N0/+ 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. [ABSTRACT FROM AUTHOR]

Objective To evaluate the frequency of bladder outlet obstruction ( BOO) and detrusor overactivity ( DO) in patients with castration-resistant prostate cancer ( CRPC) and lower urinary tract symptoms ( LUTS)., Patients and Methods Our prospective urodynamics database was queried., Inclusion criteria were CRPC and an International Prostate Symptom Score ( IPSS) ≥ 20., Exclusion criteria were previous local therapy to the prostate gland, known urethral stricture disease, and a neurological component of LUTS., Twenty-one patients were identified., Urodynamic findings were analysed and compared with those of a matched cohort of 42 patients with benign prostatic enlargement ( BPE)., Results The median age of patients in the CRPC group was 74 years, and the median prostate-specific antigen ( PSA) level at the time of the urodynamic study was 90 ng/mL., According to the BOO index, three patients (14%) were obstructed, three were equivocally obstructed (14%) and 15 were unobstructed., DO was seen in 12 patients (57%)., Compared with the BPE group, patients with CRPC had lower cystometric bladder capacities ( P = 0.003), were less likely to have BOO (14 vs 43%, P = 0.009) and more likely to have DO (57 vs 29%, P = 0.028)., Conclusions This study generates the hypothesis that only a minority of CRPC patients with LUTS have BOO, and that more than half of patients have DO., LUTS in CRPC may therefore be seldom attributable to BOO, but are, at least in part, related to DO and reduced cystometric capacity., A urodynamic investigation may be necessary before palliative transurethral resection of the prostate to select appropriate candidates., Larger prospective studies are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

Objectives • To evaluate the prognostic value of the Bajorin criteria in a multi-institutional cohort of patients with disease recurrence after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). • To investigate whether clinical, pathological and/or biological factors at time of disease recurrence are also associated with cancer-specific outcomes in these patients. Patients and Methods • We identified 242 patients with disease recurrence after RNU for UTUC from 11 centres. • With regard to the Bajorin criteria, patients were categorized into three groups based on two risk factors: Karnofsky performance status <80% and the presence of visceral metastasis. • Assessed variables included pathological characteristics, time to disease recurrence, age-adjusted Charlson comorbidity index (ACCI), American Society of Anesthesiologists (ASA) score, and laboratory tests at time of disease recurrence. Results • Overall, 185 patients died from their disease; the median survival was 9 months. The survival rates at 1 year were 53, 33, and 39% for patients with no (n = 18), one (n = 109) and two (n = 115) risk factors, respectively, with no significant difference between the groups. • In univariable analyses, higher pT-stage, tumour necrosis, non-administered salvage chemotherapy, higher ACCI score, higher ASA score, lower albumin level and higher white blood cell count were significantly associated with a shorter time to cancer-specific mortality. Conclusions • We confirmed the poor yet variable outcomes of patients with disease recurrence after RNU. • While the Bajorin criteria seem to have limited prognostic value in this specific cohort, we found several other clinical variables to be associated with worse cancer-specific mortality. • If validated, these factors should be taken into consideration for clinical trial design. [ABSTRACT FROM AUTHOR]

Objective To evaluate ABO blood group as a prognostic marker in patients with renal cell carcinoma ( RCC)., Patients and Methods This retrospective study included 556 consecutive patients who underwent surgery for RCC at a single institution., The associations of ABO blood group with clinical and pathological variables were assessed using Kruskal- Wallis and chi-squared tests., The impact on overall survival ( OS) and RCC-specific survival ( RCC-SS) was analysed using univariable and multivariable Cox proportional hazards regression models., Results Blood group O was associated with the absence of lymph node metastases (P = 0.034) and the presence of bilateral RCC (P = 0.017)., No associations with age, gender, body mass index, Charlson comorbidity index, T stage, M stage, grade and histological subtype were observed., In univariable and multivariable survival analysis, ABO blood group was not associated with OS and RCC-SS., Conclusions In the present study, ABO blood group was not linked with RCC prognosis., Blood group O may be associated with the absence of lymph node metastases and the presence of bilateral RCC., External validation in larger cohorts is necessary. [ABSTRACT FROM AUTHOR]

