Impact of Maximal Transurethral Resection on Pathological Outcomes at Cystectomy in a Large, Multi-institutional Cohort.

PURPOSE: While the presence of residual disease at the time of radical cystectomy for bladder cancer is an established prognostic indicator, controversy remains regarding the importance of maximal transurethral resection prior to neoadjuvant chemotherapy. We characterized the influence of maximal transurethral resection on pathological and survival outcomes using a large, multi-institutional cohort. MATERIALS AND METHODS: We identified 785 patients from a multi-institutional cohort undergoing radical cystectomy for muscle-invasive bladder cancer after neoadjuvant chemotherapy. We employed bivariate comparisons and stratified multivariable models to quantify the effect of maximal transurethral resection on pathological findings at cystectomy and survival. RESULTS: Of 785 patients, 579 (74%) underwent maximal transurethral resection. Incomplete transurethral resection was more frequent in patients with more advanced clinical tumor (cT) and nodal (cN) stage (P < .001 and P < .01, respectively), with more advanced ypT stage at cystectomy and higher rates of positive surgical margins (P < .01 and P < .05, respectively). In multivariable models, maximal transurethral resection was associated with downstaging at cystectomy (adjusted odds ratio 1.6, 95% CI 1.1-2.5). In Cox proportional hazards analysis, maximal transurethral resection was not associated with overall survival (adjusted HR 0.8, 95% CI 0.6-1.1). CONCLUSIONS: In patients undergoing transurethral resection for muscle-invasive bladder cancer prior to neoadjuvant chemotherapy, maximal resection may improve pathological response at cystectomy. However, the ultimate effects on long-term survival and oncologic outcomes warrant further investigation.

Treatment in the absence of disease reclassification among men on active surveillance for prostate cancer.

BACKGROUND: Maintaining men on active surveillance for prostate cancer can be challenging. Although most men who eventually undergo treatment have experienced clinical progression, a smaller subset elects treatment in the absence of disease reclassification. This study sought to understand factors associated with treatment in a large, contemporary, prospective cohort. METHODS: This study identified 1789 men in the Canary Prostate Cancer Active Surveillance Study cohort enrolled as of 2020 with a median follow-up of 5.6 years. Clinical and demographic data as well as information on patient-reported quality of life and urinary symptoms were used in multivariable Cox proportional hazards regression models to identify factors associated with the time to treatment RESULTS: Within 4 years of their diagnosis, 33% of men (95% confidence interval [CI], 30%-35%) underwent treatment, and 10% (95% CI, 9%-12%) were treated in the absence of reclassification. The most significant factor associated with any treatment was an increasing Gleason grade group (adjusted hazard ratio [aHR], 14.5; 95% CI, 11.7-17.9). Urinary quality-of-life scores were associated with treatment without reclassification (aHR comparing "mostly dissatisfied/terrible" with "pleased/mixed," 2.65; 95% CI, 1.54-4.59). In a subset analysis (n = 692), married men, compared with single men, were more likely to undergo treatment in the absence of reclassification (aHR, 2.63; 95% CI, 1.04-6.66). CONCLUSIONS: A substantial number of men with prostate cancer undergo treatment in the absence of clinical changes in their cancers, and quality-of-life changes and marital status may be important factors in these decisions. LAY SUMMARY: This analysis of men on active surveillance for prostate cancer shows that approximately 1 in 10 men will decide to be treated within 4 years of their diagnosis even if their cancer is stable. These choices may be related in part to quality-or-life or spousal concerns.

Naloxegol versus Alvimopan for Enhancing Postoperative Recovery following Radical Cystectomy for Bladder Cancer.

