ABSTRACT
While upper tract access through the insensate conduit following urinary diversion takes less time and incurs fewer costs than percutaneous kidney access does for the treatment of ureter and kidney pathology, endoscopic ureteroenteric anastomoses (UEA) identification can be difficult. We injected India Ink into the bowel mucosa near the UEA during ileal conduit diversion (IC) to determine the safety and feasibility of ink tattooing. Patients undergoing IC were prospectively randomized to receive ink or normal saline (NS) injections. The injections were placed 1 cm from UEA in a triangular configuration, and loopogram exams and looposcopy were performed to identify reflux (UR), UEA, the tattooing site and strictures in 10 and 11 patients randomized with respect to ink and NS injections, respectively. Ink patients were older (72 vs. 61 years old, p = 0.04) and had a higher Charlson Comorbidity Index (5 vs. 2, p = 0.01). Looposcopy was performed in three ink and four NS patients. Visualization of UEA was achieved in 100% of the ink and 75% of the NS patients (p = 0.26). The ink ureteroenteric anastomotic stricture (UEAS) rate was higher (N = 3 vs. N = 1) and six patients vs. one patients underwent surgery, respectively, for UEAS (p = 0.31). The study was halted early due to safety concerns. Our pilot study demonstrates that ink can be well visualized following injection near UEA during IC. However, the ink cohort had more UEAS than previously cited in the literature and our prior institutional UEAS rate of 6%. While this study sample is small, the higher incidence of UEAS after ink injection led us to question the utility and safety of ink injection following IC.
Subject(s)
Tattooing , Ureter , Urinary Bladder Neoplasms , Humans , Middle Aged , Ureter/diagnostic imaging , Ureter/surgery , Ureter/pathology , Cystectomy , Pilot Projects , Anastomosis, Surgical/methods , Retrospective StudiesABSTRACT
BACKGROUND: In May 2012, the US Preventive Services Task Force assigned prostate-specific antigen-based screening a grade D recommendation, advising against screening at any age. Our objective was to compare prostate cancer characteristics pre- and post-recommendation with an adjusted analysis of our data and a pooled analysis including other primary data sources. METHODS: We identified all incident prostate cancer diagnoses at our institution from 2007 to 2016. Multivariable log binomial regression was used to determine the relative risk (RR) of metastasis at diagnosis, ≥Gleason Group 4, and high D'Amico risk disease pre- versus post-recommendation. The meta-analysis included primary data studies evaluating these outcomes. RESULTS: At our institution, 287 (44.6%) and 224 (48.8%) patients were diagnosed in the pre- and post-cohorts. The RR of metastatic disease at diagnosis did not differ between groups (p = 0.224), nor did the risk of high D'Amico category disease (p = 0.089). The risk of ≥Gleason Group 4 was 1.58 times higher post-recommendation (p = 0.007). The pooled risk of ≥Gleason Group 4 disease was 1.5 (p < 0.001) post-recommendation and was 1.29 (p = 0.006) for high D'Amico risk disease. CONCLUSIONS: While the number of metastatic cases did not differ after the recommendation, the risk of high-grade cancers increased at both a local and aggregated level.