Aims Tumour-associated macrophages ( TAM) have been reported to be regulators of progression in various human cancers. We evaluated the prognostic relevance of TAM in a large series of patients with papillary renal cell carcinoma ( PRCC). Methods and results The impact of TAM on cancer-specific survival ( CSS) in 177 patients with PRCC was assessed using the Kaplan- Meier method and log-rank test. A multivariate Cox regression analysis was performed with respect to CSS. The presence of TAM was noted in 112 of 177 (63%) tumours and was associated statistically significantly with favourable pathological parameters, including low pathological T stage, node-negative tumours, low tumour grade, absence of vascular invasion and papillary subtype (all P < 0.05), respectively. Five-year CSS probabilities for patients with TAM-positive tumours were 93.5%, compared with 72.5% in patients with TAM-negative tumours, respectively ( P < 0.001). Multivariate analysis revealed node-positive tumours, distant metastases and UICC stage (I versus II- IV) as independent predictors of death from PRCC, whereas the presence of TAM was associated independently with favourable outcome (hazard ratio = 0.45, 95% confidence interval 0.24-0.84, P = 0.012). Conclusions The presence of TAM was shown independently to reduce the risk of death from cancer by 55%. The presence of TAM should therefore become part of routine pathology reporting in PRCC. [ABSTRACT FROM AUTHOR]

Objective To validate high-sensitivity C-reactive protein (hs- CRP) serum levels as an independent marker for disease-free survival ( DFS) in clinically localised clear cell renal cell carcinoma ( ccRCC)., Patients and Methods In all, 403 consecutive patients with clinically localised ( T1-3N0M0) ccRCC treated by radical or partial nephrectomy were enrolled., Preoperative serum levels of hs- CRP were evaluated as both a continuous and categorical variables., Associations with clinical (age, gender) and pathological variables ( T classification, grade, tumour necrosis) were assessed with the chi-square and Kruskal- Wallis tests., Univariable and multivariable Cox proportional hazards models were fitted. The prognostic accuracy ( PA) was assessed with Harrell's C-index., Results The mean hs- CRP level was 1.32 mg/dL. The hs- CRP levels were associated with T classification ( P = 0.05), high-grade disease (P < 0.001) and tumour necrosis ( P = 0.003)., After a median follow-up of 43 months, 41 patients (10.1%) had developed disease recurrence. With each unit increase in hs- CRP levels, the risk of recurrence increased by 10% (hazard ratio 1.10, P = 0.015)., The thresholds of 0.5 and 0.75 mg/dL showed the best discrimination for stratification of patients according to the probability of recurrence., These categorically coded hs- CRP levels were identified as independent prognostic factors in multivariable analyses ( P < 0.001) and led to a significant increase in the PA of a multivariable base model containing the variables of the 'Stage, Size, Grade and Necrosis' ( SSIGN) score., Conclusions This study validates preoperative serum hs- CRP levels as independent prognostic factor after surgery for localised ccRCC., Hs-CRP may be included in standard prognostic modelling after surgery and may guide surveillance and inclusion in adjuvant clinical trials. [ABSTRACT FROM AUTHOR]

