Significant Predictor Of Cancer-specific Survival Research Articles

Clinical validation of Histotype Px Colorectal in patients in a U.S. colon cancer cohort.

3622 Background: According to current guidelines, most patients with high-risk stage II and stage III colon cancer should receive adjuvant chemotherapy (ACT). However, risk determination is controversial and most patients do not benefit from ACT. Histotype Px Colorectal is a novel artificial intelligence-based biomarker validated for R0 stage II-III colorectal adenocarcinoma that analyzes digitized routine H&E-stained FFPE tumor resections. Combined with clinical parameters, patients are stratified into distinct low, intermediate, and high-risk groups. This pilot study seeks to validate the applicability of Histotype Px Colorectal in an independent cohort from the United States. Methods: This was a retrospective analysis of patients diagnosed with pathological stage II-III colon adenocarcinoma at Ohio State University from 2016-2020. Anonymized slides were collected and digitized using the Aperio AT2 scanner. Clinical parameters and outcome data were extracted from patient records. Histotype Px Colorectal biomarker was blindly applied to each scan and subsequently linked to clinical outcomes. Statistical analysis was performed using Cox proportional hazards regression analysis. The pre-specified primary outcome was cancer-specific survival with a secondary outcome of time-to-recurrence. Results: Baseline characteristics of the 159 eligible patients included median age of 63 years (range 22-91), 52% female, 52% stage III, 64% right-sided tumors, and 31% MSI. 18% of stage II and 70% of stage III patients received ACT, respectively, with FOLFOX in 61%. Median follow-up for all patients was 54.2 months. For stage II patients, 21% were classified as intermediate-risk and 79% as low-risk. Only 6 (8%) of the 76 stage II patients had a cancer-related death with 3 of those patients classified as intermediate-risk. For stage III patients, 26% were classified as high-risk, 22% as intermediate-risk, and 52% as low-risk. 18 (22%) of the 83 stage III patients had a cancer-related death with 14 of those patients classified as high or intermediate-risk. Overall, Histotype Px Colorectal was a significant predictor of cancer-specific survival with HR=7.80 (95% CI 2.96-20.56, p<0.001) for high vs. low-risk patients and 2.81 (95% CI 0.98-8.04, p=0.05) for intermediate vs. low-risk patients. In addition, it was found to be a significant predictor for time-to-recurrence with HR=7.59 (3.56-16.20, p<0.001) for high vs. low-risk patients and 2.67 (1.20-5.96, p=0.02) for intermediate vs. low-risk patients. Conclusions: The findings from this study highlight the potential utility of this innovative biomarker in guiding clinical decisions regarding ACT. Further research involving a larger and more diverse patient cohort and subsequent clinical studies are planned to solidify these initial findings and to enable personalized treatment strategies based on individual risk assessments.

Preoperative fibrinogen/CRP score predicts survival in upper urothelial tract carcinoma patients undergoing radical curative surgery

PurposeUpper tract urothelial carcinoma (UTUC) represents an often aggressive malignancy associated with poor prognosis. Therefore, finding reliable prognostic biomarkers in patients undergoing curative surgery for improved risk stratification is crucial. We evaluated the prognostic value of the Fibrinogen/C-reactive protein (FC)-score in a cohort of surgically treated UTUC patients.Methods170 patients with radiologically and histologically verified UTUC who underwent radical curative surgery between 1990 and 2020, were included. The FC-score was calculated for each patient, with patients receiving 1 point each if Fibrinogen and/or CRP levels were elevated above the 25th or 75th percentile, respectively. Patients were divided into three subgroups according to their FC-score of 0, 1 or 2 point(s). Kaplan–Meier analysis, uni- and multivariable Cox proportional hazard models were implemented. We determined cancer-specific survival (CSS) as primary endpoint, whereas overall survival (OS) and recurrence-free survival (RFS) were considered secondary endpoints.ResultsHigh FC-score (2 points) was significantly associated with adverse histological features such as vascular invasion (OR = 4.08, 95%CI 1.18–14.15, p = .0027) and tumour necrosis (OR = 6.67, 95%CI 1.35–32.96, p = 0.020). Both, uni- and multivariable Cox proportional hazard models showed the FC-score as a significant predictor for CSS (univariable analysis: FC-score = 1: HR = 1.90, 95%CI 0.92–3.93, p = 0.085 | FC-score = 2: HR = 2.86, 95%CI 1.22–6.72, p = 0.016). Furthermore, in univariable analysis, patients with higher FC-score had significantly shorter OS (FC-score = 1: HR = 1.32, 95%CI 0.70–2.49, p = 0.387 | FC-score = 2: HR = 2.19, 95%CI 1.02–4.67, p = 0.043). However, this did not prevail in multivariable analysis.ConclusionThe FC-score represents a novel potential biomarker in patients with UTUC undergoing radical curative surgery.

