Nationwide oncological networks for resection of colorectal liver metastases in the Netherlands: Differences and postoperative outcomes.

INTRODUCTION: Widespread differences in patient demographics and disease burden between hospitals for resection of colorectal liver metastases (CRLM) have been described. In the Netherlands, networks consisting of at least one tertiary referral centre and several regional hospitals have been established to optimize treatment and outcomes. The aim of this study was to assess variation in case-mix, and outcomes between these networks. METHODS: This was a population-based study including all patients who underwent CRLM resection in the Netherlands between 2014 and 2019. Variation in case-mix and outcomes between seven networks covering the whole country was evaluated. Differences in case-mix, expected 30-day major morbidity (Clavien-Dindo ≥3a) and 30-day mortality between networks were assessed. RESULTS: In total 5383 patients were included. Thirty-day major morbidity was 5.7% and 30-day mortality was 1.5%. Significant differences between networks were observed for Charlson Comorbidity Index, ASA 3+, previous liver resection, liver disease, preoperative MRI, preoperative chemotherapy, ≥3 CRLM, diameter of largest CRLM ≥55 mm, major resection, combined resection and ablation, rectal primary tumour, bilobar and extrahepatic disease. Uncorrected 30-day major morbidity ranged between 3.3% and 13.1% for hospitals, 30-day mortality ranged between 0.0% and 4.5%. Uncorrected 30-day major morbidity ranged between 4.4% and 6.0% for networks, 30-day mortality ranged between 0.0% and 2.5%. No negative outliers were observed after case-mix correction. CONCLUSION: Variation in case-mix and outcomes are considerably smaller on a network level as compared to a hospital level. Therefore, auditing is more meaningful at a network level and collaboration of hospitals within networks should be pursued.

Assessment of Textbook Outcome in Laparoscopic and Open Liver Surgery.

Importance: Textbook outcome (TO) is a composite measure that captures the most desirable surgical outcomes as a single indicator, yet to date TO has not been defined and assessed in the field of laparoscopic liver resection (LLR) and open liver resection (OLR). Objective: To obtain international agreement on the definition of TO in liver surgery (TOLS) and to assess the incidence of TO in LLR and OLR in a large international multicenter database using a propensity-score matched analysis. Design, Setting, and Participants: Patients undergoing LLR or OLR for all liver diseases between January 2011 and October 2019 were analyzed using a large international multicenter liver surgical database. An international survey was conducted among all members of the European-African Hepato-Pancreato-Biliary Association (E-AHPBA) and International Hepato-Pancreato-Biliary Association (IHPBA) to reach agreement on the definition of TOLS. The rate of TOLS was assessed for LLR and OLR before and after propensity-score matching. Factors associated with achieving TOLS were investigated. Main Outcomes and Measures: Textbook outcome, with TOLS defined as the absence of intraoperative incidents of grade 2 or higher, postoperative bile leak grade B or C, severe postoperative complications, readmission within 30 days after discharge, in-hospital mortality, and the presence of R0 resection margin. Results: A total of 8188 patients (4559 LLR; median age, 65 years [interquartile range, 55-73 years]; 2529 were male [55.8%] and 3629 OLR; median age, 64 years [interquartile range, 56-71 years]; 2204 were male [60.7%]) were included in the analysis of whom 69.1% achieved TOLS; 74.8% for LLR and 61.9% for OLR (P < .001). On multivariable analysis, American Society of Anesthesiologists grade III, previous abdominal surgery, histological diagnosis of colorectal liver metastases (odds ratio [OR], 0.656 [95% CI, 0.457-0.940]; P = .02), cholangiocarcinoma, non-CRLM, a tumor size of 30 mm or more, minor resection of posterior/superior segments (OR, 0.716 [95% CI, 0.577-0.887]; P = .002), anatomically major resection (OR, 0.579 [95% CI, 0.418-0.803]; P = .001), and nonanatomical resection (OR, 0.612 [95% CI, 0.476-0.788]; P < .001) were associated with a worse TOLS rate after LLR. For OLR, only histological diagnosis of cholangiocarcinoma (OR, 0.360 [95% CI, 0.214-0.607]; P < .001) and a tumor size of 30 mm or more (30-50 mm = OR, 0.718 [95% CI, 0.565-0.911]; P = .01; 50.1-100 mm = OR, 0.729 [95% CI, 0.554-0.960]; P = .02; >10 cm = OR, 0.550 [95% CI, 0.366-0.826]; P = .004) were associated with a worse TOLS rate. Conclusions and Relevance: In this multicenter study, TOLS was found to be a useful tool for assessing patient-level hospital performance and may have utility in optimizing patient outcomes after LLR and OLR.