BACKGROUND: The short arm of chromosome 3 (3p) harbors the von Hippel-Lindau ( VHL) tumor suppressor gene, and the long arm of chromosome 14 (14q) harbors the hypoxia-inducible factor 1α ( HIF-1α) gene. The objective of this study was to evaluate the significance of 3p loss (loss VHL gene) and 14q loss (loss HIF-1α gene) in clear cell renal cell carcinoma (ccRCC). METHODS: In total, 288 ccRCC tumors underwent a prospective cytogenetic analysis for alterations in chromosomes 3p and 14q. Tumors were assigned to 1 of 4 possible chromosomal alterations: VHL +3p/+14q (VHL wild type [VHL-WT]), VHL +3p/−14q (VHL-WT plus HIF2α [WT/H2]), −3p/+14q (HIF1α and HIF2α [H1H2]), and −3p/−14q (HIF2α [H2]). RESULTS: Among patients who had loss of 3p, tumors with −3p/−14q (H2) alterations were larger ( P = .002), had higher grade ( P = .002) and stage ( P = .001), and more often were metastatic ( P = .029) than tumors that retained 14q (H1H2). All patients who had tumors with −3p/−14q (H2) had worse cancer-specific survival ( P = .014), and patients who had localized disease ( P = .012) and primary T1 (pT1) tumors ( P = .008) had worse recurrence-free survival. In patients who had pT1 tumors, combined 3p/14q loss was an independent predictor of recurrence-free survival (hazard ratio, 11.19; 95% confidence interval, 1.91-65.63) and cancer-specific survival (hazard ratio, 15.93; 95% confidence interval, 3.09-82.16). The current investigation was limited by its retrospective design, single-center experience, and a lack of confirmatory protein analyses. CONCLUSIONS: Loss of chromosome 3p (the VHL gene) was associated with improved survival in patients with ccRCC, whereas loss of chromosome 14q (the HIF-1α gene) was associated with worse outcomes. The results of the current study support the hypothesis that HIF-1α functions as an important tumor suppressor gene in ccRCC. Cancer 2013. © 2013 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: The aim of this study was to evaluate the prevalence of chromosome 8q gain in clear cell renal cell carcinoma (CCRCC) and to correlate the findings with tumor phenotype and disease-specific survival (DSS). METHODS: The tumor karyotypes of 336 consecutive patients with CCRCC were prospectively evaluated with classical cytogenetic analysis. Chromosome 8q status was correlated with clinicopathological variables, and its impact on DSS was evaluated. RESULTS: Gain of 8q occurred in 28 tumors (8.3%). Gain of 8q was associated with a higher risk of regional lymph node (21.4% vs 6.2%, P = .011) and distant metastases (50.0% vs 24.4%, P = .006), and greater tumor sizes ( P = .030). Patients with gain of 8q had a 3.22-fold increased risk of death from CCRCC ( P < .001). In multivariable analysis, gain of 8q was identified as an independent prognostic factor (hazard ratio, 2.37; P = .006). The concordance index of a multivariable base model increased significantly following inclusion of 8q gain ( P = .0015). CONCLUSIONS: Gain of chromosome 8q occurs in a subset of CCRCCs and is associated with an increased risk of metastases and death from CCRCC. Because the proto-oncogene c-MYC is among the list of candidate genes located on 8q, our data suggest that these tumors may have unique pathways activated, which are associated with an aggressive tumor phenotype. If confirmed, defining tumors with gain of 8q may assist in identifying patients who would benefit for specific c-MYC inhibitors or agents that target the MAPK/ERK (mitogen-activated protein kinase) pathway. Cancer 2012. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: Tobacco use is a leading cause of premature death, yet few studies have investigated the effect of tobacco exposure on the outcome of patients with renal cell carcinoma (RCC). The authors of this report retrospectively studied the impact of smoking on clinicopathologic factors, survival outcomes, and p53 expression status in a large cohort of patients with RCC. METHODS: Eight hundred-two patients (457 nonsmokers and 345 smokers) who had up to 232 months of follow-up were compared for differences in their clinicopathologic features and survival outcomes. Immunohistochemical differences in p53 expression were correlated with smoking status. RESULTS: Smokers presented more commonly with pulmonary comorbidities ( P < .0001) and cardiac comorbidities ( P = .014) and with a worse performance status ( P = .031) than nonsmokers. Smoking was associated significantly with tumor multifocality ( P = .022), higher pathologic tumor classification ( P = .037), an increased risk of bulky lymph node metastases ( P = .031), and the presence of distant metastases ( P < .0001), especially lung metastases ( P < .0001). Both overall survival (OS) (62.37 months vs 43.64 months; P = .001) and cancer-specific survival (CSS) (87.43 months vs 56.57 months; P = .005) were significantly worse in patients who smoked. The number of pack-years was retained as an independent predictor of CSS and OS in patients with nonmetastatic disease. Mean expression levels of p53 were significantly higher in current smokers compared with former smokers and nonsmokers ( P = .012). CONCLUSIONS: In patients with RCC, a history of smoking was associated with worse pathologic features and survival outcomes and with an increased risk of having mutated p53. Further investigation of the genetic and molecular mechanisms associated with decreased CSS in patients with RCC who have a history of smoking is indicated. Cancer 2012;. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: Currently, there are no established diagnostic and prognostic serum markers for renal cell carcinoma (RCC). The objective of this study was to evaluate the putative significance of serum cell-free DNA. METHODS: Preoperative serum samples from 200 consecutive patients with sporadic, solid renal tumors were analyzed (157 patients with RCC and 43 patients with benign renal tumors). Quantitative real-time polymerase chain reaction was used to assess total cell-free DNA (ring finger protein 185 [ RNF185]) and CpG island methylation of Ras association domain family member 1A ( RASSF1A) von Hippel-Lindau ( VHL), prostaglandin-endoperoxidase synthase 2 ( PTGS2), and P16 (cyclin-dependent kinase inhibitor 2A). Associations with RCC, pathologic variables, and disease-specific survival were evaluated. RESULTS: Total cell-free DNA levels and CpG island methylation of RASSF1A and VHL were highly diagnostic for RCC with an area under the receiver operating characteristic curve of 0.755, 0.705, and 0.694, respectively. VHL methylation was detected more frequently in patients with clear cell RCC than in those with other subtypes ( P = .007). Total cell-free DNA levels were higher in patients with metastatic RCC ( P < .001) and necrotic RCC ( P = .003) and were associated with poorer disease-specific survival ( P < .001). In multivariate analysis, the tumor stage, size, grade, and necrosis (SSIGN) score ( P < .001) and categorized total cell-free DNA levels ( P = .028) were retained as independent prognostic factors. CONCLUSIONS: The current results indicated that cell-free DNA represents a novel serum-based diagnostic and prognostic biomarker for RCC. Total serum cell-free DNA levels and CpG island methylation of RASSF1A and VHL may be useful diagnostic biomarkers for RCC. VHL methylation of cell-free DNA is suggestive of clear cell RCC. Total serum cell-free DNA may be a useful prognostic biomarker that may assist in tailoring postoperative surveillance and therapy. External prospective validation of these data will be required. Cancer 2012;. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

