Small renal masses: Toward more rational treatment
ABSTRACTManaging small renal masses poses a common and controversial problem. Although radical nephrectomy is still the most common treatment, partial nephrectomy is the new gold standard, and thermal ablation or active surveillance are reasonable for some patients. Renal mass biopsy with molecular profiling will likely allow for more rational treatment in the near future.
KEY POINTS
- Small renal masses are a heterogeneous group of tumors, and only 20% are aggressive renal cell carcinoma.
- In general, nephron-sparing treatments are preferred to avoid chronic kidney disease, which often occurs after radical nephrectomy.
- Thermal ablation and active surveillance are valid treatment strategies in select patients who are not optimal surgical candidates or who have limited life expectancy.
RENAL MASS SAMPLING: SAFER, MORE ACCURATE THAN THOUGHT
Renal mass sampling (ie, biopsy) has traditionally had a restricted role in the management of small renal masses, limited specifically to patients with a clinical history suggesting renal lymphoma, carcinoma that had metastasized to the kidney, or primary renal abscess. However, this may be changing, with more interest in it as a way to subtype and stratify select patients with small renal masses, especially potential candidates for active surveillance.
Our thinking about renal mass sampling has changed substantially over the last 2 decades. Previously, it was not routinely performed, because of concern over high false-negative rates (commonly quoted as being as high as 18%) and its potential associated morbidity. A common perception was that a negative biopsy could not be trusted and, therefore, renal mass sampling would not ultimately change patient management. However, many of these false-negative results were actually “noninformative,” ie, cases in which the renal tumor could not be adequately sampled or the pathologist lacked a sufficient specimen to allow for a definitive diagnosis.
Recent evidence suggests that these concerns were exaggerated and that renal mass sampling is more accurate and safer than previously thought. A meta-analysis of studies done before 2001 found that the diagnostic accuracy of renal mass sampling averaged 82%, whereas contemporary series indicate that its accuracy in differentiating benign from malignant tumors is actually greater than 95%.12 In addition, false-negative rates are now consistently less than 1%.13
Furthermore, serious complications requiring clinical intervention or hospitalization occur in fewer than 1% of cases. Seeding of the needle tract with tumor cells, which was another concern, is also exceedingly rare for these small, well-circumscribed renal masses.12
Overall morbidity is low with renal mass sampling, which is routinely performed as an outpatient procedure using CT or ultrasono-graphic guidance and local anesthesia.
However, 10% of biopsy results are still noninformative. In this situation, biopsy can be repeated, or the mass can be surgically excised, or the patient can undergo conservative management if he or she is unfit or unwilling to undergo surgery.
The encouraging results with renal mass sampling have led to greater use of it at many centers in the evaluation and risk-stratification of patients with small renal masses. It may be especially useful in patients considering several treatment options.
For example, a 75-year-old patient with modest comorbidities and a 2.0-cm enhancing renal mass could be a candidate for partial nephrectomy, thermal ablation, or active surveillance, and a reasonable argument could be made for each of these options. Renal mass sampling in this instance could be instrumental in guiding this decision, as a tissue diagnosis of high-grade renal cell carcinoma would favor partial nephrectomy, whereas a diagnosis of “oncocytoma neoplasm” would support a more conservative approach.
Older, frail patients with significant comorbidities who are unlikely to be candidates for aggressive surgical management would not need renal mass sampling, as they will ultimately be managed with active surveillance or thermal ablation.
Recent studies have also indicated that molecular profiling through gene expression analysis or proteomic analysis can further improve the accuracy of renal mass sampling.14 This will likely be the holy grail for this field, allowing for truly rational management (Figure 2).
TREATMENT OPTIONS
Radical nephrectomy: Still the most common treatment
In the past, complete removal of the kidney was standard for nearly all renal masses suspected of being renal cell carcinomas. Partial nephrectomy was generally reserved for patients who had a solitary kidney, bilateral tumors, or preexisting chronic kidney disease.
Although the two procedures provide equivalent oncologic outcomes for clinical T1 lesions, Miller et al15 reported that, before 2001, only 20% of small renal masses in the United States were managed with partial nephrectomy. That percentage has increased modestly, but radical nephrectomy still predominates.
One explanation for why the radical procedure is done more frequently is that partial nephrectomy is more technically difficult, as it involves renal reconstruction. Furthermore, radical nephrectomy can almost always be performed via a minimally invasive approach, which is inherently appealing to patients and surgeons alike. Laparoscopic radical nephrectomy has been called “the great seductress” because of these considerations.16 However, total removal of the kidney comes at a great price—loss of renal function.
Over the last decade, various studies have highlighted the association between radical nephrectomy and the subsequent clinical onset of chronic kidney disease, and the potential correlations between chronic kidney disease and cardiovascular events and elevated mortality rates.17
In a landmark study, Huang et al18 evaluated the outcomes of 662 patients who had small renal masses, a “normal” serum creatinine concentration (≤ 124 μmol/L [1.4 mg/dL]), and a normal-appearing contralateral kidney who underwent radical or partial nephrectomy. Of these, 26% were found to have preexisting stage 3 chronic kidney disease (glomerular filtration rate < 60 mL/min/1.73 m2 as calculated using the Modification of Diet in Renal Disease equation). Additionally, 65% of patients treated with radical nephrectomy were found to have stage 3 chronic kidney disease after surgery vs 20% of patients managed with partial nephrectomy.
The misconception remains that the risk of chronic kidney disease after radical nephrectomy is insignificant, since the risk is low in renal transplant donors.19 However, renal transplant donors undergo stringent screening to ensure that their general health is good and that their renal function is robust, both of which are not true in many patients with small renal masses, particularly if they are elderly.
The overuse of radical nephrectomy is worrisome in light of the potential implications of chronic kidney disease, such as increased risk of morbid cardiovascular events and elevated mortality rates. Many experts believe that over-treatment of small renal masses may have contributed to the paradoxical increase in overall mortality rates observed with radical nephrectomy in some studies.4
Although radical nephrectomy remains an important treatment for locally advanced renal cell carcinoma, it should be performed for small renal masses only if nephron-sparing surgery is not feasible (Table 2).