Centralized repeated resectability assessment of patients with colorectal liver metastases during first-line treatment: prospective study.

BACKGROUND: Metastasectomy is probably underused in metastatic colorectal cancer. The aim of this study was to investigate the effect of centralized repeated assessment on resectability rate of liver metastases. METHODS: The prospective RAXO study was a nationwide study in Finland. Patients with treatable metastatic colorectal cancer at any site were eligible. This planned substudy included patients with baseline liver metastases between 2012 and 2018. Resectability was reassessed by the multidisciplinary team at Helsinki tertiary referral centre upfront and twice during first-line systemic therapy. Outcomes were resectability rates, management changes, and survival. RESULTS: Of 812 patients included, 301 (37.1 per cent) had liver-only metastases. Of these, tumours were categorized as upfront resectable in 161 (53.5 per cent), and became amenable to surgery during systemic treatment in 63 (20.9 per cent). Some 207 patients (68.7 per cent) eventually underwent liver resection or ablation. At baseline, a discrepancy in resectability between central and local judgement was noted for 102 patients (33.9 per cent). Median disease-free survival (DFS) after first resection was 20 months and overall survival (OS) 79 months. Median OS after diagnosis of metastatic colorectal cancer was 80, 32, and 21 months in R0-1 resection, R2/ablation, and non-resected groups, and 5-year OS rates were 68, 37, and 9 per cent, respectively. Liver and extrahepatic metastases were present in 511 patients. Of these, tumours in 72 patients (14.1 per cent) were categorized as upfront resectable, and 53 patients (10.4 per cent) became eligible for surgery. Eventually 110 patients (21.5 per cent) underwent liver resection or ablation. At baseline, a discrepancy between local and central resectability was noted for 116 patients (22.7 per cent). Median DFS from first resection was 7 months and median OS 55 months. Median OS after diagnosis of metastatic colorectal cancer was 79, 42, and 17 months in R0-1 resection, R2/ablation, and non-resected groups, with 5-year OS rates of 65, 39, and 2 per cent, respectively. CONCLUSION: Repeated centralized resectability assessment in patients with colorectal liver metastases improved resection and survival rates.

Prognostic assessment of resected colorectal liver metastases integrating pathological features, RAS mutation and Immunoscore.

Surgical resection of colorectal liver metastases combined with systemic treatment aims to maximize patient survival. However, recurrence rates are very high postsurgery. In order to assess patient prognosis after metastasis resection, we evaluated the main patho-molecular and immune parameters of all surgical specimens. Two hundred twenty-one patients who underwent, after different preoperative treatment, curative resection of 582 metastases were analyzed. Clinicopathological parameters, RAS tumor mutation, and the consensus Immunoscore (I) were assessed for all patients. Overall survival (OS) and time to relapse (TTR) were estimated using the Kaplan-Meier method and compared by log-rank tests. Cox proportional hazard models were used for uni- and multivariate analysis. Immunoscore and clinicopathological parameters (number of metastases, surgical margin, histopathological growth pattern, and steatohepatitis) were associated with relapse in multivariate analysis. Overall, pathological score (PS) that combines relevant clinicopathological factors for relapse, and I, were prognostic for TTR (2-year TTR rate PS 0-1: 49.8.% (95% CI: 42.2-58.8) versus PS 2-4: 20.9% (95% CI: 13.4-32.8), hazard ratio (HR) = 2.54 (95% CI: 1.82-3.53), p < 0.0000; and 2-year TTR rate I 0: 25.7% (95% CI: 16.3-40.5) versus I 3-4: 60% (95% CI: 47.2-76.3), HR = 2.87 (95% CI: 1.73-4.75), p = 0.0000). Immunoscore was also prognostic for OS (HR [I 3-4 versus I 0] = 4.25, 95% CI: 1.95-9.23; p = 0.0001). Immunoscore (HR [I 3-4 versus I 0] = 0.27, 95% CI: 0.12-0.58; p = 0.0009) and RAS mutation (HR [mutated versus WT] = 1.66, 95% CI: 1.06-2.58; p = 0.0265) were significant for OS. In conclusion, PS including relevant clinicopathological parameters and Immunoscore permit stratification of stage IV colorectal cancer patient prognosis in terms of TTR and identify patients with higher risk of recurrence. Immunoscore remains the major prognostic factor for OS.

