It's complicated: The relationship of non-narcotic medications and postoperative opioid use in radical cystectomy patients.

INTRODUCTION: The effect of individual non-narcotic analgesics in cystectomy enhanced recovery after surgery (ERAS) is unknown. Additionally, many non-narcotic medications are associated with side effects pertinent to the cystectomy population. To better understand the actual use and utility of these medications, we sought to characterize the association between non-narcotic medications and milligram morphine equivalent (MME) narcotic score during the postoperative inpatient stay. METHODS: We reviewed 260 consecutive ERAS cystectomy patients. The MME impact of non-narcotic compliance and cumulative dose of medication received was evaluated separately with general linear models. We also assessed relationship of non-narcotic compliance to patient reported pain score, length of stay (LOS), and time to return of bowel function (ROBF) and performed manual review of postoperative documentation to identify reasons for medication noncompliance. RESULTS: Compliance with postoperative acetaminophen, gabapentin, and ketorolac was low. There was an inverse relationship between ketorolac dose and MME on postoperative day 1 (-0.026 MME/mg; P = 0.004) and postoperative day 2 (-0.33 MME/mg; P < 0.001). Compliance with ketorolac was associated with lower MME on postoperative day 1 (26.1 MME v. 33.6 MME; P = 0.023). There were no such associations identified with gabapentin or acetaminophen. Gabapentin compliance was associated with earlier ROBF (3.7 days v. 4.3 days; P = 0.006). Ketorolac compliance was associated with lower pain score on POD1 (3.25 VAS v. 4.07 VAS; P = 0.019) and POD2 (3.05 VAS v. 3.85 VAS; P = 0.040) There was no association between medication compliance and LOS. The most common reasons identified for non-compliance with gabapentin and ketorolac were renal function concerns (38% and 40% respectively), bleeding concerns with ketorolac (20%) and concerns for neurologic adverse effect with gabapentin (16%). CONCLUSION: Compliance with non-narcotic medications in our ERAS cystectomy protocol was poor. There was a modest association with ketorolac and postoperative MME but no association with gabapentin or acetaminophen. Further study will clarify the role of these medications for cystectomy patients. Component specific analysis of protocolized care is valuable and may alter care pathways.

Persistent opioid and benzodiazepine use after radical cystectomy in enhanced recovery after surgery (ERAS) patients.

OBJECTIVES: Opioid use, misuse, and diversion is of paramount concern in the United States. Radical cystectomy is typically managed with some component of opioid pain control. We evaluated persistent opioid and benzodiazepine use after radical cystectomy and assessed the impact of their preoperative use on this outcome. We also explored associations between preoperative use and perioperative outcomes. METHODS AND MATERIALS: We used prospectively maintained data from our enhanced recovery after surgery (ERAS) cystectomy database and the Prescription Reporting with Immediate Medication Utilization Mapping (PRIMUM) database to identify controlled substance prescriptions for radical cystectomy patients. We separated patients by frequency of preoperative opioid and/or benzodiazepine prescriptions (0, 1, 2+) and used these cohorts to explore persistent use (prescription 3-12 months after surgery) alongside perioperative outcomes. RESULTS: Our cohort included 257 patients undergoing cystectomy at a single institution from 2017 to 2021. Preoperative opioid and benzodiazepine prescriptions were documented for 120 (46.7%) and 26 (10.1%) patients, respectively. Persistent opioid use was observed in 20 (14.6%) of opioid-naive patients (no prescriptions in 9 months prior to surgery) while 13 (19.7%) patients with 1 preoperative prescription and 28 (51.9%) patients with 2 or more preoperative prescriptions demonstrated persistent use. New persistent benzodiazepine use occurred in 6 (2.6%) patients. Overall persistent benzodiazepine use was present in 11 (4.3%) patients. In a multivariable model, preoperative opioid and benzodiazepine prescriptions were associated with persistent opioid use (P < 0.001; P = 0.027 respectively). No association was identified between preoperative opioid or benzodiazepine usage and perioperative outcomes including length of stay, return of bowel function, inpatient opioid usage, inpatient or discharge complications, readmissions, or emergency department visits. Inpatient pain scores were noted to be higher in patients with ≥ 2 preoperative opioid prescriptions (P = 0.037). CONCLUSIONS: Persistent opioid use was present in 23.7% of patients, with a new persistent use rate of 14.6%. Benzodiazepine use was less frequent than opioids, with a small number demonstrating new persistent use. Preoperative opioid and benzodiazepine use is associated with persistent opioid use postoperatively. Preoperative opioid and benzodiazepine use did not affect perioperative outcomes in our cohort.

