Methods for better identifying malignant versus benign disease before nephrectomy could provide significant benefits to patients and payers.
Limitations of current diagnotic techniques may allow some patients with presumed renal cell carcinoma (RCC) to undergo nephrectomy without definitive confirmation of malignancy.
To confirm previous estimates of postnephrectomy renal mass diagnosis and to assess the economic impact of nephrectomy.
This retrospective cohort analysis identified commercial enrollees who underwent nephrectomy with a diagnosis of RCC between July 1, 2000, and March 30, 2008. Study subjects were stratified based on medical claims for benign or malignant disease after the nephrectomy date. Cohorts were compared on resource utilization before and after nephrectomy, occurrence of postsurgical complications, and associated 1-year costs of care.
Of 10,404 patients undergoing nephrectomy for presumed RCC, 1613 (15.5%) were subsequently identified as having benign disease, despite median presurgical diagnostic expenditures of $1311 per patient (interquartile range [IQR], $467-$2606). Median expenditures for the 12 months postnephrectomy were $26,920 per patient (IQR, $16,851-$46,982) for those with malignant disease and $23,951 per patient (IQR, $14,873-$38,190) for those with benign disease (P <.0001). For patients with benign disease, 17.5% experienced a postsurgical adverse event, resulting in a 1.5-fold increase in expenditures (median $31,838 per patient for those with event vs $22,770 per patient for those without event; P <.0001).
In this study, approximately 1 in 6 patients were found to have a benign renal mass postnephrectomy. Given the risk of surgical complications and related economic consequences, methods for better identifying malignant versus benign disease prior to surgery could provide significant benefits to patients and payers.
Am J Manag Care. 2013;19(8):617-624This analysis of insured Americans suggests that 1 in 6 patients who undergo nephrectomy for suspected renal cell carcinoma are subsequently found to have benign disease.
Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancies and more than 80% of kidney cancers, causing approximately 13,000 deaths in the United States each year.1-3 It is typically characterized by a lack of early warning signs, diverse clinical manifestations, and tumor resistance to radiation and traditional chemotherapy.
The increasingly prevalent use of cross-sectional imaging for nonspecific abdominal complaints has resulted in the earlier diagnosis of RCC and a preponderance of small asymptomatic lesions. Thus, the continual rise in RCC incidence is attributed largely to enhanced detection, with more than 70% of kidney cancers now being discovered incidentally and at a size less than 7 cm.4-8 Nephron-sparing surgery is gaining acceptance as the treatment of choice for these smaller tumors, while radical nephrectomy remains the standard for larger tumors not amenable to partial nephrectomy.
Differentiating between benign and malignant renal tumors through current radiographic or clinical methods remains a challenge. While renal biopsy for molecular analysis of tissues might provide additional information in this setting, it yields nondiagnostic information in up to 20% of cases and is often available only at academic centers.9
Importantly, previous research suggests that approximately 20% of patients who undergo nephrectomy are found to have benign postoperative tumor histology, implying the possibility of surgical overtreatment.10-15 Based on current estimates of 58,000 patients with new RCC diagnoses in the United States each year, the vast majority of whom will undergo nephrectomy prior to a definitive tissue confirmation of cancer, it is conceivable that the American healthcare system is resourcing upward of 10,000 potentially avoidable nephrectomies each year.16
The objectives of this analysis were to confirm previous estimates of postnephrectomy renal mass diagnosis and to assess the economic impact of nephrectomy, both in terms of surgical costs and resource utilization related to postoperative complications, in a large population of commercially insured Americans.
MATERIALS AND METHODS
Data were obtained from the IMS LifeLink Database, which at the time of the study was composed of medical and pharmaceutical claims for approximately 60 million unique patients from 100 health plans, including health maintenance organizations (HMOs), preferred provider organizations (PPOs), point-of-service (POS) plans, indemnity plans, and other types, located throughout the United States. The database includes both inpatient and outpatient diagnoses (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] codes) and procedures (Current Procedural Terminology, Version 4 [CPT-4] and Healthcare Common Procedure Coding System codes), as well as both standard and mail order pharmacy records. Data elements include demographic variables (age, sex, geographic region), health plan type (eg, HMO, PPO, POS), payer type (eg, commercial, self-pay), provider specialty, reimbursed amount for service, date of service, and start and stop dates for plan enrollment.
Because all pertinent patient information in the database is encrypted and de-identified, and no patient contact was involved, no informed consent or approval by an institutional review board was required or sought. The data source was fully Health Insurance Portability and Accountability compliant.