Incidence and management of patients with colorectal cancer and synchronous and metachronous colorectal metastases: a population-based study.

BACKGROUND: This population-based study aimed to examine the incidence, patterns and results of multimodal management of metastatic colorectal cancer. METHODS: A retrospective population-based study was conducted on patients with metastatic colorectal cancer in Central Finland in 2000-2015. Clinical and histopathological data were retrieved and descriptive analysis was conducted to determine the pattern of metastatic disease, defined as synchronous, early metachronous (within 12 months of diagnosis of primary disease) and late metachronous (more than 12 months after diagnosis). Subgroups were compared for resection and overall survival (OS) rates. RESULTS: Of 1671 patients, 296 (17·7 per cent) had synchronous metastases, and 255 (19·6 per cent) of 1302 patients with resected stage I-III tumours developed metachronous metastases (94 early and 161 late metastases). Liver, pulmonary and intraperitoneal metastases were the most common sites. The commonest metastatic patterns were a combination of liver and lung metastases. The overall metastasectomy rate for patients with synchronous metastases was 16·2 per cent; in this subgroup, 3- and 5-year OS rates after any resection were 63 and 44 per cent respectively, compared with 7·1 and 3·3 per cent following no resection (P < 0·001). The resection rate was higher for late than for early metachronous disease (28·0 versus 17 per cent respectively; P = 0·048). Three- and 5-year OS rates after any resection of metachronous metastases were 78 and 62 per cent respectively versus 42·1 and 18·2 per cent with no metastasectomy (P < 0·001). Similarly, 3- and 5-year OS rates after any metastasectomy for early metachronous metastases were 57 and 50 per cent versus 84 and 66 per cent for late metachronous metastases (P = 0·293). CONCLUSION: The proportion of patients with metastatic colorectal cancer was consistent with that in earlier population-based studies, as were resection rates for liver and lung metastases and survival after resection. Differentiation between synchronous, early and late metachronous metastases can improve assessment of resectability and survival.

ANTECEDENTES: El objetivo de este estudio de base poblacional fue analizar la incidencia, la forma de presentación y los resultados del tratamiento multimodal del cáncer colorrectal metastásico (metastatic colorectal cancer, mCRC). MÉTODOS: Se realizó un estudio retrospectivo de base poblacional en pacientes con mCRC en la región central de Finlandia entre 2000 a 2015. Se recuperaron los datos clínicos e histopatológicos y se realizó un análisis descriptivo con el objetivo de analizar la forma de presentación de la enfermedad metastásica. La enfermedad metastásica se definió como sincrónica, metacrónica precoz (< 12 meses) y metacrónica tardía (> 12 meses después del diagnóstico de la enfermedad primaria) y se compararon las tasas de resección y de supervivencia global (overall survival, OS) en estos subgrupos. RESULTADOS: De los 1.671 pacientes revisados, 296 (17,7%) presentaron metástasis sincrónicas, mientras que de los 1.302 pacientes resecados en estadios I-III, 255 (19,6%) tuvieron metástasis metacrónicas: 94 precoces y 161 tardías. La localización metastásica más frecuente fue el hígado, los pulmones y el peritoneo. La combinación más frecuente fue la de metástasis hepáticas y pulmonares. La tasa de resección para pacientes con metástasis sincrónicas fue del 16,2%; en este subgrupo, la OS a 3 y 5 años después de cualquier tipo de resección fue del 62,6% y 44,2% versus 7,1% y 3,3% en los pacientes sin resección, respectivamente (P < 0,001). La tasa de resección fue mayor en la enfermedad metacrónica tardía que en la enfermedad metacrónica precoz (28% versus 17%, P = 0,048). Las tasas de OS a 3 y 5 años después de cualquier resección en los casos de metástasis metacrónicas fueron del 77,8% y 61,9% versus 42,1% y 18,2% en los pacientes sin metastasectomía, P < 0,001. Las tasas de OS a 3 y 5 años después de cualquier metastasectomía en los casos de metástasis metacrónicas precoces fueron del 57,4% y 50,3%, versus 84,3% y 65,6% en las tardías (P = 0,29) CONCLUSIÓN: La proporción de pacientes con mCRC fue similar a la de estudios anteriores de base poblacional, así como las tasas de resección para metástasis hepáticas y pulmonares y la supervivencia después de la resección. Diferenciar entre metástasis sincrónicas, metacrónicas precoces y tardías puede mejorar la posibilidad de resecabilidad y la supervivencia.

