Does Long-Term Bowel Function Change After Colectomy for Colon Malignancy?

INTRODUCTION: Current understanding of bowel function after colectomy for colon cancer is informed by conflicting data, making preoperative patient counseling difficult. Our previous work demonstrates bowel movement frequency increases by postoperative follow-up, while overall function does not change. Long-term changes are unknown. We aimed to evaluate changes to patient-reported bowel function after colectomy for colon malignancy. METHODS: This is an observational study of patients that underwent colectomy for colon malignancy and completed the Colorectal Functional Outcome (COREFO) questionnaire at preoperative and 30-d postoperative clinic visits. Long-term bowel function was assessed using the same questionnaire via telephone or surveillance clinic visit. Mean domain and Total COREFO scores were compared baseline to long-term using paired t-tests. Quality of life analysis was obtained using the Patient Reported Outcome Measurement Information System-10 Global Health questionnaire for patients who completed this measure at surveillance visits or via telephone. RESULTS: Sixty-six patients met inclusion criteria. Median time between baseline and long-term questionnaire completion was 16 mo (interquartile range 11-30). Stool-related aspects (pain and bleeding with bowel movements, anal skin irritation) improved significantly from baseline to long-term. There were no other differences in any domain or Total COREFO score. Patient Reported Outcome Measurement Information System-10 scores demonstrated quality of life equivalent to the general US population. CONCLUSIONS: Over the long-term, after colectomy for colon cancer, patients report improvements in stool-related aspects (pain and bleeding with bowel movements, anal skin irritation). Evidence-based preoperative patient counseling should include these findings.

Extreme Elevation of Baseline Intraoperative Parathyroid Hormone Measurements: Should Usual Protocols Apply?

INTRODUCTION: Intraoperative parathyroid hormone (IOPTH) monitoring is routinely used to facilitate minimally invasive parathyroidectomy. Many IOPTH protocols exist for predicting biochemical cure. Some patients are found to have extremely high baseline IOPTH levels (defined in this study as >500 pg/mL), which may affect the likelihood of satisfying certain final IOPTH criteria. We aimed to discover whether clinically significant differences exist in patients with extremely high baseline IOPTH and which IOPTH protocols are most appropriately applied to these patients. MATERIALS AND METHODS: This is a retrospective review of 237 patients who underwent parathyroidectomy with IOPTH monitoring for primary hyperparathyroidism (pHPT) from 2016 to 2020. Baseline IOPTH levels, drawn prior to manipulation of parathyroid glands, were grouped into categories labeled "elevated" (>65-500 pg/mL) and "extremely elevated" (>500 pg/mL). Final IOPTH levels were analyzed to determine whether there was a >50% decrease from baseline and whether a normal IOPTH value was achieved. 6-wk postoperative calcium levels were also examined. RESULTS: Of the patients in this cohort, 76% were in the elevated group and 24% in the extremely elevated group. Male sex and higher preoperative PTH levels were correlated with higher baseline IOPTH levels. Patients with extremely elevated baseline IOPTH were less likely to have IOPTH fall into normal range at the conclusion of the case (P = 0.019), and final IOPTH levels were higher (P < 0.001), but the IOPTH was equally likely to decrease >50% from baseline. There was no difference in the mean postoperative calcium levels between the two groups at 6-wk or at longer term follow-up (mean 525 d). CONCLUSIONS: Detection of baseline IOPTH levels >500 pg/mL during parathyroidectomy performed for pHPT is not uncommon. IOPTH in patients with extremely elevated baseline levels were less likely to fall into normal range, but follow-up calcium levels were equal, suggesting that applying more stringent IOPTH criteria for predicting biochemical cure may not be appropriate for this population.

Analysis of MRE11 and Mortality Among Adults With Muscle-Invasive Bladder Cancer Managed With Trimodality Therapy.

