STRATEGIES AND EVIDENCE
Radiologic Assessment and Characterization of Renal Masses
Simple renal cysts can be reliably diagnosed noninvasively on the basis of well-defined radiologic criteria. However, the term “cystic mass” is ambiguous, since it spans the spectrum from “definitively benign” to “almost certainly malignant.” The Bosniak classification system8 can be used to assign cystic masses to one of four categories that represent the range of diagnostic possibilities (Figure 1FIGURE 1
Benign Renal Masses.
). Macroscopic fat within a renal mass, identified by means of CT or magnetic resonance imaging (MRI), is diagnostic of angiomyolipoma (a benign mass), unless calcification is present, which would indicate a malignant condition.9
In the case of a solid mass or a complex cystic renal mass, but not a simple cyst, assessment of the size, shape, contour, and tissue-enhancement characteristics is important for determining the likelihood of cancer. Assessment is best performed by means of dedicated renal CT scans (with and without the administration of contrast material) or dedicated MRI scans (with and without gadolinium enhancement), obtained at a slice thickness of 3 to 5 mm.
Masses with measurable enhancement on CT or MRI (with the exception of angiomyolipoma) are classified as solid masses or complex cystic masses (Bosniak class III or class IV)8,9 (Figure 2FIGURE 2
Small Renal Masses.
). The majority of enhancing masses are malignant; no specific findings on imaging conclusively identify a mass as malignant or benign. Thus, when management decisions are being made in the case of a patient with a long life expectancy, a solid, enhancing small renal mass must be considered malignant unless proven otherwise.
The smaller the mass, the greater the chance that it is benign. In a report on 2770 surgically excised solid renal masses stratified according to size, 46% of masses that were less than 1 cm in diameter were benign, as were 22% of those that were 1 to 2.9 cm, and 20% of those that were 3 to 3.9 cm.7 Among masses that are malignant, greater size correlates with a higher pathological grade. The growth rate of small renal masses is typically slow (2 to 4 mm per year)10; in studies involving relatively short-term follow-up (≤3 years), the growth rate has been reported to be similar for masses subsequently found to be malignant (renal-cell carcinoma) and those found to be benign (oncocytoma).10,11 In one meta-analysis, 30% of small renal masses showed no growth over an observation period of 23 to 39 months.10 Masses that showed no growth were about as likely to be malignant (83%) as were those that grew (89%).12 There are no definable clinical or radiologic characteristics that effectively predict future growth; neither size at presentation nor the final histologic diagnosis (even if it is proven renal-cell carcinoma) correlates with growth rates.10 Most excised small renal cancers are classified as low grade. However, in three studies involving excised renal cancers that were 3 to 4 cm in diameter, 14 to 26% were high grade (grade 3 or 4) and 12 to 36% locally invaded perirenal fat (classified as pT3a tumors).13-15 Patients with small renal masses that lead to symptoms such as flank discomfort or hematuria seem to have a worse prognosis than patients with similar-size masses that are detected incidentally.16
At the time of diagnosis, metastases are present in 1 to 8% of patients with renal cancers that are 3 to 4 cm in diameter.10,13-15 An analysis of the National Cancer Institute's Surveillance, Epidemiology, and End Results Program database for 1998 to 2003 showed a 5.2% prevalence of metastasis at presentation among 8792 patients with pathologically confirmed small renal cancers (≤4 cm in diameter)17; for each 1-cm increase in the size of the primary cancer, the calculated prevalence of metastases increased by 3.5%.
Needle Biopsy
Typically performed under CT guidance, needle biopsies appear to be safe (with a minimal risk of bleeding or of seeding of the needle tract with malignant cells), and they have a sensitivity for the detection of cancer of 80 to 92% and a specificity of 83 to 100%.18-20 Smaller masses (≤3 cm) have higher false negative rates (negative predictive value, 60%); the false negative rate can be reduced by repeat biopsies and a high level of experience on the part of operators and pathologists.20
In most cases, benign findings on examination of a biopsy specimen cannot rule out cancer in the rest of the tumor, but a definitive benign diagnosis may be made in cases of angiomyolipoma, metanephric adenoma, or focal infection. A benign diagnosis may be strongly suggested for some oncocytomas, although chromophobe renal-cell carcinoma may have a similar appearance on biopsy.19 In the absence of findings that are diagnostic of renal-cell carcinoma or a definite benign entity, a biopsy specimen showing nondiagnostic or nonmalignant findings must be considered with caution, and surveillance imaging, repeat biopsy, or surgery should be performed.