Subject(s)
Early Detection of Cancer/methods , Prostate-Specific Antigen/blood , Prostatic Neoplasms/blood , Prostatic Neoplasms/prevention & control , Humans , Male , Practice Guidelines as Topic , Preventive Health Services , Prostatic Neoplasms/diagnosis , United StatesABSTRACT
BACKGROUND: The management of metastatic renal cell carcinoma (mRCC) has evolved rapidly, and results from the Cancer du Rein Metastatique Nephrectomie et Antiangiogéniques (CARMENA) trial bring into question the utility of cytoreductive nephrectomy (CN). The objective of this study was to examine overall survival (OS) and identify risk factors associated with patients less likely to benefit from CN in the targeted therapy era. METHODS: Patients with mRCC undergoing CN from 2005 to 2017 were identified. Kaplan-Meier methods and Cox proportional hazards regression analyses were used to assess OS and risk-stratify patients, respectively, on the basis of preoperative clinical and laboratory data. RESULTS: Six hundred eight patients were eligible with a median follow-up of 29.4 months. Ninety-five percent of the patients had an Eastern Cooperative Oncology Group performance status less than or equal to 1, and 70% had a single site of metastatic disease. In a multivariable analysis, risk factors significantly associated with decreased OS included systemic symptoms at diagnosis, retroperitoneal and supradiaphragmatic lymphadenopathy, bone metastasis, clinical T4 disease, a hemoglobin level less than the lower limit of normal (LLN), a serum albumin level less than the LLN, a serum lactate dehydrogenase level greater than the upper limit of normal, and a neutrophil/lymphocyte ratio greater than or equal to 4. Patients were stratified into 3 risk groups: low (fewer than 2 risk factors), intermediate (2-3 risk factors), and high (more than 3 risk factors). These groups had median OS of 58.9 months (95% confidence interval [CI], 44.3-66.6 months), 30.6 months (95% CI, 27.0-35.0 months), and 19.2 months (95% CI, 13.9-22.6 months), respectively (P < .0001). The median time to postoperative systemic therapy was 45 days (interquartile range, 30-90 days). CONCLUSIONS: Patients with more than 3 risk factors did not seem to benefit from CN. Importantly, OS in this group was equivalent to, if not higher than, OS for patients in the CN plus sunitinib arm of CARMENA, and this raises the possibility that a well-selected population might benefit from CN.
Subject(s)
Bone Neoplasms/drug therapy , Bone Neoplasms/surgery , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/surgery , Patient Selection , Aged , Bone Neoplasms/pathology , Bone Neoplasms/secondary , Carcinoma, Renal Cell/epidemiology , Carcinoma, Renal Cell/pathology , Cytoreduction Surgical Procedures/adverse effects , Disease-Free Survival , Female , Hemoglobins/metabolism , Humans , Kaplan-Meier Estimate , Lymphocytes/pathology , Male , Middle Aged , Neoplasm Metastasis , Nephrectomy/adverse effects , Neutrophils/pathology , Proportional Hazards Models , Risk Factors , Sunitinib/administration & dosage , Sunitinib/adverse effects , Treatment OutcomeABSTRACT
INTRODUCTION: We describe and demonstrate an efficient method for assigning clinic days to urology providers in academic and large urology group practices given their numerous scheduling constraints including evaluation and management visits, office or operating room procedures/surgeries, teaching, trainee mentorship, committee work and outreach activities. METHODS: We propose an integer programming model for scheduling providers for clinic shifts in order to maximize patient access to appointments considering the aforementioned scheduling constraints. We present results for a case study with an academic urology clinic and lessons learned from implementing the model generated schedule. RESULTS: The integer programming model produced a feasible schedule that was implemented after pairwise and 3-way switches among attending providers to account for preferences. The optimized schedule had reduced variability in the number of providers scheduled per shift (standard deviation 1.409 vs 0.999, p=0.01). While other confounding factors are possible we noted a significant increase in the number of encounters after implementing changes from the model (1,370 vs 1,196 encounters, p=0.011). CONCLUSIONS: Optimization models offer an efficient and transferable method of generating a clinic template for providers that takes into account other clinical and academic responsibilities, and can increase the number of appointments for patients. Optimization of schedules may be performed periodically to address changes in providers or provider constraints.
ABSTRACT
Lynch syndrome (LS) is defined by germline mutations in DNA mismatch repair (MMR) genes, and affected patients are at high risk for multiple cancers. Reflexive testing for MMR protein loss by immunohistochemistry (IHC) is currently only recommended for colorectal and endometrial cancers, although upper tract urothelial carcinoma (UTUC) is the third-most common malignancy in patients with LS. To study the suitability of universal MMR IHC screening for UTUC, we investigated MMR expression and microsatellite status in UTUC in comparison to bladder UC (BUC), and evaluated the clinicopathologic features of UTUC. We found that 9% of UTUC showed MMR IHC loss (8 MSH6 alone; 1 MSH2 and MSH6; 1 MLH1 and PMS2; n=117) compared with 1% of BUC (1 MSH6 alone; n=160) (P=0.001). Of these, 4/10 (40%) of UTUC (3% overall; 3 MSH6 alone; 1 MLH1 and PMS2) and none (0%) of BUC had high microsatellite instability on molecular testing (P=0.03). The only predictive clinicopathologic feature for MMR loss was a personal history of colorectal cancer (P=0.0003). However, UTUC presents at a similar age to colon carcinoma in LS and thus UTUC may be the sentinel event in some patients. Combining our results with those of other studies suggests that 1% to 3% of all UTUC cases may represent LS-associated carcinoma. LS accounts for 2% to 6% of both colorectal and endometrial cancers. As LS likely accounts for a similar percentage of UTUC, we suggest that reflexive MMR IHC screening followed by microsatellite instability testing be included in diagnostic guidelines for all UTUC.