Assessing trends in breast care surveillance metrics after implementing surgeon-specific tracking and performance reporting in a large, integrated cancer network.

BACKGROUND: There are few quality metrics and benchmarks specific to surgical oncology. Development of a surgeon-level performance metrics system based on peer comparisons is hypothesized to positively influence surgical decision-making. This study established a tracking and reporting system comprised of evidence and consensus-based metrics to assess breast care delivered by individual surgeons. METHODS: Surgeons' performance is assessed by a surveillance tracking system of metrics pertaining to referrals and surgical elements. This retrospective analysis of prospectively collected breast care data reports on recurring 6-month and cumulative data from nine care locations from 2015 to 2021. RESULTS: Breast care was provided to 6659 patients by 41 surgeons. A total of 27 breast care metrics were evaluated over 7 years. Metrics with consistent, proficient results were retired after 18 months, including the rate of core biopsy, specimen orientation, and referrals to medical oncology, genetics, and fertility, among others. In clinically node-negative, hormone receptor-positive patients 70 years of age or older, the cumulative rate of sentinel lymph node (SLN) biopsy significantly decreased by 40% over 5.5 years (p < .001). The overall breast conservation rate for T0-T2 cancer increased 10% over 7 years. At the surgeon level, improvements were made in the median number of SLNs removed and in operative note documentation. CONCLUSIONS: Implementation of a surgeon-specific, peer comparison-based metric and tracking system has yielded substantive changes in breast care management. This process and governance structure can serve as a model for quantification of breast care at other institutions and for other disease sites.

Impact of dedicated renal enhanced recovery after surgery (RERAS) program on postoperative opioid consumption and evaluation of surgeon-specific compliance to the program.

INTRODUCTION AND OBJECTIVE: Enhanced Recovery After Surgery (ERAS) protocols have been increasingly applied to urologic surgeries such as cystectomy and prostatectomy, though research defining protocols and outcomes for renal ERAS programs (RERAS) for nephrectomy remains limited. We aim to assess perioperative outcomes following implementation of our RERAS protocol modified from ERAS society cystectomy guidelines, as well as describe compliance with protocol guidelines. METHODS: We performed a retrospective cohort analysis of 400 patients who underwent partial or radical nephrectomy between October 2017 and August 2020. RERAS protocol was initiated September 30, 2018, and patients were categorized into pre- and post-RERAS implementation cohorts based on surgery date. Perioperative outcomes including complications, 30-day readmissions, length of stay, and opioid consumption were compared across pre- and post-RERAS cohorts. Protocol compliance was reported based on adherence to program recommendations. RESULTS: Among 400 patients included in analysis, the pre-RERAS cohort included 133 patients and the post-RERAS cohort included 267 patients. There were no differences in overall complications (P = 0.354) and 30-day readmissions (P = 0.078). Length of stay (P < 0.001) and postoperative opioid consumption (P < 0.001) were significantly reduced post-RERAS. We observed an increase in compliance with RERAS recommendations over time (P< 0.001). CONCLUSION: RERAS implementation was associated with decreased length of stay and opioid usage, underscoring the benefits of program adoption in an era of opioid dependence and strained hospital capacity. Successful initiation of a RERAS protocol requires intentional organization and buy in from all providers involved.

Phase II Study of Pembrolizumab in Combination with Doxorubicin in Metastatic and Unresectable Soft-Tissue Sarcoma.

