Imaging of Kidney Cancer
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Knowing the stage of the kidney cancer helps doctors plan the best treatment for you. The stage can be given before surgery clinical staging , but may be revised after surgery pathologic staging. If you have kidney cancer, your doctor will use the results of the tests described above to assign a stage of I—IV see below for more detail :. Prognosis means the expected outcome of a disease. It is not possible for anyone to predict the exact course of the disease, but your medical team can give you an idea about common issues that affect people with kidney cancer.
The stage of the cancer is the main factor in determining prognosis. In most cases, the earlier that kidney cancer is diagnosed, the better the chance of successful treatment. If the cancer is found after it has spread to other parts of the body, it is very unlikely that all of the cancer can be removed, but treatment can often keep it under control.
People who can have surgery to remove the cancer tend to have better outcomes. However, other factors such as your age, general fitness and medical history also affect prognosis. In Australia, the TNM system is the method most often used for staging kidney cancer. The TNM gives numbers to the size of the tumour T1—4 , whether or not lymph nodes are affected N0 or N1 , and whether the cancer has spread or metastasised M0 or M1.
The cancer is larger than 7 cm, may have spread to the renal vein or the outer tissue of the kidney but no further, and has not spread to any lymph nodes. The cancer is any size and has spread to nearby lymph nodes, or the cancer has spread to the adrenal gland. The cancer has spread beyond the kidney, adrenal gland and nearby lymph nodes, and is found in more distant parts of the body, such as the abdomen, distant lymph nodes, or organs such as the liver, lungs, bone or brain. Stage IV may also be called metastatic kidney cancer.
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- How Kidney Cancer Is Diagnosed and Staged!
The main type of kidney cancer is renal cell carcinoma RCC. Types of RCC include clear cell, papillary and chromophobe. Kidney cancer is most often discovered during a test or scan for an unrelated reason. Because kidney cancer often doesn't produce any symptoms, it may be present for some time before it is found. This means some kidney cancers are diagnosed at an advanced stage.
Other tests can give more information about the cancer. These tests may include urine and blood tests to see how well your kidneys are working and to look for changes caused by cancer. Call or email our experienced cancer nurses for information and support. Contact a cancer nurse. Cancer Council Victoria would like to acknowledge the traditional custodians of the land on which we live and work. We would also like to pay respect to the elders past and present and extend that respect to all other Aboriginal people.
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Early and advanced kidney cancer Some kidney cancers are diagnosed when they have already spread beyond the kidney advanced kidney cancer. Imaging scans You will usually have at least one of the following imaging scans. Ultrasound In an ultrasound, soundwaves are used to produce pictures of your internal organs. CT scan A CT computerised tomography scan uses x-rays to take many pictures of the inside of your body and then a computer compiles them into one detailed, cross-sectional picture.
MRI scan An MRI magnetic resonance imaging scan uses a powerful magnet and radio waves to build up detailed, crosssectional pictures of the inside of your body. Radioisotope bone scan A radioisotope scan is used to see if any cancer cells have spread to the bones. Tissue biopsy Removing a tissue sample from the kidney for examination under a microscope is the only way to confirm a diagnosis of kidney cancer.
Grading kidney cancer By examining a tissue sample taken during a biopsy or surgery, doctors can see how similar the cancer cells look to normal cells and estimate how fast the cancer would grow without any treatment. Staging kidney cancer The stage of a cancer describes how large it is, where it is, and whether it has spread in the body. If you have kidney cancer, your doctor will use the results of the tests described above to assign a stage of I—IV see below for more detail : stages I—II are considered early kidney cancer stages III—IV are considered advanced kidney cancer.
Prognosis Prognosis means the expected outcome of a disease. How kidney cancer is staged In Australia, the TNM system is the method most often used for staging kidney cancer. Stage I The cancer is confined to the kidney and measures less than 7 cm. Stage II The cancer is larger than 7 cm, may have spread to the renal vein or the outer tissue of the kidney but no further, and has not spread to any lymph nodes. Stage III The cancer is any size and has spread to nearby lymph nodes, or the cancer has spread to the adrenal gland.