Patients were eligible for analysis if they had at least 2 medical claims for RCC (defined as ICD-9-CM codes 189.0, 189.1, 198.0, 236.91) during the July 1, 2000, through March 30, 2008, database extraction period. Patients were further required to have a claim for nephrectomy (CPT-4 codes 50220, 50225, 50230, 50234, 50236, 50240, 50543, 50545, 50546, 50547, 50548) during the study period to be included in the analysis (note that the nephrectomy claim could coincide with 1 of the 2 required RCC diagnoses). A minimum of 2 ICD-9-CM RCC diagnoses were required to ensure all patients included in the study presented with a high preoperative clinical suspicion of presumed renal malignancy.
The date of the nephrectomy claim during that period was assigned as the index date. From that date, 6 months of preindex and up to 12 months of postindex data were collected for all health plan—eligible patients. Patients had to have continuous health plan enrollment for 6 months before and at least 6 months after the index date to ensure complete baseline and follow-up information on all patients in the study.
Two mutually exclusive study groups were identified based on medical claims. Patients were categorized as ultimately having either benign disease or malignant disease following the nephrectomy. Benign disease was defined as any patient having a medical claim with a benign diagnosis (ICD-9-CM codes benign neoplasm, kidney, except pelvis [223.0], renal pelvis [223.1]) subsequent to the index date (nephrectomy).To be conservative regarding the prevalence of benign disease postnephrectomy, all other patients (ie, those with a minimum of 2 medical claims for a diagnosis of RCC, but with no benign diagnosis subsequent to the nephrectomy) were considered to have malignant disease.
The postnephrectomy benign and malignant cohorts were compared with respect to patient demographics (age, sex, region of the United States where surgery was performed), surgery type (nephron sparing vs radical nephrectomy), and comorbid conditions (using Charlson Comorbidity Index score, individual comorbidities contributing to the score).17,18 In addition, rates of nephrectomy-related adverse events were calculated for each cohort: hemorrhage (ICD-9-CM 998.1x), deep vein thrombosis (ICD-9-CM 453.40, 453.41, 453.42), pulmonary embolism (ICD-9-CM 415.11, 415.12, 415.19), myocardial infarction (ICD-9-CM 410.x), surgical woundinfection or disruption (ICD-9-CM 686.9, 998.31, 998.32), renal or perinephric abscess (ICD-9-CM 590.2), sepsis (ICD-9-CM 038.0, 038.1, 038.2, 038.3, 038.4, 038.8), acute renal failure (ICD-9-CM 584.xx, 586.xx), and pneumothorax (ICD-9-CM 512.0, 512.1, 512.8) were all considered to be acute adverse events and were measured during the first 30 days after surgery.
Chronic kidney disease (ICD-9-CM 584.xx, 585.xx, 586. xx), dialysis (CPT-4 90935, 90937, 90945, 90947, 90968, 90969, 90970), and renal transplantation (CPT-4 50300, 50320, 50323, 50325, 50327, 50328, 50329, 50340, 50360, 50365, 50370, 50380) were considered to be long-term adverse events and were measured from 30 days after surgery up to 12 months following the date of the nephrectomy.
Finally, resource utilization prior to and following the nephrectomy was assessed and summarized for the 2 cohorts. In the period prior to nephrectomy, cost estimates were specific for the use of diagnostic procedures, including angiography (CPT-4 72191, 72198, 74175, 74185), renal biopsy (CPT-4 50200, 50205, 50555, 52354), computed tomography (CT) scan (CPT-4 72192, 72193, 72194, 74150, 74160, 74170), magnetic resonance imaging scan (CPT-4 72195, 72196, 72197, 74181, 74182, 74183), positron-emission tomography scan (CPT-4 78814, 78815, 78816), or ultrasound (CPT-4 76700, 76705, 76770, 76775, 93975). Following the nephrectomy, total medical expenditures were calculated and stratified based on the presence or absence of the adverse events listed above. Cost estimates during the postnephrectomy study period were represented as the total amount of payments made by third-party payers for inpatient, outpatient, pharmacy, and other medical claims.
Comparisons of categorical variables were conducted using the x2 test, while continuous variables were assessed using univariate analysis of variance, with an a priori level of significance of P = .05. To account for the comparisons across multiple cohorts, a Bonferroni’s adjustment (0.05 per 6 contracts = 0.008) was performed. All analyses were performed using SAS version 9.2 (SAS Institute Inc, Cary, North Carolina).
As shown in , a total of 10,404 eligible patients were identified during the study period with at least 2 medical claims consistent with an RCC diagnosis and a medical claim for a nephrectomy. All patients were tracked for 6 months prenephrectomy and followed a minimum of 6 months postnephrectomy, with a median follow-up of 12 months (interquartile range [IQR], 12-12 months).