Survival After Lobectomy vs. Sublobar Resection for Stage IA Large-Cell Neuroendocrine Carcinoma of the Lung: A Population-Based Study.

ObjectiveDue to the low incidence of pulmonary large cell neuroendocrine carcinoma (LCNEC), the survival analysis for comparing lobectomy and sublobar resection (SLR) for stage IA LCNEC remains scarce.MethodsPatients diagnosed with pathological stage IA LCNEC between 1998 and 2016 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The oncological outcomes were cancer-specific survival (CSS) and overall survival (OS). Kaplan–Meier analysis and Cox multivariate analysis were used to identify the independent prognostic factors for OS and CSS. Furthermore, propensity score matching (PSM) was performed between SLR and lobectomy to adjust the confounding factors.ResultsA total of 308 patients with stage IA LCNEC met the inclusion criteria: 229 patients (74.4%) received lobectomy and 79 patients (25.6%) received SLR. Patients who underwent SLR were older (P < 0.001), had smaller tumor size (P = 0.010), and less lymph nodes dissection (P < 0.001). The 5-year CSS and OS rates were 56.5 and 42.9% for SLR, and 67.8 and 55.7% for lobectomy, respectively (P = 0.037 and 0.019, respectively). However, multivariate analysis did not identify any differences between the SLR group and lobectomy group in CSS (P = 0.135) and OS (P = 0.285); and the PSM also supported these results. In addition, the age at diagnosis and laterality of tumor were identified as significant predictors for CSS and OS, whereas the number of lymph nodes dissection was a significant predictor for CSS.ConclusionsAlthough SLR is not inferior to lobectomy in terms of oncological outcomes for patients with stage IA LCNEC, more lymph nodes can be dissected or sampled during lobectomy. Lobectomy should still be considered as a standard procedure for patients with early-stage LCNEC who are able to withstand lobectomy.

Preoperative circulating fibrinogen to albumin ratio in predicting 5-year prognosis of oral cancer radical surgery.

Accurate prediction of oral cancer (OC) prognosis before surgery is the key to treatment. The prognosis of OC is mainly based on the Tumor-Node-Metastasis (TNM) staging system, but TNM staging cannot accurately predict clinical prognosis. Current research results show that systemic inflammatory and nutritional markers can influence the postoperative prognosis and outcome of malignant tumors. The objectives of this research are to explore the preoperative blood fibrinogen and albumin in OC patients and to determine the predictive validity of the fibrinogen to albumin ratio (FAR) over 5 years of follow-up. This retrospective cohort study queried The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University database and identified 157 cases of OC operations performed between 2014 and 2016. Survival curves were presented by the Kaplan-Meier method. Univariate and multivariate analyses were used to assess clinical value for patients with radical surgery. The FAR revealed a good prediction for 5-year cancer-specific survival (CSS). The optimal cut-off value for FAR was 0.072. Multivariate logistic regression analyses revealed that FAR was an independent risk factor for survival. Increased FAR (>0.072) is negatively associated with the CSS of patients (log-rank test, p<0.01). The preoperative FAR may provide a significant predictor of cancer-specific survival in oral cancer patients undergoing radical surgery.

Inguinal lymph node density as a powerful predictor of cancer specific survival in patients with node-positive penile cancer.