Stage IV The cancer has spread beyond the kidney, adrenal gland and nearby lymph nodes, and is found in more distant parts of the body, such as the abdomen, distant lymph nodes, or organs such as the liver, lungs, bone or brain. Key points about diagnosing kidney cancer What it is The main type of kidney cancer is renal cell carcinoma RCC.
How is it found Kidney cancer is most often discovered during a test or scan for an unrelated reason. Other tests Other tests can give more information about the cancer. Key information about the cancer The grade indicates how fast the cancer is likely to grow. The higher the grade, the faster the cancer cells are growing. The stage shows how far the cancer has spread throughout the body.
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Types of Kidney Cancer
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How Kidney Cancer Is Diagnosed and Staged
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Meet the team. Major research projects. Skin cancer prevention. Diet and obesity. Cancer screening. Cancer care and other research. Cancer Epidemiology Division. These publications were used to inform the statements presented in the guideline as Standards, Recommendations or Options. When sufficient evidence existed, the body of evidence for a particular treatment was assigned a strength rating of A high , B moderate or C low. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinion.
Patients undergoing follow-up for treated or observed renal masses should undergo a history and physical examination directed at detecting signs and symptoms of metastatic spread or local recurrence. Clinical Principle. Expert Opinion. Patients with progressive renal insufficiency on follow-up laboratory evaluation should be referred to nephrology.
Recommendation; Evidence Strength. Grade C. The Panel recommends against the performance of a bone scan in the absence of an elevated alkaline phosphatase ALP or clinical symptoms, such as bone pain, or radiographic findings suggestive of a bony neoplasm. Patients with a history of a renal neoplasm presenting with acute neurological signs or symptoms must undergo prompt neurologic cross-sectional CT or MRI scanning of the head or spine based on localization of symptomatology. Standard; Evidence Strength. Grade A.
The Panel recommends against the routine use of molecular markers, such Ki, p and VEGF, as benefits remain unproven at this time. Additional abdominal imaging US, CT or MRI may be performed in patients with low risk pT1, N0, Nx disease following a radical nephrectomy if the initial postoperative baseline image is negative. Option; Evidence Strength. Abdominal imaging US, CT, or MRI may be performed yearly for three years in patients with low risk pT1, N0, Nx disease following a partial nephrectomy based on individual risk factors if the initial postoperative scan is negative.
The Panel recommends that patients with a history of low risk pT1, N0, Nx renal cell carcinoma undergo yearly chest x-ray CXR to assess for pulmonary metastases for three years and only as clinically indicated beyond that time period. The Panel recommends site-specific imaging as warranted by clinical symptoms suggestive of recurrence or metastatic spread.
Percutaneous biopsy may be considered in patients planning to undergo active surveillance. The Panel recommends that patients undergo cross-sectional abdominal scanning CT or MRI within six months of active surveillance initiation to establish a growth rate. The Panel recommends that patients on active surveillance with biopsy proven renal cell carcinoma or a tumor with oncocytic features undergo an annual chest x-ray CXR to assess for pulmonary metastases. A urologist should be involved in the clinical management of all patients undergoing renal ablative procedures including percutaneous ablation.
The Panel recommends that all patients undergoing ablation procedures for a renal mass undergo a pretreatment diagnostic biopsy. The standardized definition of "treatment failure or local recurrence" suggested in the Clinical T1 Guideline document should be adopted by clinicians. This should be further clarified to include a visually enlarging neoplasm or new nodularity in the same area of treatment whether determined by enhancement of the neoplasm on post-treatment contrast imaging, or failure of regression in size of the treated lesion over time, new satellite or port site soft tissue nodules, or biopsy proven recurrence.
The Panel recommends that patients undergo cross-sectional scanning CT or MRI with and without intravenous IV contrast unless otherwise contraindicated at three and six months following ablative therapy to assess treatment success. Patients may undergo further scanning CT or MRI beyond five years based on individual patient risk factors. Patients undergoing ablative procedures who have either biopsy proven low risk renal cell carcinoma, oncocytoma, a tumor with oncocytic features, nondiagnostic biopsies or no prior biopsy, should undergo annual chest x-ray CXR to assess for pulmonary metastases for five years.
