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Emergency department visits and hospitalizations are common among people receiving cancer treatment, accounting for a large proportion of spending in oncology care and negatively affecting quality of life. As oncology care shifts toward value- and quality-based payment models, there is a need to develop interventions that can prevent these costly and low-value events among people receiving cancer treatment. Risk stratification programs have the potential to address this need and optimally would consist of three components: (1) a risk stratification algorithm that accurately identifies patients with modifiable risk(s), (2) intervention(s) that successfully reduce this risk, and (3) the ability to implement the risk algorithm and intervention(s) in an adaptable and sustainable way. Predictive modeling is a common method of risk stratification, and although a number of predictive models have been developed for use in oncology care, they have rarely been tested alongside corresponding interventions or developed with implementation in clinical practice as an explicit consideration. In this article, we review the available published predictive models for treatment-related toxicity or acute care events among people receiving cancer treatment and highlight challenges faced when attempting to use these models in practice. To move the field of risk-stratified oncology care forward, we argue that it is critical to evaluate predictive models alongside targeted interventions that address modifiable risks and to demonstrate that these two key components can be implemented within clinical practice to avoid unplanned acute care events among people receiving cancer treatment.

Introduction The natural history of T1b (4-7 cm) or T2a (> 7-10 cm) kidney cancers managed with observation is not well-understood. The aim of our study was to determine if the addition of histologic subtype to a predictive model of overall survival (OS) that includes covariates for competing risks in observed, biopsy-proven, T1b and T2a renal cell carcinomas (RCCs) improves the model’s performance. Materials and Methods We queried the National Cancer Database for patients with biopsy-proven stage T1b or T2a RCC and managed nonoperatively between 2004 and 2015. OS was estimated by Kaplan-Meier curves based on histologic subtype. The concordance index (c-index) from a Cox proportional hazards model was used to estimate the extent to which histologic subtypes predict survival for each stage when included in a model along with competing risks of age, gender, race/ethnicity, insurance status, area-level socioeconomic indicators, Charlson-Deyo index, and tumor grade. Results A total of 937 patients (754 with T1b and 185 with T2a) with biopsy-proven RCC were identified. Kaplan-Meier analysis suggested differences in OS by histologic subtype where sarcomatoid, followed by clear cell, papillary, and chromophobe, had the highest mortality risk at 1, 3, and 5 years. However, there was marginal improvement in the multivariable model of OS using competing risks and histology (c-index, 0.64 and 0.697) compared with competing risks alone (c-index, 0.631 and 0.671) for T1b and T2a RCCs, respectively. Conclusions In patients with T1b or T2a RCC managed with observation, incorporation of histologic subtype into a risk-stratification model to determine prognostic OS did not improve modeling of OS compared with variables representing competing risks. Histologic subtype of observed T1b and T2a RCC appears to have prognostic OS value when not considering competing risks. These findings may impact the usefulness of renal biopsy to inform decision-making when managing patients with T1b and T2a renal tumors with observation.

Introduction: There have been a number of recent advances in the management of advanced clear cell renal cell carcinoma (ccRCC). However, the majority of these studies excluded patients with non-clear cell RCC (nccRCC), and optimal management of nccRCC remains unknown. Materials and Methods: A systematic review of the literature was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to evaluate systemic treatment options in locally advanced or metastatic nccRCC between 2000-2019. Randomized controlled trials, single-arm phase II–IV trials, and prospective analyses of medication access programs were included. The primary outcome measures were progression free survival (PFS), overall survival (OS), and objective response rate (ORR). Results: A total of 31 studies were included in the final analysis. There was the highest level of evidence to support first-line treatment of nccRCC with sunitinib. Additional single-arm trials support the use of other vascular endothelial growth factor (VEGF) inhibitors with axitinib and pazopanib, as well as mammalian target of rapamycin (mTOR) inhibition with temsirolimus or everolimus +/–bevacizumab. Immune checkpoint inhibition has an emerging role in nccRCC, but optimal sequencing of available options is not clear. Prospective data to support the use of newer immunotherapy combinations are lacking. Treatment for collecting duct carcinoma remains platinum-based chemotherapy. Conclusions: The availability of randomized trials in nccRCC is limited, and most studies include outcomes for nccRCC as a group, making conclusions about efficacy by subtype difficult. This systematic review supports consensus guidelines recommending sunitinib or clinical trial enrollment as preferred first-line treatment options for nccRCC, but also suggests a more nuanced approach to management and new options for therapy such as immune checkpoint inhibition.

