Identification, characterization, and management of renal masses can be a challenge. At this year’s Genitourinary Cancers Symposium, several experts discussed imaging, biopsy, the use of active surveillance, and the preservation of renal function and other aspects of oncologic and functional follow-up during a General Session on February 10.
“Renal masses are ubiquitous,” said Stuart G. Silverman, MD, of Brigham and Women’s Hospital. He noted that the incidence of renal cell carcinoma (RCC) has doubled since the advent of CT imaging, but the mortality rate of the malignancy has barely budged in decades. “We’re overdiagnosing this disease,” he said.
Between 2000 and 2009, the number of benign renal masses that were removed for suspected RCC increased by 82% in the United States. The surgery is not without harm. Patients face health care costs, anxiety, procedural morbidity, loss in renal function, and increased cardiovascular and other cause mortality as a result of chronic kidney disease.
Dr. Dipen J. Parekh speaks during General Session 8.
A study by Welch et al, published in late 2017, assessed more than 15 million Medicare claims and showed that individuals who undergo a CT scan at some point are at higher risk of undergoing a nephrectomy.1 This is an important correlation, Dr. Silverman said, although it does not necessarily mean that imaging is entirely responsible for the higher nephrectomy rates because the study did not evaluate the appropriateness of the exam. Still, he said that it underscores the need for better education on how to interpret and manage renal mass findings on imaging.
Biopsy and Tumor Heterogeneity
Ithaar Derweesh, MD, of the University of California, San Diego, spoke about another critical part of the evaluation of renal masses. “Renal mass biopsy has evolved into an integral part of the armamentarium for urologists,” he said.
The American Urological Association includes renal mass biopsy in its guidelines for the management of renal masses; the guidelines state that the procedure should be considered when a mass is suspected to be hematologic, metastatic, inflammatory, or infectious. It is not necessary, however, for young or healthy patients who may not be willing to accept uncertainties associated with renal mass biopsy and for older or frail patients whose disease will be managed conservatively regardless of the biopsy’s findings.
Positive biopsy results can generally be trusted, Dr. Derweesh said, with a sensitivity of 98%, a specificity of 96%, and a positive predictive value of 99.8%. He noted, though, that a nonmalignant renal mass biopsy result may not truly indicate that a benign mass is present.
The ASCO clinical practice guideline, Management of Small Renal Masses, recommends the use of renal tumor biopsy in any patient with a small renal mass in which the results may alter management.2 The procedure can also be used in patients undergoing surveillance to assess the risk of metastasis, but it is not necessary in all such patients. Renal tumor biopsy also is a trustworthy test, with a sensitivity of 99.7% and a specificity of 93.2%.
Dr. Derweesh also discussed the tumor heterogeneity seen with these biopsies. In one series, he said, 81.3% of samples from 32 patients with cT1a tumors were heterogeneous—multiple grades were present.3 “Heterogeneity with respect to grade can confound the ability of biopsy to predict outcomes and guide management,” he said. “The presence of high-grade disease even in predominantly low-grade tumors can worsen prognosis.”
He noted that both grade and histology affect the success of ablation, and that it may be worth considering an increase in the number of biopsy cores to three or more when possible, to increase diagnostic yield.
With the increase in diagnosis seen in recent years, there has been a move toward treating some patients with active surveillance or ablation. Tony Finelli, MD, MSc, of the Princess Margaret Cancer Center, University of Toronto, in Canada, discussed the optimal patient selection for these options.
He said it is important to keep in mind that surveillance does not mean simply ignoring a patient’s tumor entirely. “These are individuals [whose tumors] we follow and we pull the trigger if we feel that we can salvage and cure [the disease], not someone who will never be considered a surgical candidate,” Dr. Finelli said.
Dr. Steven Campbell speaks during General Session 8.
A meta-analysis published in 2012 covered 880 patients with 936 masses who underwent surveillance; of those, 18 patients experienced progression to metastases in a mean of 40.2 months.5 Six of the included studies, covering 259 patients and 284 masses, had individual-level data that could be pooled for analysis. After a mean follow-up time of 33.5 months, 23% of the masses exhibited zero net growth under surveillance, and none of those progressed to metastasis.
Patient selection is important for active surveillance. In that analysis, increased age was a predictor of metastasis, as were larger tumor diameter and tumor volume as well as higher linear and volumetric growth rates. Dr. Finelli said it is important for clinicians to consider competing causes of death in patients with localized RCC.
Surveillance has reached the point at which it is mentioned in recent ASCO and American Urological Association treatment guidelines. “There are strong data to support a more rational approach to the management of small renal masses,” Dr. Finelli said. “Initial active surveillance is appropriate for many patients, and in particular those with tumors less than 2 cm and/or competing health risks and tumors less than 4 cm.” He also noted that papillary type 1 and chromophobe tumors are particularly suited for active surveillance.
Types of Treatment and Follow-Up Considerations
Of course, not all patients will be candidates for surveillance, and there are important considerations about treatment choices and the aftermath of treatment for renal masses. Dipen J. Parekh, MD, of the University of Miami Miller School of Medicine, and Steven C. Campbell, MD, PhD, of the Cleveland Clinic, spoke about some issues with renal function preservation and oncologic and functional follow-up after renal mass treatment.
“The most important goal of surgery is oncologic efficacy,” Dr. Parekh said, but it is important to remember other goals, including the preservation of renal function. He discussed an EORTC Intergroup study in which 541 patients from 17 countries were randomly assigned to either nephron-sparing surgery (NSS) or radical nephrectomy (RN).6 The 10-year overall survival rates were 75.7% for NSS and 81.1% for RN (HR 1.50; p = 0.03); importantly, only 2.8% of deaths were related to cancer during the median follow-up period of 9.3 years.
Data from the same trial in a separate publication found that patients in the NSS arm had less incidence of moderate chronic kidney disease, although incidences of advanced disease and renal failure were the same.7 More patients in the RN arm had a lowest estimated glomerular filtration rate of less than 60 mL/min (85.7% vs. 64.7%; p < 0.001).
“Has the EORTC trial put this issue to rest? The answer is an unequivocal ‘no,’” Dr. Parekh said. He said that NSS is the preferred option for T1a tumors, whereas RN is preferred for T3-4 tumors; for the T1b and T2 tumors, both are possibilities, and a decision should be made on the basis of tumor and patient factors as well as surgeon experience.
Dr. Campbell noted that that low rate of deaths as a result of kidney cancer highlights the importance of functional follow-up after treatment. Patients who are at the greatest risk for functional decline include those with less than 50% of a single kidney remaining after surgery, he said, as well as patients with pre-existing chronic kidney disease. In one study, patients with pre-existing disease had a 4.7% decline in GFR per year, compared with only 0.7% decline in those with chronic kidney disease that developed after surgery.8
Functional follow-up, Dr. Campbell said, is relatively simple and cheap; it involves lab tests, simple exams, and medical consults. Oncologic follow-up can be more challenging and, when imaging is involved, far more expensive and also emotionally charged for the patient. “Does intensive surveillance extend survival? We would love to have level 1 data,” he said, such as what exists in colon cancer and other malignancies, but these data are lacking in RCC.
“For oncologic surveillance, it should be tailored to the risk of recurrence,” Dr. Campbell said. “The main focus should be on local recurrences after partial nephrectomy.” He also said that it is relevant to consider competing causes of death, because at some point surveillance no longer makes sense if an individual is far more likely to die of other causes. “We need to be sensible; cost effectiveness needs to be factored into the equation,” he said.