Subject(s)
Biomarkers, Tumor/genetics , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , DNA Mismatch Repair , DNA Repair Enzymes/genetics , Early Detection of Cancer/methods , Immunohistochemistry , Microsatellite Instability , Urologic Neoplasms/genetics , Urothelium/chemistry , Adult , Aged , Aged, 80 and over , Colorectal Neoplasms, Hereditary Nonpolyposis/pathology , DNA Mutational Analysis , DNA-Binding Proteins/genetics , Databases, Factual , Female , Genetic Predisposition to Disease , Humans , Male , Middle Aged , Mismatch Repair Endonuclease PMS2/genetics , MutL Protein Homolog 1/genetics , MutS Homolog 2 Protein/genetics , Mutation , Phenotype , Predictive Value of Tests , Reproducibility of Results , Urologic Neoplasms/pathology , Urothelium/pathologyABSTRACT
BACKGROUND: We performed a comparative survival analysis of patients undergoing robotic-assisted versus laparoscopic or open surgery for upper tract urothelial carcinoma (UTUC). MATERIALS AND METHODS: Patients diagnosed with non-metastatic UTUC undergoing removal of the kidney and/or ureter were identified using Medicare-linked Surveillance, Epidemiology, and End Results Program data (2004-2013). Patients aged 65-85 years were categorized based on surgical approach (open, laparoscopic, or robotic-assisted). Kaplan-Meier methods were used to determine survival (overall and cancer-specific) and intravesical recurrence rates, the former using a propensity score-weighted model. Independent predictors of survival were determined using multivariable Cox proportional hazards regression analysis. RESULTS: We identified a total of 3801 patients meeting the final inclusion criteria: open (n = 1862), laparoscopic (n = 1624), and robotic (n = 315). Robotic surgery was associated with the shortest length of hospital stay (p < 0.001) but highest in-hospital charges (p < 0.001), with no difference in readmission rates (p = 0.964). No difference was found in overall or cancer-specific survival in the robotic cohort when compared with open or laparoscopic surgery. In addition, no difference in the rate of intravesical recurrence was noted in robotic-assisted laparoscopy compared with the other groups. The sole predictor of improved survival was extent of lymphadenectomy, which was highest in the robotic cohort. CONCLUSIONS: Using a large, population-based cancer database, there was no survival difference when a robotic-assisted approach was utilized in patients undergoing surgery for UTUC. These findings are important with the increased use of robotic surgery in the management of UTUC.
Subject(s)
Carcinoma, Transitional Cell/surgery , Kidney Neoplasms/surgery , Laparoscopy , Robotic Surgical Procedures , Ureteral Neoplasms/surgery , Urinary Bladder Neoplasms/secondary , Aged , Aged, 80 and over , Carcinoma, Transitional Cell/secondary , Female , Hospital Charges , Humans , Kaplan-Meier Estimate , Kidney Neoplasms/pathology , Laparoscopy/economics , Length of Stay , Lymphatic Metastasis , Male , Patient Readmission , Proportional Hazards Models , Robotic Surgical Procedures/economics , SEER Program , Survival Rate , Ureteral Neoplasms/pathologySubject(s)
Embolization, Therapeutic , Prostatic Neoplasms , Arteries , Humans , Male , Prostate-Specific AntigenABSTRACT
We report a new type of carbon nanotube ring (CNTR) coated with gold nanoparticles (CNTR@AuNPs) using CNTR as a template and surface attached redox-active polymer as a reducing agent. This nanostructure of CNTR bundle embedded in the gap of closely attached AuNPs can play multiple roles as a Raman probe to detect cancer cells and a photoacoustic (PA) contrast agent for imaging-guided cancer therapy. The CNTR@AuNP exhibits substantially higher Raman and optical signals than CNTR coated with a complete Au shell (CNTR@AuNS) and straight CNT@AuNP. The extinction intensity of CNTR@AuNP is about 120-fold higher than that of CNTR at 808 nm, and the surface enhanced Raman scattering (SERS) signal of CNTR@AuNP is about 110 times stronger than that of CNTR, presumably due to the combined effects of enhanced coupling between the embedded CNTR and the plasmon mode of the closely attached AuNPs, and the strong electromagnetic field in the cavity of the AuNP shell originated from the intercoupling of AuNPs. The greatly enhanced PA signal and photothermal conversion property of CNTR@AuNP were successfully employed for imaging and imaging-guided cancer therapy in two tumor xenograft models. Experimental observations were further supported by numerical simulations and perturbation theory analysis.