PURPOSE: Doxorubicin is standard therapy for advanced soft-tissue sarcoma (STS) with minimal improvement in efficacy and increased toxicity with addition of other cytotoxic agents. Pembrolizumab monotherapy has demonstrated modest activity and tolerability in previous advanced STS studies. This study combined pembrolizumab with doxorubicin to assess safety and efficacy in frontline and relapsed settings of advanced STS. PATIENTS AND METHODS: This single-center, single-arm, phase II trial enrolled patients with unresectable or metastatic STS with no prior anthracycline therapy. Patients received pembrolizumab 200 mg i.v. and doxorubicin (60 mg/m2 cycle 1 with subsequent escalation to 75 mg/m2 as tolerated). The primary endpoint was safety. Secondary endpoints included overall survival (OS), objective response rate (ORR), and progression-free survival (PFS) based on RECIST v1.1 guidelines. RESULTS: Thirty patients were enrolled (53.3% female; median age 61.5 years; 87% previously untreated) with 4 (13.3%) patients continuing treatment. The study met its primary safety endpoint by prespecified Bayesian stopping rules. The majority of grade 3+ treatment-emergent adverse events were hematologic (36.7% 3+ neutropenia). ORR was 36.7% [95% confidence interval (CI), 19.9-56.1%], with documented disease control in 80.0% (95% CI, 61.4-92.3%) of patients. Ten (33.3%) patients achieved partial response, 1 (3.3%) patient achieved complete response, and 13 (43.3%) patients had stable disease. Median PFS and OS were 5.7 months (6-month PFS rate: 44%) and 17 months (12-month OS rate: 62%), respectively. Programmed cell death ligand-1 (PD-L1) expression was associated with improved ORR, but not OS or PFS. CONCLUSIONS: Combination pembrolizumab and doxorubicin has manageable toxicity and preliminary promising activity in treatment of patients with anthracycline-naive advanced STS.

Implementation of a Dedicated Enhanced Recovery after Surgery (ERAS) Program for Radical Cystectomy Patients is Associated With Decreased Postoperative Inpatient Opioid Usage and Pain Scores.

OBJECTIVE: To measure differences in post-operative opioid usage and pain scores between pre- and post-Enhanced Recovery after Surgery (ERAS) radical cystectomy (RC) patients in an effort to optimize outcomes. STUDY DESIGN: We performed a retrospective cohort study from a single institution from January 1, 2015 to July 31, 2018 among 86 and 108 pre- and post-ERAS RC patients. The primary endpoints were total mean opioid usage (morphine equivalent daily dosing or MEDD) and mean pain scores (Visual Analog Scale) on postoperative days (POD) 1-3. Secondary endpoints were number of opioid pills prescribed at discharge and within 30 days of discharge. Multivariable model selection was carried out with forward selection and backward elimination to identify variables associated with key outcomes. RESULTS: Total mean usage of opioids and mean pain scores were significantly lower in post-ERAS vs pre-ERAS patients across POD 1-3, respectively (32.90 MEDD vs 99.86 MEDD, P ≤ .001; 3.51 vs 4.17, P = .003). The median number of opioid pills prescribed at discharge was significantly lower in the post-ERAS group compared to pre-ERAS (30 pills vs 45 pills, P = .046) as well as the median number opioid pills prescribed within 30 days of discharge (40 pills vs 50 pills, P = .001). CONCLUSION: Our study suggests that a dedicated ERAS protocol following RC might be superior to traditional, non-ERAS methods in reducing postoperative opioid use and pain scores.

Necessity of Bony Fusion After Surgical Treatment of Metastatic Spine Tumors.

INTRODUCTION: The role of bony fusion in influencing patient outcome and surgical revision rates in the treatment of metastatic spine disease is poorly defined. The goals of this study were, therefore, to evaluate the effect of fusion on revision surgery as well as on overall survival (OS) and functional status in patients with metastatic disease of the spine. METHODS: A retrospective cohort study of a prospective database at a major cancer center was conducted. A total of 25 patients who met the inclusion criteria from January 2010 to December 2015 were included. Functional status, patient and tumor characteristics, fusion status, and survival were analyzed, and regression analyses were done. Bony fusion was classified as either present (seen across a minimum of three levels and crossing the tumor site) or absent as evidenced through CT images at minimum of 1-year postoperatively. RESULTS: Twenty-five subjects with 28 surgical sites met the eligibility criteria to be included in this study cohort. Five surgical sites were found to have evidence of fusion on CT scans at 1 year after surgery, and 23 sites had no evidence of bridging fusion. No differences were found between the two groups in terms of OS, and ambulatory status (P > 0.10). Multivariate analysis did not reveal any specific factors affecting fusion. Mean follow-up was 23.7 months. DISCUSSION: The lack of bony fusion is not an independent predictor of the need for revision surgery. The lack of bony fusion in patients with metastatic disease of the spine does not appear to negatively affect their OS or their ambulatory status. A discussion of factors affecting fusion is complex, and there are other factors that may also play a role. Large multicenter trials are needed to corroborate the preliminary findings seen in this complex patient cohort.