Penile cancer (PC) is an aggressive malignancy in which the most important prognostic factor for cancer specific survival (CSS) is the involvement of regional lymph nodes (LNs). Lymph node density (LND) could become a superior prognostic tool for CSS, by accounting for both extent of dissection and nodal disease burden. We aim to validate LND as a prognostic factor for CSS in a contemporary series of patients with PC treated and followed at a single high-volume center, treating more than 25 PC patients per year, over a 13-year period. Clinical charts of all patients with PC who underwent surgical treatment between 2007 and 2020 were reviewed. Clinicopathological data was collected and analyzed retrospectively. We only included patients with ≥ 8 LNs removed in a unilateral ILND or ≥16 LNs when a bilateral approach was used. We attempted to find an optimal threshold for LND, capable of maximizing effect difference in terms of CSS and RFS between dichotomized groups. To determine this threshold, we used the chi-squared and the Mann-Whitney tests, and it was required to fulfill the proportional hazards assumption. We assessed different thresholds previously reported in the literature. In our study the optimal threshold for LND was determined to be ≤ 20% Descriptive statistics were used to summarize patient characteristics, CSS and RFS were graphically represented by Kaplan-Meier estimates. Harrell's C index for CSS and RFS were calculated for LND and pN stage, to determine which variable has a superior predictive capacity RESULTS: We identified 110 patients with PC who underwent ILND at our institution, of these, 87 were node-positive and were included in the final analysis. Overall estimates of CSS showed a 3-year CSS of 43% (95% CI: 32-54), the estimated 3-year CSS for the patients with a LND ≤ 20% was 69% (95% CI: 50-82) and 26% (95% CI: 14-39) in the group with a LND >20% (Log-rank P = 0.001). The estimated 3-year RFS for the patients with LND ≤ 20% was 61% (95% CI: 42-76) and 30% (95% CI: 16-44) in the group with a LND >20% (Log-rank P = 0.009). The results of univariate analysis indicate that in patients with a LND >20% the risk for cancer specific mortality was increased (HR 2.68; 95% CI: 1.45-4.98, P = 0.002) compared with LND ≤ 20%. In the and Cox multivariate analysis after Adjusting for age and pN stage the association increased (HR 2.73; 95%, CI 1.38-5.40, P = 0.004). Harrell´s C index for CSS was 0.63 for LND vs. 0.54 for pN stage, suggesting a 9% higher concordance for LND and CSS. Lymph node density stands as a promising tool for risk-stratifying patients with node-positive PC after ILND. In this retrospective study, LND was a significant predictor of CSS and RFS when using a LND >20% threshold, and also showed a superior predictive ability than pN stage. These results support the use of the LND parameter in clinical practice with a final goal to improve risk stratification, and individualized adjuvant treatment decision-making to patients with high-risk of cancer specific mortality.

Validation of the COBRA nomogram for the prediction of cancer specific survival in patients treated with radical cystectomy for bladder cancer: An international wide cohort study

BackgroundRecently, the Cancer of the Bladder Risk Assessment (COBRA) score has been introduced to estimate cancer specific survival (CSS) after radical cystectomy for bladder cancer. ObjectivesAim of our study was to validate the COBRA score, assessing the effect of age, tumor stage and lymph-nodes status on CSS after cystectomy in patients with bladder cancer. Design, setting, and participantsA consecutive series of 2395 patients with primitive or recurrent bladder cancer treated with radical cystectomy in 4 centers were evaluated. Outcome measurements and statistical analysisThe role of COBRA score as predictor of CSS was assessed using the Kaplan Meier and Cox proportional hazards analyses. Accuracy of COBRA score was evaluated by Harrell's C test. Results and limitationsMedian age was 66 (IQR 58/73) years. Overall, at a median follow-up of 48 (IQR 22/92) months, 642 patients (27%) died of bladder cancer. On Cox proportional hazards analyses, COBRA score was a significant predictor of CSS (HR 1.54, 95%CI 1.47–1.61) (Table 1). The predictive accuracy of the COBRA score was 0.71. A sub analysis including pooled COBRA score (0 vs 1–3 vs 4 vs 5–7) improved the clinical applicability with the same accuracy. ConclusionIn our experience, the COBRA score is an excellent tool to predict cancer specific survival. The COBRA Score represents a practical and easy tool that may help urologists to classify the CSS of patients treated with radical cystectomy, to predict the oncological outcome and finally to counsel bladder cancer patients.

Impact of Preoperative Social Frailty on Overall Survival and Cancer-Specific Survival among Older Patients with Gastrointestinal Cancer

ObjectivesFrailty is a multidimensional syndrome. However, typical frailty scales used in oncology clinics assess physical impairment and/or malnutrition but do not consider the social domain. Our study aimed to clarify the relationship between preoperative social frailty and overall survival (OS) and cancer-specific survival (CSS) among older patients with gastrointestinal cancer. DesignThis was a prospective cohort study. Setting and ParticipantsThis single-center study recruited 195 patients with gastrointestinal cancer scheduled for curative surgery and aged >60 years. MethodsThe outcomes considered were the OS and CSS of surgery. Primary associated factors included frailty defined as a Geriatric 8 score ≤14; social frailty defined as 2 or more of the following—going out less frequently, rarely visiting friends, feeling unhelpful to friends or family, living alone, and not talking with someone daily, and combinations therein [no frailty without social frailty (−/−), frailty without social frailty (+/−), no frailty with social frailty (−/+), and frailty with social frailty (+/+)]. We used the Cox proportional hazards model and the Fine and Gray proportional subdistribution hazard model adjusting for confounding factors. ResultsOf the 195 patients, 181 (mean age, 72.0 years) were included for analysis. The median follow-up time was 994 days. Social frailty (hazard ratio 3.10) and their combinations [6.35; frailty with social frailty (+/+) vs no frailty without social frailty (−/−)] were significant predictors of OS. Social frailty (subdistribution hazard ratio 3.23) and their combinations (7.57) were significant predictors of CSS. Conclusions and ImplicationsPreoperative social frailty is a predictor of OS and CSS in older patients with gastrointestinal cancer. Screening for social frailty, frailty, and their combinations in older patients with cancer is important.