Importance: Bladder-preserving trimodality therapy can be an effective alternative to radical cystectomy for treatment of muscle-invasive bladder cancer (MIBC), but biomarkers are needed to guide optimal patient selection. The DNA repair protein MRE11 is a candidate response biomarker that has not been validated in prospective cohorts using standardized measurement approaches. Objective: To evaluate MRE11 expression as a prognostic biomarker in MIBC patients receiving trimodality therapy using automated quantitative image analysis. Design, Setting, and Participants: This prognostic study analyzed patients with MIBC pooled from 6 prospective phase I/II, II, or III trials of trimodality therapy (Radiation Therapy Oncology Group [RTOG] 8802, 8903, 9506, 9706, 9906, and 0233) across 37 participating institutions in North America from 1988 to 2007. Eligible patients had nonmetastatic MIBC and were enrolled in 1 of the 6 trimodality therapy clinical trials. Analyses were completed August 2020. Exposures: Trimodality therapy with transurethral bladder tumor resection and cisplatin-based chemoradiation therapy. Main Outcomes and Measures: MRE11 expression and association with disease-specific (bladder cancer) mortality (DSM), defined as death from bladder cancer. Pretreatment tumor tissues were processed for immunofluorescence with anti-MRE11 antibody and analyzed using automated quantitative image analysis to calculate a normalized score for MRE11 based on nuclear-to-cytoplasmic (NC) signal ratio. Results: Of 465 patients from 6 trials, 168 patients had available tissue, of which 135 were analyzable for MRE11 expression (median age of 65 years [minimum-maximum, 34-90 years]; 111 [82.2%] men). Median (minimum-maximum) follow-up for alive patients was 5.0 (0.6-11.7) years. Median (Q1-Q3) MRE11 NC signal ratio was 2.41 (1.49-3.34). Patients with an MRE11 NC ratio above 1.49 (ie, above first quartile) had a significantly lower DSM (HR, 0.50; 95% CI, 0.26-0.93; P = .03). The 4-year DSM was 41.0% (95% CI, 23.2%-58.0%) for patients with an MRE11 NC signal ratio of 1.49 or lower vs 21.0% (95% CI, 13.4%-29.8%) for a ratio above 1.49. MRE11 NC signal ratio was not significantly associated with overall survival (HR, 0.84; 95% CI, 0.49-1.44). Conclusions and Relevance: Higher MRE11 NC signal ratios were associated with better DSM after trimodality therapy. Lower MRE11 NC signal ratios identified a poor prognosis subgroup that may benefit from intensification of therapy.

What Are the Long-Term Changes to Bowel Function Patient-reported Outcomes After Elective Sigmoidectomy for Diverticular Disease?: Observational Study of Patients Undergoing Elective Sigmoidectomy for Diverticular Disease.

Objective: To evaluate long-term changes to bowel function after elective sigmoidectomy for diverticular disease. Background: For patients with diverticular disease, choosing surgery is often based on the presumption of improvement in preoperative symptoms. Our group previously reported bowel function does not change in the early perioperative period; however, studies of long-term outcomes are limited. Methods: This is an observational study of patients that underwent elective sigmoidectomy for diverticular disease and completed the Colorectal Functional Outcome (COREFO) questionnaire before surgery. Patients were stratified into two groups based on presence or absence of a preoperative symptomatic score (i.e., total COREFO ≥ 15). Long-term bowel function (>1 year from surgery) was assessed using the COREFO questionnaire via telephone or subsequent clinic visit. Paired t-tests compared mean preoperative scores to mean long-term scores. Results: Fifty-one patients met inclusion criteria (21 symptomatic, 30 asymptomatic). All symptomatic patients had uncomplicated disease, whereas 90% of asymptomatic patients had complicated disease. Median time from operation to questionnaire completion was 23 months (IQR = 13-34). Asymptomatic patients demonstrated impaired bowel function, predominantly driven by changes in the social impact domain. Symptomatic patients demonstrated improved bowel function, driven by changes in the incontinence, social impact, stool-related aspects, and need for medication domains. Conclusions: In the long-term after elective sigmoidectomy for diverticular disease, patients with symptomatic bowel function preoperatively improve substantially, while those with asymptomatic preoperative scores demonstrate statistically significant impairment. Patients determined to be symptomatic with patient-reported outcomes likely benefit long-term from sigmoid resection.Mini-Abstract: In this manuscript, long-term changes to patient-reported bowel function were assessed using a validated questionnaire after sigmoidectomy for diverticular disease. We found that in patients with symptomatic preoperative bowel function, long-term bowel function improved after elective resection. Alternatively, patients with asymptomatic preoperative bowel function demonstrated long-term impairment in bowel function.

Does Bowel Function Change After Colectomy for Colon Malignancy?