We sought to assess if adding a biopsy proven histologic subtype to a model that predicts overall survival that includes variables representing competing risks in observed, biopsy proven, T1a renal cell carcinomas, enhances the model's performance.The National Cancer Database was assessed (years 2004-2015) for patients with observed T1a renal cell carcinoma who had undergone renal mass biopsy. Kaplan-Meier curves were utilized to estimate overall survival stratified by histologic subtype. We utilized C-index from a Cox proportional hazards model to evaluate the impact of adding histologic subtypes to a model to predict overall survival for each stage.Of 132 958 T1a renal masses identified, 1614 had biopsy proven histology and were managed non-operatively. Of those, 61% were clear cell, 33% papillary, and 6% chromophobe. Adjusted Kaplan-Meier curves demonstrated a difference in overall survival between histologic subtypes (P = 0.010) with greater median overall survival for patients with chromophobe (85.1 months, hazard rate 0.45, P = 0.005) compared to clear cell (64.8 months, reference group). Adding histology to a model with competing risks alone did not substantially improve model performance (C-index 0.65 vs 0.64 respectively).Incorporation of histologic subtype into a risk stratification model to determine prognostic overall survival did not improve modeling of overall survival compared with variables representing competing risks in patients with T1a renal cell carcinoma managed with observation. These results suggest that performing renal mass biopsy in order to obtain tumor histology may have limited utility. Future studies should further investigate the overall utility of renal mass biopsy for observed T1a kidney cancers.

Enfortumab vedotin (EV) is a novel antibody-drug conjugate approved for advanced urothelial cancer (aUC) refractory to prior therapy. In the Urothelial Cancer Network to Investigate Therapeutic Experiences (UNITE) study, the authors looked at the experience with EV in patient subsets of interest for which activity had not been well defined in clinical trials.UNITE was a retrospective study of patients with aUC treated with recently approved agents. This initial analysis focused on patients treated with EV. Patient data were abstracted from chart reviews by investigators at each site. The observed response rate (ORR) was investigator-assessed for patients with at least 1 post-baseline scan or clear evidence of clinical progression. ORRs were compared across subsets of interest for patients treated with EV monotherapy.The initial UNITE analysis included 304 patients from 16 institutions; 260 of these patients were treated with EV monotherapy and included in the analyses. In the monotherapy cohort, the ORR was 52%, and it was40% in all reported subsets of interest, including patients with comorbidities previously excluded from clinical trials (baseline renal impairment, diabetes, and neuropathy) and patients with fibroblast growth factor receptor 3 (FGFR3) alterations. Progression-free survival and overall survival were 6.8 and 14.4 months, respectively. Patients with a pure urothelial histology had a higher ORR than patients with a variant histology component (58% vs 42%; P = .06).In a large retrospective cohort, responses to EV monotherapy were consistent with data previously reported in clinical trials and were also observed in various patient subsets, including patients with variant histology, patients with FGFR3 alterations, and patients previously excluded from clinical trials with an estimated glomerular filtration rate30 mL/min and significant comorbidities.Enfortumab vedotin, approved by the Food and Drug Administration in 2019, is an important new drug for the treatment of patients with advanced bladder cancer. This study looks at the effectiveness of enfortumab vedotin as it has been used at multiple centers since approval, and focuses on important patient populations previously excluded from clinical trials. These populations include patients with decreased kidney function, diabetes, and important mutations. Enfortumab vedotin is effective for treating these patients. Previously reported clinical trial data have been replicated in this real-world setting, and support the use of this drug in broader patient populations.