Comparison of Treatment, Cost, and Survival in Patients With Metastatic Colorectal Cancer in Western Washington, United States, and British Columbia, Canada.

PURPOSE: Few studies have directly compared health care utilization, costs, and outcomes between patients treated in the US multipayer health system and Canada's single-payer system. Using cancer registry and claims data, we assessed treatment types, costs, and survival for patients with metastatic colorectal cancer (mCRC) in Western Washington State (WW) and British Columbia (BC). MATERIALS AND METHODS: Patients age ≥ 18 years diagnosed with mCRC in 2010 and later were identified from the BC Cancer database and a regional database linking WW SEER to claims from Medicare and two large commercial insurers. Demographics, treatment characteristics, costs of systemic therapy, and survival data were obtained from these databases and compared between the two regions. RESULTS: A total of 1,592 patients from BC and 901 from WW were included in the study. Median age was similar (BC, 66 years; WW, 63 years), but patients in BC were more likely to be male (57.1% v 51.2%; P ≤ .01) and to have de novo metastatic disease (61.0% v 38.3%; P ≤ .01). The use of radiation therapy was similar between regions (BC, 31.2%; WW, 33.9%; P = .18), but primary tumor resection was more common in BC (74.1% v 66.3%; P ≤ .01) as was hepatic metastasectomy (12.4% v 2.3%; P ≤ .01). Similar percentages of patients received systemic therapy (BC, 68.8%; WW, 67.1%; P = .40), but costs were significantly higher for first-line systemic therapy in WW ($6,226 v $15,792 per patient per month; P ≤ .01). Median overall survival was similar (BC, 16.9 months; WW, 18 months). CONCLUSION: Cost of systemic therapy for mCRC was significantly higher for patients in WW than in BC, but this did not translate to a difference in overall survival.

Facilities that service economically advantaged neighborhoods perform surgical metastasectomy more often for patients with colorectal liver metastases.

BACKGROUND: Metastasectomy of isolated colorectal liver metastases (CRLM) requires significant clinical expertise and may not be readily available or offered. The authors hypothesized that hospitals that treat a greater percentage of patients from higher income catchment areas are more likely to perform metastasectomies regardless of patient or tumor characteristics. METHODS: Using the National Cancer Data Base, the authors classified facilities into facility income quartiles (FIQs) based on the percentage of patients from the wealthiest neighborhoods (by zip code). Quartile 1 included facilities with <2.1% of the patients residing within the highest income zip codes, quartile 2 included facilities with 2.2% to 15.6% of patients residing within the highest income zip codes, quartile 3 included facilities with 15.7% to 40.2% of patients residing within the highest income zip codes, and quartile 4 included facilities with 40.3% to 90.5% of patients residing within the highest income ZIP codes. Patient, tumor, and facility characteristics were analyzed using a multivariate logistic regression to identify associations between metastasectomy and FIQ. RESULTS: Patients with CRLM were more likely to undergo metastasectomy at facilities in the highest FIQ compared with the lowest FIQ (18% vs 11% in FIQ4; P = .001). This trend was not observed in the resection of primary tumors for nonmetastatic CRLM (rates of 95% vs 93%; P = .94). After adjusting for individual insurance status, distance traveled, zip code-level individual income, tumor, and host, patients who were treated at the highest FIQ facilities were found to be more likely to undergo metastasectomy (odds ratio, 1.29; 95% CI, 1.02-1.72 [P = .03]). CONCLUSIONS: Metastasectomy for CRLM is more likely to occur at facilities that serve a greater percentage of patients from high-income catchment areas, regardless of individual patient characteristics. This disparity uniquely affects those patients with advanced cancers for which specialized expertise for therapy is necessary.