BACKGROUND: Colon cancer patients often ask how surgery will affect bowel function. Current understanding is informed by conflicting data, making preoperative patient counseling difficult. We aimed to evaluate patient-reported bowel function changes after colectomy for colon malignancy. MATERIAL AND METHODS: This was a retrospective analysis of a prospectively collected institutional database from July 2015 to June 2019. The included patients underwent colectomy for adenocarcinoma of the colon, and completed the Colorectal Functional Outcome (COREFO) questionnaire at preoperative presentation and postoperative followup. Preoperative and postoperative scores were compared using paired t-tests. Multivariable analysis was performed using domains demonstrating statistical significance on bivariate analysis, assessing the factors that were associated with symptomatic bowel function. RESULTS: We identified 117 patients with a mean age of 64 ± 13 y. The median time between preoperative and postoperative questionnaire completion was 52 d (interquartile range 45-70). Bowel movement frequency increased significantly from a mean preoperative score of 9.72 to a mean postoperative score of 14.2 (P = 0.003). There were no significant differences in the remaining four domains of bowel function or global function. Multivariable analysis demonstrated higher likelihood of symptomatic postoperative frequency scores in male patients (OR 3.85, 95% CI 1.44-11.11, P = 0.007) and patients with symptomatic preoperative frequency (OR 5.56, 95% CI 1.62-19.02, P = 0.006). CONCLUSIONS: Patient-reported bowel movement frequency worsens at postoperative follow-up after colectomy for colon cancer, while overall bowel function does not change. Men and patients with preoperative symptomatic frequency have an increased likelihood of reporting symptomatic postoperative frequency. These findings should guide more personalized and evidence-based preoperative patient counseling.

Clinical characteristics and outcomes of nonurothelial cell carcinoma of the bladder: Results from the National Cancer Data Base.

OBJECTIVES: To determine the clinical characteristics, treatment patterns, and outcomes of patients with nonurothelial cell bladder cancer (NUBC) in the United States. METHODS: A total of 163,683 patients with bladder cancer from 1998 to 2014 in the National Cancer Data Base were identified. Of all, 153,262 had urothelial cell (UC) carcinoma (93.6%) and 10,421 had NUBC (6.4%) further classified as: squamous cell carcinoma (SC, 2.4%), adenocarcinoma (AC, 1.7%), neuroendocrine (NE, 1.3%), micropapillary (MP, a UC variant histology, 0.3%), lymphoid/haematopoietic (LH, 0.3%), and sarcoma/mesenchymal (SM, 0.3%). Analyses were run on the entire cohort, those with non-muscle-invasive disease (T0-1, N0, M0), muscle-invasive disease (MIBC, T2-4A, N0, M0), and metastatic disease (T4B or N+ or M+). Clinical characteristics and treatment received (surgery, chemotherapy, and radiation) were reported by histologic subtype. Survival analysis was performed via Kaplan-Meier estimates and Cox proportional hazards models. RESULTS: Patients with NE, SC, MP, and AC were more likely to be diagnosed with metastatic disease (11.5% for UC vs. 40%, 31.3%, 17.8%, and 30.6%, respectively, P<0.001). Patients with NUBC were also more likely to have MIBC compared to UC (43% vs. 32.5%, respectively). For all patients, those with UC may be less likely to undergo cystectomy, chemotherapy, and radiation therapy (P<0.001). For all patients, NUBC, with the exception of LH, SM, and MP, was associated with inferior survival compared to UC (P<0.001). CONCLUSIONS: This encompassing clinical characterization and prognosis of NUBC patients in the United States shows NUBC patients have significantly different disease characteristics compared to those with UC, and present with more advanced disease, receive more treatment, and overall have inferior outcomes. Further work is needed to help improve outcomes for these patients.

Temporal Trends and the Impact of Race, Insurance, and Socioeconomic Status in the Management of Localized Prostate Cancer.

BACKGROUND: Numerous management options exist for patients with prostate cancer; however, recent trends and their influencing factors are not well described. OBJECTIVE: To describe modern patterns of care and factors associated with management choice using the National Cancer Database. DESIGN, SETTING, AND PARTICIPANTS: Patients with localized prostate cancer diagnosed between 2004 and 2012 were included and grouped according to National Comprehensive Cancer Network guidelines into low, intermediate, or high risk. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Trend analyses and multivariate logistic regression was used to identify factors associated with management. RESULTS AND LIMITATIONS: There were 598 640 patients who met the study criteria; 36.3% were classified as low risk, 43.8% intermediate risk, and 20.0% high risk. Over the study period, among low-risk patients, observation increased from 9.2% to 21.3%, while radical prostatectomy (RP) increased from 29.5% to 51.1% (p<0.001 for both). In contrast, external beam radiotherapy decreased from 24.3% to 14.5%, while brachytherapy decreased from 31.7% to 11.1%. A similar pattern was seen for patients with intermediate-risk or high-risk disease. Among high-risk patients, RP increased from 25.1% to 43.4% replacing external beam radiotherapy as the dominant therapy. On multivariate analysis, racial minorities, the uninsured, and low-income patients were less likely to receive RP. Low-risk patients in similar subgroups were significantly more likely to be observed. Limitations include potential miscoding or misclassification of variables. CONCLUSIONS: Patterns of care in localized prostate cancer are changing rapidly. While use of observation is increasing in low-risk groups, the use of RP is increasing across all risk groups with a concomitant decline in use of radiotherapy. Socioeconomic factors appear to influence management choice. PATIENT SUMMARY: In this report we identify a recent significant increase in the use of radical prostatectomy for prostate cancer patients. Socioeconomic factors such as race, insurance type, and income may affect treatments offered to and received by patients.