The article offers information on a study which determined whether deletion of chromosome 9p in clear cell renal cell carcinoma (ccRCC) predicted worse disease-specific survival (DSS) and recurrence-free survival (RFS). The study also investigated the possible association between the deletion and aggressive behavior in small renal masses. Methods used include fluorescence in situ hybridization and cytogenetics. A discussion on the research findings is detailed. The benefits of preoperative identification of patients with 9p deletions are mentioned.

Study Type – Therapy (case series) Level of Evidence 4 OBJECTIVE To outline the features and outcomes of renal cell carcinoma (RCC) in native kidneys of renal transplant recipients, who are at increased risk of developing this disease. PATIENTS AND METHODS We retrospectively studied the clinicopathological features and survival of 28 surgically treated RCCs, which developed in 24 renal transplant recipients. Features and outcomes were compared with 671 patients with RCC who had no renal transplant. RESULTS The median interval between renal transplantation and the occurrence of RCC was 5.6 years. Acquired cystic kidney disease was present in 83% of the transplanted patients. Compared with the patients with RCC and no renal transplant, RCCs of native kidneys in transplant recipients were more frequently incidental findings (92% vs 77%, P = 0.092), multifocal (39% vs 15%, P < 0.001), bilateral (17% vs 4%, P = 0.006), had lower T stages ( P = 0.040), were smaller ( P = 0.027), of lower grades ( P = 0.010), were more frequently papillary (43% vs 19%, P = 0.019) and occurred at a significantly younger age ( P = 0.022). After a median follow-up of 6.7 years, eight renal transplant recipients had died (33%), but only two deaths were due to RCC. Survival with metastatic RCC was only 4 months, if a full resection of all metastatic sites was not achieved. In multivariate analysis the presence of a renal transplant had no effect on survival. CONCLUSIONS Most RCCs in renal transplant recipients are incidental low-stage, low-grade tumours with a favourable prognosis. The outstanding pathological findings are bilateral occurrence, papillary subtype and multifocality. Prognosis of metastatic RCC is poor but might be favourable if all metastases are resected. Screening for early detection of asymptomatic RCC is advocated. [ABSTRACT FROM AUTHOR]

The article presents a study that aims to assist in the creation of management guidelines on central nervous system (CNS) surveillance or treatment of patients with renal cell carcinoma brain metastases (RCCBM). It was found that patients with metastatic RCC should be examined with CNS screening to identify smaller and asymptomatic lesions, which maybe amenable to less invasive treatment. Findings show that patients with a solitary BM are less likely to develop CNS recurrence.

Objectives: To analyze risk factors, management, histology, and outcome of bilateral testicular germ cell tumors (TGCT) based on a 25-year single center experience. Methods: Out of 612 patients treated for TGCT between 1982 and 2007, 17 (3%) were found to have bilateral disease. Data of these patients were reviewed and analyzed. Results: Eleven patients (65%) were identified with metachronous and 6 (35%) with synchronous bilateral TGCT. One patient had a cryptorchism in childhood. Patients with metachronous bilateral disease presented at lower stages than those with synchronous bilateral disease (stage I: 82% vs 33%, P = 0.02). In metachronous bilateral TGCT, the interval between the tumors ranged from 4 months to 25 years with a median of 47 months. The risk of developing a TGCT in the contralateral testicle was 26-fold higher than the a-priori risk for a healthy individual to develop TGCT. Overall, 74% of the bilateral tumors were seminomas and >50% of the patients had similar histology on both sides. After a median follow up of 121 months for patients with synchronous and 95 months for patients with metachronous bilateral TGCT, all patients were alive with no evidence of disease. Conclusions: Most bilateral TGCT develop metachronously and are seminomas. Although patients with synchronous bilateral disease present at higher stages, both synchronous and metachronous bilateral TGCT carry a similar, excellent prognosis. Patients with unilateral TGCT require careful long-term monitoring of the remaining testicle due to a 26-fold increased risk of contralateral disease and a potentially long risk interval of up to 25 years. [ABSTRACT FROM AUTHOR]

The article features the research conducted by Tobias Klatte and colleagues on the significance of carbonic anhydrase IX as a molecular marker in Los Angeles, California. Result shows carbonic anhydrase IX (CAIX) is a bladder cancer-specific antigen that is not expressed in normal urothelial tissue but is expressed in 70-90% of transitional cell carcinoma (TCC). It reveals that the expression is usually heterogeneous with a maximum staining seen on the luminal surfaces of the papillae.