INTRODUCTION AND OBJECTIVE:Sarcopenia, or severe muscle wasting, has been well documented as a risk factor for mortality, complications, and non-home discharge disposition for patients with bladder...

PURPOSE To evaluate the safety and efficacy of gemcitabine and cisplatin in combination with the immune checkpoint inhibitor pembrolizumab as neoadjuvant therapy before radical cystectomy (RC) in muscle-invasive bladder cancer. METHODS Patients with clinical T2-4aN0/XM0 muscle-invasive bladder cancer eligible for RC were enrolled. The initial six patients received lead-in pembrolizumab 200 mg once 2 weeks prior to pembrolizumab 200 mg once on day 1, cisplatin 70 mg/m2 once on day 1, and gemcitabine 1,000 mg/m2 once on days 1 and 8 every 21 days for four cycles. This schedule was discontinued for toxicity and subsequent patients received cisplatin 35 mg/m2 once on days 1 and 8 without lead-in pembrolizumab. The primary end point was pathologic downstaging (< pT2N0) with null and alternative hypothesis rates of 35% and 55%, respectively. Secondary end points were toxicity including patient-reported outcomes, complete pathologic response (pT0N0), event-free survival, and overall survival. Association of pathologic downstaging with programmed cell death ligand 1 staining was explored. RESULTS Thirty-nine patients were enrolled between June 2016 and March 2020 (72% cT2, 23% cT3, and 5% cT4a). Patients received a median of four cycles of therapy. All patients underwent RC except one who declined. Twenty-two of 39 patients (56% [95% CI, 40 to 72]) achieved < pT2N0 and 14 of 39 (36% [95% CI, 21 to 53]) achieved pT0N0. Most common adverse events (AEs) of any grade were thrombocytopenia (74%), anemia (69%), neutropenia (67%), and hypomagnesemia (67%). One patient had new-onset type 1 diabetes mellitus with ketoacidosis related to pembrolizumab and no patients required steroids for immune-related AEs. Clinicians consistently under-reported AEs when compared with patients. CONCLUSION Neoadjuvant gemcitabine and cisplatin plus pembrolizumab met its primary end point for improved pathologic downstaging and was generally safe. A global study of perioperative chemotherapy plus pembrolizumab or placebo is ongoing.

Over the past several decades, adult weight gain and excess weight have emerged as risk factors for cancers of the esophagus, pancreas, liver, colorectal, breast (postmenopausal), endometrium, and kidney, as well as probable evidence for cancers of the stomach (cardia), mouth/pharynx/larynx, gallbladder, ovary, and prostate. In the USA, overweight and obesity account for 55% of cancers in women and 24% in men. The evidence of risks, outcomes, and interventions is most developed in the literature pertaining to women with early breast cancer (Stage I–III). Primarily with the oncology clinician-patient relationship in mind, this chapter provides an overview of weight trajectories in women with early breast cancer, implications for prognosis and survival, nutrition and exercise for weight management, and the role of oncology clinicians. Lessons learned from the breast cancer population are illustrative for other types of cancers. Culturally sensitive, person-centered language about the importance of weight management in survivorship is essential to clinician-patient communication and other interventions to help adults with cancer to understand the importance of weight management and other benefits from exercise and a healthy diet. Equally important, but not within the scope of this chapter, is the urgency of lowering cancer risk and adverse outcomes through effective and widespread community-based obesity interventions.

Established and novel radiotracers are under active investigation for patients with bladder cancer. 18F-FDG PET/CT may be useful for lymph node staging or assessment of distant metastatic disease but is of limited utility for primary tumor staging due to urinary excretion of the radiotracer. 11C-choline and 11C-acetate both overcome the issue of urinary excretion, but their short half-life necessitates an onsite cyclotron. Ongoing studies aim to evaluate whether PET imaging can predict or accurately assess treatment response. 99mTc-MDP or 18F-NaF radiotracers permit assessment of bone metastases, with limitations of each modality. Several novel radiotracers are under investigation for future utility.