Management and outcomes of clinical stage IIA/B seminoma: Results from the National Cancer Data Base 1998-2012.

PURPOSE/OBJECTIVE: Disease-specific survival for testicular seminoma approaches 100%, even for those with node-positive disease. We sought to describe modern practice patterns, survival outcomes, and factors associated with postoperative therapy for patients with clinical stage (CS) IIA/B disease. METHODS AND MATERIALS: Data on patients diagnosed with CS IIA/B seminoma from 1998 to 2012 were extracted from the National Cancer Data Base. Demographic, clinical, treatment, and payer characteristics were evaluated using multivariate regression to identify factors associated with receipt of chemotherapy or radiation therapy (RT) within 6 months of orchiectomy. Five-year Kaplan-Meier overall survival (OS) by CS and treatment was calculated. A Cox proportional hazards regression for 5-year OS was performed. RESULTS: A total of 1885 patients were included; 38.5% received chemotherapy and 61.5% received RT. On multivariate analysis, factors associated with receipt of postorchiectomy RT rather than chemotherapy included CS IIA (odds ratio [OR], 3.04; P < .01) and community treatment setting (OR, 1.81-2.76; P < .01). Reduced likelihood of receiving RT was associated with Medicaid insurance (OR, 0.50; P < .01), more recent year of diagnosis (continuous OR, 0.93; P < .01), and primary pathologic tumor 3/4 stage (OR, 0.47; P < .01). On multivariate Cox regression, decreased 5-year OS was associated with receipt of chemotherapy in CS IIA patients (hazard ratio, 13.33; P < .01) but not in CS IIB patients (hazard ratio, 1.39; P = .45). For CS IIA, 5-year OS was 99.4% for orchiectomy and RT versus 91.2% for orchiectomy and chemotherapy (log-rank P < .01). For CS IIB, 5-year OS was 96.1% for orchiectomy and RT versus 92.8% for orchiectomy and chemotherapy (log-rank P = .08). CONCLUSIONS: Consistent with national guideline recommendations, our analysis supports preferred status for RT in CS IIA. In addition, these data also support use of RT for CS IIB. CS, treatment year, primary pathologic tumor stage, insurance, and facility type were associated with type of postoperative therapy. Longer follow-up to account for potential late effects of treatment is needed.

Androgen deprivation with or without radiation therapy for clinically node-positive prostate cancer.

BACKGROUND: Clinically lymph node-positive (cN+) prostate cancer (PCa) is an often-fatal disease. Its optimal management remains largely undefined given a lack of prospective, randomized data to inform practice. We sought to describe modern practice patterns in the management of cN+ PCa and assess the effect of adding radiation therapy (RT) to androgen deprivation therapy (ADT) on survival using the National Cancer Data Base. METHODS: Patients with cN+ PCa and without distant metastases diagnosed between 2004 and 2011 were included. Five-year overall survival for patients diagnosed between 2004 and 2006 and treated with ADT alone or ADT+RT were compared. Propensity score (PS) matching was used to balance baseline characteristics, and Cox multivariate regression analysis was used to estimate hazard ratios (HRs) for all-cause mortality. RESULTS: Of 3540 total patients, 32.2% were treated with ADT alone and 51.4% received ADT+RT. Compared with ADT alone, patients treated with ADT+RT were younger and more likely to have private insurance, lower comorbidity scores, higher Gleason scores, and lower PSA values. After PS matching, 318 patients remained in each group. Compared with ADT alone, ADT+RT was associated with a 50% decreased risk of five-year all-cause mortality (HR = 0.50, 95% CI = 0.37 to 0.67, two-sided P < .001; crude OS rate: 71.5% vs 53.2%). CONCLUSIONS: Using a large national database, we have identified a statistically significant survival benefit for patients with cN+ PCa treated with ADT+RT. These data, if appropriately validated by randomized trials, suggest that a substantial proportion of such patients at high risk for prostate cancer death may be undertreated, warranting a reevaluation of current practice guidelines.

