Active Surveillance Of Small Renal Tumors

The standard of care for small localized renal neoplasms is either radical or partial nephrectomy (53,54).

The rationale for immediate surgery is that early detection and treatment of a small tumor will lead to an improved cancer-specific prognosis.

Nephron-sparing surgery for smaller renal cell carcinomas, originally proposed for patients with a solitary kidney, impaired renal function or bilateral tumors, is becoming the standard of care as an alternative to radical nephrectomy (25,42,43,55,56). Cancer-free survival appears equivalent (25). Laparoscopic partial nephrectomy is now widely performed and is perceived to be the preferred alternative to open partial nephrectomy (57,58). Although morbidity from nephrectomy has decreased with improved techniques, it is still significant and is reported to occur in 11% to 40% of cases in recent series (25,55,59-61).

The median age at diagnosis of renal cell carcinoma is 66 years (2). More incidental tumors are detected in the elderly who are more likely to undergo radiological examinations for other medical issues. These patients frequently have significant comorbidities and have a higher risk of perioperative mortality and morbidity. With aging populations and the increased use of imaging in developed countries, it is therefore reasonable to predict that the issue of appropriate management of small renal tumors will become even more important (17,62).

The lack of a decrease in the mortality of renal cell carcinoma in the last decades, despite the significant increase in the diagnosis of localized neoplasms, may imply that a proportion of small incidentally detected tumors have an indolent behavior (7). In fact, there has been a modest increase in mortality compared to incidence of renal cell carcinoma in the United States, which may be due to a lead time bias or may indicate that many small renal tumors have a long natural history and are not destined to progress, while the ones likely to do so are probably resected too late despite their localized radiographic appearance (2-4,63).

Reports from autopsy series performed before the widespread use of imaging show that 67% to 74% of renal cell carcinoma remained undetected until death and that only 8.9% to 20% of undiagnosed renal cell carcinoma were eventually responsible for the patient's death (5,64,65). This supports the hypothesis that many incidentally detected renal tumors grow slowly. Finally, some authors report that the observation that the age at diagnosis is lower in symptomatic than in incidental cases does not support the concept of incidental tumors as inevitable preclinical phase of the symptomatic ones (14,19,64,66).

There are few reports of watchful waiting of small renal masses in the literature. Most studies are retrospective and have a small sample size, but the results are consistent and provide a better understanding of the previously unknown natural history of renal tumors.

There is important variability in the growth patterns of small renal masses. A small number of tumors grow rapidly after diagnosis, but most of them have a natural history of slow growth and are not likely to metastasize (44,48,49,51,52). In our experience, only 34% renal masses had a clinically significant growth over time (51). The association between growth rate and tumor size at diagnosis was not found to be statistically significant (48,51). It is important to note that in all the series no tumor progressed with metastases during the surveillance period.

Possible measurement error at imaging is a concern in the conservative management of patients with small renal tumors.

A single or bidimensional diameter has been generally used to measure the tumor growth rate (44,48). We prefer to use tumor volume because we believe that it may better estimate the tumor cell burden. Small tumors are often spherical but may be ellipsoid, especially with increasing size. In our opinion, using three dimensions can therefore improve accuracy although error of measurement will be exponentially expressed (49,51).

In most studies, the small renal masses were radiologically consistent with renal cancer, but not all were histologically proven renal cell carcinoma. The accuracy of contemporary imaging modalities in the diagnosis of renal cell carcinoma is considered 85% to 90%, but this percentage may need to be revised downwards as recent reports suggest that the chance of benign pathology increases as the mass diameter decreases (34,67,68). Furthermore, the large majority of small renal cell carcinomas are low-grade tumors (34). This may explain why most small masses grow slowly or do not grow at all.

Based on these observations and interpretation of current data, it seems appropriate to reexamine the current practice of immediate surgery for all newly diagnosed small renal masses (19,44,45,48,49,63,66,69). In fact, many small incidentally discovered renal neoplasms may not be histologically or clinically malignant and therefore may not be an immediate threat to the patient's life. A period of initial observation with surgical treatment reserved for those tumors that exhibit fast growth, i.e. those that have rapid doubling times or whose volumes or bidimensional diameters reach a threshold demonstrated to be unsafe may be appropriate in patients who are elderly or infirm. This is the definition of active surveillance. In our study, we arbitrarily defined a fast growing mass as a mass that doubles its volume within one year and/or reaches 4 cm in maximum dimension (51). An upper limit of 3-4 cm in diameter is commonly used to identify the renal masses that are at very low risk of developing metastases and have a better survival rate (38,39,41,45,70-72). Further experience is required before we can define thresholds for treatment, but these appear to be conservative and reasonable upper limits for size and growth rate until which continued surveillance might be considered before triggering therapeutic intervention in selected patients.

Possible measurement error at imaging is a concern in the conservative management of patients with small renal tumors.

Several authors reported reproducible and accurate tumor volume measurements by the use of computed tomography scan and magnetic resonance imaging (73-76). A higher degree of inter- and intraobserver variability in measurements seems to occur with the use of ultrasonography (77,78). Edge detection of an irregular mass at imaging may be difficult or inaccurate, particularly when features such as cystic masses, haemorrhage, pyelonephritis, localization near or invasion of the collecting system, cysts or dilated calices adjacent to the tumor, and multiple cysts within the kidney are present (79). We have performed a study of inter- and intraobserver variability in computed tomography measurement of small renal masses and compared imaged with postoperative volumes (80). It is well known that these measurements may be different with a reduction in diameter after surgery, presumably largely due to initial ligation of the arterial blood supply with a decrease in kidney and tumor blood volume (74,81). We have demonstrated that the measurement of tumor dimension based on computed tomography and magnetic resonance imaging of the mass is an effective method of assessing tumor growth (80).

Masses with cystic components represent a special problem because there can be a significant difference between overall volume and tumor cell volume. Tumor growth rate can be easily either overestimated or underestimated if the volume of cystic fluid grows at a different rate than the tumor cell volume. Some authors observed that the prognosis for patients with cystic renal cell carcinoma is better than that for patients with solid tumors but, as the tumors were all managed by surgery, these reports do not give us information about the natural history of this type of tumor (82-85). In our experience, the complex cystic renal masses had a comparable growth rate compared to the solid ones (p = 0.41) (51).

SUMMARY

In the absence of other prognostic factors, the measurement of tumor growth rate may be helpful

for initial conservative management of patients with small renal tumors.

The risk of progression to metastatic disease during the surveillance period appears to be

minimal, but longer follow-up is needed to confirm this observation.

At the present time, active surveillance of small renal masses is an experimental approach that

should only be considered for the elderly or patients with significant comorbidity.

■ New techniques of functional imaging or molecular and genomic studies, possibly using needle biopsies, may be useful in identifying small renal tumors with different aggressiveness and metastatic potential, therefore allowing the clinician to differentiate those that are likely to progress and require immediate surgery from those that are indolent and may benefit from active surveillance avoiding unnecessary surgery.

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