INTRODUCTION: µ-Opioid-receptor antagonists are a standard component of enhanced recovery after surgery (ERAS) pathways following radical cystectomy (RC) as they reduce ileus and shorten length of stay (LOS). Prior studies have used alvimopan; however, naloxegol is a less expensive medication in the same class. We compared differences in postoperative outcomes between patients receiving alvimopan or naloxegol following RC. METHODS: We retrospectively reviewed all patients undergoing RC over 20 months at an academic center during which standard practice transitioned from using alvimopan to naloxegol, while maintaining all other components of our ERAS pathway. We utilized bivariate comparisons as well as negative binomial and logistic regression to compare return of bowel function, rates of ileus and LOS following RC. RESULTS: Of 117 eligible patients, 59 (50%) received alvimopan and 58 (50%) received naloxegol. There were no differences in baseline clinical, demographic or perioperative factors. Median postoperative LOS was 6 days in each group (p=0.3). Time to flatus (2 versus 2 days, p=0.2) and ileus (14% versus 17%, p=0.6) were similar between the alvimopan and naloxegol groups, respectively. In multivariable models controlling for patient and surgical factors, µ-opioid antagonist agent was associated with neither LOS nor ileus. Cost difference was -$344.20/day, equivalent to a $2,065.20 savings over a 6-day hospital stay with naloxegol. CONCLUSIONS: In patients undergoing RC managed with a standard ERAS pathway, there were no differences in postoperative recovery based on the use of alvimopan versus naloxegol. Substitution of naloxegol for alvimopan may allow for significant cost savings without compromising outcomes.

Reframing Financial Incentives Around Reducing Readmission After Radical Cystectomy.

OBJECTIVE: To better understand the financial implications of readmission after radical cystectomy, an expensive surgery coupled with a high readmission rate. Currently, whether hospitals benefit financially from readmissions after radical cystectomy remains unclear, and potentially obscures incentives to invest in readmission reduction efforts. MATERIALS AND METHODS: Using a 20% sample of national Medicare beneficiaries, we identified 3544 patients undergoing radical cystectomy from January 2010 to November 2014. We compared price-standardized Medicare payments for index admissions and readmissions after surgery. We also examined the variable financial impact of length of stay and the proportion of Medicare payments coming from readmissions based on overall readmission rate. RESULTS: Medicare patients readmitted after cystectomy had higher index hospitalization payments ($19,164 readmitted vs $18,146 non-readmitted, P = .03) and an average readmission payment of $7356. Adjusted average Medicare readmission payments and length of stay varied significantly across hospitals, ranging from $2854 to $15,605, and 2.0 to 17.1 days, respectively (both P <.01), with longer length of stay associated with increased payments. After hospitals were divided into quartiles based on overall readmission rates, the percent of payments coming from readmissions ranged from 5% to 13%. CONCLUSION: Readmissions following radical cystectomy were associated with increased Medicare payments for the index hospitalization, and the readmission payment, potentially limiting incentives for readmission reduction programs. Our findings highlight opportunities to reframe efforts to support patients, caregivers, and providers through improving the discharge and readmission processes to create a patient-centered experience, rather than for fear of financial penalties.

Dynamic readmission prediction using routine postoperative laboratory results after radical cystectomy.

OBJECTIVE: To determine if the addition of electronic health record data enables better risk stratification and readmission prediction after radical cystectomy. Despite efforts to reduce their frequency and severity, complications and readmissions following radical cystectomy remain common. Leveraging readily available, dynamic information such as laboratory results may allow for improved prediction and targeted interventions for patients at risk of readmission. METHODS: We used an institutional electronic medical records database to obtain demographic, clinical, and laboratory data for patients undergoing radical cystectomy. We characterized the trajectory of common postoperative laboratory values during the index hospital stay using support vector machine learning techniques. We compared models with and without laboratory results to assess predictive ability for readmission. RESULTS: Among 996 patients who underwent radical cystectomy, 259 patients (26%) experienced a readmission within 30 days. During the first week after surgery, median daily values for white blood cell count, urea nitrogen, bicarbonate, and creatinine differentiated readmitted and nonreadmitted patients. Inclusion of laboratory results greatly increased the ability of models to predict 30-day readmissions after cystectomy. CONCLUSIONS: Common postoperative laboratory values may have discriminatory power to help identify patients at higher risk of readmission after radical cystectomy. Dynamic sources of physiological data such as laboratory values could enable more accurate identification and targeting of patients at greatest readmission risk after cystectomy. This is a proof of concept study that suggests further exploration of these techniques is warranted.