Ductal Carcinoma In Situ with Microinvasion on Core Biopsy: Evaluating Tumor Upstaging Rate, Lymph Node Metastasis Rate, and Associated Predictive Variables.

INTRODUCTION: The role of sentinel lymph node biopsy (SLNB) when ductal carcinoma in situ with microinvasion (DCISM) is identified on core biopsy is unclear. OBJECTIVE: Our aim was to assess the upstage rate to invasive cancer and axillary lymph node metastasis in patients diagnosed with DCISM, and whether predictive variables could be identified that may help inform who would most likely benefit from a surgical axillary evaluation. METHODS: We performed a retrospective review of 70 patients diagnosed with DCISM on core biopsy. Patients with concomitant or prior invasive cancer were excluded. Demographic, clinical, radiographic, histologic, and treatment data were collected. Fisher's exact test and univariable and multivariable logistic regression were performed to identify variables that may be associated with tumor upstaging and nodal metastasis. Time-to-event distributions were summarized using the Kaplan-Meier method. RESULTS: On final surgical pathology, 49 patients (70%) had a final diagnosis of DCISM or T1mi cancer, whereas 21 patients (30%) were upstaged to measurable invasive cancer (> 1 mm). One of 49 patients (2%) with DCISM on final pathology and 4 of 21 patients (19%) with measurable invasive cancer showed sentinel lymph node metastases. CONCLUSION: Although the upstage rate to measurable invasive cancer in our cohort of patients with DCISM on core biopsy was 30%, findings of a positive SLNB remain low at 7%. No predictive variables were identified to inform whether the routine practice of SLNB may be omitted in some patients with DCISM.

Discordance of high PD-L1 expression in primary and metastatic urothelial carcinoma lesions.

Immune checkpoint inhibitors (ICI) targeting PD-(L)1 are effective in select patients with advanced urothelial carcinoma (UC). High PD-L1 expression enriches for response to ICIs; however, the predictive value of PD-L1 expression is limited, which may be due in part to dynamic expression of PD-L1 in the tumor environment. We sought to characterize PD-L1 expression in primary UC and paired metastatic lesions to gain insight into the potential discordance of tumor PD-L1 expression during the metastatic process. MATERIALS AND METHODS: Immunohistochemical staining for PD-L1 using the SP-142 antibody was performed on primary tumors and matched metastatic specimens in 77 evaluable subjects with advanced UC. Immunohistochemical staining was scored for the percentage of cells positive (<5%, ≥5%) in tumor cell (TC) and immune cell (IC) compartments. Correlation of PD-L1 expression in TCs and ICs was estimated using Spearman's correlation coefficients (rho, ρ). Cohen's kappa statistics (κ) were utilized to assess the agreement in PD-L1 expression between groups. RESULTS: High (≥5%) PD-L1 expression in primary and metastatic biopsies, respectively, was observed in 6.0% and 7.7% of TCs and in 14.5% and 11.5% of ICs. IC PD-L1 expression in primary tumors was not correlated with IC PD-L1 expression in paired metastatic lesions (ρ = 0.05, P = 0.67) and there was poor agreement in high expression rates between primary and metastatic lesions in the IC compartment (κ= 0.086). CONCLUSION: High PD-L1 IC expression is temporally and spatially discordant between primary and metastatic UC lesions. Future studies of PD-(L)1 targeted therapies in patients with metastatic UC may benefit from use of fresh biopsies of metastatic lesions to define PD-L1 expression when feasible.

Survival Outcomes and Factors Associated with Revision Surgery for Metastatic Disease of the Spine.

