Renal Cell Carcinoma-specific Mortality Research Articles

Intermediate- and long-term oncological outcomes of active surveillance for localized renal masses: a systematic review and quantitative analysis.

To evaluate intermediate- and long-term oncological outcomes of active surveillance (AS) for localized renal masses (LRMs). 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 3years' 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; ≤4cm) and non-SRMs (>4cm). We analysed 18 unique cohorts comprising 2066 patients. The pooled initial maximum tumour size was 2.8cm (95% confidence interval [CI] 2.7-3.0) and the percutaneous biopsy rate was 28%. The pooled mean annual growth rate was 2.8mm (95% CI 2.1-3.4). Within a pooled mean follow-up of 53months, 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. 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.

Radiologic indicators prior to renal cell cancer thrombectomy: Implications for vascular reconstruction and mortality.

Background:Renal cancer may invade the inferior vena cava (IVC) creating more complex surgical intervention. We investigate radiologic findings that may predict vascular reconstruction prior to surgery and future renal cancer-specific mortality.Materials and Methods:Radiologic findings included Mayo Clinic risk factors for vascular reconstruction: Right-sided tumor, anteroposterior diameter of the IVC at the ostium of the renal vein ≥24.0 mm, and radiologic identification of complete occlusion of the IVC. Additional factors included thrombus in the lumen of the hepatic veins and metastasis. Along with other demographic factors, analysis included Chi-squared analysis for vascular reconstruction and logistic regression for mortality. A Kaplan–Meier curve was created for the most significant radiologic factor.Results:Thirty-seven patients underwent IVC tumor thrombectomy at two institutions from April 2007 to February 2015. We found that Mayo risk factors of 0, 1, 2, and 3 and the proportions of vascular reconstruction of 0%, 0%, 12.5%, and 13.6%, respectively (P = 0.788). Hepatic vein involvement was the most significant determinate of renal cell carcinoma-specific mortality in multivariable analysis, controlling for the size of IVC at the hepatic veins, pulmonary metastasis, and Fuhrman grade (P = 0.02, Log-rank P = 0.002).Conclusion:Mayo risk factors did not predict vascular reconstruction in our small cohort of Level II–Level IV IVC thrombus undergoing IVC thrombectomy. Tumor thrombus traveling into the lumen of the hepatic veins was a significant risk factor for accelerated mortality.

IJU this issue

This issue deals with a wide range of clinical topics of urology, and contains two Review Articles, eleven Original Articles and one Urological Notes. Microribonucleic acids, a class of small non-coding ribonucleic acids, regulate protein-coding gene expression by repressing translation or cleaving ribonucleic acid transcripts in a sequence-specific manner. Using eight genome-wide microribonucleic acid expression signatures, the Review Article by Goto et al. (Chiba, Japan) reported microribonucleic acids contributing to prostate cancer development, progression and metastasis, such as miR-221/222, miR-143/145, miR-23b/27b/24-1 and miR-1/133a. They also discussed the functional significance of the differentially expressed microribonucleic acids and the molecular pathways/targets regulated by these microribonucleic acids. The other Review Article by Minagawa and Ishizuka (Matsumoto, Japan) deals with urological Kampo medicine. Currently, more than 10 Kampo formulations can be used for urological problems. Among them, they listed representative urological Kampo formulations used for lower urinary tract symptoms, and discuss their roles in the urological field, including their position in Japanese clinical guidelines. They also introduced the essence of general Kampo medicine, including its history and current status in Japan. Finally, they proposed the multi-organ targeting strategy using Kampo formulations as a future vision. C-reactive protein is a non-specific, acute phase, hepatic protein secreted in response to various cytokines, but primarily interleukin-6. Using the cohort of 516 patients undergoing surgery for renal cell carcinoma, Hsiao et al. (Atlanta, USA) have generated four nomograms with stage, grade, C-reactive protein levels and presence of metastatic disease, using overall mortality and renal cell carcinoma-specific mortality as end-points, two each for pre- and postoperative counseling. The factor with the largest effect on all nomograms was preoperative C-reactive protein. Although their findings require external validation, their nomograms seem to be applicable for all common histological subtypes of RCC. Matsuyama et al. (Ube, Japan) performed a randomized study comparing running suture with interrupted suture for vesicourethral anastomosis in retropubic radical prostatectomy. They demonstrated that running suture for vesicourethral anastomosis was feasible during retropubic radical prostatectomy. Furthermore, it offered better outcomes than the conventional standard interrupted suture technique, with a higher likelihood of improvement in patients' health-related quality of life. On the other hand, Yumioka et al. (Yonago, Japan) evaluated the influence of prior abdominal surgery on surgical outcomes of robot-assisted radical prostatectomy in an early single center experience in Japan. From their results, robot-assisted radical prostatectomy appears to be a safe approach for patients with prior abdominal surgery without increasing total operative time, robotic console time, positive surgical margin or the incidence of perioperative complications. In the field of neurogenic detrusor overactivity secondary to spinal cord injury, Sengoku et al. (Kobe, Japan) reported multi-institutional experience of botulinum toxin A injection in Japanese patients. They examined the efficacy and safety of onabotulinumtoxinA (Botox) injection into the bladder wall after a 2-week washout of anticholinergics. The mean number of urinary incontinence episodes decreased from 4.3 to 1.5 times/day (P = 0.004), and the maximum cystometric capacity increased from 100 mL to 296 mL (P = 0.0004). Clinically significant adverse events were not observed. The approval of this drug is desired in Japan. Tanaka et al (Osaka, Japan) examined the difference in improvement of lower urinary tract symptoms between morning and evening dosing of α1-blocker naftopidil, using 177 male patients with nocturia. From their randomized study, evening dosing of naftopidil seems to be more effective in treating nocturia in male patients with lower urinary tract symptoms. This information is useful for daily outpatient clinic. None declared.

