The three established risk factors for renal cell cancer are cigarette smoking, hypertension, and being overweight or obese. The findings for these risk factors are consistent across most studies. Cigarette smoking has a positive, dose-response association with renal cell cancer, in that the risk increases with an increase in pack-years of smoking. In addition, there is evidence that risk decreases when smoking ceases. The higher a patient's usual body mass index (BMI), the greater the risk for renal cell cancer as well, though the effect of weight loss on risk is not clear. The positive association of hypertension with renal cell cancer is independent of the patient's BMI. Improvement of risk with BP control is not as well understood.3
Other potential risk factors with an apparent positive association include diabetes, parity, and exposure to trichloroethylene, an industrial degreaser for metal that may also be found as an environmental contaminant.3 Factors with an apparent inverse association with renal cell cancer include physical activity and alcohol intake (slightly more than 1 alcoholic drink per day lowered risk by 28%).3 In studies of each of these suspected risk factors, exposure precedes the renal cancer development and there is a dose-response relationship. However, for some of these factors, evidence is mixed or the level of exposure is difficult to measure. In addition, the effect of any of these factors independent of known risk factors may be difficult to ascertain.3
Renal cell cancer is discovered incidentally more than half the time.4,5 Incidentally discovered tumors tend to be diagnosed earlier and have a better prognosis. In an epidemiologic study of presentation and treatment patterns of more than 4,000 renal masses, Laguna and colleagues found that two-thirds of the sample's masses were discovered incidentally, half of the patients had comorbid hypertension, and almost one-quarter of them had at least stage 3 chronic kidney disease (CKD).6
Most patients with renal cell cancer have no symptoms when the mass is discovered. When renal cell cancer causes symptoms, they often arise from the growth of the tumor locally, associated bleeding, metastases, or paraneoplastic syndromes. Patients may present with flank pain related to hemorrhage, obstruction of the ureter, or advanced disease. The classic triad comprises flank pain, palpable abdominal mass, and gross hematuria.4 This triad is seen rarely and generally only with more advanced disease.5
History and physical examination findings may be more useful for identifying a nonneoplastic cause of an incidentally discovered renal mass. For example, a patient whose renal mass has an infectious cause may have fever, flank pain, and urinary white blood cells.7 The physical examination is less useful for making an early diagnosis than for uncovering signs of advanced or metastatic disease, or paraneoplastic syndromes. Signs of more advanced disease include a palpable abdominal mass, bilateral lower extremity edema, enlarged lymph nodes, or a nonreducing varicocele from an obstructed renal or testicular vein.8 About one of five patients with renal cell cancer has an associated paraneoplastic syndrome that may present with polycythemia, hypercalcemia, and hypertension.4,5
Almost 40% of adults have an incidental renal mass discovered in their lifetimes.9 Most of the masses are cystic and require no further workup.9 However, a patient who presents with an incidental finding that is suspicious for renal cell cancer on an imaging study, unexplained flank pain, a palpable abdominal mass, or microscopic hematuria should first undergo a comprehensive history and physical examination.10 The history will uncover unreported symptoms, risk factors, family history of genetic disorders, and any other comorbidities that may affect management and prognosis. The physical examination often is unremarkable but may demonstrate a palpable mass or tenderness in the flank or back.
Laboratory evaluation of a patient with suspected kidney cancer includes urinalysis (looking for hematuria), complete blood cell count (anemia or polycythemia), and chemistry panel (possibly elevated liver enzymes or calcium, as well as baseline kidney function with blood urea nitrogen and creatinine). When urothelial cancer is suspected, urine cytology, ureteroscopy, and possibly biopsy are included in the evaluation.10
Incidentally discovered masses may have been detected through ultrasound, IV pyelography, or conventional radiographs ordered for unrelated symptoms.7 Imaging workup of the incidental mass often begins with contrast abdominopelvic CT to locate and estimate the size of a tumor.5 In addition, enhancement of a solid lesion is consistent with neoplasm.7,11 MRI can better-differentiate masses that were poorly defined by CT.9 MRI also is acceptable for patients who cannot tolerate contrast administration, have a history of CKD, or in whom advanced local disease is suspected.5,11 However, CT imaging with and without contrast remains the diagnostic study of choice. Although a CT scan may be the most commonly ordered test for documenting the size of the mass and informing treatment decisions, it raises concern about the level of radiation exposure, particularly for patients who are followed initially with active surveillance that may involve more than one scan per year.