Imaging beyond five years is optional based on individual patient risk factors and the determination of treatment success. The Panel recommends against further radiologic scanning in patients who underwent an ablative procedure with pathological confirmation of benign histology at or before treatment and who have radiographic confirmation of treatment success and no evidence of treatment related complications requiring further imaging. The alternatives of observation, repeat treatment and surgical intervention should be discussed, and repeat biopsy should be performed if there is radiographic evidence of treatment failure within six months if the patient is a treatment candidate.
A progressive increase in size of an ablated neoplasm, with or without contrast enhancement, new nodularity in or around the treated zone, failure of the treated lesion to regress in size over time, satellite or port side lesions, should prompt lesion biopsy. Follow-up for adult cancer survivors has traditionally focused on the early detection of a cancer recurrence based on the presumption that treatment of a lower tumor burden would result in better patient outcomes, although the evidentiary data supporting this presumption is limited.
The recommended essential elements of adult cancer survivorship care now include not only monitoring for cancer recurrence, secondary cancers and treatment effects, but also the prevention of recurrences or new tumors, medical interventions for the consequences of cancer and its treatment effects and the coordination between specialists and primary care physicians to meet survivors' needs.
Several recent concerns have made the development of this guideline document a high priority for the American Urological Association AUA. There is now an increasing rate of detection and subsequent treatment of small renal masses of uncertain biological potential as well as a widening spectrum of contemporary treatment options with varied treatment related effects.
The advent of a new generation of targeted systematic therapy now holds the promise of prolonged survival of patients with metastatic disease. Additionally, patients with renal cell cancer tend to be older and have a greater incidence of pre-existing kidney disease, which places them at an increased risk for either the development or progression of chronic kidney disease following therapy. Since effective treatment strategies are available to slow the progression of chronic kidney disease and reduce cardiovascular risks, it would seem prudent to include renal function monitoring in the follow-up of renal cancer patients to facilitate early interventions or referral to nephrology.
Keeping these issues in mind, the Panel sought to create evidence-based guidelines for the follow-up and surveillance of clinically localized renal cancers treated with surgery or renal ablative procedures, biopsy-proven untreated clinically localized renal cancers followed on surveillance and radiographically suspicious but biopsy-unproven renal neoplasms either treated with renal ablative procedures or followed on active surveillance. These guideline recommendations have been systematically developed based on a comprehensive search of the English-language peer-reviewed and published literature, with a methodologically rigorous assessment of the quality of evidence for the prognosis, diagnosis and therapy of renal masses.
The recommendations made in this document as to the extent to which the benefits of a given management strategy outweigh potential risks reflect the judgments of the multidisciplinary panel and are based on the currently available "best" evidence. These guidelines will provide an outline of judicious follow-up that balances patient risk and possible benefits of therapy. The following document details those evidence-based recommendations of the AUA, and a summary of the suggested follow-up protocols based on procedure are listed in Appendix A.
Process for Literature Selection. A systematic review was conducted to identify published articles relevant to key questions specified by the Panel See Appendix B related to kidney neoplasms and their follow-up imaging, renal function, markers, biopsy, prognosis. This search covered articles in English published between January and Study designs consisting of clinical trials randomized or not , observational studies cohort, case-control, case series and systematic reviews were included.
All other study types were excluded. Studies with full-text publication available were included, but studies in abstract form only were excluded. Patients with metastatic renal cell carcinoma, transitional cell carcinoma and hereditary syndromes as well as those treated with radiation or systemic therapy were excluded. Additionally, studies involving pediatric patients or those in which outcomes among qualifying index cases could not be separated from other cases or other malignancies were excluded as well. Management strategies considered include active surveillance, surgery partial or radical nephrectomy and ablative procedures cryoablation or radiofrequency ablation.
All other management strategies or treatment itself were excluded. Studies with less than 30 patients were excluded given the unreliability of the statistical estimates and conclusions that can be derived from them. Articles with abstracts fulfilling the outlined inclusion criteria that addressed one or more of the posed questions were retrieved in full text for further review. Reason for exclusion of rejected articles was recorded. Studies reported within multiple publications were scrutinized in order to retrieve the most recent, non-redundant and inclusive data.