Impact of Lymphovascular Invasion on Prognosis in the Patients with Bladder Cancer-Comparison of Transurethral Resection and Radical Cystectomy.

(1) Background: This study aimed to evaluate the associations of lymphovascular invasion (LVI) at first transurethral resection of bladder (TURBT) and radical cystectomy (RC) with survival outcomes, and to evaluate the concordance between LVI at first TURBT and RC. (2) Methods: We analyzed 216 patients who underwent first TURBT and 64 patients who underwent RC at Toho University Sakura Medical Center. (3) Results: LVI was identified in 22.7% of patients who underwent first TURBT, and in 32.8% of patients who underwent RC. Univariate analysis identified ≥cT3, metastasis and LVI at first TURBT as factors significantly associated with overall survival (OS) and cancer-specific survival (CSS). Multivariate analysis identified metastasis (hazard ratio (HR) 6.560, p = 0.009) and LVI at first TURBT (HR 9.205, p = 0.003) as significant predictors of CSS. On the other hand, in patients who underwent RC, ≥pT3, presence of G3 and LVI was significantly associated with OS and CSS in univariate analysis. Multivariate analysis identified inclusion of G3 as a significant predictor of OS and CSS. The concordance rate between LVI at first TURBT and RC was 48.0%. Patients with positive results for LVI at first TURBT and RC displayed poorer prognosis than other patients (p < 0.05). (4) Conclusions: We found that the combination of LVI at first TURBT and RC was likely to provide a more significant prognostic factor.

Development and validation of nomograms for predicting survival of elderly patients with stage I small-cell lung cancer.

There is a lack of predictive models to determine the prognosis of elderly patients diagnosed with Stage I small-cell lung cancer (SCLC). The purpose of this study was to establish a useful nomogram to predict cancer-specific survival (CSS) in the elderly patient population. Based on the Surveillance, Epidemiology, and End Results registry database, patients aged ≥ 65 years with pathological AJCC (American Joint Committee on Cancer) Stage I SCLC from 2004 to 2014 were identified. The CSS was evaluated by the Kaplan-Meier method. Patients were randomly split into training and validation sets. In the training cohort, univariate analysis and multivariate analysis using the Cox regression identified risk factors that affected CSS, and the results were utilized to construct a nomogram for prediction of the 1-, 3-, and 5-year CSS rates of elderly patients with Stage I SCLC. The effectiveness of the nomogram was validated internally and externally by the bootstrap method. The clinical practicability and accuracy of the nomogram were evaluated by the concordance index (C-index), calibration curve, receiver operating characteristic curve, and decision curve analysis. In total, we extracted 1,623 elderly patients with Stage I SCLC. The median CSS was 34 months, and the 5-year CSS was 41%. Multivariate analysis revealed that histologic type, tumor size, age, and AJCC Stage were significant predictors of CSS. A nomogram was constructed according to the results of multivariate COX analysis. The C-indices of the nomogram for training and validation sets were 0.68 and 0.62, indicating that the nomogram demonstrated a favorable level of discrimination. The calibration curves exhibited satisfactory agreement between the actual observation and nomogram prediction. The net benefit of the nomogram was better than the AJCC TNM staging. A practical nomogram to predict the CSS of elderly patients with Stage I SCLC is constructed. The predictive tool is helpful for patient counseling and treatment decision-making.

Impact of sarcomatoid differentiation and rhabdoid differentiation on prognosis for renal cell carcinoma with vena caval tumour thrombus treated surgically