Racial and Socioeconomic Disparities in Access and Utilization of Adrenal Metastasectomy.

BACKGROUND: There is substantial evidence that resecting adrenal metastases can be safely accomplished and extend overall survival in select patients. However, patient access to this operation has not been studied at the population level. The purpose of this study was to determine differences in utilization rates of adrenal metastasectomy (ADMX) across patient populations. METHODS: The Healthcare Utilization Project National Inpatient Sample was used to identify patients who had adrenal metastases (ADM) and who underwent ADMX from 2007 to 2011. Patients were identified by ICD-9-CM diagnosis and procedure codes. Predictor variables included sex, race, median household income, and primary insurance payer. Primary outcomes included receiving an ADMX and same hospitalization mortality. Secondary outcomes included length of stay, infection, cardiac, pulmonary, and renal complications. Univariable and multivariable logistic regression models were used to identify statistical associations. RESULTS: 32,331 ADM and 1070 ADMX patients identified in the database. Despite similar comorbidities, Black patients had 0.30 (95% CI 0.21-0.41) lower odds to receive an ADMX compared to White patients. Medicaid patients had 0.38 (0.28-0.52) less odds and Private Insurance patients 1.18 (1.00-1.39) more odds to receive an ADMX compared to Medicare patients. Women had a 1.39 (1.22-1.58) higher odds ratio of undergoing ADMX compared to men. Of the ADMX cohort, there was no difference in same hospitalization mortality or surgical complications. CONCLUSIONS: Black and Medicaid patients underwent fewer adrenal metastasectomies despite similar comorbidities and postoperative outcomes. This suggests a potential disparity in access to this treatment that disproportionately affects Black and low-income patients, and prompts further study, outreach attempts, as well as, research into improving access.

Surgery for metastases of renal cell carcinoma: outcome of treatments and preliminary assessment of Leuven-Udine prognostic groups in the targeted therapy era.

AIM: This study was conducted to evaluate the efficacy of surgical treatment for metastases accompanied by modern targeted therapies and to evaluate the performance of the Leuven-Udine (L.U.) prognostic groups model. METHODS: This retrospective analysis included 97 consecutive patients with metastatic renal cell carcinoma (mR.C.C.) who underwent surgery for metastases at Helsinki University Hospital between 2006 and 2017. The endpoints were overall survival (O.S.), cancer-specific survival (C.S.S.), recurrence-free survival (R.F.S.) and interval from diagnosis to oncological treatment. RESULTS: The median follow-up time was 46 months (interquartile range, I.Q.R. = 24-74). The estimated median O.S. was 67 months (I.Q.R. = 30-130). A radical surgical result at metastasectomy was achieved in 46 of 97 patients (47%). Of those 46 patients, 28 (61%) experienced recurrence after complete metastasectomy. Median R.F.S. after complete metastasectomy was 10 months (I.Q.R. = 3-37). Five-year O.S. was 59% for patients with complete metastasectomy and 44% for patients with non-complete metastasectomy (p = .035). The median interval from diagnosis to the initiation of targeted oncological treatment was 19 months for patients with non-complete metastasectomy and has hitherto not been reached for patients with complete metastasectomy (p = .006). A statistically significant validation of the prognostic value of the L.U. prognostic groups for predicting C.S.S. was not obtained (p = .420). CONCLUSIONS: Metastasectomy is an option for selected patients with mR.C.C. Complete resection should be attempted when feasible. The data failed to support the prognostic significance of the L.U. model in patients with mR.C.C.

Complications After Metastasectomy for Renal Cell Carcinoma-A Population-based Assessment.

