Introduction

Small renal masses (SRMs) are enhancing asymptomatic lesions in the kidney that measure 4 cm or less and represent nearly half of newly diagnosed kidney cancers.¹ The incidence of SRMs is rising due to the widespread use of cross-sectional imaging studies such as CT and MRI.¹

The traditional management of SRMs has been surgical resection with partial/radical nephrectomy, or ablative therapies such as cryotherapy/radiofrequency ablation. More recently, active surveillance (AS) has emerged as a mainstay treatment option for SRMs. The uptake of AS, however, has been low with reports suggesting only 10% of eligible patients undergoing AS.²

AS

When an SRM is detected, oncologic staging is an important first step. Nguyen et al studied over 24,000 renal tumors and found that the prevalence of metastasis at presentation was 1.4%, 2.5%, 4.7%, and 7.4% for tumors 0-1 cm, 1-2 cm, 2-3 cm, and 3-4 cm, respectively.³ This highlights that a few patients with SRMs will present with metastatic disease.

On AS, patients undergo abdominal imaging every 3-6 months for 1 year, then every 6-12 months thereafter with a chest x-ray annually, although the need for chest imaging has been debated. Treatment is generally recommended for rapid growth rates >0.5 cm/y, increased tumor diameter >4 cm, detection of metastatic disease, or patient preference. In a cohort of 544 SRMs treated with AS, the rates of intervention were 9%, 22%, 29%, 35%, and 42% at 1, 2, 3, 4, and 5 years, respectively.⁴

For patients with solid SRMs, 20%-30% are benign lesions, with the most common histology being oncocytoma.⁵ Of the remaining SRMs that are renal cell carcinomas (RCCs), 70%-80% are low grade with little metastatic potential.⁶ SRMs grow at a rate of approximately 0.28 cm/y and the 3-year risk of metastatic progression is ∼2%.^7,8 A systematic review found that tumors that metastasized were larger at presentation (4.1 vs 2.3 cm, P < .0001) and had a higher growth rate (0.8 vs 0.3 cm/y, P = .0001).⁹

Cancer-specific survival for patients on AS vs primary intervention is similar. The results from a prospective, nonrandomized trial reported 5-year cancer-specific survival rates of 99% and 100% for primary intervention and AS, respectively (P = .30). It should be noted, however, that 5-year overall survival was worse for AS compared to primary intervention (75% vs 92%, P = .06), but this is likely explained by the fact that AS patients were older, had worse Eastern Cooperative Oncology Group scores, had more total comorbidities, and were more likely to have multiple or bilateral lesions.¹⁰ Although the short-term safety of AS has been established, the longer-term outcomes beyond 3 years remain to be reported.

The Role of Renal Mass Biopsy

Renal mass biopsy (RMB) can help identify the underlying histology of SRMs to help drive clinical management. In a single center’s 13-year experience, RMB was able to identify a wide variety of benign and malignant histologies.¹¹ The diagnostic rate of RMB in a systematic review of over 5,000 patients was greater than 90% with a sensitivity of 99.1% and specificity of 99.7%. The rate of subtype concordance of RMB of SRMs with final surgical pathology was 96%.¹²

In a biopsy-characterized cohort of SRMs, clear cell RCC grew faster than papillary type 1 SRMs (0.25 vs 0.02 cm/y on average, P = .0003). Some clear cell RCCs showed accelerated growth only after an initial period of stability. The rate of metastatic progression was 4% in this study, with all metastatic patients having clear cell histology. Of note, one patient who developed metastatic disease showed no local tumor growth after 2 years on AS.¹³ A tumor-specific, genomic signature–informed approach will be crucial for optimizing patient selection for AS and minimizing the risk of disease under- or overtreatment.

Current Guideline Recommendations

Guidelines from the American Urological Association in 2021, Canadian Urological Association in 2022, European Association of Urology in 2022, and American Society of Clinical Oncology in 2017 are fairly consistent with respect to the use of AS for SRMs. All of them recommend AS as the preferred management strategy for patients with significant comorbidity, limited life expectancy, excessive perioperative risk, or marginal renal function. The Canadian Urological Association guideline recommends AS as the preferred option for all patients with SRMs <2 cm. For tumors between 2-4 cm, there was no consensus on the preferred management strategy, with 40% of guideline members feeling that definitive treatment with surgery or ablation should be the option of choice. Shared decision-making and using RMB when it will impact management are common amongst guidelines. Other special considerations which may impact AS decisions are that thermal ablation is most effective for tumors less than 3 cm, and the complexity of the partial nephrectomy required for surgical extirpation.

Future Directions

There has been recent interest in using imaging modalities to predict SRM histology. A retrospective analysis found that MRI had a sensitivity of 85% and 80% for detecting clear cell and papillary RCC, respectively, but fared worse for predicting chromophobe, oncocytoma, and fat-poor angiomyolipomas.¹⁴ The ZIRCON study, presented at the 2023 American Society of Clinical Oncology Genitourinary Symposium, evaluated a novel positron emission tomography/CT-based imaging modality using ⁸⁹Zr-DFO-girentuximab. Girentuximab is a monoclonal antibody that binds to carbonic anhydrase IX, an enzyme highly expressed in clear cell RCC. The study included 300 patients with indeterminate renal masses who underwent positron emission tomography/CT imaging prior to surgery, and the results showed a sensitivity and specificity of 86% and 87%, respectively, for detecting clear cell RCC.¹⁵ The imaging modality may emerge as an adjunct or replacement for RMBs in select situations.

Conclusion

AS has emerged as a safe and effective option for the management of SRMs. RMB can help identify the underlying histology of the SRM to inform clinical management. Patients are best served through an individualized approach to management considering tumor factors (such as size, growth rate, histology, and location) and patient factors (such as age, competing health risks, and preferences).