Characterising 'bounce-back' readmissions after radical cystectomy.

OBJECTIVE: To examine predictors of early readmissions after radical cystectomy (RC). Factors associated with preventable readmissions may be most evident in readmissions that occur within 3 days of discharge, commonly termed 'bounce-back' readmissions, and identifying such factors may inform efforts to reduce surgical readmissions. PATIENTS AND METHODS: We utilised the Healthcare Cost and Utilization Project's State Inpatient Databases to examine 1867 patients undergoing RC in 2009 and 2010, and identified all patients readmitted within 30 days of discharge. We assessed differences between patients experiencing bounce-back readmission compared to those readmitted 8-30 days after discharge using logistic regression models and also calculated abbreviated LACE scores to assess the utility of common readmissions risk stratification algorithms. RESULTS: The 30-day and bounce-back readmission rates were 28.4% and 5.6%, respectively. Although no patient or index hospitalisation characteristics were significantly associated with bounce-back readmissions in adjusted analyses, bounce-back patients did have higher rates of gastrointestinal (14.3% vs 6.7%, P = 0.02) and wound (9.5% vs 3.0%, P < 0.01) diagnoses, as well as increased index and readmission length of stay (5 vs 4 days, P = 0.01). Overall, the median abbreviated LACE score was 7, which fell into the moderate readmission risk category, and no difference was observed between readmitted and non-readmitted patients. CONCLUSION: One in five readmissions after RC occurs within 3 days of initial discharge, probably due to factors present at discharge. However, sociodemographic and clinical factors, as well as traditional readmission risk tools were not predictive of this bounce-back. Effective strategies to reduce bounce-back readmission must identify actionable clinical factors prior to discharge.

Characterising potential bone scan overuse amongst men treated with radical prostatectomy.

OBJECTIVES: To characterise bone scan use, and potential overuse, after radical prostatectomy (RP) using data from a large, national integrated delivery system. Overuse of imaging is well documented in the setting of newly diagnosed prostate cancer, but whether overuse persists after RP remains unknown. PATIENTS AND METHODS: We identified 12 269 patients with prostate cancer treated with RP between 2005 and 2008 using the Veterans Administration Central Cancer Registry. We used administrative and laboratory data to examine rates of bone scan use, including preceding prostate-specific antigen (PSA) levels, and receipt of adjuvant or salvage therapy. We then performed multivariable logistic regression to identify factors associated with post-RP bone scan use. RESULTS: At a median follow-up of 6.8 years, one in five men (22%) underwent a post-RP bone scan at a median PSA level of 0.2 ng/mL. Half of bone scans (48%) were obtained in men who did not receive further treatment with androgen-deprivation or radiation therapy. After adjustment, post-RP bone scan was associated with a prior bone scan (adjusted odds ratio [aOR] 1.55, 95% confidence interval [CI] 1.32-1.84), positive surgical margin (aOR 1.68, 95% CI 1.40-2.01), preoperative PSA level (aOR 1.02, 95% CI 1.01-1.03), as well as Hispanic ethnicity, Black race, and increasing D'Amico risk category, but not with age or comorbidity. CONCLUSION: We found a substantial rate of bone scan utilisation after RP. The majority were performed for PSA levels of <1 ng/mL where the likelihood of a positive test is low. More judicious use of imaging appears warranted in the post-RP setting.

Role of Post-Acute Care on Hospital Readmission After High-Risk Surgery.