BACKGROUND: The treatment landscape for metastatic clear cell renal cell carcinoma (mRCC) is rapidly changing. It is unknown how adoption of new types of therapies may differ by patient age. OBJECTIVE: To compare trends in first-line therapy use for older (≥70 years) and younger (

Neoadjuvant cisplatin-based chemotherapy (NAC; 70 mg/m2) is standard of care for muscle-invasive bladder carcinoma (MIBC). Many patients (pts) cannot receive cisplatin because of renal impairment, and administration of cisplatin 35 mg/m2 on day 1 + 8 or 1 + 2 (i.e., split schedule) is a commonly used alternative. In this retrospective analysis, we compared complete (pT0) and partial (

396 Background: Cisplatin-based neoadjuvant chemotherapy is standard of care in MIBC with improved pathologic response and overall survival (OS) compared to RC alone. Pembrolizumab (pembro) is active in high-risk non-muscle invasive and metastatic bladder cancer and is generally well tolerated. This phase II trial evaluated the safety and efficacy of gemcitabine and split-dose cisplatin (GC) + pembro as neoadjuvant therapy prior to RC (NCT02690558). Methods: Patients with clinical T2-4a N0/X M0 urothelial carcinoma of the bladder eligible for RC were enrolled. Patients received pembro 200mg on day 1 with cisplatin 35mg/m2 and gemcitabine 1000mg/m2 on days 1 and 8 every 3 weeks for 4 cycles, followed by RC within 4-8 weeks. The first 6 patients received full-dose cisplatin (70mg/m2 on day 1) and a lead-in pembro dose; this schedule was discontinued for excess toxicity. Primary endpoint was pathologic downstaging rate ( < pT2) with the null and alternative hypothesis rates = 35% and 55%, respectively. Secondary endpoints were toxicity, pT0 rate, event free survival, and OS. Exploratory objectives include association of response with molecular subtype and post-treatment changes in immune microenvironment (predicted neoantigens, immune gene expression, and T cell receptor repertoire). Results: Between May 2016 and July 2020, 39 patients were enrolled (72% cT2, 23% cT3, 5% cT4a) with a median age of 66 and 82% male. Patients received a median of 4 cycles of therapy. All patients underwent RC except one who declined but is included in intention to treat analysis. Rate of < pT2N0 was 56% (22/39) and pT0N0 rate was 36% (14/39). Most common adverse events (AEs) of any grade were thrombocytopenia (29/39; 74%), anemia (27/39; 69%), neutropenia (26/39; 67%), and hypomagnesemia (26/39; 67%). Most common grade 3/4 AEs were neutropenia (16/39; 41%), thrombocytopenia (13/39; 33%), febrile neutropenia (5/39; 13%), and anemia (4/39; 10%). One patient had new onset type 1 diabetes mellitus with ketoacidosis related to pembrolizumab and no patients required steroids for immune-related AEs. Nine patients (23%) discontinued GC + pembro due to AEs, including 4 of the 6 patients who received full-dose cisplatin with pembro lead-in. Survival data are not yet mature and correlative studies are ongoing. Conclusions: Neoadjuvant GC + pembro was generally safe and met its primary endpoint for improved pathologic downstaging. Correlative analyses are ongoing. Additional investigation of this combination is warranted. Clinical trial information: NCT02690558.