Combining histologic and molecular or cytogenetic techniques may improve the accuracy of a diagnosis that was based on needle biopsy. As compared with histologic analysis alone, the addition of molecular diagnostic algorithms that incorporate RNA extraction and polymerase chain reaction for four gene products to distinguish subtypes of renal-cell carcinoma improved the sensitivity (100% vs. 87%) and negative predictive value (100% vs. 87.5%) of needle biopsies for the diagnosis of clear-cell renal-cell carcinoma.21 However, these findings require validation at other centers, and currently, molecular diagnostic algorithms are not used routinely in practice.
Management Options
Options for the management of small renal masses that are worrisome because of the risk of malignant conditions include active surveillance, surgery, and ablation. Data from randomized, controlled trials comparing various treatment options are lacking; thus, available data are observational or are based on case series (Table 1TABLE 1
Treatment Considerations for a Patient with a Small Renal Mass.
). Decision making should take into account a patient's coexisting conditions, life expectancy, and preferences and the treatment provider's level of experience.
Active Surveillance
Active surveillance involves the monitoring of tumor size by means of serial ultrasonography, CT, or MRI.22 Although comparative data are lacking, CT or MRI is generally preferred over ultrasonography, owing to greater resolution and reproducibility. The typical recommendation is to perform repeat imaging at intervals of 6 to 12 months; however, the financial costs of serial imaging and the risks associated with radiation from serial CT scanning in particular (30 to 90 mSv per CT study23) should be taken into consideration.
The growth of or the metastasis from initially asymptomatic, incidental small renal masses has been extremely uncommon, although the available studies of case series involved a short follow-up, of only 23 to 39 months10; therefore, active surveillance is an attractive option mostly for elderly or infirm patients with a short life expectancy. This strategy also seems reasonable for masses that are 1 cm in diameter or smaller, regardless of the patient's age, although data are needed to help determine the frequency and duration of follow-up imaging in these cases. In selected patients who are undergoing active surveillance, intervention can be performed if the tumor grows; such delayed intervention does not seem to compromise future treatment options.24 However, given the limitations of the available data (including relatively short follow-up, limited sample size, and insufficient histologic assessment) and the fact that imaging studies can neither definitively rule out cancer nor predict its behavior, active surveillance is not generally recommended for young, healthy patients. However, surveillance data do provide reassurance that treatment is generally not warranted urgently.
Nephron-Sparing Surgery
Radical (total) nephrectomy was for many years the accepted standard treatment for all organ-confined kidney tumors, but nephron-sparing surgery (partial nephrectomy) has now become the preferred treatment for small renal masses for which surgery is warranted. Nephron-sparing surgery, which may be performed by an open or a laparoscopic approach, involves targeted excision of the tumor along with an adequate rim of normal renal parenchyma, thereby preserving the uninvolved portion of that kidney.25 Chronic kidney disease is increasingly common (one study showed previously unrecognized chronic kidney disease in one quarter of the patients who had a small renal mass26); therefore, renal functional preservation is an important consideration in management.
In the only randomized trial comparing partial with radical nephrectomy for tumors less than 5 cm in diameter, the authors concluded that partial nephrectomy could be safely performed but would have slightly higher rates of complications than would radical nephrectomy. The complications included severe hemorrhage (3.1% vs. 1.2%), urine leak (4.4% vs. 0%), and reoperation (4.4% vs. 2.4%). However, this report did not include oncologic outcomes. 27 Data from case series have indicated low 5-year and 10-year cancer-specific mortality rates after open partial nephrectomy (2.4% and 5.5%, respectively); these data are similar to the outcomes for radical nephrectomy.25,28 In an observational study comparing partial with radical nephrectomy, partial nephrectomy was associated with a significantly lower risk of renal insufficiency (12% vs. 22%) and proteinuria (35% vs. 55%) at the 10-year follow-up.29 In one report, the risk of stage 3 or higher chronic kidney disease was 20% after partial nephrectomy and 65% after radical nephrectomy (P