OBJECTIVES To compare cancer-specific mortality in patients with unclassified renal cell carcinoma (URCC) vs clear cell RCC (CRCC) after nephrectomy, as URCC is a rare but very aggressive histological subtype. PATIENTS AND METHODS Eighty-five patients with URCC and 4322 with CRCC were identified within 6530 patients treated with either radical or partial nephrectomy at 18 institutions. Of 85 patients with URCC, 55 were matched with 166 of 4322 for grade, tumour size, and Tumour, Node and Metastasis stages. Kaplan-Meier and life-table analyses were used to address RCC-specific survival. Subsequently, multivariate Cox regression analyses were used to test for differences in RCC-specific survival in unmatched samples. RESULTS Of patients with URCC, 80% had Fuhrman grades III or IV, vs 37.8% for CRCC. Moreover, 36.5% of patients with URCC had pathologically confirmed nodal metastases, vs 8.6% with CRCC. Finally, 54.1% of patients with URCC had distant metastases at the time of nephrectomy, vs 16.8% with CRCC. Despite these differences in the overall analyses, after matching for tumour characteristics, the URCC-specific mortality rate was 1.6 times higher ( P = 0.04) in matched analyses and 1.7 times higher ( P = 0.001) in multivariate analyses. CONCLUSIONS These findings indicate that URCC presents with a higher stage and grade, and even after controlling for the stage and grade differences, predisposes patients to 1.6–1.7 times the mortality of CRCC. [ABSTRACT FROM AUTHOR]

OBJECTIVE To evaluate peri-operative peripheral and renal venous plasma levels of vascular endothelial growth factor (VEGF), platelet-derived growth factor type BB (PDGF-BB), transforming growth factor (TGF)-β1, endostatin, and thrombospondin-1 (TSP-1) in relation to pathological variables and prognosis, as pro- and anti-angiogenic factors are important for tumour growth and treatment of patients with renal cell carcinoma (RCC). PATIENTS AND METHODS The study included 74 consecutive patients with sporadic RCC who had tumour nephrectomy. Peripheral venous blood was drawn 1 day before, immediately and 1, 3 and 5 days after surgery. Renal venous blood was collected in a subgroup of 33 patients during surgery. The variables were analysed using quantitative enzyme-linked immunoassay kits, and associated with pathological variables and disease-specific survival. RESULTS Soon after surgery, peripheral venous VEGF, PDGF-BB and TGF-β1 levels were decreased, whereas endostatin levels were significantly increased. Renal venous VEGF, PDGF-BB and TGF-β1 levels were higher than in the general venous blood pool. Renal venous VEGF levels were correlated with tumour diameter and associated with grade and vascular invasion. After a mean follow-up of 30 months, higher peripheral preoperative, early peripheral postoperative and renal venous VEGF levels were associated with a poorer prognosis. However, in a multivariate analysis only Tumour-Node-Metastasis stage and Eastern Cooperative Oncology Group performance status were independent prognosticators of disease-specific survival. CONCLUSIONS Circulating pro- and anti-angiogenic factors change early after nephrectomy. VEGF, PDGF-BB and TGF-β1 are higher in the renal vein than in the general venous blood pool. Higher renal venous and peripheral levels of VEGF might be associated with a poorer prognosis. [ABSTRACT FROM AUTHOR]

An interesting group of papers in this section is headed by two papers on synchronous bilateral renal tumours, one from an international group of authors and one from Germany. The large series of patients are examined carefully by both groups, and the findings should be useful for all who are interested in this area. Authors from the UK examine the role of lactate dehydrogenase as a prognostic factor for testicular cancer. They found that it had limited sensitivity, specificity and positive predictive value for detecting relapse, with false-positive elevations being common. OBJECTIVE To present a multicentre experience and the largest cohort to date of nonmetastatic (N0M0) synchronous bilateral renal cell carcinoma (RCC), as because it is rare the single-institutional experience is limited. PATIENTS AND METHODS We retrospectively studied 10 337 patients from 12 urological centres to identify patients with N0M0 synchronous bilateral RCC; the clinicopathological features and cancer-specific survival were compared to a cohort treated for N0M0 unilateral RCC. RESULTS In all, 153 patients had synchronous bilateral solid renal tumours, of whom 135 (88%) had synchronous bilateral RCC, 118 with nonmetastatic disease; 91% had nonfamilial bilateral RCC. Bilateral clear cell RCC was the major histological subtype (76%), and papillary RCC was the next most frequent (19%). Multifocality was found in 54% of bilateral RCCs. Compared with unilateral RCC, patients did not differ in Eastern Cooperative Oncology Group performance status (ECOG PS) and T classification, but bilateral RCCs were more frequently multifocal (54% vs 16%, P < 0.001) and of the papillary subtype (19% vs 12%), and less frequently clear cell RCC (76% vs 83%, P = 0.005). For the outcome, patients with nonmetastatic synchronous bilateral RCC and unilateral RCC had a similar prognosis ( P = 0.63); multifocality did not affect survival ( P = 0.60). Multivariate analysis identified ECOG PS, T classification, and Fuhrman grade, but not laterality, as independent prognostic factors for cancer-specific survival. CONCLUSIONS Patients with N0M0 synchronous bilateral RCC and N0M0 unilateral RCC have a similar prognosis. The frequency of a familial history for RCC (von Hippel-Lindau disease or familial RCC) was significantly greater in bilateral synchronous than in unilateral RCC. The significant pathological findings in synchronous bilateral RCC are papillary subtype and multifocality. [ABSTRACT FROM AUTHOR]

