The results of this meta-analysis indicate that when selecting among the four diagnostic imaging modalities examined, the anatomical site to be evaluated was more important than the clinical scenario (ie, staging or surveillance). Among the four diagnostic imaging modalities for the assessments of lymph node metastasis, ultrasonography was superior to CT, PET, and PET-CT. PET-CT had the highest positive predictive value for the surveillance of distant metastasis; however, the higher number of false-positive results (ie, lower specificity) from PET-CT lead to the loss of precision. Furthermore, for patients at low risk of metastasis, the positive predictive value of PET-CT (ie, 33%, 95% CI = 9% to 61%) indicated that use of PET-CT is not warranted without additional clinical indications.
Practice guidelines are becoming an increasingly important element in disseminating treatment algorithms to physicians who treat patients in a community setting (116
), and investigators have suggested that these guidelines can be used as a means of measuring the quality of care delivered (124
). However, evidence-based surveillance strategies for survivors of most cancers including melanoma do not exist. A recent report (125
) that was based on Surveillance, Epidemiology, and End Results–Medicare data acknowledges geographic and patient variation in the receipt of surveillance after treatment of primary melanoma. With the increasing number of melanoma survivors and rapid advances in health-care technology, the costs of caring for these survivors are rising (126
). In 1997, Mooney et al. (128
) reported that screening for melanoma recurrence (in this report for asymptomatic pulmonary metastasis) accounted for approximately 80% of program costs, totaling between $27 and $32 million for a 20-year program. As technological advances permit us to more precisely determine metastatic tumor spread, physicians and patients alike are faced with making clinical decisions on the basis of contemporary risk assessment. Nevertheless, controversy continues to surround the optimal imaging modality and interval of patient surveillance.
Sentinel lymph node biopsy is the acknowledged gold standard for the pathological staging of clinically lymph node–negative melanoma (3
). A recent study by Sanki et al. (5
) comparing ultrasonography with sentinel lymph node biopsy found that the sensitivity of targeted high-resolution ultrasound was only 24.3% (95% CI = 19.5% to 28.7%) compared with that of the sentinel lymph node biopsy. The combination of preoperative ultrasound and fine needle biopsy in select high-risk patients can, however, eliminate the need for sentinel lymph node biopsy by preoperatively identifying lymph node metastases, which indicate the need for therapeutic lymph node dissection (52
). The primary utility of ultrasonography for the assessment of metastases in regional lymph nodes is for lymph node surveillance (31
). PET-CT was superior for detection of distant metastases. Given the low positive-predictive value of CT, PET, and PET-CT in the surveillance of patients at low risk of lymph node metastasis, ultrasonography is the only justifiable imaging choice for lymph node surveillance.
The overall point estimates for the diagnostic test characteristics in this study are lower than those reported in two recently published prospective studies (6
) that evaluated the utility of ultrasonography, CT, and PET in primary staging. Voit et al. (6
) reported that ultrasonography combined with fine needle aspiration cytology had a sensitivity of 65% and a specificity of 99% in a cohort of 400 consecutive melanoma patients. Another study (132
) reported the sensitivities of PET and CT for 251 patients with clinically palpable (stage III) lymph nodes as 86% and 78%, respectively, with a specificity of 94% for both tests. These discrepancies likely relate to heterogeneity among patient populations in these studies.