Related references contained in each article were perused to ensure the inclusion of all pertinent material. Accepted articles were extracted using customized forms. Given the pool size of eligible articles, independent double extraction was not possible for most articles. Instead, the methodologist reviewed the work of the extractors and searched for inconsistencies and missing information in the data extracted with emphasis on outcomes. The methodological quality of the studies was evaluated using the QUADAS tool 8 for questions framed in the context of a "diagnostic" problem.
Many studies included retrospective cohorts reporting on the follow-up of patients. For these studies, the framework proposed by Hayden et al. This framework evaluates potential sources of bias within six domains: sample representativity, attrition, adequate measurement of prognostic factors, adequate measurement of outcomes, assessment and control of potential confounders and appropriate statistical analysis. This framework's implementation was adapted to the question context. Overall quality scores together with study design and consistency of estimates across studies were used to grade the strength of the evidence into three levels: A strong , B moderate and C weak.
These were also used to identify factors that could explain heterogeneity of estimates, if found. Meta-analyses were performed on questions in which at least four studies were available. These estimates were based on DerSimonian-Laird random effects. Analyses were performed in the R platform version 2. For most outcomes, a meta-analysis of proportions was performed.
For these, raw counts for numerator and denominator were extracted from each study. The other meta-analyses were performed on the hazard rate survival after surgery , hazard ratio from multivariable Cox regression models and area under the characteristic AUC curve and their corresponding standard error. Hazard rates were obtained from survival rates at a minimum of five years, assuming that the curve exhibited an exponential distribution.
The assumption of an exponential distribution could be confirmed graphically from a group of articles that provided corresponding survival curves. The resulting overall hazard rate was used to build a cumulative incidence function that covered five years of follow-up.
The proportion of events in quarters for the first two years and biannually for the following three years were determined in order to guide the selection of an appropriate follow-up frequency for cases of clinically localized renal mass undergoing curative surgery without adjuvant or salvage treatment. Since partial and radical nephrectomy have been considered equivalent in terms of cancer control outcomes for T1 disease, these were included in the same analysis to increase the number of studies available. The standard error was estimated from available data when it was not provided directly by the individual studies.
In the case of survival curves, Kaplan-Meier curves with number of individuals at risk were transformed to their corresponding standard error. In the case of the AUC, actual numbers of individuals diseased and non-diseased and numbers of individuals labeled as diseased and non-diseased by a threshold were used for determining the standard error as proposed by Hanley and McNeil. AUC was used for assessing kidney function, and disease refers to patients with kidney insufficiency.
When standard error was not available or could not be estimated the study was excluded from analysis. For some clinical issues, there was little or no evidence from which to construct evidence-based statements. Where gaps in the evidence existed, the Panel provides guidance in the form of Clinical Principles or Expert Opinions with consensus achieved using a modified Delphi technique if differences of opinion existed among Panel members. Expert Opinion refers to a statement, achieved by consensus of the Panel, that is based on members' clinical training, experience, knowledge and judgment and for which there is no evidence.
The completed evidence report may be requested through AUA. Panel Selection and Peer Review Process. All panel members were subject to and remain subject to the AUA conflict of interest disclosure criteria for guideline panel members and chairs. The AUA conducted an extensive peer review process. The initial draft of this Guideline was distributed to 67 peer reviewers; 39 responded with comments. The Panel reviewed and discussed all submitted comments and revised the draft as needed. Once finalized, the Guideline was submitted for approval to the PGC. Funding of the Panel was provided by the AUA.
Panel members received no remuneration for their work. Radiologic Imaging Benefits and Risks. For follow-up of patients with treated or untreated renal carcinoma or patients with neoplasms suspected to represent renal carcinoma, radiologic imaging is a valuable tool and is, in fact, the mainstay of surveillance management of these patients. Radiologic imaging modalities that play an important role in detecting disease regression, progression, recurrence or metastasis include computed tomography CT , magnetic resonance imaging MRI , diagnostic ultrasound US and plain film chest x-ray CXR.
Positron emission tomography PET scanning with labeled antibody 16 is under evaluation for imaging of renal carcinoma and may play a role in the future but is currently not standard or recommended diagnostic measure. CT and MRI are used both for detection and characterization of neoplasms suspected to represent renal carcinoma; advantages of these two higher-resolution imaging modalities include their noninvasive nature and superior diagnostic accuracy. Despite the advantages of CT and MRI, the potential adverse effects and cost should also be kept in mind.