To differentiate the diagnostic accuracy of the imaging options for patients with a mass, Mucksavage and colleagues performed a retrospective review of 776 patients who underwent ultrasound and CT, ultrasound and MRI, CT and MRI, or all three studies before either partial or radical nephrectomy.12 They found no significant differences in measurements of the masses. However, statistically significant, strong positive correlations were found among the preoperative measures of the renal mass diameters for any combination of the imaging studies.12
TO BIOPSY OR NOT?
Although tissue diagnosis informs treatment decisions for most cancers, kidney biopsy is somewhat controversial. Biopsy of a solid renal mass less than 4 cm in diameter is generally well tolerated, with low risk of complications. Historically, seeding of the cancer cells along the biopsy track was a concern but this has not been borne out by more recent studies.13 Sampling error is less of a concern than it once was. Ha and colleagues report a diagnostic accuracy up to 98% for fine-needle aspiration.13 National Comprehensive Cancer Network guidelines recommend limiting needle biopsy to patients with small lesions to confirm the diagnosis and inform surveillance or treatment decisions.10 In larger lesions with classic imaging findings, biopsy before surgery usually is not needed.10
METASTATIC WORKUP AND STAGING
When the characteristic findings of renal carcinoma are present on initial imaging, further CT imaging of the patient's chest and abdomen is necessary for staging purposes. Bone scan and brain imaging are recommended only if the patient has clinical symptoms or laboratory findings suggestive of disease, such as elevated alkaline phosphatase.4,5
The tumor-node-metastasis (TNM) classification system is most often used for clinical staging of renal cell cancer.
- T1 and T2 tumors are limited to the kidney and distinguished by size: T1a, 4 cm or less in diameter; T1b, more than 4 cm and less than 7 cm; T2a, more than 7 cm and less than 10 cm; T2b, more than 10 cm.
- T3 tumors extend beyond the kidney into perinephric tissues or major veins but do not reach the adrenal gland or any further than Gerota fascia.
- T4 tumors extend beyond Gerota fascia.
- N indicates whether the cancer has metastasized to regional lymph nodes: N0 indicates no and N1 indicates lymph node metastases in the region of the kidney.
- M indicates whether the cancer has distant metastases: M0 for none and M1 when present.
These classifications are then used for clinical staging:
- Stage I—smaller tumors confined to the kidney (T1) and no lymph node or distant metastases.
- Stage II—larger tumors limited to the kidney (T2) and no lymph node involvement or distant metastases.
- Stage III—regional lymph node involvement with a T1 or T2 tumor, or a T3 tumor with or without regional node involvement.
- Stage IV—all T4 tumors and all patients with distant metastases regardless of the T classification of the primary tumor.10
Management involves active surveillance, surgery, pharmacologic treatment, or some combination of these approaches. Active surveillance is an increasingly accepted observational approach to incidental small renal masses. When following patients with active surveillance, recommended protocols include annual contrast-enhanced CT or MRI to monitor for metastasis.14 Small masses, especially those less than 3 cm, present a low risk of developing metastases and for that reason, active surveillance is increasingly employed. Older adults also may benefit from active surveillance. In patients over age 66 years, the risk of death or a cardiovascular event was significantly lower with surveillance compared with surgery.15
However, an observational approach is not ideal for every patient and experts do not agree on when it is the best option. Recent data support percutaneous biopsy as a means to determine when observation alone is an appropriate initial step.16 In addition, no standard surveillance protocol exists. For these reasons, active surveillance is restricted to patients with a limited life expectancy, comorbidities, or other factors that increase their risk for more invasive treatments.7