Demographic information for the included patients is presented in and . A total of 1613 patients, or 15.5% of the sample, had medical claims indicative of benign disease subsequent to their nephrectomy date. These patients were more often female (48.4% vs 37.4%; P <.01), were less likely to undergo radical nephrectomy (63.3% vs 78.5%; P <.01), and had fewer comorbid conditions as evidenced by the mean Charlson Comorbidity Index scores (2.4 [standard deviation 2.5]) vs 3.0 [standard deviation 2.8]; P <.01), than patients with a retained malignant diagnosis. Duration of postnephrectomy follow-up was identical between the benign and malignant cohorts.
During the study period, median medical expenditures for diagnostic procedures performed prior to the nephrectomy (preindex date) were $1311 (IQR, $467-$2606) per patient. This cost was driven primarily by use of preoperative imaging procedures such as CT scans, with more than 90% of study patients having at least 1 CT scan, and 3689 (35.5% overall, 36.9% in benign cohort, 35.2% in malignant cohort) having 2 or more CT procedures during the preindex study period. Use of diagnostic tests () and associated expenditures () were similar across the benign and malignant cohorts. Biopsy was performed in fewer than 10% of all patients (4% in benign cohort, 10% in malignant). In contrast to preindex resource utilization, median expenditures incurred from date of admission to discharge and deemed related directly to the nephrectomy procedure were $17,793 (IQR, $10,068-$24,718) per patient, with the median length of inpatient hospital stay being 5 days (IQR, 4-7 days).
Approximately 17% of patients experienced at least 1 surgical complication within 30 days of the nephrectomy (). The most common acute events were acute renal failure (6.5% and 7.9% of patients with benign and malignant disease, respectively; P = .05), pneumothorax (3.8% and 3.4% of patients with benign and malignant disease, respectively; P = .43), and hemorrhage (2.6% and 2.9% of patients with benign and malignant disease, respectively; P = .48). Longterm effects (those documented between 30 days and up to 12 months postnephrectomy) were less common, occurring in approximately 4% of patients overall. New diagnosis of chronic kidney disease accounted for the majority of cases (2.4% and 3.3% of patients with benign and malignant disease,respectively; P = .06), followed by dialysis (1.4% and 2.7% of patients with benign and malignant disease, respectively;P <.01).
Medical expenditures for the 1-year period following nephrectomy are presented in Figure 5. Overall, the median medical expenditure per patient was $23,951 (IQR, $14,873- $38,190) for patients with a benign diagnosis and $26,920 (IQR, $16,851-$46,982) for those with a retained malignant postsurgical diagnosis (P <.0001). However, within both cohorts, expenditures varied significantly depending on the presence or absence of nephrectomy-related complications. For example, the occurrence of an adverse event in patients with benign disease was associated with a 1.5-fold increase in healthcare expenditures. Patients with no complications incurred median costs of $22,770 per patient (IQR, $14,611-$34,688) in 12-month postnephrectomy healthcare expenditures, whereas those with an adverse event had resource expenditures of $31,838 per patient (IQR, $18,166-$61,289; P <.0001). Similarly, patients with a malignant postsurgical diagnosis with no complications incurred median costs of $25,088 (IQR,$16,124-$40,731), whereas those patients with an adverse event sustained 12-month postnephrectomy median resource expenditures of $41,410 (IQR, $22,134-$83,555; P <.0001).
Approximately 1 in 6 patients who underwent nephrectomy for suspected renal cancer subsequently had medical claims indicative of benign disease. The median per patient cost of medical care, inclusive of and within 12 months of surgery, was $26,405 for the overall study population. It was $26,920 for those defined as having RCC and $23,951 for those with benign disease. The cost varied significantly across the cohorts depending on the occurrence of surgeryrelated adverse events. While administrative claims data didnot allow for confirmation of the diagnosis nor the necessity for the original nephrectomy, these results reveal that a substantial number of patients might have been spared the inherent morbidity and cost of surgery and postoperative care had better preoperative characterization of their tumor been available.
More than 90% of patients underwent at least 1 diagnostic procedure, with the majority receiving a CT scan prior to nephrectomy. Little difference in preoperative testing use was documented across the benign and malignant cohorts. The median per patient cost of preoperative diagnostic procedures for the total study population was $1311 (benign $1370 vs malignant $1299). Furthermore, we found that approximately one-third of patients underwent 2 or more CT scans in the preoperative period, suggesting redundant and possibly inefficient use of diagnostic imaging. Given that as having a benign renal tumor, our results corroborate others indicating that current imaging procedures may not be consistently capable of reliably distinguishing between benign and malignant renal masses.9-15 Importantly, all patients included in the current study were required to have at least 2 separate ICD-9-CM diagnoses of RCC, indicating a high degree of preoperative clinical suspicion for renal malignancy to ensure a conservative estimate of imaging misdiagnosis. Thus, although not captured in this analysis, it is feasible that a proportion of patients with benign renal masses mayaccurately be distinguished as such using current imaging techniques.
