Resource Use in the Last Year of Life Among Patients Who Died With Versus of Prostate Cancer.

UNLABELLED: We conducted a retrospective analysis of Surveillance, Epidemiology, and End Results-Medicare data of men with prostate cancer. Among 34,727 patients, those who died of their prostate cancer had more hospice and outpatient use, less inpatient and intensive care unit use, and lower overall costs. Efforts to shift care toward the outpatient setting might provide more efficient and judicious care for patients during the end of life. BACKGROUND: Prostate cancer poses a significant financial burden in the United States. However, most men with prostate cancer will die from noncancer causes. Concerns about increased resource utilization at the end of life have not been appropriately examined in this context. MATERIALS AND METHODS: We conducted a retrospective analysis of Surveillance, Epidemiology, and End Results-Medicare data of men who were diagnosed with and died of, as opposed to with, prostate cancer between 2000 and 2007. Within these 2 populations, we compared changes in the use of medical interventions, hospice, and overall health care costs to Medicare in the last year of life. RESULTS: Among 34,727 patients, those who died of prostate cancer had lower costs ($43,572 vs. $45,830; P < .001), largely because of lower mean inpatient costs ($20,769 vs. $29,851) and fewer hospitalizations (1.8 vs. 2.1), inpatient days (12.2 vs. 15.7), intensive care unit (ICU) days (1.4 vs. 3.4), and skilled nursing facility days (11.7 vs. 14.7; P < .001 for all). Outpatient and hospice costs were significantly greater among patients who died of prostate cancer, as was use of chemotherapy and androgen deprivation therapy. Patients who died of prostate cancer had approximately 12% lower costs than patients who died from other causes in adjusted analyses (fold-change, 0.88; 95% confidence interval [CI], 0.85-0.92). The single strongest predictor of increased costs at the end of life was receipt of multiple invasive procedures (fold increase in costs, 2.39; 95% CI, 2.22-2.58). CONCLUSION: Patients who died of prostate cancer rather than from other causes had more hospice and outpatient use, less inpatient and ICU use, and lower overall costs. Efforts to shift care toward outpatient settings might provide more efficient and judicious care for patients during the end of life.

Comparison of partial nephrectomy and percutaneous ablation for cT1 renal masses.

BACKGROUND: Partial nephrectomy (PN) is a preferred treatment for cT1 renal masses, whereas thermal ablation represents an alternative nephron-sparing option, albeit with higher reported rates of recurrence. OBJECTIVE: To review our experience with PN, percutaneous radiofrequency ablation (RFA), and percutaneous cryoablation for cT1 renal masses. DESIGN, SETTING, AND PARTICIPANTS: A total of 1803 patients with primary cT1N0M0 renal masses treated between 2000 and 2011 were identified from the prospectively maintained Mayo Clinic Renal Tumor Registry. INTERVENTION: PN compared with percutaneous ablation. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Local recurrence-free, metastases-free, and overall survival rates were estimated using the Kaplan-Meier method and compared with log-rank tests. RESULTS AND LIMITATIONS: Of the 1424 cT1a patients, 1057 underwent PN, 180 underwent RFA, and 187 underwent cryoablation. In this cohort, local recurrence-free survival was similar among the three treatments (p=0.49), whereas metastases-free survival was significantly better after PN (p=0.005) and cryoablation (p=0.021) when compared with RFA. Of the 379 cT1b patients, 326 patients underwent PN, and 53 patients were managed with cryoablation (8 RFA patients were excluded). In this cohort, local recurrence-free survival (p=0.81) and metastases-free survival (p=0.45) were similar between PN and cryoablation. In both the cT1a and cT1b groups, PN patients were significantly younger, with lower Charlson scores and had superior overall survival (p<0.001 for all). Limitations include retrospective review and selection bias. CONCLUSIONS: In a large cohort of sporadic cT1 renal masses, we observed that recurrence-free survival was similar for PN and percutaneous ablation patients. Metastases-free survival was superior for PN and cryoablation patients when compared with RFA for cT1a patients. Overall survival was superior after PN, likely because of selection bias. If these results were validated, an update to clinical guidelines would be warranted. PATIENT SUMMARY: Partial nephrectomy and percutaneous ablation for small (<7-cm) and localized renal masses are associated with similar rates of local recurrence.

Radical prostatectomy in high-risk and locally advanced prostate cancer: Mayo Clinic perspective.