Surgical treatment of incidental renal masses has evolved significantly over the past 2 decades. Historically, radical nephrectomy was the mainstay of treatment for nearly all renal masses, regardless of size.17 Because of the increase in incidental detection of smaller renal masses, less-radical alternatives are favored, such as nephron-sparing procedures and laparoscopic radical or partial nephrectomy. Radical nephrectomy in a patient with a small renal mass is an independent predictor of CKD.17 In addition, higher risk of surgical complications and longer recovery time make it the less-favorable strategy. In one study, rates of contralateral recurrence and metastasis were similar in patients who had undergone radical nephrectomy and those who had nephron-sparing treatment. Ipsilateral recurrence rates, however, were slightly higher in the nephron-sparing group. Patients in the radical nephrectomy group had a significantly higher risk for proteinuria.18 In current practice, radical nephrectomy is reserved for cases in which the anatomical location of the mass or the technical skill of the surgeon prohibits a nephron-sparing approach.16,17
The nephron-sparing approach involves focal removal of the tumor and a small amount of surrounding normal tissue, sparing the unaffected portion of the kidney and preserving renal function. Huang and colleagues report a significant decrease in all-cause mortality for patients undergoing partial nephrectomy compared with those undergoing radical nephrectomy.19 They also examined cardiovascular outcomes, finding more cardiovascular events in the radical nephrectomy group but the difference was not statistically significant when controlled for demographics and comorbidities (HR 1.21, P = .1).19 Nephron-sparing techniques include open partial nephrectomy, laparoscopic partial nephrectomy, or techniques such as cryoablation and radiofrequency ablation. Open partial nephrectomy is the nephron-sparing technique with the most reported data and most extensive clinical experience.17 Current trends favor laparoscopic surgery for improving morbidity and perioperative outcomes while still achieving oncologic treatment goals. Improvements in technique have increased the effectiveness of laparoscopy for incidental renal masses. However, the technique remains more surgically challenging, thereby limiting its use. Long-term data are still lacking but initial studies confirm findings of equivalent oncologic efficacy compared with open techniques.20
Ablative therapies include cryotherapy and radiofrequency ablation. These techniques involve placing probes in the renal mass and generating cytocidal temperatures to ablate the involved tissue. Although these techniques lack randomized controlled trials to support their efficacy, they remain initial treatment options for older adults or those with excessive surgical risks or comorbidities.10
Pharmacologic treatment is not the standard of care for renal masses believed to be localized renal cell cancer.5 However, it may be appropriate for patients who relapse after initial therapy or who have advanced disease.10
After surgical excision of a localized tumor, up to 30% of patients experience a relapse. The average time of relapse after surgery is 1 to 2 years, and most patients present within 3 years.10 As with treatment decisions, a patient-centered approach is taken in developing a follow-up surveillance strategy. For a patient with stage I disease, follow-up includes a clinical evaluation twice per year for the first 2 years and then annually for 3 more years. Abdominal imaging studies are repeated 3 to 12 months after initial surgery for patients who have had partial or radical nephrectomies. After the initial follow-up, patients who underwent partial nephrectomy undergo repeat abdominal studies annually for 3 years. Subsequent follow-up for those who had radical nephrectomy is usually an annual evaluation, at the discretion of the physician. For patients with stage 2 or 3 cancers, clinical evaluation and abdominal imaging are recommended every 3 to 6 months for 3 years and then once per year for 2 more years. Beyond 5 years, follow-up occurs as clinically indicated.
Additionally for patients with stage 1 cancer, chest imaging is recommended annually for 3 years and then as needed. For patients with stage 2 or 3 cancer, chest imaging is recommended two to four times per year for the first 3 years and then annually for 2 more years. Pelvic, brain, spine imaging, and bone scans are performed only if clinically indicated.
