Small renal masses: Toward more rational treatment

Partial nephrectomy: The new gold standard for most patients

Over the last 5 years, greater emphasis has been placed on lessening the risk of chronic kidney disease in the management of all urologic conditions, including small renal masses.

The overuse of radical nephrectomy prompted the American Urological Association to commission a panel to provide guidelines for the management of clinical stage T1 renal masses.¹⁷ After an extensive review and rigorous meta-analysis, the panel concluded that partial nephrectomy is the gold standard for most patients (Table 1, Table 2).

Partial nephrectomy involves excision of the tumor with a small margin of normal tissue, preserving as much functional renal parenchyma as possible, followed by closure of the collecting system, suture ligation of any transected vessels, and reapproximation of the capsule. Tumor excision is usually performed during temporary occlusion of the renal vasculature, allowing for a bloodless field. Regional hypothermia (cold ischemia) can also be used to minimize ischemic injury.

Contemporary series have documented that partial and radical nephrectomy have comparable oncologic efficacy for patients with small renal masses.^20,21 Local recurrence rates are only 1% to 2% with partial nephrectomy, and 5- and 10-year cancer-specific survival rates of 96% and 90% have been reported.²²

Furthermore, some studies have shown that patients undergoing partial nephrectomy have higher overall survival rates than those managed with radical nephrectomy—perhaps in part due to greater preservation of renal function and a lower incidence of subsequent chronic kidney disease.^23,24 At Cleveland Clinic, we are now studying the determinants of ultimate renal function after partial nephrectomy in an effort to minimize ischemic injury and optimize this technique.²⁵

Complications. Partial nephrectomy does have a potential downside in that it carries a higher risk of urologic complications such as urine leak and postoperative hemorrhage, which is not surprising because it requires a reconstruction that must heal. In a recent meta-analysis, urologic complications occurred in 6.3% patients who underwent open partial nephrectomy and in 9.0% of patients who underwent laparoscopic partial nephrectomy.¹⁷ Fortunately, most complications associated with partial nephrectomy can be managed with conservative measures.

Postoperative bleeding occurs in about 1% to 2% of patients and is the most serious complication. However, it is typically managed with superselective embolization, which has a high success rate and facilitates renal preservation.

Urine leak occurs in about 3% to 5% of cases and almost always resolves with prolonged drainage, occasionally complemented with a ureteral stent to promote antegrade drainage.

A new refinement, robotic-assisted partial nephrectomy promises to reduce the morbidity of this procedure. This approach takes less time to learn than standard laparoscopic surgery and has expanded the indications for minimally invasive partial nephrectomy, although more-difficult cases are still better done through a traditional, open surgical approach.

Thermal ablation: Another minimally invasive option

Cryoablation and radiofrequency ablation (collectively called thermal ablation) have recently emerged as alternate minimally invasive treatments for small renal masses. They are appealing options for patients with small renal tumors (< 3.5 cm) who have significant comorbidities but still prefer a proactive approach. They can also be considered as salvage procedures in patients with local recurrence after partial nephrectomy or in select patients with multifocal disease.

Both procedures can be performed percutaneously or laparoscopically, offering the potential for rapid convalescence and reduced morbidity.^26,27 A laparoscopic approach is necessary to mobilize the tumor from adjacent organs if they are juxtaposed, whereas a percutaneous approach is less invasive and is better suited for posterior renal masses.²⁸ Renal mass sampling should be performed in these patients before treatment to define the histology and to guide surveillance and should be repeated postoperatively if there is suspicion of local recurrence based on imaging.

Cryoablation destroys tumor cells through rapid cycles of freezing to less than −20°C (−4°F) and thawing, which can be monitored in real time via thermocoupling (ie, a thermometer microprobe strategically placed outside the tumor to ensure that lethal temperatures are extended beyond the edge of the tumor) or via ultrasonography, or both. Treatment is continued until the “ice ball” extends about 1 cm beyond the edge of the tumor.