443 Background: Enfortumab vedotin (EV) is an antibody-drug conjugate targeting Nectin-4, which is FDA approved for patients (pts) with treatment-refractory advanced urothelial cancer (aUC). The activity of EV in pt subsets of interest such as those with distinct histological variants has not been well defined. Methods: A retrospective study of pts with aUC treated with ≥1 dose of EV as standard of care (SOC) or on a clinical trial (if trial results already reported) at 12 US sites was undertaken. Objective response rate (ORR) was investigator-assessed for pts with at least one post-baseline scan or clear evidence of clinical progression. ORR was compared across subsets of interest using proportion test. Results: A total of 184 patients with aUC were included; median age at diagnosis 70, 20% women and 60% with definitive surgery. Most common primary sites included bladder (70%) and upper tract (28%). Majority of pts (72%) had pure urothelial histology (UH) per local review, but 26% had at least a component of variant histology (VH), most commonly squamous (14%), micropapillary (8%) or plasmacytoid (3%). EV was given as monotherapy in 84% and as SOC in 58%; and 81% had ≥ 1 prior treatment in the metastatic (met) setting. ECOG PS was ≥2 in 15%; 37% had baseline neuropathy, 15% diabetes and 9% had GFR≤30. At median follow-up of 37.0 (IQR: 20.5-60.2) months from initial diagnosis, median time from met diagnosis to EV start was 11.7 (IQR: 4.3 – 20.5) months. Median duration of EV was 5.5 (IQR: 1.4 – 6.7) months, and 84% of pts were evaluable for response. ORR for evaluable pts was 53% (8% CR, 45% PR); 25% had SD and 21% PD. Median PFS and OS were not yet reached. At data cutoff in 9/2020, 55% had stopped EV (36% due to PD, 19% intolerance) and 65% were alive. Comparison of ORR in subgroups of interest for 127 evaluable pts treated with EV monotherapy is shown in the table below. Notably, among 31 pts with FGFR3 alterations, 26 were evaluable and ORR was 46%. Conclusions: In a large, retrospective, multi-institutional cohort, responses to EV were observed across a broad range of aUC pts, including pts with variant histology component, FGFR3 alterations and also in populations previously excluded from clinical trials such as pts with GFR

423 Background: Malnutrition and sarcopenia are linked to decreased functional status in older adults with malignancy, but their effect on geriatric assessment (GA) impairment in patients with bladder cancer (BC) undergoing radical cystectomy (RC) is unknown. We investigated the association between malnutrition and sarcopenia with GA impairment and postoperative outcomes. Methods: Patients with BC undergoing RC between 2012 – 2019 were enrolled in a prospective cohort study of GA before RC. Malnutrition was evaluated by a dietitian pre-RC per the Academy of Nutrition and Dietetics and American Society for Parenteral and Enteral Nutrition diagnostic criteria. Sarcopenia, defined by a skeletal muscle index of < 52.4 cm2/m2 in males and < 38.5 cm2/m2 in females, was determined using SliceOmatic software to analyze pre-RC CT images at the L3 vertebra. Patients with vs without malnutrition and those with vs without sarcopenia were compared using Fisher’s exact and Wilcoxon rank sum tests. Results: Of 73 patients, 59 had GA + nutrition evaluation and 51 had GA + sarcopenia assessment (overall median age 68 [IQR 62-74], 76% male). The prevalence of malnutrition was 7% and sarcopenia was 63%. A numerically greater proportion of patients with malnutrition or sarcopenia were impaired on ≥ 1 GA measure compared to those without malnutrition (100% vs 78%, p=0.57) or sarcopenia (78% vs 68%, p=0.52), although this was not statistically significant (Table). Median hospital length of stay (LOS) was increased for patients with vs without sarcopenia (4 vs 5 days, p=0.005). Post-RC complication rate was similar for patients with vs without malnutrition (100% vs 75%, p=0.56) and patients with vs without sarcopenia (81% vs 74%, p=0.73), but malnourished patients were more likely to have Clavien-Dindo grade 3+ complications than those without malnutrition (100% vs 27%, p = 0.009). Conclusions: In our cohort of patients with BC undergoing RC, those with malnutrition or sarcopenia may have an increased rate of impairment on GA compared to those without malnutrition or sarcopenia. Sarcopenia was associated with increased LOS while malnutrition was associated with increased major complications. Our results are limited by small sample size, and future work is needed to elucidate whether addressing these modifiable factors improves functional status and postoperative outcomes. Research Sponsor: U.S. National Institutes of Health[Table: see text]