Recent attention has been paid to the cumulative radiation exposure of the population attributable to the widespread and increasing use of CT scanning. Indeed, the use of CT has markedly increased in recent decades. It is estimated that more than 62 million CT scans are currently obtained each year in the United States, as compared with about 3 million in An underlying assumption for these extrapolations is that the long term biological damage caused by ionizing radiation essentially the cancer risk is directly proportional to the dose regardless of how small the exposure linear no-threshold LNT model.
Nevertheless, there is some indirect evidence linking exposure to low-level ionizing radiation at doses used in CT to subsequent development of cancer. Epidemiologic data in the report includes a study of populations who had received low doses of radiation, including populations who received exposures from diagnostic radiation. Doses received by individuals in whom an increased risk of cancer was documented were similar to doses associated with commonly used CT studies.
Initiatives to better educate patients, referring physicians, radiologic technologists and radiology residents on radiation safety and patient dose have begun. In addition, risks related to administration of iodinated intravenous IV contrast for CT, including contrast hypersensitivity and contrast-induced renal failure, should also be kept in mind when considering the use of CT in the workup and follow-up of renal cancer. In designing follow-up imaging protocols for renal cancer, the Panel has kept these risks in mind.
For MRI, which does not involve the use of ionizing radiation, the prime adverse effect to consider is the development of nephrogenic systemic fibrosis NSF due to IV gadolinium administration. NSF is a rare but potentially debilitating or even fatal fibrosing condition that most often affects the skin but can involve multiple organs. There is currently no effective treatment for this condition, 22 which was first reported in In a study, five of nine patients with end-stage renal disease who underwent gadolinium-enhanced magnetic resonance MR angiography developed NSF, and since then additional studies have supported the causative role of gadolinium contrast agent in the development of NSF.
Gadolinium has been found in the skin biopsies of affected patients. In this study, 12 patients developed NSF, all of whom had undergone gadolinium contrast-enhanced MR imaging using a double dose of IV contrast. Four of the 12 patients developed acute renal failure related to hepatorenal syndrome; all four patients underwent liver transplantation within 17 days of MR imaging.
One patient had renal transplant failure two weeks prior to undergoing MR imaging. The remaining seven patients had chronic renal failure from a variety of causes. Eight of the 12 patients had undergone vascular surgery, had deep venous thrombosis or had coagulopathies in the interval between contrast agent injection and the development of NSF.
Risk factors for development of NSF include high doses of gadolinium-based contrast agents, both acute and chronic renal failure and vascular injury. Food and Drug Administration FDA currently recommends against the use of gadolinium-based contrast agents in patients with acute or chronic renal insufficiency, with a glomerular filtration rate GFR less than 30 mL per minute per 1. Although US is an attractive modality for imaging renal masses owing to its less invasive nature and availability as compared to CT and MRI, the use of US as a tool for de novo detection of renal mass lesions is limited by its lower sensitivity, especially for detection of small mass lesions, lesions that are similar in echogenicity to the renal parenchyma, and lesions that do not deform the renal contour.
Renal Function Assessment. Preservation of renal function in patients with renal neoplasms is a key clinical consideration that factors heavily in management decisions and, therefore, deserves appropriate assessment during follow-up. Table 2 provides data reviewed on the incidence of renal function impairment among patients undergoing either partial or radical nephrectomy indicating the large proportion of patients meeting criteria for chronic kidney disease following renal surgery and relative insensitivity of isolated serum creatinine measurements in assessing this impact.
Renal function may be estimated by a variety of methodologies including timed voided creatinine collections, inulin clearance, nuclear renal scan or standardized mathematical formulas, though none are currently validated for use in the follow-up of patients covered by this guideline. Recognition of the variability in nephrologic outcomes associated with aspects of treatment and the central role of renal physiology has refocused efforts in quantifying dynamic changes in functional renal outcomes.
Functional renal imaging studies including MRI and radioscintigraphy are used with increasing regularity throughout the course of management to evaluate differential contribution of renal function, the impact of therapy and factors that may influence the effects of treatment on global renal function.