Subject(s)
Gold/chemistry , Hyperthermia, Induced/methods , Metal Nanoparticles/chemistry , Nanotubes, Carbon/chemistry , Photochemotherapy/methods , Theranostic Nanomedicine/methods , Animals , Cell Line, Tumor , Electromagnetic Fields , Gold/therapeutic use , Metal Nanoparticles/therapeutic use , Mice, Nude , Neoplasms/diagnosis , Neoplasms/therapy , Spectrum Analysis, Raman , Surface Properties , Xenograft Model Antitumor AssaysABSTRACT
The beneficial effect of cytoreductive nephrectomy on survival of patients with metastatic renal cell carcinoma in the immunotherapy era was based on two prospective randomized trials. Unfortunately, such evidence does not yet exist in the present-day period of targeted therapy. Despite this, cytoreductive nephrectomy remains integral in the multimodal management of patients with metastatic renal cell carcinoma. Multiple retrospective studies as well as data from prospective studies examining targeted therapy support the continued use of cytoreductive nephrectomy in the properly selected patient. Ongoing studies will hopefully fine-tune the role and timing of cytoreductive nephrectomy in the context of targeted therapy.
Subject(s)
Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/surgery , Cyclin-Dependent Kinase Inhibitor p16/genetics , Gene Expression Regulation, Neoplastic , Lymph Node Excision , Neoplasm Recurrence, Local/genetics , Papillomavirus Infections/complications , Papillomavirus Infections/epidemiology , Penile Neoplasms/genetics , Penile Neoplasms/pathology , Penile Neoplasms/surgery , Penile Neoplasms/virology , Humans , MaleABSTRACT
OBJECTIVES: Despite level 1 evidence demonstrating a survival benefit of cytoreductive nephrectomy (CN) in well-selected patients with metastatic renal cell carcinoma (mRCC) in the cytokine era, its role in the contemporary period of targeted therapy remains understudied. To help facilitate improved patient selection for CN and clinical trial design in the targeted therapy era, this study sought to identify factors associated with RCC-specific survival in patients diagnosed with mRCC and undergoing CN between 2005 and 2010 using a large population-based cohort. MATERIALS AND METHODS: Patients diagnosed with mRCC and undergoing CN between 2005 and 2010 were identified from the Surveillance Epidemiology and End Results cancer database. Kaplan-Meier methods were used to calculate disease-specific survival. Stepwise multivariable Cox proportional hazards regression analysis was used to identify factors independently associated with risk of RCC-specific death. RESULTS: A total of 2,478 patients were identified who were eligible for analysis with a median disease-specific survival of 21 months (95% CI: 19, 22). Factors independently associated with an increased risk of RCC-specific death included age at diagnosis≥60 years, African American race, higher American Joint Committee on Cancer T stage (≥T3), high Fuhrman nuclear grade (3 or 4), primary tumor size≥7 cm, regional lymphadenopathy, both distant lymph node and visceral metastases, and sarcomatoid histology. A higher number of adverse factors correlated with an increased risk of RCC-specific death (P<0.001). CONCLUSIONS: Factors associated with RCC-specific survival identified in this large population-based study can be used to better stratify patients suitable for CN and to help with future clinical trial design and interpretation.