211 Background: Cancer patients have many medical and psychosocial needs, which may increase during the coronavirus pandemic and may be difficult to identify or address in the absence of in-person patient visits. We sought to (1) risk stratify hematology/oncology patients using general medicine and cancer-specific methods to identify those at high risk for acute care utilization, (2) measure the correlation between risk-stratification methods, and (3) perform a phone-based needs assessment with intervention for these patients. Methods: Patients were risk-stratified using a general medical health composite score (HCS) embedded in the electronic medical record, and a cancer-specific risk (CSR) stratification based on disease and treatment characteristics. The correlation between HCS and CSR was measured using Spearman’s correlation. A multi-disciplinary team developed a focused needs assessment script with recommended interventions for patients categorized as high-risk by either method. The number of patient needs identified and referrals for services made in the first month of outreach are reported. Results: 1,421 patients were risk stratified, with 15% high-risk using HCS and 21.2% high-risk using CSR. Overall correlation between HCS and CSR was modest (r = 0.39). During the first month of the pilot, 287 patients were called for outreach with 245 contacted (85%). Commonly identified needs were financial difficulties (17%), uncontrolled symptoms (15%), and interest in advance care planning (13%), resulting in referral for supportive services for 33% of patients. Conclusions: There is a high burden of unmet medical and psychosocial needs in hematology/oncology patients during the coronavirus pandemic. A phone-based outreach program results in identification of and intervention for these needs, however additional cancer-specific risk models are needed to improve targeting to high-risk patients. This process can serve as a framework for other institutions wishing to implement similar outreach programs during this pandemic. [Table: see text]

The treatment landscape for bladder cancer has undergone a rapid evolution in the past five years with the approval of seven new agents. New classes of medications have improved outcomes for many patients who previously had limited treatment options, but there is still much to learn about how to optimize patient selection for these agents and the role of combination therapies. The aims of this review are to discuss these newly approved agents for bladder cancer and to feature promising drugs and combinations—including immune checkpoint inhibitors, targeted therapies, and antibody–drug conjugates—that are in development.

e17010 Background: Older patients with muscle-invasive bladder cancer (MIBC) may not be offered standard of care treatment with neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) based on their chronological age and concern for functional decline following therapy. Age-based differences in post-RC functional status or time to recovery are unknown. Methods: A total of 80 patients were included in this study. Patients ≥ 70 years were categorized as “older” and < 70 years as “younger.” To measure functional status, patients completed an initial geriatric assessment (GA) post-NAC and pre-RC, which was repeated at 1, 3, and 12 months post-RC. Results: Median age was 62 years for younger patients (41-69 years; n = 42) and 75 years for older patients (70-83 years; n = 38). Clinical stage at presentation was not different between groups, but older patients were significantly less likely to receive NAC (63% vs 83%, p = 0.047). There was no significant difference between groups in any physical function measure at baseline. At 1 month post-RC, older patients had significantly lower clinician (c) and patient (p) rated Karnofsky Performance Status (KPS) than younger patients (cKPS: 70 vs 80, p = 0.02; pKPS 60 vs 80, p = 0.03), with a significantly greater decrease from baseline (20 points vs 0 points) in both KPS scores compared to younger patients (cKPS p = 0.001; pKPS p = 0.005). Both groups had a significant decline in ability to complete instrumental activities of daily living (IADLs), but older patients also had significantly increased social activity limitations. At 3 months post-RC, older patients took significantly longer to complete the timed up and go test than younger patients (10.2 secs vs 9 secs, p = 0.02), but had no other differences in physical function measures. Older patients had no significant difference in any measure at 3 months post-RC compared to baseline, while younger patients had a significant improvement in social activity over this time frame. Conclusions: Older patients with MIBC experience a greater short-term decline in functional status post-RC compared to younger patients. However, they return to their baseline status within the same time frame as younger patients.