Serum creatinine is commonly used as a benchmark of renal function; however, as a byproduct of creatine phosphate metabolism in muscle, it is predominantly cleared by the glomerulus, with serum levels subject to influence by a number of factors, including gender, age and genetic variations, among others. Therefore, it is more clinically relevant and appropriate to utilize serum creatinine to calculate an individual's estimated glomerular filtration rate eGFR using a mathematical formula that can correct for these main variables.
While both formulas utilize the same four variables serum creatinine, age, gender, ethnicity , sufficient differences in their performance characteristics suggest that they are not interchangeable. The CKD-EPI formula was devised and validated to address this and is based on an isotope dilution mass spectrometry standard that must be utilized by the clinical testing laboratory. In clinical practice, assessment of renal function should be used to identify patients who may benefit from medical management strategies which may prevent or delay the progression of chronic kidney disease.
Threshold values of renal dysfunction have been identified with guidelines for management established by the National Kidney Foundation. Early detection and effective treatment may prevent or delay the progression of renal dysfunction in patients with risk factors. Many of these underlying risk factors are well-known, including hypertension and diabetes, requiring chronic management for which referral may be made to an appropriate medical physician.
Secondary Malignancies. Several articles that deal with the incidence of secondary malignancies after the diagnosis of renal cell carcinoma were identified from the general query. These results include the following: Chakraborty et al. They identified 3, cases for a slightly increased standardized incidence ratio SIR 1 of 1.
Race, age and sex were associated with particular sites. Interestingly, they found that the risk of a secondary malignancy was slightly higher in patients who did not receive radiation therapy compared to those who did SIR 1. Among those who received radiation therapy, the adrenal glands and the thyroid were the most likely sites of secondary malignancy, and the risk was significantly increased only between months after the renal cell carcinoma diagnosis, suggesting an observer bias.
Leukemias were also increased in the radiation treated group. Skin and urinary bladder were the more likely sites among those who did not receive radiation.
In multivariable analysis, age younger than 60, lack of history of radiation treatment and 12 or more months between the diagnosis of renal cell carcinoma and the identification of a secondary malignancy were associated with increased overall survival. It is important to highlight that this study included children, and thus a genetic component cannot be discarded in the younger group since this information is not available in the SEER registry.
Liu et al. Among the patients with renal cell carcinoma, 8. The SIR for a second metachronous renal cell carcinoma beyond one year after the first diagnosis was 5. The SIR for other second malignancies among the renal cell carcinoma cases was 1. Eighty-four second parenchymal kidney cancers occurred during the first year after diagnosis 20 clear cell and 28 at one year or beyond 3 clear cell. In this study, cases with a secondary within one year were considered synchronous. Ojha et al. For the year age the SIR was 3. The highest risk for this secondary malignancy was within one year of the renal cell carcinoma diagnosis.
Needle Biopsy Considerations.
Advances in our knowledge of the molecular characteristics of most renal epithelial neoplasms have led to a better and more clinically relevant morphological classification system. With the increase of incidentally detected and smaller tumors, the number of benign or low-grade neoplasms has increased.
For example, in a recent study by Przybycin et al, only 1 of 74 Chromophobe carcinomas resected with a size of 4 cm or less developed metastatic disease, with a median clinical follow-up period of over six years. This approach is particularly appropriate in older patients and those with significant comorbidities, whether this is appropriate in young patients is debatable.
See Table 3 below for a complete list of the incidence of benign cases from biopsy reviewed in this guideline. The average proportion prevalence of benign cases is 0. Further, two studies of FNA conducted in had a proportion of benign cases that was considerably large 0. Re-estimating the proportion of benign cases excluding these two FNA studies results 0.
Benign cases ranged between 0. The accuracy of percutaneous biopsy has improved substantially over the past several years due to further refinements in CT- and MRI-guided techniques, and several systematic reviews have addressed this specific diagnostic procedure, 58,59 focusing on several key issues. Lastly, the incidence of symptomatic complications is relatively low, with only a very small percentage requiring any form of intervention.