Declining Use of Radiotherapy for Adverse Features After Radical Prostatectomy: Results From the National Cancer Data Base.

BACKGROUND: Patterns of postoperative radiotherapy (RT) use in prostate cancer (PCa) after the publication of major randomized trials have not been well characterized. OBJECTIVE: To describe patterns of postoperative RT use after radical prostatectomy (RP) in patients with adverse pathologic features in the United States. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of 97 270 patients with PCa diagnosed between 2005 and 2011 whose presentation and outcomes were recorded in the National Cancer Data Base. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Temporal changes in receipt of postoperative RT and factors associated with receipt of this treatment using the Cochran-Armitage trend test and multiple logistic regression, respectively. RESULTS AND LIMITATIONS: Between 2005 and 2011, receipt of postoperative RT decreased steadily from 9.1% to 7.3% (ptrend<0.001). Use of RT with or without androgen deprivation therapy monotonically decreased with advancing age from 8.5% in patients aged 18-59 yr to 6.8% in patients aged 70-79 yr (ptrend<0.001). Receipt of RT was higher at community cancer programs compared with teaching/research centers (14% vs 7.3%; odds ratio [OR]: 2.16; p<0.001), in those with pT3-4 disease and positive margins compared with those with pT3-4 and negative margins (17% vs 5.9%; OR: 2.89; p<0.001), and in patients with a Gleason score of 8-10 compared with those with a Gleason score of 2-6 (17% vs 4.2%; OR: 3.50; p<0.001). Limitations include lack of postprostatectomy prostate-specific antigen level. CONCLUSIONS: Postoperative RT use for localized PCa in patients with adverse pathologic features is declining in the United States. PATIENT SUMMARY: In this report, we show that use of postoperative radiotherapy in patients with prostate cancer with adverse pathologic features is declining. Patients treated at community cancer programs, those with locally advanced disease and positive margins, and those with a high Gleason score were more likely to receive postoperative radiotherapy.

From bench to bedside: bipolar androgen therapy in a pilot clinical study.

Prostate cancer remains a leading cause of cancer death in Europe and the United States and is an emerging problem in Asia despite significant improvements in available treatments over the last few decades. Androgen deprivation therapy (ADT) has been the core treatment of advance-staged disease since the discovery of prostate cancer's androgen dependence in 1941 by Huggins et al. [1] Options for initial medical treatment include gonadotropin-releasing hormone analogues such as leuprolide (LHRH agonist) and degarelix (LHRH antagonist) and androgen receptor (AR) binding agents such as bicalutamide. Although most patients will initially respond to either surgical or medical castration, there is almost always progression to castration-resistant prostate cancer (CRPC) necessitating treatment with more novel agents. [2] However, even drugs such as abiraterone and enzalutamide, two next-generation agents used commonly in metastatic CRPC, have failed to demonstrate persistent efficacy in most patients. [3] ,[4].

Management trends in stage I testicular seminoma: Impact of race, insurance status, and treatment facility.

BACKGROUND: The management of stage I testicular seminoma is evolving rapidly. This study examined modern trends in the management of stage I testicular seminoma and the effects of sociodemographic factors on therapy choice. METHODS: Data from the National Cancer Data Base on 34,067 patients with stage I testicular seminoma who were treated between 1998 and 2011 were analyzed. Multivariate logistic regression models were used to assess factors associated with adjuvant management strategies. RESULTS: For patients with stage IA/B testicular seminoma, rates of observation after orchiectomy increased from 23.7% to 54.0%, the receipt of adjuvant chemotherapy increased from 1.5% to 16.0%, and the receipt of radiotherapy decreased from 70.8% to 28.8%. A similar pattern was seen in stage IS testicular seminoma, although these patients were more likely to receive adjuvant radiotherapy/chemotherapy (60.7% vs 44.8% for stage IA/B in 2011, P < .001). For patients with stage IA/B testicular seminoma, observation after orchiectomy was more common in racial minorities (odds ratio [OR] for blacks vs whites, 1.31, P < .001; OR for Hispanics vs whites, 1.39, P < .001) and in the uninsured (OR for uninsured vs privately insured, 1.33, P < .001) and less common at community centers (OR for community centers vs National Cancer Institute-designated cancer centers, 0.80, P = .044). In those with stage IA/B testicular seminoma who received adjuvant radiotherapy/chemotherapy, the receipt of chemotherapy was more common at academic centers and for patients with nonprivate insurance. CONCLUSIONS: Postorchiectomy observation in stage I testicular seminoma has increased significantly in recent years, as has the receipt of chemotherapy, whereas the receipt of radiotherapy has declined, particularly at academic centers. Race, insurance status, and facility type are strongly associated with the choice of adjuvant management.