Nomograms incorporating serum C-reactive protein effectively predict mortality before and after surgical treatment of renal cell carcinoma.

To incorporate C-reactive protein into nomograms estimating survival in patients with renal cell carcinoma. Patients undergoing surgery for renal cell carcinoma from 2005-2012 were studied retrospectively. Multivariable Cox proportional hazards regression and competing risks regression models including stage, grade, C-reactive protein levels and presence of metastatic disease were constructed. Outcomes analyzed include overall mortality overall mortality and renal cell carcinoma-specific mortality. The cohort included 516 patients with a mean follow up of 1.7 years (SD 1.4 years). One- and 3-year renal cell carcinoma-specific mortality was 8.8% and 13.5%, respectively. Four nomograms were generated using overall mortality and renal cell carcinoma-specific mortality as end-points, two each for pre- and postoperative counseling. The factor with the largest effect on all nomograms was preoperative C-reactive protein. Based on the internal validation with bootstrapping, the concordance indices for renal cell carcinoma-specific mortality in the preoperative nomogram, postoperative nomogram, and the Mayo Clinic stage, size, grade and necrosis score were 0.889, 0.893, and 0.832, respectively (P = 0.005 and 0.002 comparing with stage, size, grade and necrosis scores for preoperative or postoperative nomograms). For overall mortality, the preoperative nomogram, postoperative nomogram, and stage, size, grade and necrosis score showed concordance indices of 0.866, 0.897, and 0.828, respectively (P = 0.123 and 0.008 compared with stage, size, grade and necrosis score for preoperative or postoperative nomograms). We have generated nomograms incorporating serum C-reactive protein levels that effectively predict overall mortality and renal cell carcinoma specific mortality. Our findings warrant external validation.

The Prognostic Value of Erythrocyte Polyamine in the Post-Nephrectomy Stratification of Renal Cell Carcinoma Specific Mortality

The polyamines spermine and spermidine are ubiquitous polycationic structures which are essential for cell proliferation and differentiation. Circulating polyamines, spermine and spermidine, represent valuable prognostic markers in prostate cancer, acute leukemia and supratentorial malignant glioma. We tested whether spermine and spermidine could improve the prognostic ability of several established predictors of cancer specific mortality after partial or radical nephrectomy for renal cell carcinoma. Testing was performed on 399 patients with stages T(1-4), N(0-2), M(0-1) renal cell carcinoma who were treated with radical or partial nephrectomy at a single institution between 1990 and 2007. Univariable and multivariable Cox regression models tested the prognostic ability of spermine and spermidine levels in cancer specific mortality predictions. Covariates consisted of TNM stage, Fuhrman grade, tumor size and symptom classification. Harrell's concordance index (c-index) quantified accuracy and 200 bootstrap resamples were used to correct for overfit bias. The 5-year cancer specific mortality-free survival of patients with spermine levels 3 or less, 3.1 to 8, 8.1 to 13 and greater than 13 nmol/8x10(9) erythrocytes was 88.8%, 75.8%, 40.2% and 21.8%, respectively. Similarly the 5-year cancer specific mortality-free survival of patients with spermidine levels 12 or less, 12.1 to 15, 15.1 to 21 and greater than 21 nmol/8x10(9) erythrocytes was 79.0%, 56.6%, 53.2% and 27.4%, respectively. On multivariable analyses addressing cancer specific mortality after surgery spermine (p = 0.007) and spermidine (p = 0.04) achieved independent predictor status. Consideration of spermine and spermidine also improved the accuracy of established cancer specific mortality predictors by 2.2% (p <0.001). Spermine and spermidine may significantly improve the prognostic value of established cancer specific mortality predictors after partial or radical nephrectomy for all stages of renal cell carcinoma. Independent external validation of our findings is required.