Subject(s)
Carcinoma, Renal Cell/surgery , Kidney Neoplasms/surgery , Nephrectomy/methods , Aged , Carcinoma, Renal Cell/epidemiology , Carcinoma, Renal Cell/therapy , Cohort Studies , Cytokines/metabolism , Female , Humans , Kaplan-Meier Estimate , Kidney Neoplasms/epidemiology , Kidney Neoplasms/therapy , Male , Middle Aged , Molecular Targeted Therapy/methods , Proportional Hazards Models , Regression Analysis , SEER Program , Treatment Outcome , United StatesABSTRACT
PURPOSE: We evaluated the survival of patients with muscle invasive bladder cancer undergoing radical cystectomy without neoadjuvant chemotherapy to confirm the utility of existing clinical tools to identify low risk patients who could be treated with radical cystectomy alone and a high risk group most likely to benefit from neoadjuvant chemotherapy. MATERIALS AND METHODS: We identified patients with muscle invasive bladder cancer who underwent radical cystectomy without neoadjuvant chemotherapy at our institution between 2000 and 2010. Patients were considered high risk based on the clinical presence of hydroureteronephrosis, cT3b-T4a disease, and/or histological evidence of lymphovascular invasion, micropapillary or neuroendocrine features on transurethral resection. We evaluated survival (disease specific, progression-free and overall) and rate of pathological up staging. An independent cohort of patients from another institution was used to confirm our findings. RESULTS: We identified 98 high risk and 199 low risk patients eligible for analysis. High risk patients exhibited decreased 5-year overall survival (47.0% vs 64.8%) and decreased disease specific (64.3% vs 83.5%) and progression-free (62.0% vs 84.1%) survival probabilities compared to low risk patients (p <0.001). Survival outcomes were confirmed in the validation subset. On final pathology 49.2% of low risk patients had disease up staged. CONCLUSIONS: The 5-year disease specific survival of low risk patients was greater than 80%, supporting the distinction of high risk and low risk muscle invasive bladder cancer. The presence of high risk features identifies patients with a poor prognosis who are most likely to benefit from neoadjuvant chemotherapy, while many of those with low risk disease can undergo surgery up front with good expectations and avoid chemotherapy associated toxicity.
Subject(s)
Carcinoma, Transitional Cell/mortality , Patient Selection , Urinary Bladder Neoplasms/mortality , Aged , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/therapeutic use , Carcinoma, Transitional Cell/drug therapy , Carcinoma, Transitional Cell/pathology , Carcinoma, Transitional Cell/surgery , Cystectomy , Female , Humans , Male , Middle Aged , Neoadjuvant Therapy , Neoplasm Staging , Survival Analysis , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/surgeryABSTRACT
BACKGROUND: Few data exist regarding the impact on survival of definitive treatment of the prostate in men diagnosed with metastatic prostate cancer (mPCa). OBJECTIVE: To evaluate the survival of men diagnosed with mPCa based on definitive treatment of the prostate. DESIGN, SETTING, AND PARTICIPANTS: Men with documented stage IV (M1a-c) PCa at diagnosis identified using Surveillance Epidemiology and End Results (SEER) (2004-2010) and divided based on definitive treatment of the prostate (radical prostatectomy [RP] or brachytherapy [BT]) or no surgery or radiation therapy (NSR). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Kaplan-Meier methods were used to calculate overall survival (OS). Multivariable competing risks regression analysis was used to calculate disease-specific survival (DSS) probability and identify factors associated with cause-specific mortality (CSM). RESULTS AND LIMITATIONS: A total of 8185 patients were identified: NSR (n=7811), RP (n=245), and BT (n=129). The 5-yr OS and predicted DSS were each significantly higher in patients undergoing RP (67.4% and 75.8%, respectively) or BT (52.6 and 61.3%, respectively) compared with NSR patients (22.5% and 48.7%, respectively) (p<0.001). Undergoing RP or BT was each independently associated with decreased CSM (p<0.01). Similar results were noted regardless of the American Joint Committee on Cancer (AJCC) M stage. Factors associated with increased CSM in patients undergoing local therapy included AJCC T4 stage, high-grade disease, prostate-specific antigen ≥20 ng/ml, age ≥70 yr, and pelvic lymphadenopathy (p<0.05). The major limitation of this study was the lack of variables from SEER known to influence survival of patients with mPCa, including treatment with systemic therapy. CONCLUSIONS: Definitive treatment of the prostate in men diagnosed with mPCa suggests a survival benefit in this large population-based study. These results should serve as a foundation for future prospective trials. PATIENT SUMMARY: We used a large population-based cancer database to examine survival in men diagnosed with metastatic prostate cancer (mPCa) undergoing definitive therapy for the prostate. Local therapy (LT) appeared to confer a survival benefit. Therefore, we conclude that prospective trials are needed to further evaluate the role of LT in mPCa.