e17008 Background: Standard of care treatment for muscle-invasive bladder cancer (MIBC) includes neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC), which can be associated with major toxicity. It is unknown whether patients who receive NAC have differences in functional impairment prior to RC, degree of functional decline post-RC, or time to return to baseline functional status post-RC compared to patients who do not receive NAC. Methods: A total of 80 patients were included in this study. Patients completed an initial geriatric assessment (GA) post-NAC but prior to RC, which was repeated at 30, 90 days, and 1 year post-cystectomy. Patients were classified as impaired or not impaired on each GA domain based on previously established cut points. Percentage impairment was calculated as the number of domains impaired out of the total number of domain assessments completed for each patient at each time point. Results: Median age was 68 for patients who received NAC (66% received gemcitabine/cisplatin) and 72 for patients who did not (p = 0.06), with elevated creatinine as the most common reason for not receiving NAC (57%). Overall, 74% of patients were impaired on at least 1 GA domain pre-surgery (NAC 75%; no NAC 71%) and 86% at 30 days post-RC (NAC 86%; no NAC 87%). Groups did not differ significantly in percentage of patients impaired on each GA domain or median percentage impairment at any time point. For both groups, median percentage impairment increased significantly at 30 days post-RC compared to pre-RC (NAC: 36% vs. 15%, p < 0.001; No NAC: 32% vs. 15%, p = 0.002), followed by a decrease in percentage impairment at 90 days post-RC compared to 30 days post-RC (NAC: 14% vs. 36%, p < 0.001; No NAC: 16% vs. 32%, p = 0.15). There was no difference in impairment at 90 days post-RC compared to pre-RC (NAC: 14% vs. 15%, p = 0.41; No NAC: 16% vs. 15%, p = 0.31). Conclusions: Patients with MIBC frequently have functional impairments at baseline, and their degree of impairment worsens in the short term post-RC. However, patients return to their baseline function by 3 months post-RC. Receipt of NAC was not associated with increased levels of functional impairment at any time point or a delayed return to baseline.

Background: Platelet-rich plasma (PRP) has anti-inflammatory effects with potential applications in the treatment of osteoarthritis (OA). Purpose: To use an in vitro coculture model of OA in human cartilage and synovium to investigate the anti-inflammatory effects of 2 different PRP preparations. Study Design: Controlled laboratory study. Methods: A coculture system was created using osteoarthritic cartilage and synovium from 9 patients undergoing total knee arthroplasty. Interleukin-1β (IL-1β) was added to each coculture to induce inflammation. Two PRP preparations were obtained—one yielding low white blood cell and platelet concentrations (PRPLP) and one yielding high platelet and white blood cell concentrations (PRPHP). Either PRPLP, PRPHP, or medium was added to the coculture wells. Control wells contained OA cartilage and synovium but neither IL-1β nor PRP. Normal, non-OA cartilage was obtained to establish baseline gene expression levels. Quantitative polymerase chain reaction was used to measure changes in markers of inflammation in the tissues (a disintegrin and metalloproteinase with thrombospondin motifs–5 [ADAMTS-5], tissue inhibitor of metalloproteinases–1 [TIMP-1], vascular endothelial growth factor [VEGF], aggrecan, and type I collagen) at 0, 24, 48, and 72 hours. Results: Treatment with PRPLP or PRPHP significantly decreased expression of TIMP-1 and ADAMTS-5 in cartilage, increased aggrecan expression in cartilage, and decreased ADAMTS-5, VEGF, and TIMP-1 expression in synovium compared with control cocultures ( P < .05). There was significantly less nitric oxide production in the PRPLP and PRPHP groups compared with controls ( P < .05). There were significant differences in gene expression in the normal cartilage compared with all 4 groups of OA cartilage at all 4 time points. Treatment with either PRPLP or PRPHP returned some gene expression to the same levels in normal cartilage but not for all markers of inflammation. Conclusion: This coculture model assessed 2 different PRP preparations and their anti-inflammatory effects over time on human OA cartilage and synovium. Both had a significant anti-inflammatory effect on gene expression; however, there was no difference in the anti-inflammatory effect between the 2 preparations. Clinical Relevance: Osteoarthritis is a leading cause of chronic disability, and less invasive treatment methods are needed. Study results suggest that PRP injections may be an effective alternative anti-inflammatory agent in the treatment of OA.