BackgroundSarcomatoid differentiation in renal cell carcinoma (RCC) with vena caval tumour thrombus has been shown to be associated with aggressive behaviours and poor prognosis; however, evidence of the impact of rhabdoid differentiation on prognosis is lacking. This study evaluated the impact of sarcomatoid differentiation and rhabdoid differentiation on oncological outcomes for RCC with vena caval tumour thrombus treated surgically.MethodsWe retrospectively analysed patients treated surgically for RCC with vena caval tumour thrombus at our institute from Jan 2015 to Nov 2018. Prognostic variables were evaluated for associations with progression-free survival (PFS) and cancer-specific survival (CSS) by Kaplan–Meier survival analysis and log-rank test. Univariate and multivariate analyses were performed to determine independent prognostic variables.ResultsWe identified 125 patients with RCC and vena caval tumour thrombus, including 17 (13.6%) with sarcomatoid differentiation alone, 8 (6.4%) with rhabdoid differentiation alone and 3 (2.4%) with both sarcomatoid and rhabdoid differentiation. Compared to pure RCC, patients with sarcomatoid differentiation but not rhabdoid differentiation have worse PFS (p = 0.018 and p = 0.095, respectively). The univariate and multivariate analyses both showed sarcomatoid differentiation as a significant predictor of PFS. Compared to pure RCC, patients with sarcomatoid differentiation (p = 0.002) and rhabdoid differentiation (p = 0.001) both had significantly worse CSS. The univariate analysis showed sarcomatoid differentiation, rhabdoid differentiation, metastasis and blood transfusion as significant predictors of CSS (All, p < 0.05). In the multivariate analysis, sarcomatoid differentiation (HR 3.90, p = 0.008), rhabdoid differentiation (HR 3.01, p = 0.042), metastasis (HR 3.87, p = 0.004) and blood transfusion (HR 1.34, p = 0.041) all remained independent predictors of CSS.ConclusionsSarcomatoid differentiation and rhabdoid differentiation are both independent predictors of poor prognosis in RCC with vena caval tumour thrombus treated surgically.

A novel combined miRNA and methylation marker panel (miMe) for prediction of prostate cancer outcome after radical prostatectomy.

Improved prognostic biomarkers are needed to guide personalized prostate cancer (PC) treatment decisions. Due to the prominent molecular heterogeneity of PC, multimarker panels may be more robust. Here, 25 selected top-candidate miRNA and methylation markers for PC were profiled by qPCR in malignant radical prostatectomy (RP) tissue specimens from 198 PC patients (Cohort 1, training). Using GLMnet, we trained a novel multimarker model (miMe) comprising nine miRNAs and three methylation markers that predicted postoperative biochemical recurrence (BCR) independently of the established clinicopathological CAPRA-S nomogram in Cox multivariate regression analysis in Cohort 1 (HR [95% CI]: 1.53 [1.26-1.84], p < 0.001). This result was successfully validated in two independent RP cohorts (Cohort 2, n = 159: HR [95% CI]: 1.35 [1.06-1.73], p = 0.015. TCGA, n = 350: HR [95% CI]: 1.34 [1.01-1.77], p = 0.04). Notably, in CAPRA-S low-risk patients, a high miMe score was associated with >6 times higher risk of BCR, suggesting that miMe may help identify PC patients at high risk of progression despite favorable clinicopathological factors postsurgery. Finally, miMe was a significant predictor of cancer-specific survival (p = 0.019, log-rank test) in a merged analysis of 357 RP patients. In conclusion, we trained, tested and validated a novel 12-marker panel (miMe) that showed significant independent prognostic value in three RP cohorts. In the future, combining miMe score with existing clinical nomograms may improve PC risk stratification and thus help guide treatment decisions.

Is the extirpative surgery for primary tumor helpful for the patients with metastatic urothelial cancer at the time of diagnosis?

The stagnant mortality rates for metastatic urothelial cancer (UC) have provoked efforts to find novel treatments. To test the utility of the extirpative surgery for primary tumor as an option for these patients, we investigated the perioperative and oncologic outcomes of surgery for primary tumors in metastatic UC patients.We reviewed the medical records of 130 metastatic UC patients (bladder: 88, upper tract UC: 42) at diagnosis from November 2005 to November 2016. A total of 56 patients (surgery group) underwent chemotherapy with extirpative surgery for the primary tumor, and 74 patients (non-surgery group) received chemotherapy. We evaluated perioperative outcomes, cancer-specific survival (CSS), and overall survival (OS) using Kaplan-Meier methods and factors related to OS and CSS using Cox regression models.Surgery group showed similar perioperative outcome and postoperative complications to those previously reported in UC patients without metastasis, and fewer urinary complications than non-surgery group. Surgery group showed better oncological outcomes than non-surgery group for median CSS (16.0 vs 10.0 months, P = 0.014) and median OS (14.0 vs 9.0 months, P = 0.043). Multivariate analysis showed Eastern Cooperative Oncology Group performance status and metastasis to liver as significant predictors of CSS and OS. Surgery was not related with OS, but a significant predictor of CSS.Extirpative surgery for primary tumor in metastatic UC can be feasible and it might have survival benefits, especially those patients with a tolerable general condition and no liver metastasis. In addition, LT reduces the possibility of a surgical procedure towing to urinary complications.