Subject(s)
Adenocarcinoma/secondary , Adenocarcinoma/therapy , Prostatic Neoplasms/pathology , Prostatic Neoplasms/therapy , Adenocarcinoma/mortality , Age Factors , Aged , Brachytherapy , Humans , Kaplan-Meier Estimate , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Grading , Neoplasm Staging , Prostate-Specific Antigen/blood , Prostatectomy , Prostatic Neoplasms/mortality , SEER Program , Survival RateABSTRACT
OBJECTIVE: To determine if prostatic inflammation at the time of radical prostatectomy (RP) was associated with the International Prostate Symptom Score (IPSS). METHODS: We performed a proof of principle analytic case control study of patients who underwent RP between January 2005 and August 2008 for lower urinary tract symptoms (LUTS). We reviewed pathology slides of those who had a change of 4 points or greater, as measured by the IPSS and correlated inflammation with change in IPSS. Multivariate linear regression analyses were performed to determine the association of IPSS with degree of inflammation based on the number of inflammatory cells. RESULTS: Of 249 patients, 136 had complete data and 47 (18.8%) underwent pathologic review. The median change in IPSS for the study cohort was -7.0 points compared to +1.0 point for the control cohort. On univariate analysis, the average improvement in IPSS in patients with severe inflammation was (r = -6.02, 95% confidence interval [CI] -11.0 to -1.1, P = .018) after RP. On multivariate analysis, adjusting for age, body mass index (BMI), year of surgery, history of prostatitis, Gleason score, prostate-specific antigen (PSA), prostate weight, and nerve sparing status, only patients with severe prostatic inflammation had significant improvement in their IPSS (r = -5.93, 95% CI -10.81 to -1.04, P = .004). CONCLUSION: Prostatic inflammation measured in prostatectomy specimens is associated with worse baseline IPSS than matched cohorts. Specifically, severe inflammation is an independent predictor of IPSS improvement at 1 year after RP.
Subject(s)
Lower Urinary Tract Symptoms/complications , Lower Urinary Tract Symptoms/surgery , Prostatectomy , Prostatitis/complications , Prostatitis/surgery , Aged , Humans , Male , Middle Aged , Prostatitis/diagnosis , Remission Induction , Retrospective Studies , Severity of Illness IndexABSTRACT
BACKGROUND: There is limited evidence to guide patient selection for cytoreductive nephrectomy (CN) following the diagnosis of metastatic renal cell carcinoma (mRCC). OBJECTIVE: Given the significant variability in oncologic outcomes following surgery, we sought to develop clinically relevant, individualized, multivariable models for the prediction of cancer-specific survival at 6 and 12 mo after CN. The development of this nomogram will better help clinicians select patients for cytoreductive surgery. DESIGN, SETTING, AND PARTICIPANTS: We identified 601 consecutive patients who underwent CN for kidney cancer at a single tertiary cancer center. INTERVENTION: CN for mRCC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The development cohort was used to select predictive variables from a large group of candidate predictors. The discrimination, calibration, and decision curves were corrected for overfit using 10-fold crossvalidation that included stepwise variable selection. RESULTS AND LIMITATIONS: With a median follow-up of 65 mo (range: 6-199) for the entire cohort, 110 and 215 patients died from kidney cancer at 6 and 12 mo after surgery, respectively. For the preoperative model, serum albumin and serum lactate dehydrogenase were included. Final pathologic primary tumor stage, nodal stage, and receipt of blood transfusion were added to the previously mentioned parameters for the postoperative model. Preoperative and postoperative nomograms demonstrated good discrimination of 0.76 and 0.74, respectively, when applied to the validation data set. Both models demonstrated excellent calibration and a good net benefit over large ranges of threshold probabilities. The retrospective study design is the major limitation of this study. CONCLUSIONS: We have developed models for accurate prediction of cancer-specific survival after CN, using either preoperative or postoperative variables. While these tools need validation in independent cohorts, our results suggest that the models are informative and can be used to aid in clinical decision making.