Metastasectomy has long been considered a valid treatment option for patients with oligometastatic renal cell carcinoma (oligo-mRCC). However, the literature on complications in this setting is scarce. Our objective was to describe in-hospital complications after metastasectomy in a contemporary cohort of patients with mRCC. Using the National Inpatient Sample database (2000-2011), 45 279 mRCC patients were identified. Of those, 1102 underwent metastasectomies. The metastatic sites were the lungs, bone, liver, lymph nodes, adrenal glands, and brain in, respectively, 52%, 29%, 19%, 14%, 11%, and 3.4% of patients. The overall complication rate was 45.7%. Major complications (Clavien III-V) constituted 27.5%. Resections of hepatic lesions were significantly associated with higher odds of overall complications compared with any other site (odds ratio 2.59, 95% confidence interval 1.84-3.62, p<0.001). While metastasectomy remains a potential treatment option in RCC with oligometastatic disease, the associated complication rates are non-negligible; therefore, careful patient selection is warranted. PATIENT SUMMARY: We studied outcomes of patients with metastatic kidney cancer treated with metastasectomy. While metastasectomy is a treatment option for metastatic renal cell carcinoma, complications are not insignificant and our results may guide preoperative counseling.

Parenchymal-sparing Hepatectomy as the New Doctrine in the Treatment of Liver-metastatic Colorectal Disease: Beyond Oncological Outcomes.

Colorectal cancer is one of the leading causes of mortality in the Western world. Half of patients with colorectal cancer will develop liver-metastatic (CLM) disease, with fewer than 30% having surgically resectable disease at diagnosis. It is well established in the literature that major hepatectomy offers a high rate of R0 resection, however, with concommitant increased rates of mortality and morbidity. Emerging literature during the past two decades has demonstrated the potential superiority of parenchymal-sparing hepatectomy (PSH) in treating CLM disease in terms of oncological outcomes, survival and re-operation in cases of recurrence (salvageability). To date, no data regarding the evaluation of quality of life and cost after PSH have been published. PSH seems to be correlated with less mortality and morbidity, which can be translated in lower re-admission rates, better quality of life and, therefore, reduced relevant cost. Prospective studies and clinical trials evaluating the multiple beneficial role of a PSH surgical strategy in CLM disease are mandatory to support or reject the emerging belief that PSH could be the gold standard of treatment of CLM disease.

Preoperative evaluation of pancreatic ductal adenocarcinoma with synchronous liver metastasis: Diagnosis and assessment of unresectability.

AIM: To identify predictors for synchronous liver metastasis from resectable pancreatic ductal adenocarcinoma (PDAC) and assess unresectability of synchronous liver metastasis. METHODS: Retrospective records of PDAC patients with synchronous liver metastasis who underwent simultaneous resections of primary PDAC and synchronous liver metastasis, or palliative surgical bypass, were collected from 2007 to 2015. A series of pre-operative clinical parameters, including tumor markers and inflammation-based indices, were analyzed by logistic regression to figure out predictive factors and assess unresectability of synchronous liver metastasis. Cox regression was used to identify prognostic factors in liver-metastasized PDAC patients after surgery, with intention to validate their conformance to the indications of simultaneous resections and palliative surgical bypass. Survival of patients from different groups were analyzed by the Kaplan-Meier method. Intra- and post-operative courses were compared, including complications. PDAC patients with no distant metastases who underwent curative resection served as the control group. RESULTS: CA125 > 38 U/mL (OR = 12.397, 95%CI: 5.468-28.105, P < 0.001) and diabetes mellitus (OR = 3.343, 95%CI: 1.539-7.262, P = 0.002) independently predicted synchronous liver metastasis from resectable PDAC. CA125 > 62 U/mL (OR = 5.181, 95%CI: 1.612-16.665, P = 0.006) and age > 62 years (OR = 3.921, 95%CI: 1.217-12.632, P = 0.022) correlated with unresectability of synchronous liver metastasis, both of which also indicated a worse long-term outcome of liver-metastasized PDAC patients after surgery. After the simultaneous resections, patients with post-operatively elevated serum CA125 levels had shorter survival than those with post-operatively reduced serum CA125 levels (7.7 mo vs 16.3 mo, P = 0.013). The survival of liver-metastasized PDAC patients who underwent the simultaneous resections was similar to that of non-metastasized PDAC patients who underwent curative pancreatectomy alone (7.0 mo vs 16.9 mo, P < 0.001), with no higher rates of either pancreatic fistula (P = 0.072) or other complications (P = 0.230) and no greater impacts on length of hospital stay (P = 0.602) or post-operative diabetic control (P = 0.479). CONCLUSION: The criterion set up by CA125 levels could facilitate careful diagnosis of synchronous liver metastases from PDAC, and prudent selection of appropriate patients for the simultaneous resections.