BACKGROUND: Payment models, including the Hospital Readmissions Reduction Program and bundled payments, place pressures on hospitals to limit readmissions. Against this backdrop, we sought to investigate the association of post-acute care after major surgery and readmission rates. METHODS: We identified patients undergoing high-risk surgery (abdominal aortic aneurysm repair, coronary bypass grafting, aortic valve replacement, carotid endarterectomy, esophagectomy, pancreatectomy, lung resection, and cystectomy) from 2005 to 2010 using the Healthcare Cost and Utilization Project's State Inpatient Database. The primary outcome was readmission rates after major surgery. Secondary outcome was readmission length of stay. RESULTS: We identified 135,523 patients of whom 56,720 (42%) received post-acute care. Patients receiving post-acute care had higher readmission rates than those who were discharged home (16% versus 10%, respectively; P < 0.001). The risk-adjusted readmission length of stay was greatest for patients who received care from a skilled nursing facility, followed by those who received home care, and lowest for those who did not receive post-acute care (7.1 versus 5.4 versus 4.8 d, respectively; P < 0.001). CONCLUSIONS: The use of post-acute care was associated with higher readmission rates and higher readmission lengths of stay. Improving the support of patients in post-acute care settings may help reduce readmissions and readmission intensity.

Potential Savings in Medicare Part D for Common Urological Conditions.

INTRODUCTION: Millions of patients take prescription medications each year for common urological conditions. Generic and brand-name drugs have widely divergent pricing despite similar therapeutic benefit and side effect profiles. We examined prescribing patterns across provider types for generic and brand-name drugs used to treat 3 common urological conditions, and estimated economic implications for Medicare Part D spending. METHODS: We extracted 2014 prescription claims and payments from Medicare Part D and categorized oral medications used to treat 3 urological conditions, namely benign prostatic hyperplasia, erectile dysfunction and overactive bladder. We examined claims and payments for each medication among urologists and nonurologists. Lastly, we estimated potential savings by selecting a low cost or generic drug as a cost comparator for each class. RESULTS: There were significant differences in prescribing patterns across these conditions, with urologists prescribing more brand-name and expensive medications (p <0.001). The total potential savings related to prescriptions of more expensive and nongeneric drugs in 2014 was $1 billion (benign prostatic hyperplasia $348,454,910, erectile dysfunction $10,211,914 and overactive bladder $698,130,833). These potential savings comprised 53% of the total spending for these medications in 2014. CONCLUSIONS: Within Medicare Part D the potential savings associated with generic substitution for higher cost and nongeneric drugs for 3 common urological conditions surpassed $1 billion, with urologists more likely to prescribe brand-name and more expensive drugs. Increasing low cost and generic drug use where available evidence of efficacy is equivocal represents a promising policy target to optimize prescription drug spending.

The Receipt of Industry Payments is Associated With Prescribing Promoted Alpha-blockers and Overactive Bladder Medications.

OBJECTIVE: To determine the impact of physicians' financial relationships with the pharmaceutical industry on prescribing marketed alpha-blockers and overactive bladder (OAB) medications. We also aim to examine if the number or total value of transactions is influential. MATERIALS AND METHODS: We linked the Open Payments Program database of industry payments to prescribers with Medicare Part D prescription data. We used binomial logistic regression to identify the association between receipt of industry payment and prescribing of marketed alpha-blockers (silodosin) and OAB medications (fesoterodine, solifenacin, and mirabegron). We also evaluated the impact of increasing total value and number of payments on prescribing of marketed drugs. RESULTS: The receipt of industry payment was associated with increased odds of prescribing the marketed drug for all included drugs: silodosin (odds ratio [OR] 34.1), fesoterodine (OR 5.9), solifenacin (OR 2.7), and mirabegron (OR 6.8) (all P <.001). We also found that increasing value of total payment and increasing frequency of payments were both independently associated with increased odds of prescribing with a dose-response effect. CONCLUSION: There is a consistent association between receipt of industry payment and prescribing marketed alpha-blockers and OAB medications. Both the total value and number of transactions were associated with prescribing.

The effects of cystoscopy and hydrodistention on symptoms and bladder capacity in interstitial cystitis/bladder pain syndrome.