Background The benefit of surveillance after curative cystectomy in bladder cancer is unproven, but might be justified if detection of asymptomatic recurrence improves survival. Previous studies showing a benefit of surveillance might have been affected by lead-time or length-time bias. Materials and Methods We conducted a retrospective cohort study among 463 cystectomy patients at the University of Pennsylvania. Patients were followed according to a standardized protocol and classified according to asymptomatic or symptomatic recurrence detection. Primary outcome was all-cause mortality. Adjusted Cox regression models were used to assess the effect of mode of recurrence on survival from time of cystectomy (model 1) and time of recurrence (model 2) to account for lead and length time. Results One hundred ninety-seven patients (42.5%) recurred; 71 were asymptomatic (36.0%), 107 were symptomatic (54.3%), and 19 (9.6%) were unknown. Relative to patients with asymptomatic recurrence, patients with symptomatic recurrence had significantly increased risk of death (model 1: hazard ratio [HR], 1.67; 95% confidence interval [CI], 1.07-2.61; model 2: HR, 1.74, 95% CI, 1.13-2.69) and had lower 1-year overall survival from time of recurrence (29.37% vs. 55.66%). Symptomatic patients were diagnosed with recurrence a median of 1.7 months before asymptomatic patients, yet their median survival from recurrence was 8.2 months less. Conclusion Symptomatic recurrence is associated with worse outcomes than asymptomatic recurrence, which cannot be explained by lead- or length-time bias. Similar methods to account for these biases should be considered in studies of cancer surveillance. Shortening surveillance intervals might allow for detection of more recurrences in an asymptomatic phase.

4545Background: Neoadjuvant cisplatin (70mg/m2) based chemotherapy (NAC) prior to cystectomy is standard of care for MIBC. Many patients (pts) cannot receive cisplatin due to impaired renal functio...

e16021 Background: The benefit of surveillance after curative treatment in bladder cancer is controversial, but might be justified if early detection of asymptomatic recurrence improves survival. Prior studies demonstrating a benefit of surveillance may have been impacted by lead-time bias, which is the overestimation of survival duration due to earlier detection of disease. To avoid this bias, we examined time-dependent differences in survival with symptomatic vs. asymptomatic diagnosis of recurrence after cystectomy. Methods: We conducted a retrospective cohort study among 463 cystectomy patients between 1987 and 2011 at the University of Pennsylvania. Patients were followed by standardized protocol and classified by mode of recurrence detection (asymptomatic or symptomatic). Primary outcome was all-cause mortality. To reduce lead-time bias, we used cox regression models with varying cohort-entry times to assess the impact of mode of recurrence on survival from both time of cystectomy (Model 1) and time of recurrence (Model 2), adjusted for time to recurrence. Results: 197 patients (42.5%) recurred; 71 were asymptomatic (36.0%), 107 were symptomatic (54.3%), and 19 (9.6%) were unknown. In all models, relative to asymptomatic patients, patients with symptomatic recurrence had significantly increased risk of death (Model 1 HR 1.74, 95% CI 1.13-2.68, Model 2 HR 1.98, 95% CI 1.27-3.10) and had lower 1 year overall survival (30.43% vs. 55.66%). Group differences in median survival (246 days) were greater than the estimated lead-time (10 days). Conclusions: Symptomatic recurrence is associated with worse outcomes than asymptomatic recurrence, even after lead-time bias adjustment. These data support consensus guidelines for intensive surveillance post-cystectomy. Similar methods to account for lead-time bias should be considered in future studies evaluating the benefit of surveillance following curative cancer resection.