PURPOSE: Men diagnosed with high-risk prostate cancer represent the cohort of prostate cancer patients at greatest risk for subsequent disease-specific mortality. Unfortunately, however, the classification of high-risk tumors remains imprecise and heterogeneous. There has been a historical reluctance to offer such patients aggressive local treatment, and considerable debate exists regarding the optimal management in this setting. METHODS: We present here our institutional experience, as well as data from several other centers, with radical prostatectomy for high-risk tumors. RESULTS: We discuss that surgery affords accurate pathological staging, thereby improving the identification of patients for secondary therapies. Moreover, prostatectomy not only provides durable local disease control but in addition numerous contemporary surgical series in high-risk patients have shown radical prostatectomy to be associated with excellent long-term cancer-specific survival. Further, although studies comparing surgical and radiotherapy modalities in high-risk prostate patients have been wrought with methodological challenges, consistently these observational studies have found equivalent to improved oncologic outcomes when surgery is utilized as the primary treatment. CONCLUSIONS: Herein, we review the advantages, long-term outcomes, and technique of surgery for high-risk prostate cancer.

Mortality after radical cystectomy: impact of obesity versus adiposity after adjusting for skeletal muscle wasting.

PURPOSE: We assess the impact of obesity, as measured conventionally by body mass index vs excess adiposity as measured by fat mass index, on mortality after radical cystectomy for bladder cancer, adjusting for the presence of skeletal muscle wasting. MATERIALS AND METHODS: This retrospective cohort study included 262 patients treated with radical cystectomy for bladder cancer between 2000 and 2008 at the Mayo Clinic. Lumbar skeletal muscle and adipose compartment areas were measured on preoperative imaging. Overall survival was compared according to gender specific consensus fat mass index and skeletal muscle index thresholds as well as conventional body mass index based criteria. Predictors of all cause mortality were assessed by multivariable modeling. RESULTS: Increasing body mass index correlated with improved overall survival (p=0.03) while fat mass index based obesity did not (p=0.08). After stratification by sarcopenia, no obesity related 5-year overall survival benefit was observed (68% vs 51.4%, p=0.2 obese vs normal and 40% vs 37.4%, p=0.7 sarcopenia vs sarcopenic/obese). On multivariable analysis class I obesity according to body mass index (HR 0.79, p=0.33) or fat mass index criteria (HR 0.85, p=0.45) was not independently associated with all cause mortality after adjusting for sarcopenia (HR 1.7, p=0.01) as well as age, performance status, pTN stage and smoking status. However, in patients with normal lean muscle mass each 1 kg/m(2) increase in weight or adipose mass was associated with a 7% to 14% decrease in all cause mortality. CONCLUSIONS: After adjusting for lean muscle wasting, neither measurements of obesity nor adiposity were significantly associated with all cause mortality in patients treated with radical cystectomy, although subanalyses suggest a potential benefit among those with normal lean muscle mass.

Clinical and radiographic predictors of the need for inferior vena cava resection during nephrectomy for patients with renal cell carcinoma and caval tumour thrombus.

OBJECTIVE: To evaluate the clinical and radiographic predictors of the need for partial or circumferential resection of the inferior vena cava (IVC) requiring complex vascular reconstruction during venous tumour thrombectomy for renal cell carcinoma (RCC). PATIENTS AND METHODS: Data were collected on 172 patients with RCC and IVC (levels I-IV) venous tumour thrombus who underwent radical nephrectomy with tumour thrombectomy at the Mayo Clinic between 2000 and 2010. Preoperative imaging was re-reviewed by one of two radiologists blinded to details of the patient's surgical procedure. Univariable and multivariable associations of clinical and radiographic features with IVC resection were evaluated by logistic regression. A secondary analysis was used to assess the ability of the model to predict histological invasion of the IVC by the tumour thrombus. RESULTS: Of the 172 patients, 38 (22%) underwent IVC resection procedures during nephrectomy. Optimum radiographic thresholds were determined to predict the need for IVC resection based on preoperative imaging included a renal vein diameter at the renal vein ostium (RVo) of 15.5 mm, maximum anterior-posterior (AP) diameter of the IVC of 34.0 mm and AP and coronal diameters of the IVC at the RVo of 24 and 19 mm, respectively. On multivariable analysis, the presence of a right-sided tumour (odds ratio 3.3; P = 0.017), an AP diameter of the IVC at the RVo of ≥24.0 mm (odds ratio 4.4; P = 0.017), and radiographic identification of complete occlusion of the IVC at the RVo (odds ratio 4.9; P < 0.001) were associated with a significantly increased risk of IVC resection. The c-index for the model was 0.81. CONCLUSIONS: We present a multivariable model of the radiographic features associated with the need for IVC resection during tumour thrombectomy. Pending external validation, this model may be used for preoperative planning, patient counselling and planned involvement of vascular surgical colleagues in anticipation of the need for complex vascular repair.