AIMS: The use of cystoscopy and hydrodistention in the management of interstitial cystitis/bladder pain syndrome (IC/BPS) varies widely between providers. Current evidence regarding the risks and benefits of hydrodistention, as well as the long term effects of repeated hydrodistention are not well established. We sought to characterize the effects of hydrodistention on IC/BPS symptoms as well as bladder capacity. METHODS: We retrospectively queried our institutional records for patients with non-ulcerative IC/BPS who underwent hydrodistention over an 11-year period to obtain demographic and clinical factors at the time of diagnosis and treatment. Symptom relief and bladder capacity changes were assessed, and multivariable models were used to predict response to treatment. RESULTS: There were 328 patients who underwent hydrodistention during the study period, of whom 36% received the procedure multiple times, and overall median follow-up was 38.6 months. Patients with repeated hydrodistentions were more likely to be female, have more comorbid pain disorders, and have trialed anticholinergic medications and intravesical instillations. No decrease in mean bladder capacity was observed over time (P = 0.40). Significant decreases in symptom scores were observed following the procedure on multiple questionnaires. CONCLUSIONS: Hydrodistention does not decrease bladder capacity even with multiple procedures, and measurably improves symptoms in some patients with IC/BPS. Continuing efforts to better identify those patients most likely to benefit from this procedure are justified.

The implications of baseline bone-health assessment at initiation of androgen-deprivation therapy for prostate cancer.

OBJECTIVES: To assess bone-density testing (BDT) use amongst prostate cancer survivors receiving androgen-deprivation therapy (ADT), and downstream implications for osteoporosis and fracture diagnoses, as well as pharmacological osteoporosis treatment in a national integrated delivery system. PATIENTS AND METHODS: We identified 17 017 men with prostate cancer who received any ADT between 2005 and 2014 using the Veterans Health Administration cancer registry and administrative data. We identified claims for BDT within a 3-year period of ADT initiation. We then used multivariable regression to examine the association between BDT use and incident osteoporosis, fracture, and use of pharmacological treatment. RESULTS: We found that a minority of patients received BDT (n = 2 502, 15%); however, the rate of testing increased to >20% by the end of the study period. Men receiving BDT were older at diagnosis and had higher-risk prostate cancer (both P < 0.001). Osteoporosis and fracture diagnoses, use of vitamin D ± calcium, and bisphosphonates were all more common in men who received BDT. After adjustment, BDT, and to a lesser degree ≥2 years of ADT, were both independently associated with incident osteoporosis, fracture, and osteoporosis treatment. CONCLUSIONS: BDT is rare amongst patients with prostate cancer treated with ADT in this integrated delivery system. However, BDT was associated with substantially increased treatment of osteoporosis indicating an underappreciated burden of osteoporosis amongst prostate cancer survivors initiating ADT. Optimising BDT use and osteoporosis management in this at-risk population appears warranted.

Implications of Prostate Cancer Treatment in Men With Inflammatory Bowel Disease.

OBJECTIVE: To investigate the influences of inflammatory bowel disease (IBD), a rare but morbid disease with increasing incidence, on prostate cancer management decisions. We examined whether prostate cancer treatment differed for men with IBD, and whether treatment choice was associated with risk of IBD flare. MATERIALS AND METHODS: Using Veterans Health Administration cancer registry and administrative data, we identified 52,311 men diagnosed with prostate cancer from 2005 to 2008. We used International Classification of Diseases-9 codes and pharmacy and utilization data to identify IBD diagnoses, IBD-directed therapy, and flares (glucocorticoid escalation, hospitalization, and surgical intervention). We compared characteristics across men with and without IBD, and used multivariable regression to examine IBD flares after treatment according to treatment type. RESULTS: Two hundred and forty men (0.5%) had IBD prior to prostate cancer diagnosis. Compared to non-IBD patients, IBD patients were more likely Caucasian (P < .001) with lower-risk cancer (P = .02). Surgery was more common in IBD patients (41% vs 28%, P < .001). In the year following prostate cancer treatment, 18% of IBD patients experienced flares. After adjustment, the only predictor of flare in the year after treatment was flare in the year prior to treatment (adjusted odds ratio, 12.5; 95% confidence interval, 5.4-29.2). CONCLUSION: IBD patients were more likely to have lower-risk disease and be treated with surgery. Choice of prostate cancer treatment did not predict flares in the subsequent year. Better understanding of the intersection of IBD and prostate cancer can help inform treatment decisions for the increasing number of men managing both diseases.