In most studies only a fraction of patients who underwent percutaneous aspiration or needle core biopsy went on to nephrectomy, making the assessment of sensitivity and specificity of the diagnostic procedures less reliable. Whether the size of the tumor affects diagnostic accuracy has not been studied well, a potentially important issue given the inherent heterogeneity seen in renal neoplasms. Needle-tract seeding, once a common fear of renal biopsy, also appears to be exceedingly rare.
The overall accuracy of renal biopsy varied slightly according to biopsy technique, specifically core biopsy technique versus fine needle aspiration FNA. The variance was primarily attributed to the difference in non-diagnostic biopsy rate. Importantly, when non-diagnostic biopsies are discarded from analyses, sensitivity for core v. FNA is When both diagnostic and non-diagnostic samples are considered, core biopsies are more sensitive but less specific than FNA, although not statistically significantly different for either parameter. Attempts to improve the accuracy of biopsy such as incorporation of molecular analysis have shown promise and remain a future research priority.
Early studies that investigated the utility of percutaneous needle biopsy of renal masses were disappointing. However, more recent studies are more promising because of improvements in biopsy techniques, familiarity among pathologists with this type of specimen and the ability to apply ancillary tools, such as immunohistochemistry and fluorescent in situ hybridization to aid in the diagnosis. Fuhrman nuclear grade, particularly in clear cell carcinoma, has been shown to be an important predictor of progression and may influence subsequent treatment decisions. Given the heterogeneity seen in any given tumor, it is unlikely that grading a tumor on an aspirate or core biopsy will be reliable, nor has it shown to be reliable in studies.
Needle Biopsy Post-Ablation. Percutaneous needle core biopsy or FNA cytology after ablation is done when there is clinical suspicion that there is residual viable disease. In this setting interpretation of pathologic material is difficult because it is likely that the number of tumor cells present is small and the growth pattern distorted by the prior ablative procedure.
For this reason it is particularly important for the biopsy to be taken from an enhancing area of the neoplasm, avoiding the center of the mass that is commonly fibrotic. Evaluation of specimen adequacy at the time of biopsy is essential, assuring that sufficient diagnostic material remains for subsequent tumor characterization.
In the post ablation setting it may be more important to perform ancillary studies, such as immunohistochemistry or fluorescent in situ hybridization, to arrive at the correct diagnosis. It is also helpful to review the pathology of the biopsy material performed prior to the initial ablation as a means of comparison. Laboratory Data and Biomarkers. While no prospective validation currently exists for the use of common laboratory parameters in the early detection of metastases, following established practice provides an overall assessment of biochemical parameters, which in combination with a history and clinical exam provide the clinician a good estimate of a patient's overall condition and renal function.
There are several laboratory values that have been utilized both in the staging and monitoring of patients with renal cell carcinoma following treatment for recurrence. The identification of non-metastatic patients at high risk for relapse and those who are likely to benefit from adjuvant therapy with specific molecularly targeted agents is a long-term goal to optimize post-operative follow-up and management.
Many of the following guidelines are clinical principle or expert opinion only and cannot be substantiated due to the limited clinical evidence:. Interval patient history and physical examination are an integral part of medical care, offering the opportunity to yield critical information regarding the presence of disease recurrence or adverse events related to treatment effects.
A myriad signs and symptoms including weight loss, night sweats, shortness of breath, dermatologic involvement, musculoskeletal pain or weakness may herald disease progression or developing complication and serve as an indication for further investigation. Please see the renal assessment background section for a discussion of the benefits of monitoring renal function and referral to nephrology. LDH is included in several nomograms where it provides prognostic information, in particular for patients with advanced disease. Although no strong evidence exists for the use of these laboratory tests in the follow-up of patients with clinically localized renal cancers, a common sense approach dictates that measures of general organ function are part of routine follow-up for patients who are diagnosed with cancer.
While elevated pre-operative ALP is a potential prognostic marker for renal cell carcinoma, 64 additional retrospective reviews do not demonstrate utility of either bone scan or ALP in the initial evaluation or follow-up of asymptomatic patients with of renal cell carcinoma. The long term impact of renal dysfunction increases risks of osteoporosis, anemia, metabolic and cardiovascular disease, hospitalization and death. Effective treatment strategies are available to slow the progression of chronic kidney disease and reduce cardiovascular risks, and therefore timely identification of progressive renal dysfunction can provide opportunity for medical intervention when indicated.