The association between metformin use and oncologic outcomes among surgically treated diabetic patients with localized renal cell carcinoma.

INTRODUCTION: Metformin inhibits renal cell carcinoma (RCC) cell proliferation both in vitro and in vivo; however, clinical data regarding the effect of metformin in patients with RCC are lacking. We evaluated the association of metformin use with outcomes among patients with surgically treated localized RCC. MATERIALS AND METHODS: We identified 283 consecutive diabetic patients treated surgically for localized RCC between January 1, 1994 and December 31, 2008. Clinicopathologic features were compared between patients exposed to metformin (n = 83, 29%) and those who were not (n = 200, 71%). Progression-free, cancer-specific, and overall survival rates were estimated with the Kaplan-Meier analysis, and Cox models were used to evaluate the association of metformin use with outcomes. RESULTS AND CONCLUSIONS: Patients receiving metformin had a better renal function (median estimated glomerular filtration rate = 65 vs. 55 ml/min/1.73 m(2), P<0.001), performance status (Eastern Cooperative Oncology Group<1: 89% vs. 71%, P = 0.001), and lower Charlson comorbidity index (median = 2 vs. 3, P = 0.02) compared with those who did not, but were otherwise similar across other clinicopathologic features (P>0.05 for all). At a median postoperative follow-up of 8.1 years, patients exposed to metformin had similar 5-year progression-free (80% vs. 75%, P = 0.6) and cancer-specific survival rates (91% vs. 81%, P = 0.16), but significantly improved overall survival rate (79% vs. 62%, P = 0.01). However, metformin was not independently associated with the risks of progression, RCC-specific mortality, or all-cause mortality on multivariable analyses. In this surgical cohort of diabetic patients with M0 RCC, preoperative metformin exposure was associated with improved overall survival on unadjusted analysis. Although metformin was not independently associated with oncologic or survival outcomes, future studies appear warranted.

Evaluation of the National Comprehensive Cancer Network and American Urological Association renal cell carcinoma surveillance guidelines.

PURPOSE: The National Comprehensive Cancer Network (NCCN) and American Urological Association (AUA) provide guidelines for surveillance after surgery for renal cell carcinoma (RCC). Herein, we assess the ability of the guidelines to capture RCC recurrences and determine the duration of surveillance required to capture 90%, 95%, and 100% of recurrences. PATIENTS AND METHODS: We evaluated 3,651 patients who underwent surgery for M0 RCC between 1970 and 2008. Patients were stratified as AUA low risk (pT1Nx-0) after partial (LR-partial) or radical nephrectomy (LR-radical) or as moderate/high risk (M/HR; pT2-4Nx-0/pTanyN1). Guidelines were assessed by calculating the percentage of recurrences detected when following the 2013 and 2014 NCCN and AUA recommendations, and associated Medicare costs were compared. RESULTS: At a median follow-up of 9.0 years (interquartile range, 5.7 to 14.4 years), a total of 1,088 patients (29.8%) experienced a recurrence. Of these, 390 recurrences (35.9%) were detected using 2013 NCCN recommendations, 742 recurrences (68.2%) were detected using 2014 NCCN recommendations, and 728 recurrences (66.9%) were detected using AUA recommendations. All protocols missed the greatest amount of recurrences in the abdomen and among pT1Nx-0 patients. To capture 95% of recurrences, surveillance was required for 15 years for LR-partial, 21 years for LR-radical, and 14 years for M/HR patients. Medicare surveillance costs for one LR-partial patient were $1,228.79 using 2013 NCCN, $2,131.52 using 2014 NCCN, and $1,738.31 using AUA guidelines. However, if 95% of LR-partial recurrences were captured, costs would total $9,856.82. CONCLUSION: If strictly followed, the 2014 NCCN and AUA guidelines will miss approximately one third of RCC recurrences. Improved surveillance algorithms, which balance patient benefits and health care costs, are needed.

Does the multidisciplinary approach improve oncological outcomes in men undergoing surgical treatment for prostate cancer?