Predictors of operative failure in parathyroidectomy for primary hyperparathyroidism.

INTRODUCTION: Many adjuncts guide surgical decision making in parathyroidectomy, yet their independent associations with outcome are poorly characterized. We examined a broad range of perioperative factors and used multivariate techniques to identify independent predictors of operative failure (persistent disease) after parathyroidectomy. METHODS: This was a retrospective review of 2239 patients with primary hyperparathyroidism who underwent parathyroidectomy at a single-center from 1999 to 2014. We used multivariate logistic regress to measure associations between multiple perioperative factors and an operative failure (persistent hypercalcemia). RESULTS: Operative failure was identified in 67 patients (3.0%). The following variables were independently associated with operative failure on multivariate analysis: IOPTH criteria met (protective, OR = 0.22, P < 0.001), preoperative calcium (risk factor, OR = 2.27 per unit increase, P < 0.001), weight of excised gland(s) (protective, OR = 0.70 per two-fold increase, P = 0.003), and preoperative PTH (protective, OR = 0.55 per two-fold increase, P = 0.008). CONCLUSION: In addition to the well-established IOPTH criteria, we suggest that consideration of the above independent perioperative risk factors may further inform surgical decision-making in parathyroidectomy.

One-year postoperative resource utilization in sarcopenic patients.

BACKGROUND: It is well established that sarcopenic patients are at higher risk of postoperative complications and short-term health care utilization. Less well understood is how these patients fare over the long term after surviving the immediate postoperative period. We explored costs over the first postoperative year among sarcopenic patients. METHODS: We identified 1279 patients in the Michigan Surgical Quality Collaborative database who underwent inpatient elective surgery at a single institution from 2006-2011. Sarcopenia, defined by gender-stratified tertiles of lean psoas area, was determined from preoperative computed tomography scans using validated analytic morphomics. Data were analyzed to assess sarcopenia's relationship to costs, readmissions, discharge location, intensive care unit admissions, hospital length of stay, and mortality. Multivariate models were adjusted for patient demographics and surgical risk factors. RESULTS: Sarcopenia was independently associated with increased adjusted costs at 30, 90, and 180 but not 365 d. The difference in adjusted postsurgical costs between sarcopenic and nonsarcopenic patients was $16,455 at 30 d and $14,093 at 1 y. Sarcopenic patients were more likely to be discharged somewhere other than home (P < 0.001). Sarcopenia was not an independent predictor of increased readmission rates in the postsurgical year. CONCLUSIONS: The effects of sarcopenia on health care costs are concentrated in the immediate postoperative period. It may be appropriate to allocate additional resources to sarcopenic patients in the perioperative setting to reduce the incidence of negative postoperative outcomes.

Inhibition of CCL2 signaling in combination with docetaxel treatment has profound inhibitory effects on prostate cancer growth in bone.

The C-C chemokine ligand 2 (CCL2) stimulates migration, proliferation, and invasion of prostate cancer (PCa) cells, and its signaling also plays a role in the activation of osteoclasts. Therefore targeting CCL2 signaling in regulation of tumor progression in bone metastases is an area of intense research. The objective of our study was to investigate the efficacy of CCL2 blockade by neutralizing antibodies to inhibit the growth of PCa in bone. We used a preclinical model of cancer growth in the bone in which PCa C4-2B cells were injected directly into murine tibiae. Animals were treated for ten weeks with neutralizing anti-CCL2 antibodies, docetaxel, or a combination of both, and then followed an additional nine weeks. CCL2 blockade inhibited the growth of PCa in bone, with even more pronounced inhibition in combination with docetaxel. CCL2 blockade also resulted in increases in bone mineral density. Furthermore, our results showed that the tumor inhibition lasted even after discontinuation of the treatment. Our data provide compelling evidence that CCL2 blockade slows PCa growth in bone, both alone and in combination with docetaxel. These results support the continued investigations of CCL2 blockade as a treatment for advanced metastatic PCa.