Conditional Survival Predictions After Nephrectomy for Renal Cell Carcinoma

Conditional survival implies that on average long-term cancer survivors have a better prognosis than do newly diagnosed individuals. We explored the effect of conditional survival in renal cell carcinoma. We studied 3,560 patients with renal cell carcinoma of all stages treated with nephrectomy. We applied conditional survival methodology to a previously reported posttreatment nomogram predicting survival after nephrectomy for patients with renal cell carcinoma stage I to IV. We used the same predictor variables that were integrated in the original multivariable Cox regression models, namely TNM stage, Fuhrman grade, tumor size and symptom classification. To validate the conditional survival nomogram we used an independent cohort of 3,560 patients from 15 institutions. The 5-year survival of patients immediately after nephrectomy was 74.2%, which increased to 80.4%, 85.1%, 90.6% and 89.6% at 1, 2, 5 and 10 years after nephrectomy, respectively. The predicted probabilities varied by as much as 50% when, for example, predictions of renal cell carcinoma specific mortality at 10 years were made after nephrectomy vs 5 years later. Within the external validation cohort the accuracy of the conditional nomogram was 89.5%, 90.5%, 88.5% and 86.7% at 1, 2, 5 and 10 years after nephrectomy. We developed (2,530) and externally validated (3,560) a conditional nomogram for predicting renal cell carcinoma specific mortality that allows consideration of the length of survivorship. Our tool provides the most realistic prognosis estimates with high accuracy.

Development and External Validation of a New Outcome Prediction Model for Patients With Clear Cell Renal Cell Carcinoma Treated With Nephrectomy Based on Preoperative Serum C-Reactive Protein and TNM Classification: The TNM-C Score

C-reactive protein has been shown to be a prognostic factor for renal cell carcinoma. We developed a new prediction model including C-reactive protein in patients with clear cell renal cell carcinoma. This study is based on 2 cohorts of Japanese patients with clear cell renal cell carcinoma, including 249 for evaluating prognostic factors and developing the prediction model, and 290 for external validation. Analyzed factors included TNM classification, tumor size, Fuhrman nuclear grade, tumor necrosis and preoperative serum C-reactive protein (cutoff 0.5 mg/dl). We developed a scoring model based on multivariate analysis to predict cancer specific survival. Predictive ability of the model was evaluated using the concordance index. Multivariate analysis showed that pT stage, lymph node involvement, distant metastasis, tumor necrosis and C-reactive protein were independent predictors of cancer specific survival. A new scoring model was developed, consisting of C-reactive protein and the TNM classification. The 5-year cancer specific survival rate in patients with a score of 0, 1 and 2, 3 and 4, and 5 or more was 99%, 89%, 69% and 18%, respectively. Cancer specific survival rates were clearly discriminated by the stratification according to the scoring model (p <0.001). The concordance index of the new model was 0.820, which was externally validated as a concordance index of 0.865. In patients with clear cell renal cell carcinoma a new simple scoring model based on serum C-reactive protein and the TNM classification is a useful and easy to use tool for predicting outcome.

Age at diagnosis is a determinant factor of renal cell carcinoma– specific survival in patients treated with nephrectomy

Based on combined data for 4880 patients, 2 previous studies reported that advanced age is a predictor of increased renal cell carcinoma-specific mortality (RCC-SM). We explored the effect of age in cubic spline analyses to identify the age groups with the most elevated risk for renal cell carcinoma (RCC). Our study included 3595 patients from 14 European centres who had partial or radical nephrectomies. We used the Kaplan-Meier method to compile life tables, and we performed Cox regression analyses to assess RCC-SM. Covariates included age at diagnosis, sex, TNM (tumour, node, metastasis) stage, tumour size, Fuhrman grade, symptom classification and histological subtype. Age ranged from 10 to 89 (mean 63, median 67) years. The median duration of follow-up was 2.9 years. The median survival for the cohort was 13.4 years. Stage distribution was as follows: 1915 patients (53.3%) had stage I disease, 388 (10.8%) had stage II, 895 (24.9%) had stage III and 397 (11.0%) had stage IV disease. In multivariate analyses, we coded age at diagnosis as a cubic spline, and it achieved independent predictor status (p < 0.001). The risk of RCC-SM was lowest among patients younger than 50 years. We observed an increase in RCC-SM until the age of 50, at which point the level of risk reached a plateau. We observed a second increase among patients aged 75-89 years. We found similar patterns when we stratified patients according to the 2002 American Joint Committee on Cancer (AJCC) stages. The effect of age shows prognostic significance and indicates that follow-up and possibly secondary treatments might need to be adjusted according to the age of the patient.