Subject(s)
Carcinoma, Renal Cell/surgery , Decision Support Techniques , Kidney Neoplasms/surgery , Nephrectomy , Patient Selection , Precision Medicine , Biomarkers, Tumor/blood , Blood Transfusion/mortality , Carcinoma, Renal Cell/blood , Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/secondary , Disease-Free Survival , Female , Humans , Kidney Neoplasms/blood , Kidney Neoplasms/mortality , Kidney Neoplasms/pathology , L-Lactate Dehydrogenase/blood , Logistic Models , Male , Middle Aged , Multivariate Analysis , Neoplasm Staging , Nephrectomy/adverse effects , Nephrectomy/mortality , Odds Ratio , Retrospective Studies , Risk Assessment , Risk Factors , Serum Albumin/analysis , Serum Albumin, Human , Tertiary Care Centers , Texas , Time Factors , Transfusion Reaction , Treatment OutcomeABSTRACT
UNLABELLED: Study Type--Diagnostic (cohort) Level of Evidence: 2b. What's known on the subject? and What does the study add? Although there have been many investigations of biopsy for small renal masses, there are scant data on the accuracy of biopsy in the setting of metastatic renal cell carcinoma (mRCC). We report a large series of biopsies and compare with nephrectomy pathology in patients with mRCC. The present study highlights the inaccuracy of biopsy in the setting of metastatic disease, which is related to sampling error because of heterogeneity within the tumour and among metastases. These limitations are important to realize when designing trials that depend on pathological findings from biopsy and not nephrectomy. In addition, we found that biopsy of primary tumours were more likely than biopsy of metastatic sites to be diagnostic of RCC. Future studies with multiquadrant biopsies of primary tumours could yield the most accurate pathological results for future studies. OBJECTIVE: ⢠To evaluate the ability of preoperative biopsy to identify high-risk pathological features by comparing pathology from preoperative metastatic site and primary tumour biopsies with nephrectomy pathology in patients with metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: ⢠We reviewed clinical and pathological data from patients who underwent biopsy before cytoreductive nephrectomy for mRCC at MD Anderson Cancer Center (MDACC) from 1991 to 2007. ⢠Percutaneous biopsy techniques included fine-needle aspiration, core needle biopsy or a combination of both techniques. RESULTS: ⢠The pathology of 405 preoperative biopsies (239 metastatic site, 166 primary tumour) from 378 patients was reviewed at MDACC before cytoreductive nephrectomy. ⢠The biopsy and nephrectomy specimens had the same histological subtype in 96.0% of clear-cell renal cell carcinomas (RCCs) and 72.7% of non-clear-cell RCCs. ⢠Of 76 nephrectomy specimens where sarcomatoid de-differentiation was identified, only seven (9.2%) were able to be identified from the preoperative biopsy. ⢠In 38.3% of patients, the same Fuhrman grade was identified in both the biopsy and nephrectomy specimens. ⢠A definitive diagnosis of RCC was more likely to be reported in primary tumour biopsies than in metastatic site biopsies. (P < 0.001). CONCLUSIONS: ⢠Preoperative biopsy has limited ability to identify non-clear-cell histological subtype, Fuhrman grade or sarcomatoid features. ⢠When surgical pathology is not available, a biopsy obtaining multiple samples from different sites within the primary tumour should be recommended rather than limited metastatic site biopsy to identify patients for clinical trials.