The purpose of staging and surveillance is to detect treatable tumors, monitor success of therapy, and provide reassurance and support to patients (133
). However, these benefits must be balanced with the risks of testing to patients and their associated costs. Costs for CT, PET, and PET-CT can often be more than twice that of ultrasonography, with differences in charges of up to four times more. Although sufficient evidence regarding clinical effectiveness is not yet available to justify the use of new technologies, such as PET-CT, instead of the best existing alternatives, they are already widely used in oncology. Imaging is one of the fastest growing health-care services (135
) and is a prime example of technology that must be examined in the context of comparative effectiveness to “improve the quality and affordability of US health care” (136
). Quality medical care has been summarized by Earle et al. (137
) as the “delivery of optimal health services” (138
), with “technical proficiency” (139
); “avoiding overuse, underuse, or misuse of technologies”(140
); and “incorporating patient centered preferences in shared decision making” (141
Inappropriate imaging, which adds to health-care costs without improving the quality of care, has been attributed to both physician and patient factors (142
). Lack of knowledge (143
) and fear of liability for missed diagnoses (144
) attributed to physicians have commonly resulted in the inappropriate use of imaging. In addition, patients with a newly diagnosed cancer often expect certain examinations (145
), particularly whole-body imaging. A negative imaging result, even when unnecessary, is often reassuring for the patient and physician and is often perceived to come with few if any negative consequences. However, levels of radiation exposure are known to vary widely even with the same imaging modality, potentially leading to health consequences, including increased lifetime risk of cancer (146
). Furthermore, incidental abnormalities that can be identified on by imaging that do not affect health but require additional evaluation (eg, further imaging or interventional procedures) can result in additional associated costs, complications, and patient anxiety (142
Compared with previous meta-analyses (7
) that examined test characteristics of diagnostic imaging modalities in patients with melanoma, this analysis has a number of strengths. First, all eligible studies from January 1, 1990 through June 30, 2009 with sufficient data on four widely used contemporary imaging modalities (ie, ultrasonography, CT, PET, and PET-CT) were examined. Patient-level data from these studies were extracted and analyzed according to specific clinical scenarios (eg, initial staging vs surveillance); these data have been reported by few studies, despite the large potential impact of diagnostic imaging on both the quality and cost of medical care (148
). Second, Bayesian bivariate binomial models were used for the meta-analysis of diagnostic test characteristics to capture the variability in both sensitivity and specificity simultaneously, as well as their intercorrelation. Such models are applicable to both large and small studies without ad hoc correction (36
). Because of the methodological advantages of bivariate models, Harbord et al. (149
) have recommended that such models be considered standard methods for meta-analysis of diagnostic accuracy.
This study has several limitations that must also be considered. First, technology has advanced over the last two decades, and the diagnostic criteria for each modality have varied during the period studied. Second, selection bias and work-up bias inherent to each individual study could be considerable in this pooled analysis because most of the studies of patients undergoing the index test were retrospective in design. Third, partial verification bias may exist when only those patients undergoing a reference test are included in a sample, and no data were reported on the remaining patients who only underwent the index test. Another well-described drawback of meta-analyses is publication bias because studies with favorable results have a higher likelihood of being published than those with unfavorable results. The studies examining the diagnostic accuracy of ultrasonography reported widely varying estimates of sensitivity and specificity ranging from 5% to 100% with similar variations observed for PET imaging. There are several potential explanations for such variation including small sample sizes in some studies, differing study designs, varying quality of imaging equipment, and differing imaging criteria for diagnosis. An inherent strength of a meta-analysis in evaluating a large body of literature is that it can overcome limitations of small sample sizes and heterogeneous designs of individual trials by pooling the data and obtaining summary sensitivities and specificities.
With the ever-increasing number of melanoma survivors and limited health-care resources, the need to tailor current consensus-based National Comprehensive Cancer Network guidelines toward an evidence-based cost-effective surveillance program is becoming increasingly critical. Test characteristics and performance are considered the first two levels of the evidence hierarchy for all diagnostic technologies (150
). The objective of this analysis was to use contemporary techniques of meta-analysis to summarize the existing evidence for four common diagnostic imaging modalities that are used in the staging and surveillance of regional and distant metastasis for patients with melanoma. Future comparative effectiveness analyses should use decision-analytic modeling to simulate the effectiveness and cost-effectiveness of various surveillance strategies with respect to imaging modality and frequency on stage-specific patient outcomes.
In summary, when diagnostic imaging is indicated for staging or surveillance, we found that ultrasonography was the best diagnostic imaging test to detect lymph node metastases and that PET-CT was more suitable for the detection of distant metastases in patients at intermediate or high risk or when distant metastases are clinically indicated. Results of this meta-analysis should provide information for clinical decisions on the staging and surveillance of patients with melanoma.