Initial series reported local tumor control rates in the range of 90% to 95%; however, follow-up was very limited.²⁹ In a more robust single-institution experience,³⁰ renal cryoablation demonstrated 5-year cancer-specific and recurrence-free survival rates of 93% and 83%, respectively, substantially lower than what would be expected with surgical excision in a similar patient population.

Another concern with cryoablation is that options are limited for surgical salvage if the initial treatment fails. Nguyen and Campbell³¹ reported that partial nephrectomy and minimally invasive surgery were often precluded in this situation because of the extensive fibrotic reaction caused by the prior treatment. If cryoablation fails, surgical salvage thus often requires open, radical surgery.

Radiofrequency ablation produces tumor coagulation via protein denaturation and disruption of cell membranes after heating tissues to temperatures above 50°C (122°F) for 4 to 6 minutes.³² One of its disadvantages is that one cannot monitor treatment progress in real time, as there is no identifiable change in tissue appearance analagous to the ice ball that is seen with cryoablation.

Although the outcomes of radiofrequency ablation are less robust than those of cryoablation, most studies suggest that local control is achieved in 80% to 90% of cases based on radiographic loss of enhancement after treatment.^17,30,33 A recent meta-analysis comparing these treatments found that lesions treated with radiofrequency ablation had a significantly higher rate of local tumor progression than those treated with cryoablation (12.3% vs 4.7%, P < .0001).³⁴ Both of these local recurrence rates are substantially higher than that seen after surgical excision, despite much shorter follow-up after thermal ablation.

Tempered enthusiasm. Because thermal ablation has been developed relatively recently, its long-term outcomes and treatment efficacy have not been well established, and current studies have confirmed higher local recurrence rates with thermal ablation than with surgical excision (Table 1). Furthermore, there are significant deficiencies in the literature about thermal ablation, including limited follow-up, lack of pathologic confirmation, and controversies regarding histologic or radiologic definitions of success (Table 2).

Although current enthusiasm for thermal ablation has been tempered by suboptimal results, further refinement in technique and acknowledgment of its limitations will help to define appropriate candidates for these treatments.

Active surveillance for select patients

In select patients with extensive medical comorbidities or short life expectancy, the risks associated with proactive management may outweigh the benefits, especially considering the indolent nature of many small renal masses. In such patients, active surveillance is reasonable.

A recent meta-analysis found that most small enhancing renal masses grew relatively slowly (median 0.28 cm/year) and posed a low risk of metastasis (1%–2%).^17,22 Furthermore, almost all renal lesions that progressed to metastatic disease demonstrated rapid radiographic growth, suggesting that the radiographic growth of a renal mass under active surveillance may serve as an indicator for aggressive behavior.³⁵

Unfortunately, the growth rates of small renal masses do not reliably predict malignancy, and one study reported that 83% of tumors without demonstrable growth were malignant.³⁶

Studies of active surveillance to date have had several other important limitations. Many did not incorporate pathologic confirmation, so that about 20% of the tumors were actually benign, thus artificially reducing the risk of adverse outcomes.^5,22,37 Furthermore, the follow-up has been short, with most studies including data for only 2 to 3 years, which is clearly inadequate for this type of malignancy.^37,38 Finally, most series had significant selection bias towards small, homogenous masses. In general, small renal masses that appear to be more aggressive are treated and thus excluded from these surveillance populations (Table 2).

Another concern about active surveillance is the small but real risk of tumor progression to metastatic disease, rendering these patients incurable even with new, targeted molecular therapies. Additionally, some patients may lose their window of opportunity for nephron-sparing surgery if significant tumor growth occurs during observation, rendering partial nephrectomy unfeasible. Therefore, active surveillance is not advisable for young, otherwise healthy patients (Table 2).

In the future, advances in renal mass sampling with molecular profiling may help determine which renal lesions are less biologically aggressive and, thereby, help identify appropriate candidates for observation (Figure 2).