Training and validation of a novel 4-miRNA ratio model (MiCaP) for prediction of postoperative outcome in prostate cancer patients

BackgroundNew molecular biomarkers for prostate cancer (PC) prognosis are urgently needed. Ratio-based models are attractive, as they require no additional normalization. Here, we train and independently validate a novel 4-miRNA prognostic ratio model for PC. Patients and methodsBy genome-wide miRNA expression profiling of PC tissue samples from 123 men who underwent radical prostatectomy (RP) (PCA123, training cohort), we identified six top candidate prognostic miRNAs and systematically tested their ability to predict postoperative biochemical recurrence (BCR). The best miRNA-based prognostic ratio model (MiCaP) was validated in two independent cohorts (PCA352 and PCA476) including >800 RP patients in total. Clinical end points were BCR and prostate cancer-specific survival (CSS). The prognostic potential of MiCaP was assessed by univariate and multivariate Cox-regression analyses and Kaplan–Meier analyses. ResultsWe identified a 4-miRNA ratio model, MiCaP (miR-23a-3p×miR-10b-5p)/(miR-133a×miR-374b-5p), that predicted time to BCR independently of routine clinicopathologic variables in the training cohort (PCA123) and was successfully validated in two independent RP cohorts. In addition, MiCaP was a significant predictor of CSS in univariate analysis [HR 3.35 (95% CI 1.34−8.35), P=0.0096] and in multivariate analysis [HR 2.43 (95% CI 1.45–4.07), P=0.0210]. As proof-of-principle, we also analyzed MiCaP in plasma samples from 111 RP patients. A high MiCaP score in plasma was significantly associated with BCR (P=0.0036, Kaplan–Meier analysis). Limitations include low mortality rates (CSS: 5.4%). ConclusionsWe identified a novel 4-miRNA ratio model (MiCaP) with significant independent prognostic value in three RP cohorts, indicating promising potential to improve PC risk stratification.

Long-term Outcomes of Nephrectomy and Inferior Vena Cava Thrombectomy in Patients with Advanced Renal Cell Carcinoma

Background/Purpose: This study evaluated the long-term outcomes of nephrectomy and inferior vena cava (IVC) thrombectomy in patients with advanced renal cell carcinoma (RCC). Methods: From January 1996 to December 2013, we retrospectively collected the clinical data of 31 patients with pathologically confirmed RCC and IVC tumor thrombus. All patients received nephrectomy and IVC thrombectomy. We examined the clinical outcomes, including cancer-specific survival, progression-free survival, and postoperative complications, during a 90-day period. The associated prognostic factors were also analyzed. This study is registered with the National Taiwan University Hospital Research Ethics Committee (number 201305059RINC). Results: The median follow-up period was 24 months. Of 20 patients with nonmetastatic disease, 15 developed metastases during the study period. The overall 5-year cancer-specific survival rate was 30.8% in the nonmetastatic group versus 12.5% in the metastatic group. The level of IVC thrombus (Levels I–II vs. Levels III–IV) was not significantly associated with the 5-year cancer-specific survival (P = 0.43). The Fuhrman grade and sarcomatoid type were statistically significant predictors of cancer-specific survival (Fuhrman Grades III–IV vs. Grades I–II: Hazard ratio [HR] = 0.11, P = 0.04; sarcomatoid type: HR = 0.136, P = 0.001). Fuhrman grade, capsular invasion, and positive surgical margins were associated with 1-year progression-free survival (Fuhrman Grades III–IV vs. Grades I–II: HR = 0.08, P = 0.04; capsular invasion: HR = 0.15, P = 0.04; positive surgical margins: HR = 0.16, P = 0.05). The most common perioperative complication was massive blood loss. The most common recurrence sites were bones, liver, and lungs. Conclusion: The pathologic Fuhrman grade, sarcomatoid type, positive surgical margins, and capsular invasion were significant predictors of oncological outcomes in patients with advanced RCC and IVC thrombus.

Effects of thiazolidinedione in patients with active bladder cancer.