OBJECTIVES: To determine whether oncological outcomes are improved in prostate cancer patients by using a multidisciplinary strategy as compared with a standard clinic paradigm, and whether time to treatment is delayed when using a multidisciplinary approach. METHODS: We retrospectively analyzed patients who were evaluated and pursued radical prostatectomy as primary treatment, by the same surgeons, in the prostate cancer multidisciplinary clinic (n = 194) and standard urology clinic (n = 741) at Duke University Medical Center from 2005 to 2009. Comparisons of baseline characteristics were examined using rank sum and χ(2) -tests. Differences in time to radical prostatectomy and oncological outcomes were evaluated using multivariate linear and Cox regression, respectively. RESULTS: A greater proportion of high-risk patients (D'Amico criteria) were evaluated at the multidisciplinary clinic compared with the urology clinic (23.2% vs 15.6%, P = 0.014). Mean-adjusted time from biopsy to radical prostatectomy was shorter for multidisciplinary clinic patients (85.6 vs 96.8 days, P = 0.006). After a median follow up of 21 months, no significant difference was found between the multidisciplinary clinic and urology clinic in the risk of biochemical recurrence after radical prostatectomy, whether controlling for clinical (hazard ratio 0.71, P = 0.249) or pathological variables (hazard ratio 0.75, P = 0.349). CONCLUSIONS: Despite higher-risk disease, men evaluated using the multidisciplinary approach have similar oncological outcomes compared with men undergoing standard evaluation. Furthermore, time to radical prostatectomy is not delayed by the multidisciplinary management of these patients.

Diabetes mellitus is independently associated with an increased risk of mortality in patients with clear cell renal cell carcinoma.

PURPOSE: Conflicting data exist on the interaction of diabetes mellitus with outcomes in patients with renal cell carcinoma. We evaluated the association of diabetes mellitus with survival in patients with clear cell renal cell carcinoma treated with nephrectomy. MATERIALS AND METHODS: We reviewed the records of 1,964 patients treated surgically for sporadic, unilateral, M0 clear cell renal cell carcinoma between 1990 and 2008. One pathologist re-reviewed all specimens to confirm clear cell renal cell carcinoma. We matched 257 patients with diabetes 1:2 to referent patients without diabetes according to clinicopathological and surgical features. Cancer specific and overall survival was estimated using the Kaplan-Meier method. Cox models were used to evaluate associations with outcomes. RESULTS: A total of 257 patients (13%) had diabetes mellitus. They were significantly older and more likely to be obese, and had higher Charlson scores, renal impairment and smoking rates, and worse performance status at surgery (p <0.001). Pathological features were similar between the groups. Median postoperative followup was 8.7 years. Five-year cancer specific survival was similar in patients with and without diabetes (82% vs 86%, p = 0.1) while 5-year overall survival was significantly worse in those with diabetes (65% vs 74%, p <0.001). On multivariable analysis diabetes mellitus independently predicted cancer specific mortality (HR 1.55, 95% CI 1.08-2.21, p = 0.02) and all-cause mortality (HR 1.32, 95% CI 1.06-1.64, p = 0.01). CONCLUSIONS: Our results suggest that diabetes mellitus is independently associated with decreased cancer specific and overall survival in patients with surgically treated clear cell renal cell carcinoma.

Sarcopenia in patients with bladder cancer undergoing radical cystectomy: impact on cancer-specific and all-cause mortality.

BACKGROUND: The authors evaluated sarcopenia as a predictor of cancer-specific survival (CSS) and overall survival (OS) among patients with urothelial cancer of the bladder undergoing radical cystectomy (RC). METHODS: The lumbar skeletal muscle index (SMI) of 205 patients treated with RC for urothelial cancer between 2000 and 2007 was measured. Sarcopenia was classified according to international consensus definitions (SMI of < 55 cm(2)/m(2) for men and < 39 cm(2)/m(2) for women). The CSS and OS were estimated using the Kaplan-Meier method and compared with the log-rank test. Variables associated with CSS and all-cause mortality were summarized with hazard ratios (HRs). RESULTS: Of 205 patients, 141 (68.8%) were sarcopenic. Patients with sarcopenia were older, but were otherwise similar to patients without sarcopenia with respect to sex, Charlson comorbidity index, American Society of Anesthesiologists score, Eastern Cooperative Oncology Group performance status, receipt of neoadjuvant chemotherapy, TNM stage of disease, and tumor grade (P > .05 for all). The median follow-up was 6.7 years, during which time 135 patients died, including 91 who died of bladder cancer. Sarcopenic patients had significantly worse 5-year CSS (49% vs 72%; P = .003) and OS (39% vs 70%; P = .003) compared with patients without sarcopenia. Moreover, sarcopenia was found to be independently associated with both increased CSS (HR, 2.14; P = .007) and all-cause mortality (HR, 1.93; P = .004) on multivariable analysis. CONCLUSIONS: The presence of sarcopenia was found to significantly increase a patient's risk of CSS and all-cause mortality after undergoing RC for bladder cancer.

Pretreatment expectations of patients undergoing robotic assisted laparoscopic or open retropubic radical prostatectomy.