Subject(s)
Carcinoma, Renal Cell/pathology , Kidney Neoplasms/pathology , Kidney/pathology , Nephrectomy/methods , Adolescent , Adult , Aged , Aged, 80 and over , Biopsy, Fine-Needle/standards , Carcinoma, Renal Cell/surgery , Female , Humans , Kidney Neoplasms/surgery , Male , Middle Aged , Neoplasm Metastasis , Preoperative Care/methods , Retrospective Studies , Sensitivity and Specificity , Young AdultABSTRACT
BACKGROUND: In metastatic renal cell carcinoma (mRCC) patients treated with targeted agents and their primary tumor (PT) in situ, early PT decrease in size correlates with improved overall PT response, but the effect on overall survival (OS) is unknown. OBJECTIVE: To evaluate whether early PT size reduction is associated with improved OS in patients with mRCC undergoing treatment with sunitinib. DESIGN, SETTING, AND PARTICIPANTS: We reviewed the clinical and radiographic data of all mRCC patients seen at our institution between January 2004 and December 2009 without prior systemic treatment who received sunitinib with their PT in situ. MEASUREMENTS: Two independent reviewers measured the diameter of the PT and metastatic disease at baseline and subsequent scans to assess response. Early minor response was defined as ≥10% decrease within 60 d of treatment initiation. Univariate and multivariate analyses were used to calculate a hazard ratio (HR) corresponding to the risk of death based on clinical and pathologic factors as well as PT response. RESULTS AND LIMITATIONS: We identified 75 consecutive patients with a median follow-up of 15 mo. All patients were intermediate or poor risk by common risk stratification systems. Median initial PT diameter was 9.7cm. Median maximum PT size reduction was -10.2% overall and -36.4% in patients who had early minor PT response. Median OS for patients without minor PT response, with minor PT response after 60 d, and with early minor PT response was 10.3, 16.5, and 30.2 mo, respectively. On multivariate analysis, early minor response was an independent predictor of improved OS (HR: 0.26; p=0.031). Other significant predictors included venous thrombus, multiple bone metastases, lactate dehydrogenase above the upper limit of normal, symptoms at presentation, and more than two metastatic sites. CONCLUSIONS: Early minor PT response is associated with improved OS. Future studies should evaluate this prognostic factor to identify patients with prolonged OS.
Subject(s)
Angiogenesis Inhibitors/therapeutic use , Carcinoma, Renal Cell/drug therapy , Indoles/therapeutic use , Kidney Neoplasms/drug therapy , Pyrroles/therapeutic use , Adult , Aged , Aged, 80 and over , Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/secondary , Female , Humans , Kaplan-Meier Estimate , Kidney Neoplasms/mortality , Kidney Neoplasms/pathology , Male , Middle Aged , Odds Ratio , Retrospective Studies , Risk Assessment , Risk Factors , Sunitinib , Survival Rate , Texas , Time Factors , Treatment Outcome , Tumor Burden/drug effects , Young AdultABSTRACT
BACKGROUND: In patients with metastatic renal cell carcinoma (mRCC), the timing of systemic targeted therapy in relation to cytoreductive nephrectomy (CN) is under investigation. OBJECTIVE: To evaluate postoperative complications after the use of presurgical targeted therapy prior to CN. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review of all patients who underwent a CN at The University of Texas M.D. Anderson Cancer Center from 2004 to 2010 was performed. Inclusion in this study required documented evidence of mRCC, with treatment incorporating CN. INTERVENTIONS: Patients receiving presurgical systemic targeted therapy prior to CN were compared to those undergoing immediate CN. MEASUREMENTS: Complications were assessed using the modified Clavien system for a period of 12 mo postoperatively. RESULTS AND LIMITATIONS: Presurgical therapy was administered to 70 patients prior to CN (presurgical), while 103 patients had an immediate CN (immediate). A total of 232 complications occurred in 57% of patients (99 of 173). Use of presurgical systemic targeted therapy was predictive of having a complication>90 d postoperatively (p=0.002) and having multiple complications (p=0.013), and it was predictive of having a wound complication (p<0.001). Despite these specific complications, presurgical systemic targeted therapy was not associated with an increased overall complication risk on univariable or multivariate analysis (p=0.064 and p=0.237) and was not predictive for severe (Clavien ≥3) complications (p=0.625). This study is limited by its retrospective nature. As is inherent to any retrospective study reporting on complications, we are limited by reporting bias and the potential for misclassification of specific complications. CONCLUSIONS: Despite an increased risk for specific wound-related complications, overall surgical complications and the risk of severe complications (Clavien ≥3) are not greater after presurgical targeted therapy in comparison to upfront cytoreductive surgery.