Background: The mammalian target of rapamycin (mTOR) pathway is up-regulated in many human cancers, and agents targeting the mTOR pathway are in various stages of clinical development. The goal of the study was to evaluate the potential and limitations of targeting the mTOR pathway in renal cell carcinoma (RCC).Methods: Immunohistochemical analysis using antibodies against pAkt, PTEN, p27, and pS6 was performed on a tissue microarray constructed from paraffin-embedded specimens from 375 patients treated by nephrectomy for RCC. The expression was associated with pathological parameters and survival.Results: The mTOR pathway was more significantly altered in clear-cell RCC, high-grade tumors, and tumors with poor prognostic features. PS6 and PTEN showed the strongest associations with pathological parameters. Survival tree analysis regarding expression of cytoplasmic pAkt, nuclear pAkt, PTEN, cytoplasmic p27, and pS6 identified staining percentages of 40%, 10%, 75%, 7%, and 70%, respectively, as ideal cutoff values for stratification, with corresponding P-values of .03, .001, .02, .005, and <.0001, respectively. Interestingly, high nuclear pAkt expression was associated with a favorable prognosis, whereas high cytoplasmic pAkt expression was associated with a poor prognosis. In multivariate Cox regression analysis, ECOG PS, T classification, N classification, M classification, cytoplasmic Akt, nuclear pAkt, PTEN, and pS6 were independent prognostic factors of DSS.Conclusions: Components of the mTOR pathway are significantly associated with pathological features and survival. Not all RCC tumor types seem to be equally amenable to mTOR targeted therapy. PTEN, pAkt, p27, and pS6 may serve as surrogate parameters for patient selection and predicting prognosis. Patients with a highly activated mTOR pathway should benefit most from this therapy. External validation of our results is recommended. [ABSTRACT FROM AUTHOR]

OBJECTIVE To define the prognostic relevance of capsular involvement (invasion with no penetration) and collecting-system invasion in patients with stage I (pT1N0M0) and stage II (pT2N0M0) renal cell carcinoma (RCC), by evaluating the outcome of patients treated with nephrectomy. PATIENTS AND METHODS In all, 519 patients from a kidney cancer database treated with nephrectomy for stage I and II RCC between 1985 and 2005 were assessed retrospectively. The primary endpoint was recurrence-free survival time. The prognostic relevance of capsular involvement and collecting-system invasion were examined using univariate and multivariate survival analysis. RESULTS Capsular involvement and collecting-system invasion were evident in 112 (21.6%) and 39 (7.5%) patients, respectively. Capsular involvement was associated with higher Fuhrman grades and larger tumours. The incidence of collecting-system invasion was higher in patients with microvascular invasion. The median follow-up was 49 months. In univariate analysis, patients with capsular involvement and collecting-system invasion had a worse prognosis than patients without ( P = 0.007 and <0.001, respectively). In multivariate analysis, capsular involvement (hazard ratio 1.84, P = 0.036) and collecting-system invasion (3.78, P < 0.001) were independent prognostic factors of recurrence-free survival. Interestingly, there was no survival difference between patients with capsular involvement in stage I/II and patients with invasion of perinephric tissue (pT3aN0M0). CONCLUSIONS These findings suggest that capsular involvement and collecting-system invasion are poor prognostic findings in stage I and II RCC. They should both be considered when planning the follow-up. A revised pT3a stage including patients with capsular involvement could improve its prognostic validity. [ABSTRACT FROM AUTHOR]