A recent analysis of the Surveillance, Epidemiology and End Results—Medicare (SEER-Medicare) database reported that 37% of patients treated surgically for RCC experienced a postoperative complication during hospitalization or within 30 days following surgery.19 While this finding is substantially higher than the 17% acute complication rate identified in our study, their population was older and presumably had more comorbidities. It only included those 65 years or older with documented kidney cancer. Furthermore, their catalogue of measured complications was somewhat broader (including, for example, Patient Safety Indicators, Version 4.2, which are generalizable to all surgical procedures20). Nonetheless, this SEER-Medicare analysis corroborates our assertion that a significant proportion of patients undergoing nephrectomy experience postoperative complications that, in turn, increase healthcare resource utilization and underscore the importance of accurately discerning, a priori, the malignant potential of a newly detected renal mass.
Current treatment options for the small renal mass include radical nephrectomy, partial nephrectomy, local ablative therapy, or active surveillance, and management decisions are individualized based on physician and patient assessment of risk versus benefit.9 The present study quantifies the cost of extirpative care, but does not address resource utilization associated with nonoperative surveillance. A search of the literature failed to identify any prospective, retrospective, or case-control analysis estimating the true cost associated with active surveillance of small renal masses; however, Heilbrun and colleagues report the findings of a Markov state transition model evaluating the cost-effectiveness of immediate treatment, percutaneous biopsy, and active surveillance in a hypothetical cohort of 60-year-old men with incidentally detected small renal masses.21 Using the assumption of a 15% annualized rate of transition to treatment for the active surveillance strategy to account for growth seen on serial imaging and patient preference, the authors calculated a lifetime attributable cost of $33,015, $49,500, and $51,357 for active surveillance, percutaneous biopsy, and immediate treatment, respectively. While each of these estimates exceed the $26,405 median per patient cost of medical care during our study period, they suggest that active surveillance may be cost-effective on a relative basis for appropriately selected individuals, particularlywhen the preoperative index of suspicion for renal malignancy may be reduced with improvements in noninvasive tumor characterization.
Utilizing a geographically diverse and broadly representative health plan claims database, we sought to measure postnephrectomy outcomes in patients preoperatively diagnosedwith RCC and to quantify the associated costs of medical care. Although such analyses provide a unique opportunity to view actual practice patterns and assess the economic impacts of treatment in samples larger than can be obtained in a clinic setting, there are significant limitations that must be considered in interpretation of the findings. Attribution of causality to outcomes may be confounded by imperfect or imprecise data collection. Specifically, it is possible that underlying but nonmeasurable factors explained why certain patients underwent nephrectomy in the face of an inconclusive preoperative diagnosis. For example, nephrectomy might have been necessary for a symptomatic benign renal mass, or in situations of impending kidney dysfunction related to tumor location, size, or growth rate. The absence of source data verification precluded recognition and exclusion of such clinical cases, and did not allow for a measure of claim accuracy or reliability. Claims analyses can also suffer from miscoding of information, missing data, and consequent biases in estimation of effect. However, our estimate of the prevalence of benign disease subsequent to nephrectomy is in line with previous studies that utilized different techniques, suggesting that these results are robust.22,23
In this analysis of commercially insured patients in the United States, approximately 1 in 6 who underwent a nephrectomy for suspected RCC were subsequently identified as having benign disease. The economic impacts of this finding are substantial, representing approximately $26,500 per patient overall; for patients who experience complications after surgery, expenditures may exceed $40,000 in the year following surgery. These monetary figures cannot capture the effect that surgical overtreatment may have on patient health—related quality of life, and more research is warranted to fully appreciate the impact of preoperative diagnostic accuracy on economic and clinical burden associated with the current management of renal tumors.Author Affiliations: From IBA Molecular (AGA-A, NL), Dulles, VA; Health Net of California (MJF), Huntington Beach, CA; Memorial Sloan-Kettering Cancer Center (PR), New York, NY; Xcenda (TM, EMF), Palm Harbor, FL; Huntsman Cancer Institute (WL), University of Utah, Salt Lake City, UT.
Funding Source: IBA Molecular, Dulles, Virginia.
Author Disclosures: Dr LaFrance and Ms Asnis-Alibozek report employment with IBA Molecular. Drs McLaughlin and Farrelly report employment with Xcenda, which received funding from IBA Molecular to conduct this study. Dr Lowrance reports that he received consulting fees from Xcenda. The other authors (MJF, PR) report no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article.
Authorship Information: Concept and design (MJF, EMF, NL, WL); analysis and interpretation of data (AGA-A, PR, TM, EMF, WL); drafting of the manuscript (AGA-A, MJF, PR, TM, EMF); critical revision of the manuscript for important intellectual content (AGA-A, MJF, PR, TM, NL, WL); statistical analysis (EMF, WL); obtaining funding (NL); and supervision (PR, NL).
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