PURPOSE: We previously found that patients undergoing robotic assisted laparoscopic radical prostatectomy vs radical retropubic prostatectomy had a higher likelihood of not being satisfied, independent of side effect profile. We hypothesized that differential preoperative expectations might contribute to this finding. In the current study we compared expectations of patients undergoing robotic assisted laparoscopic radical prostatectomy vs radical retropubic prostatectomy. MATERIALS AND METHODS: A questionnaire on expectations regarding recovery was administered to 171 patients electing to undergo robotic assisted laparoscopic radical prostatectomy or radical retropubic prostatectomy from 2008 to 2010. We prospectively collected data on patient expectations before surgery. Differences between patients undergoing robotic assisted laparoscopic radical prostatectomy vs radical retropubic prostatectomy were assessed with adjusted proportional odds models. RESULTS: Patients who underwent robotic assisted laparoscopic radical prostatectomy (97) did not differ significantly from those treated with radical retropubic prostatectomy (74) in age, race, income, time between survey and surgery, and prostate specific antigen (p ≥0.4). Patients who underwent radical retropubic prostatectomy had significantly higher clinical stage and Gleason grade disease (p ≤0.007). After adjusting for socioeconomic factors, clinical stage and grade on multivariate analysis, patients who underwent robotic assisted laparoscopic radical prostatectomy expected a significantly shorter length of stay (OR 0.07, p <0.001) and earlier return to physical activity (OR 0.36, p = 0.005). The choice of robotic assisted laparoscopic radical prostatectomy (OR 0.41, p = 0.012), younger age (OR 0.49, p = 0.001) and higher preoperative International Index of Erectile Function-5-item version score (OR 0.60, p = 0.017) were independently associated with the expectation of earlier return of erections but not of continence on multivariate analysis. CONCLUSIONS: The body of evidence surrounding robotic assisted laparoscopic radical prostatectomy supports shorter hospitalization but there is no conclusive evidence that the robotic approach results in earlier return to physical activity or improved disease specific outcomes. Nonetheless we found that patients who underwent robotic assisted laparoscopic radical prostatectomy had higher expectations regarding these outcomes, particularly that of erectile function recovery, than did their radical retropubic prostatectomy counterparts.

Effects of family history and genetic polymorphism on the cost-effectiveness of chemoprevention with finasteride for prostate cancer.

PURPOSE: Improvement in the cost-effectiveness of chemoprevention for prostate cancer could be realized through the identification of patients at higher risk. We estimated the cost-effectiveness of prostate cancer chemoprevention across risk groups defined by family history and number of risk alleles, and the cost-effectiveness of targeting chemoprevention to higher risk groups. MATERIALS AND METHODS: We developed a probabilistic Markov model to estimate costs, survival and quality adjusted survival across risk groups for patients receiving or not receiving chemoprevention with finasteride. The model uses data from national cancer registries, online sources and the medical literature. RESULTS: The incremental cost-effectiveness of 25 years of chemoprevention with finasteride in patients 50 years old was an estimated $89,300 per quality adjusted life-year (95% CI $58,800-$149,800), assuming finasteride decreased all grades of prostate cancer by 24.8%. Among patients with a positive family history (without genetic testing) chemoprevention provided 1 additional quality adjusted life-year at a cost of $64,200. Among patients with a negative family history at $400 per person tested, the cost-effectiveness of genetically targeted chemoprevention ranged from $98,100 per quality adjusted life-year when limiting finasteride to individuals with 14 or more risk alleles, to $103,200 per quality adjusted life-year when including those with 8 or more risk alleles. CONCLUSIONS: Although there are small differences in the cost-effectiveness of genetically targeted chemoprevention strategies in patients with a negative family history, genetic testing could reduce total expenditures if used to target chemoprevention for higher risk groups.

How to appraise the effectiveness of treatment.

INTRODUCTION: Advances in treatment and disease prevention occur frequently in urology. Urologists must identify a framework within which to evaluate these therapeutic innovations. MATERIALS AND METHODS: The evidence-based approach to critical appraisal is described using an example from the urological literature. A three-part assessment of the trial validity, treatment effect, and applicability of results will permit the urologist to critically incorporate medical and surgical advances into practice. RESULTS: Validity of clinical trials hinges upon balancing patient prognosis at the initiation, execution, and conclusion of the trial. Readers should be aware of not only the magnitude of the estimated treatment effect, but also its precision. Finally, urologists should consider all patient-important outcomes as well as the balance of potential benefits, harms, and costs, and patient values and preferences when making treatment decisions. CONCLUSION: Use of this framework for critical appraisal will lead to a more evidence-based application of new therapies for patients. Incorporation of a more evidence-based practice within urology will lead to an increase in the quality of patient care.