OBJECTIVE To test the combination of docetaxel with two different doses of estramustine in patients with hormone-refractory prostate cancer (HRPC), to improve response rates and to lower side-effects, as docetaxel-based chemotherapy is an increasing option for men with advanced HRPC, and alone or combined with estramustine, docetaxel improves median survival. PATIENTS AND METHODS In all, 72 patients with metastatic HRPC were randomly assigned to receive docetaxel (70 mg/m2 intravenously, on day 2 every 21 days) and estramustine (3 × 280 mg/day oral starting 1 day before docetaxel, for 5 consecutive days) for arm A, or estramustine (3 × 140 mg/day oral starting 1 day before docetaxel, for 3 consecutive days) for arm B. Premedication with oral dexamethasone at a total daily dose of 16 mg, in divided doses twice a day was administered in arm A on day 1–5 and in arm B on day 1–3. Initially, six cycles were administered. Chemotherapy was restarted after a significant increase in prostate-specific antigen (PSA) level. Patients were monitored for any measurable PSA response and toxicity. RESULTS Between the arms there was no statistically significant difference in time to progression and overall survival. However, treatment B had less treatment-related toxicity than A. Independent prognostic variables were baseline factors like PSA level, haemoglobin level, Eastern Cooperative Oncology Group performance status, and bone pain at presentation. CONCLUSIONS In this randomized phase II study the combination of docetaxel and estramustine had substantial activity in HRPC, with a significant incidence of severe toxicity, both haematological and not. Nevertheless, treatment-related toxicity was predictable and manageable. There was no better effect with a higher dose of estramustine with docetaxel than for a lower dose. There was a slight tendency to higher toxicity for high-dose estramustine but this was not statistically significant. The present results support the assertion that estramustine is not necessary in docetaxel-based treatment regimens. [ABSTRACT FROM AUTHOR]

The effect of seminal leucocytes on sperm DNA integrity has been discussed controversially in literatures. Moreover, the studies investigating the in vivo effect of pro‐inflammatory cytokines interleukin‐6 and interleukin‐8 on sperm DNA fragmentation are scarce and inconsistent. The association of standard sperm parameters with sperm DNA fragmentation is also a matter of ongoing discussion. Hence, the aims of this study were, first, to evaluate the effect of seminal leucocytes, interleukin‐6 and interleukin‐8 on sperm DNA integrity and, second, to examine whether standard semen parameters are associated with sperm DNA fragmentation. Seminal leucocytes, interleukin‐6, interleukin‐8 and standard semen parameters, including total sperm number, sperm concentration, progressive motility, nonprogressive motility, immotility and normal morphology, were determined in 134 consecutive men. The concentrations of seminal leucocytes, interleukin‐6 and interleukin‐8, did not correlate with sperm DNA fragmentation. In contrast, total sperm number, sperm concentration, progressive motility, nonprogressive motility and normal morphology exhibited significant inverse correlations with sperm DNA fragmentation. Immotile spermatozoa were directly correlated with sperm DNA fragmentation. In conclusion, seminal leucocytes, interleukin‐6 and interleukin‐8, are not associated with sperm DNA fragmentation. Poor standard semen parameters are significantly related to the high levels of sperm DNA fragmentation. [ABSTRACT FROM AUTHOR]

The author reflects on optimal surgery and systemic therapy. Topics that he discusses include, lymph node (LN) metastases in patients with clinically negative LNs, radical cystectomy (RC) and extended pelvic LN dissection of patients with bladder cancer, and multimodal therapy of patients with LN-positive bladder cancer.