Predicting cancer-control outcomes in patients with renal cell carcinoma

Several novel treatment modalities have been introduced for patients across all renal cell carcinoma stages. Observation or a variety of minimally invasive approaches can be applied to small renal masses. Conversely, aggressive loco-regional resections may be performed for locally advanced disease. Cytoreductive partial nephrectomy has become an alternative to radical nephrectomy. Finally, targeted therapies improve cancer control in unresectable or metastatic renal cell carcinoma. The variety of modes and stages at presentation and the number of treatment options may render medical decision-making highly complex. Various prognostic models and nomograms can assist with treatment decision-making in patients with renal cell carcinoma. The multivariable risk-factor approach to renal cell carcinoma-specific mortality has been pioneered. In 1999 was proposed a multivariate model for prediction of individual survival in patients with metastatic renal cell carcinoma. Since then several prenephrectomy and postnephrectomy models have been developed. These models can be distinguished according to their target populations, discriminant properties (accuracy of predictions) and confirmed validity within independent cohorts. We give a comparative outline of these model characteristics within existing tools. Our work provides the clinician with a complete list of such tools, including comparisons of their relative advantages and disadvantages.

1245: The Presence of Tumor Necrosis within the Primary Tumor Cannot Independently Predict Renal Cell Carcinoma-Specific Mortality after Nephrectomy

1245: The Presence of Tumor Necrosis within the Primary Tumor Cannot Independently Predict Renal Cell Carcinoma-Specific Mortality after Nephrectomy

Editorial Comment on: Platelet Count and Preoperative Haemoglobin Do Not Significantly Increase the Performance of Established Predictors of Renal Cell Carcinoma-Specific Mortality

Editorial Comment on: Platelet Count and Preoperative Haemoglobin Do Not Significantly Increase the Performance of Established Predictors of Renal Cell Carcinoma-Specific Mortality

Platelet Count and Preoperative Haemoglobin Do Not Significantly Increase the Performance of Established Predictors of Renal Cell Carcinoma-Specific Mortality

ObjectiveAnaemia and/or thrombocytosis were identified as independent predictors of poor survival in renal cell carcinoma (RCC). We tested the extent to which these markers worsen the prognosis in these patients. MethodsAnalyses targeted 1828 patients with renal cell carcinoma. Univariable, multivariable, and predictive accuracy analyses addressed RCC-specific mortality (RCC-SM). ResultsIn univariable and multivariable analyses, both platelet count and preoperative haemoglobin level were statistically significant predictors of RCC-SM. However, neither platelet count nor preoperative haemoglobin level increased the combined multivariable accuracy of established RCC-SM (predictive accuracy gain=0.3%) predictors. ConclusionsPatients who present with severe anaemia or elevated platelets are at no higher risk of RCC-SM than that related to their stage, grade, histologic subtype, and Eastern Cooperative Oncology Group-Performance Status.

ECOG performance status 0 or 1 and symptom classification do not improve the ability to predict renal cell carcinoma-specific survival

Objectives We tested and compared the improvement in prognostic ability related to the consideration of either ECOG performance status (ECOGPS) and/or symptom classification (S-CLASS) in renal cell carcinoma specific mortality (RCC-SM) predictions. Methods Univariate and multivariate Cox regression analyses targeted RCC-SM in 2570 RCC patients treated with either partial or radical nephrectomy. The increment in predictive accuracy related to the addition of either ECOGPS, S-CLASS or both was quantified using Harrell’s concordance index. Results Follow-up ranged from 0.1 to 23 years (median 3.2) and 610 patients (23.7%) died of RCC. In multivariable analyses, ECOGPS and S-CLASS represented independent predictors of RCC-SM. The addition of ECOGPS to established RCC-SM predictors increased the predictive accuracy by 0.3% ( p = 0.8) versus 0.6% ( p = 0.5) for S-CLASS versus 0.6% ( p = 0.5) for both. Conclusions Neither ECOGPS nor S-CLASS improves the ability to predict RCC-SM. Therefore, these variables may be safely omitted when RCC-SM risk is quantified.