To examine the influence of perioperative thiazolidinedione (TZD) on cancer-specific outcomes in patients with diabetes mellitus (DM) undergoing radical cystectomy (RC) for urothelial carcinoma (UC). A retrospective cohort of 173 patients with DM undergoing RC from 2005 to 2010 was identified. Of those, 53 were on TZD treatment at the time of RC, with 33 patients taking pioglitazone. Baseline clinicopathological characteristics, as well as cancer-specific survival (CSS), recurrence-free survival (RFS), and overall survival (OS) were compared between the patients on and off TZD therapy at the time of RC. In subgroup analysis, outcomes in patients specifically taking pioglitazone at the time of RC were compared to those not on a TZD. Baseline clinicopathological characteristics were similar between patients on and off TZD therapy at the time of RC. Overall, the median CSS rate was not reached in either group (P = 0.7). The estimated 5-year CSS was 67.8% in the non-TZD group and 66.3% in the TZD group. On multivariate analysis incorporating patient age, pathological T-staging, and adjuvant chemotherapy, TZD use was found not to be a significant predictor for CSS (hazard ratio 1.20, 95% confidence interval 0.66-2.17; P = 0.5). Additionally, RFS (P= 0.3) and OS (P = 0.2) were also similar between the two groups without adjusting for other variables. Comparison between patients taking pioglitazone vs patients not taking TZD yielded similar CSS (P = 0.2), RFS (P = 0.5), and OS (P= 0.2). CSS, as well as RFS and OS after RC were not compromised in patients on TZD therapy at the time of RC. Additional investigation is warranted in patients with non-muscle-invasive bladder cancer and muscle-invasive bladder cancer undergoing bladder-sparing procedures to assess the safety of using TZD in the setting of active UC.

Long-term outcomes of nephrectomy and inferior vena cava thrombectomy in patients with advanced renal cell carcinoma: A single-center experience

Background/purposeThis study evaluated the long-term outcomes of nephrectomy and inferior vena cava (IVC) thrombectomy in patients with advanced renal cell carcinoma (RCC). MethodsFrom January 1996 to December 2013, we retrospectively collected the clinical data of 31 patients with pathologically confirmed RCC and IVC tumor thrombus. All patients received nephrectomy and IVC thrombectomy. We examined the clinical outcomes, including cancer-specific survival, progression-free survival, and postoperative complications, during a 90-day period. The associated prognostic factors were also analyzed. This study is registered with the National Taiwan University Hospital Research Ethics Committee (number 201305059RINC). ResultsThe median follow-up period was 24 months. Of 20 patients with nonmetastatic disease, 15 developed metastases during the study period. The overall 5-year cancer-specific survival rate was 30.8% in the nonmetastatic group versus 12.5% in the metastatic group. The level of IVC thrombus (levels I–II versus levels III–IV) was not significantly associated with the 5-year cancer-specific survival (p = 0.43). The Fuhrman grade and sarcomatoid type were statistically significant predictors of cancer-specific survival [Fuhrman grades III–IV versus grades I–II: hazard ratio (HR) = 0.11, p = 0.04; sarcomatoid type: HR = 0.136, p = 0.001]. Fuhrman grade, capsular invasion, and positive surgical margins were associated with 1-year progression-free survival (Fuhrman grades III–IV versus grades I–II: HR = 0.08, p = 0.04; capsular invasion: HR = 0.15, p = 0.04; positive surgical margins: HR = 0.16, p = 0.05). The most common perioperative complication was massive blood loss. The most common recurrence sites were bones, liver, and lungs. ConclusionThe pathologic Fuhrman grade, sarcomatoid type, positive surgical margins, and capsular invasion were significant predictors of oncological outcomes in patients with advanced RCC and IVC thrombus.

Association between demographic factors and prognosis in urothelial carcinoma of the upper urinary tract: a systematic review and meta-analysis

We aimed to assess the prognostic significance of demographic factors, including age, sex, performance status, smoking status, obesity, and race in upper urinary tract urothelial carcinoma (UTUC) patients treated with radical nephroureterectomy through a systematic review and meta-analysis. We conducted PubMed search for all articles published until December 2014 according to Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. Survival outcomes of interest were intravesical recurrence (IVR) free survival, progression free survival (PFS), cancer-specific survival (CSS), and overall survival (OS). Seventy-nine studies, including numbers of subjects ranging from 24 to 9899, met the inclusion criteria. Advanced age was significantly associated with worse PFS [hazard ratio (HR) 1.01] and OS (HR 1.05). The significant predictors of CSS were age (HR 1.02) and performance status (HR 1.35). Female gender (HR 0.81) and smoking (HR 1.38) were the significant predictors only for IVR free survival. No significant associations with survival outcomes were observed in obesity and race. Our study reveals that age is one of the most important demographic predictor of survival in UTUC. Also, male gender, poor performance status, and smoking are also significantly related to worse survival outcomes. However, large well-designed prospective studies are required to investigate the precise prognostic significance of demographics.

Prognostic impact of preoperative neutrophil-to-lymphocyte ratio after radical prostatectomy in localized prostate cancer.