STUDY DESIGN: Retrospective review of a prospective database. OBJECTIVE: Certain subset of patients undergoing surgical treatment for spinal metastasis will require a revision surgery in their disease course; however, factors predictive of revision surgery and survival outcomes are largely unknown. The goal of this study is to report on survival outcomes as well as factors predictive of revision surgery in this unique patient population. METHODS: A total of 55 patients who met the inclusion criteria were included from January 2010 to December 2015. Twelve (22%) of these patients underwent a revision surgery. Patient and tumor characteristics were summarized and survival outcomes were evaluated using Kaplan-Meier methods and Cox proportional hazards regression. RESULTS: Both the revision and the nonrevision groups were similarly matched with respect to spine disease burden, neurological status at time of initial presentation, primary malignancy types, and the use of adjuvant treatment modalities. Tumor progression (66.7%) was the most common reason for necessitating a revision followed by nonunion (16.7%), wound dehiscence (8.3%), and construct failure (8.3%). Following multivariate model selection procedures, smokers were found to have 3.5 times increased odds of undergoing revision compared to nonsmokers (p = 0.05). Analysis of survival curves showed that the median survival in the revision group was 3.0 years (95% CI: 1.5, 4.1), while the median survival in the nonrevision group was 1.5 years (95% CI: 1.1, 2.3; log-rank test, p = 0.105). CONCLUSION: Despite aggressive treatment, tumor progression is the most common reason for revision surgery. Smoking is an independent risk factor for revision. Revision surgery should be considered in patients when indicated as it does not appear to detrimentally affect survival.

Functional and survival outcomes in patients undergoing surgical treatment for metastatic disease of the spine.

BACKGROUND: Retrospective review of a prospective database. Spine metastasis has been shown to occur in 40% of cancer patients with an annual incidence of over 18,000 cases in North America alone. In this study, we sought to explore the functional and survival outcomes of patients undergoing surgical treatment for metastatic disease of the spine. METHODS: A retrospective cohort study of a prospective database at a major cancer center was conducted. A total of 55 patients who met the inclusion criteria from January 2010 to December 2015 were included. Functional status was assessed through patient's ambulatory status. Patient and tumor characteristics were analyzed and regression analyses were performed. RESULTS: Renal cell carcinoma (RCC) was the most common subtype encountered (27.3%). Excluding patients who had spinal metastasis at time of diagnosis, the median time to spinal metastasis from cancer diagnosis was 2.5 years. Median overall survival (OS) time was 1.8 years post diagnosis and 1.6 years post-surgical intervention. Age and tumor subtype were independent predictors of death (P<0.05). Post-surgical intervention, only 3.6% of patients were unable to ambulate-an improvement from 12.7% seen in the immediate preoperative period, P=0.0253. However, at the time of final follow-up, this number had risen to nearly 37%, P<0.0001. CONCLUSIONS: Spinal metastasis portends a debilitating prognosis. Ambulatory status is improved or maintained in the post-surgical period. However, long-term outlook remains dismal with median survival at only 1.8 years following diagnosis of spinal metastasis and ambulatory status declining precipitously at the time of final follow-up.

Application of ACOSOG Z1071: Effect of Results on Patient Care and Surgical Decision-Making.

BACKGROUND: The ACOSOG (American College of Surgeons Oncology Group) Z1071 assessed the feasibility of performing sentinel lymph node biopsy (SLNB) in node-positive patients who completed neoadjuvant chemotherapy (NACT). Historically, adoption of clinical research into practice takes years. The goal of this study was to determine the effect of Z1071 on our practice. MATERIALS AND METHODS: This is a retrospective review of Z1071's influence on a single institution's practice. Patients with biopsy-proven positive axillary lymph nodes before NACT were eligible for the study. After NACT, patients with nodal response according to imaging and exam were candidates for SLNB. Two cohorts were stratified according to diagnosis date before and after Z1071 results were presented on December 5, 2012 at the San Antonio Breast Cancer Symposium. Fisher exact tests and nonparametric rank tests were used to compare cohorts. RESULTS: The pre-Z1071 cohort included 74 patients and the post-Z1071 cohort 56 for a total of 130 patients. Post-Z1071, 73% (41/56) underwent a SLNB with an average of 4 nodes removed. Moreover, 27% (15/56) of patients had an axillary lymph node dissection as first intervention post-Z1071, compared with 99% (73/74) pre-Z1071. Axillary pathologic complete response pre-Z1071 was 35% (26/74) and post-Z1071 was 27% (15/56) (P = .35). CONCLUSION: This report shows that meaningful practice changes can be implemented rapidly. Changes in practice generated by clinical trial results should be monitored and outcomes followed.