Clinical outcomes for patients with liver-limited metastatic colorectal cancer: Arguing the case for specialist hepatobiliary multidisciplinary assessment.

In patients with liver-limited metastatic colorectal cancer, hepatic resection can offer a significant survival benefit over systemic therapy alone. Specialist hepatobiliary multidisciplinary meetings are currently believed to provide the best forum to discuss the management for these patients. A retrospective analysis was undertaken of patients diagnosed with liver-limited metastatic colorectal cancer over 6 months within a cancer network in the United Kingdom. In addition, patients who were diagnosed but not referred to the hepatobiliary meeting were discussed within a virtual multi-disciplinary setting. Contributors were blinded and proposed management recorded. 159 newly diagnosed patients with liver-limited metastatic colorectal cancer were identified. 68 (43%) were referred at initial diagnosis and 38 (24%) referred following systemic treatment. 35 (51%) who were discussed at baseline underwent a subsequent hepatectomy or radiofrequency ablation, as did 18 (47%) patients referred after chemotherapy. Of the remaining 53 (33%) patients not referred, imaging was available for 31 (58%). Decisions regarding potential liver-directed therapy were discussed within a multi-disciplinary setting. 13 (42%) were identified as resectable or potentially resectable and 11 (36%) may have been suitable for a clinical trial. In reality, none of these 31 patients (100%) underwent surgery or ablation. Whilst the majority of patients with liver-limited metastatic colorectal cancer were referred appropriately, this study demonstrates that a significant number with potentially resectable disease are not being discussed at specialist meetings. A review of all diagnosed cases would ensure that an increased number of patients are offered hepatic resection or ablation.

Open versus laparoscopic liver resection for colorectal liver metastases (the Oslo-CoMet Study): study protocol for a randomized controlled trial.

BACKGROUND: Laparoscopic liver resection is used in specialized centers all over the world. However, laparoscopic liver resection has never been compared with open liver resection in a prospective, randomized trial. METHODS/DESIGN: The Oslo-CoMet Study is a randomized trial into laparoscopic versus open liver resection for the surgical management of hepatic colorectal metastases. The primary outcome is 30-day perioperative morbidity. Secondary outcomes include 5-year survival (overall, disease-free and recurrence-free), resection margins, recurrence pattern, postoperative pain, health-related quality of life, and evaluation of the inflammatory response. A cost-utility analysis of replacing open surgery with laparoscopic surgery will also be performed. The study includes all resections for colorectal liver metastases, except formal hemihepatectomies, resections where reconstruction of vessels/bile ducts is necessary and resections that need to be combined with ablation. All patients will participate in an enhanced recovery after surgery program. A biobank of liver and tumor tissue will be established and molecular analysis will be performed. DISCUSSION: After 35 months of recruitment, 200 patients have been included in the trial. Molecular and immunology data are being analyzed. Results for primary and secondary outcome measures will be presented following the conclusion of the study (late 2015). The Oslo-CoMet Study will provide the first level 1 evidence on the benefits of laparoscopic liver resection for colorectal liver metastases. TRIAL REGISTRATION: The trial was registered in ClinicalTrals.gov (NCT01516710) on 19 January 2012.

Cost-utility analysis of operative versus non-operative treatment for colorectal liver metastases.