Neutrophil-to-lymphocyte ratio (NLR) has a prognostic value in patients with metastatic castration-resistant prostate cancer receiving systemic therapy. However, the prognostic significance of NLR was never previously evaluated in patients who underwent radical prostatectomy (RP) for prostate cancer. In the present study, we investigated the influence of NLR on survival after a RP for prostate cancer. We retrospectively reviewed clinical data of 2301 patients with prostate cancer who underwent RP at our institution between 2000 and 2010. Among these patients, we considered only patients who had a preoperative complete blood count with differential result available. Patients who received neoadjuvant or postoperative adjuvant treatment (radiation, androgen deprivation therapy or both) and those without adequate medical record were excluded. A Kaplan-Meier analysis was performed to analyze biochemical recurrence-free survival (BCRFS), overall survival (OS) and prostate cancer-specific survival (CSS). Univariate and multivariate Cox regression models were used for each end point. In total, 2067 patients were evaluated; median follow-up time was 78 months (interquartile range (IQR) 65-96), median age at RP was 66 years (IQR 61-70) and median preoperative NLR was 1.76 (IQR 1.35-2.40). A Kaplan-Meier analysis showed a significant association between high NLR (⩾1.76) and decreased CSS (P=0.005) and OS (P=0.003) but not with BCRFS (P=0.223). In the univariate and multivariate regression analyses, a high NLR was a significant predictor of CSS (hazard ratio (HR) 2.012, 95% confidence interval (CI) 1.222-3.310, P=0.006) and OS (HR 1.650, 95% CI 1.127-2.416, P=0.010). This study shows that in patients with prostate cancer preoperative NLR is an independent prognostic factor for OS and CSS after a RP and suggests that a preoperative hematologic workup should be considered in the risk assessment of these patients.

Impact of tumour size on prognosis of upper urinary tract urothelial carcinoma after radical nephroureterectomy: a multi-institutional analysis of 795 cases.

To evaluate the prognostic impact of tumour size on survival outcomes in upper urinary tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). Data on 795 patients treated with RNU for UTUC from seven centres were retrospectively analysed with focus on tumour size. Clinicopathological features and relevant prognostic factors were compared between patients with tumours ≤3.0 cm and those with tumours >3.0 cm in size. The primary endpoints were cancer-specific survival (CSS), disease recurrence-free survival (RFS) and overall survival (OS). At a median follow-up of 32 months, 313 (39.4%) patients died from UTUC, 321 (40.4%) developed cancer recurrence, and 359 (45.1%) died from all causes. Tumour size >3.0 cm was associated with unfavourable clinicopathlogical features. Kaplan-Meier analysis showed that tumour size was significantly correlated with worse CSS, RFS and OS (all P < 0.001). Multivariate analysis showed that tumour size was an independent predictor of CSS (hazard ratio [HR] 2.296; P < 0.001), RFS (HR 2.193; P < 0.001) and OS (HR 2.417; P < 0.001). Tumour size >3.0 cm was a significant predictor of CSS, RFS and OS after RNU for patients with UTUC. Further studies are warranted before tumour size is included in risk prediction tools.

The Natural History, Treatment Pattern, and Outcomes of Patients With Micropapillary Bladder Carcinoma

Micropapillary bladder carcinoma (MPBC) is a rare variant of urothelial cancer. Most literature on MPBC is from case series reports. This study's objective was to examine the epidemiology, natural history, and prognostic factors of MPBC using a population-based registry, in addition to a literature review. The Surveillance, Epidemiology, and End Results (SEER) database identified 98 histologically confirmed MPBC patients from 2001 and 2007. In addition, 213 MPBC cases were identified in published literature. The clinical, demographic characteristics, treatment, and survival outcomes were compared between these 2 cohorts. Among patients identified in SEER, MPBC accounted for approximately 0.01% of primary bladder tumors, with the median age of 72 years (range, 26 to 95 y). Among the MPBC cases, 56.1% had muscle invasive disease, 75.5% had poor or undifferentiated histology, and 30.6% underwent a radical or partial cystectomy. The 1-, 3-, and 5-year overall survival rates for the SEER cohort were estimated at 84.5%, 57.3%, and 42.3%, respectively. Using multivariate analysis, tumor stage and marital status were the most significant predictors for cancer-specific survival. When comparing published single-institution studies to the SEER cohort, significant differences existed in demographic characteristics including age at diagnosis, male-to-female ratio, tumor stage, cystectomy treatment, and survival outcomes, likely reflecting differences in practice patterns. This is the first population-based study to analyze MPBC's epidemiology, tumor characteristics, and survival rates. Emphases on early detection, cystectomy, and multimodality in treatment are needed.