Follow-up after ablative techniques includes twice-yearly clinical evaluation for 2 years, then annually for 3 more years. Abdominal imaging is repeated 3 to 6 months after the procedure, and then once per year for up to 5 years.10
Five-year survival outcomes for patients with renal cell carcinoma differ markedly by stage at initial evaluation.5 Overall survival at 5 years for all patients diagnosed with renal cell carcinoma is 74.1%.1 For those with advanced disease (distant metastases), the 5-year survival is only 11.7%; however, 92.6% of those diagnosed while their disease was localized to the kidney were alive 5 years after diagnosis.1
The patient in the opening scenario was evaluated by urology and underwent a chest CT and bone scan. She had no evidence of metastasis. Based on the radiologic features of the tumor, including its size and location, the urologist recommended radical nephrectomy. The patient tolerated the procedure well and had an uneventful postoperative course. Histology confirmed the suspected diagnosis of renal cell cancer. She had no lymph node involvement and a 7.5-cm tumor (T2a), putting her disease in stage 2. She was followed clinically every 3 months, with repeat contrast CT at 6 and 12 months, and to date remains in remission with serum creatinine levels within the normal range. Surveillance for recurrent renal cell cancer will continue for 5 years, and she will be closely monitored because of her risk factors for CKD.
Renal cell cancer often is discovered incidentally when a patient undergoes an imaging study for an unrelated complaint. Because incidental masses are increasingly common, clinicians must understand their evaluation and management to provide optimal patient care.
1. National Cancer Institute. SEER cancer stat facts: kidney
and renal pelvis cancer. Bethesda, MD. http://seer.cancer.gov/statfacts/html/kidrp.html. Accessed September 13, 2017.
2. American Cancer Society. About kidney
/content/dam/CRC/PDF/Public/8659.00.pdf. Accessed September 13, 2017.
3. Chow WH, Dong LM, Devesa SS. Epidemiology and risk factors for kidney
cancer. Nat Rev Urol
4. Escudier B, Porta C, Schmidinger M, et al Renal cell carcinoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol
. 2014;25(suppl 3):iii49–iii56.
5. Campbell S, Uzzo RG, Allaf ME, et al Renal mass and localized renal cancer: AUA guideline. J Urol
6. Laguna MP, Algaba F, Cadeddu J, et al Current patterns of presentation and treatment of renal masses: a clinical research office of the Endourological Society prospective study. J Endourol
7. Israel GM, Silverman SG. The incidental renal mass
. Radiol Clin North Am
8. El-Saeity NS, Sidhu PS. “Scrotal varicocele, exclude a renal tumour.” Is this evidence based. Clin Radiol
9. Bradley AJ, Lim YY, Singh FM. Imaging features, follow-up, and management of incidentally detected renal lesions. Clin Radiol
10. Motzer RJ, Jonasch E, Agarwal N, et al NCCN clinical practice guidelines in oncology: kidney
cancer, version 2. 2017. https://www.nccn.org
.pdf. Accessed May 19, 2017.
11. Chen DY, Uzzo RG. Evaluation and management of the renal mass. Med Clin North Am
12. Mucksavage P, Ramchandani P, Malkowicz SB, Guzzo TJ. Is ultrasound imaging inferior to computed tomography or magnetic resonance imaging in evaluating renal mass size. Urology
13. Ha SB, Kwak C. Current status of renal biopsy for small renal masses. Korean J Urol
14. Silverman SG, Israel GM, Trinh QD. Incompletely characterized incidental renal masses: emerging data support conservative management. Radiology
15. Huang WC, Pinheiro LC, Russo P, et al Surveillance for the management of small renal masses: utilization and outcomes in a population-based cohort. J Clin Oncol
. 2013;31(suppl 6; abstract 343).
16. Pandharipande PV, Gervais DA, Hartman RI, et al Renal mass biopsy to guide treatment decisions for small incidental renal tumors: a cost-effectiveness analysis. Radiology
17. Nalavenkata S, Jarvis TR, Rashid P. Incidental small renal mass: current management. ANZ J Surg
18. Lau WK, Blute ML, Weaver AL, et al Matched comparison of radical nephrectomy
surgery in patients with unilateral renal cell carcinoma and a normal contralateral kidney
. Mayo Clin Proc
19. Huang WC, Elkin EB, Levey AS, et al Partial nephrectomy versus radical nephrectomy
in patients with small renal tumors: is there a difference in mortality and cardiovascular outcomes. J Urol
20. Lane BR, Gill IS. 7-year oncological outcomes after laparoscopic and open partial nephrectomy. J Urol
Keywords:Copyright © 2018 American Academy of Physician Assistants
incidental renal mass; renal cell cancer; nephron-sparing; radical nephrectomy; staging; kidney