BACKGROUND: Surgical resection of colorectal liver metastases (CRLMs) is the standard of care when possible, although this strategy has not been compared with non-operative interventions in controlled trials. Although survival outcomes are clear, the cost-effectiveness of surgery is not. This study aimed to estimate the cost-effectiveness of resection for CRLMs compared with non-operative treatment (palliative care including chemotherapy). METHODS: Operative and non-operative cohorts were identified from a prospectively maintained database. Patients in the operative cohort had a minimum of 10 years of follow-up. A model-based cost-utility analysis was conducted to quantify the mean cost and quality-adjusted life-years (QALYs) over a lifetime time horizon. The analysis was conducted from a healthcare provider perspective (UK National Health Service) in a secondary care (hospital) setting. RESULTS: Median survival was 41 and 21 months in the operative and non-operative cohorts respectively (P < 0·001). The operative strategy dominated non-operative treatments, being less costly (€22,200 versus €32,800) and more effective (4·017 versus 1·111 QALYs gained). The results of extensive sensitivity analysis showed that the operative strategy dominated non-operative treatment in every scenario. CONCLUSION: Operative treatment of CRLMs yields greater survival than non-operative treatment, and is both more effective and less costly.

Percutaneous cryoablation of metastatic lesions from non-small-cell lung carcinoma: initial survival, local control, and cost observations.

PURPOSE: To assess feasibility, complications, local tumor recurrences, overall survival (OS), and estimates of cost effectiveness for multisite cryoablation (MCA) of oligometastatic non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: A total of 49 computed tomography- and/or ultrasound-guided percutaneous MCA procedures were performed on 60 tumors in 31 patients (19 women and 12 men) with oligometastatic NSCLC. Average patient age was 65 years. Tumor location was grouped according to common metastatic sites. Median OS was determined by Kaplan-Meier method and defined life-years gained (LYGs). Estimates of MCA costs per LYG were compared with established values for systemic therapies. RESULTS: Total numbers of tumors and cryoablation procedures for each anatomic site were as follows: lung, 20 and 18; liver, nine and seven; superficial, 12 and 11; adrenal, seven and seven; paraaortic/isolated, two and two; and bone, 10 and seven. A mean of 1.6 procedures per patient were performed, with a median clinical follow-up of 11 months. Major complication and local recurrence rates were 8% (four of 49) and 8% (five of 60), respectively. Median OS for MCA was 1.33 years, with an estimated 1-year survival rate of approximately 53%. MCA appeared cost-effective even when added to the cost of best supportive care or systemic regimens, with an adjunctive cost-effectiveness ratio of $49,008-$87,074. CONCLUSIONS: MCA was associated with very low morbidity and local tumor recurrence rates for all anatomic sites, and possibly increased OS. Even as an adjunct to systemic therapies, MCA appeared cost-effective for palliation of oligometastatic NSCLC.

Percutaneous cryoablation of metastatic renal cell carcinoma for local tumor control: feasibility, outcomes, and estimated cost-effectiveness for palliation.

PURPOSE: To assess complications, local tumor recurrences, overall survival (OS), and estimates of cost-effectiveness for multisite cryoablation (MCA) of oligometastatic renal cell carcinoma (RCC). MATERIALS AND METHODS: A total of 60 computed tomography- and/or ultrasound-guided percutaneous MCA procedures were performed on 72 tumors in 27 patients (three women and 24 men). Average patient age was 63 years. Tumor location was grouped according to common metastatic sites. Established surgical selection criteria graded patient status. Median OS was determined by Kaplan-Meier method and defined life-years gained (LYGs). Estimates of MCA costs per LYG were compared with established values for systemic therapies. RESULTS: Total number of tumors and cryoablation procedures for each anatomic site are as follows: nephrectomy bed, 11 and 11; adrenal gland, nine and eight; paraaortic, seven and six; lung, 14 and 13; bone, 13 and 13; superficial, 12 and nine; intraperitoneal, five and three; and liver, one and one. A mean of 2.2 procedures per patient were performed, with a median clinical follow-up of 16 months. Major complication and local recurrence rates were 2% (one of 60) and 3% (two of 72), respectively. No patients were graded as having good surgical risk, but median OS was 2.69 years, with an estimated 5-year survival rate of 27%. Cryoablation remained cost-effective with or without the presence of systemic therapies according to historical cost comparisons, with an adjunctive cost-effectiveness ratio of $28,312-$59,554 per LYG. CONCLUSIONS: MCA was associated with very low morbidity and local tumor recurrence rates for all anatomic sites, with apparent increased OS. Even as an adjunct to systemic therapies, MCA appeared cost-effective for palliation of oligometastatic RCC.