Aggressive therapy for patients with non-small cell lung carcinoma and synchronous brain-only oligometastatic disease is associated with long-term survival.

OBJECTIVES: Optimal therapy for patients with non-small cell lung carcinoma (NSCLC) presenting with synchronous brain-only oligometastases (SBO) is not well defined. We sought to analyze the effect of differing therapeutic paradigms in this subpopulation. MATERIALS AND METHODS: We retrospectively analyzed NSCLC patients with 1-4 SBO diagnosed between 1/2000 and 1/2011 at our institution. Patients with T0 tumors or documented Karnofsky Performance Status <70 were excluded. Aggressive thoracic therapy (ATT) was defined as resection of the primary disease or chemoradiotherapy whose total radiation dose exceeded 45 Gy. Cox proportional hazards and competing risks models were used to analyze factors affecting survival and first recurrence in the brain. RESULTS: Sixty-six patients were included. Median follow-up was 31.9 months. Intrathoracic disease extent included 9 stage I, 10 stage II and 47 stage III patients. Thirty-eight patients received ATT, 28 did not. Patients receiving ATT were younger (median age 55 vs. 60.5 years, p=0.027) but were otherwise similar to those who did not. Receipt of ATT was associated with prolonged median overall survival (OS) (26.4 vs. 10.5 months; p<0.001) with actuarial 2-year rates of 54% vs. 26%. ATT remained associated with OS after controlling for age, thoracic stage, performance status and initial brain therapy (HR 0.40, p=0.009). On multivariate analysis, the risk of first failure in the brain was associated with receipt of ATT (HR 3.62, p=0.032) and initial combined modality brain therapy (HR 0.34, p=0.046). CONCLUSION: Aggressive management of thoracic disease in NSCLC patients with SBO is associated with improved survival. Careful management of brain disease remains important, especially for those treated aggressively.

Clinical-pathologic stage discrepancy in bladder cancer patients treated with radical cystectomy: results from the national cancer data base.

PURPOSE: To examine the accuracy of clinical staging and its effects on outcome in bladder cancer (BC) patients treated with radical cystectomy (RC), using a large national database. METHODS AND MATERIALS: A total of 16,953 patients with BC without distant metastases treated with RC from 1998 to 2009 were analyzed. Factors associated with clinical-pathologic stage discrepancy were assessed by multivariate generalized estimating equation models. Survival analysis was conducted for patients treated between 1998 and 2004 (n=7270) using the Kaplan-Meier method and Cox proportional hazards models. RESULTS: At RC 41.9% of patients were upstaged, whereas 5.9% were downstaged. Upstaging was more common in females, the elderly, and in patients who underwent a more extensive lymphadenectomy. Downstaging was less common in patients treated at community centers, in the elderly, and in Hispanics. Receipt of preoperative chemotherapy was highly associated with downstaging. Five-year overall survival rates for patients with clinical stages 0, I, II, III, and IV were 67.2%, 62.9%, 50.4%, 36.9%, and 27.2%, respectively, whereas those for the same pathologic stages were 70.8%, 75.8%, 63.7%, 41.5%, and 24.7%, respectively. On multivariate analysis, upstaging was associated with increased 5-year mortality (hazard ratio [HR] 1.80, P<.001), but downstaging was not associated with survival (HR 0.88, P=.160). In contrast, more extensive lymphadenectomy was associated with decreased 5-year mortality (HR 0.76 for ≥10 lymph nodes examined, P<.001), as was treatment at an National Cancer Institute-designated cancer center (HR 0.90, P=.042). CONCLUSIONS: Clinical-pathologic stage discrepancy in BC patients is remarkably common across the United States. These findings should be considered when selecting patients for preoperative or nonoperative management strategies and when comparing the outcomes of bladder sparing approaches to RC.