Please refer to the Renal Assessment section for additional information. Recommendation; Evidence Strength: Grade C. Studies that address the utility of an initial bone scan in the work up of patients with of renal cell carcinoma show that, although bone scan has a reasonable sensitivity and specificity, the probability of finding bony neoplasms in the absence of elevated ALP or bone pain is low.
As such, the routine use of bone scan in the absence of bone pain or elevated ALP may be unnecessary. There are no compelling data in the literature supporting the use of bone scan in the follow-up of patients with non-metastatic disease. Routine imaging of these patients would result in a high rate of false-positive findings necessitating further burdensome, potentially invasive and resource intensive studies. As such, the routine use of bone scan in the absence of bone pain or elevated ALP is not required.
Standard; Evidence Strength: Grade A. CT may be used in the setting of acute neurological signs or symptoms to diagnose abnormalities that require emergent treatment, 71 but MRI is the most sensitive and specific imaging test for detection of metastatic neoplasms to the brain. Although there is some data indicating that an increase in molecular pathological markers, such Ki, p and VEGF, may be associated with a worse prognosis, none of the molecular markers have been prospectively validated in large series of patients; therefore, their utility in the current follow-up of patients is unknown.
At the time these guidelines were published, no prospectively validated biomarkers were available for use in either pre-treatment staging or post-treatment risk of recurrence for patients with of renal cell carcinoma, nor had any agents shown benefit in the adjuvant setting. However, as part of the analysis performed for the Guideline, molecular markers were assessed for their accuracy in predicting the risk of local recurrence, secondary tumors, metastases and cancer-specific deaths from of renal cell carcinoma in general and at one, two, three and five years.
No meta-analyses assessing the predictive role of markers on of renal cell carcinoma were found in the literature. A recent review of the literature 72 qualitatively summarizes the evidence for the different markers and their prognostic relevance and identifies the need for clinical trials that test candidate biomarkers prospectively.
Our literature search gave articles dealing with biomarkers, cancer-control outcomes and characterization of subtypes. There were four articles reporting the same cohort from UCLA. The most recent article, which was also more comprehensive in terms of number of markers assessed, was selected. These exclusions led to only 15 articles with potential data for meta-analysis. All but one study was based on renal cell carcinoma tissue from radical or partial nephrectomy specimens, rather than biopsy or FNA.
The quality of the potential conclusions derived from tumor tissue with a more accurate characterization than that observed in the reports for ablation or observation and a moderate sample size was somewhat diminished by the retrospective design used by all but one study. These studies were conducted before Most outcomes were represented by only two studies. For all outcomes and markers, an increase in the putative marker translated into a worse prognosis.
Surgical management with resection of the primary tumor provides for immediate local control of renal tumors and valuable pathologic data that may aid in understanding prognosis and guide patient follow-up. Post-operative follow-up seeks to satisfy several goals: the assessment of disease-specific outcomes; local, regional or distant recurrence; the adequacy of resection; evidence of residual disease and evaluation of ongoing or potential post-operative complications, such as loss of renal function or post-operative sequelae that may influence or require subsequent intervention.
Though the predictability of these outcomes may be partly quantified based on patient- and pathology-derived factors, standardized follow-up paradigms will ideally optimize post-operative care by providing opportunity for timely intervention of detected abnormalities with the expectation of patient benefit. The presumption, thus far untested, is that earlier detection of recurrent or metastatic disease will lead to earlier treatment and better outcomes for patients.
However, with the advent of a new generation of targeted systematic therapy, adjuvant therapy in patients identified with metastatic disease may hold the promise of a prolonged survival. Post-operative clinically-accepted standards for routine medical evaluation include thorough patient history and physical examination and laboratory studies as well as directed imaging procedures that focus primarily on the likely sites of local recurrence or metastatic progression.
The frequency and timing of these evaluations are influenced by a variety of factors in an individual patient. These include the stage and grade of the primary tumor, tumor histology and margin status as well as method of tumor extirpation e. In reviewing the literature, other factors appear to demonstrate prognostic significance including patient performance status, 73,74 the presence of sarcomatoid histology, 75,76 tumor grade, the presence of histologic tumor necrosis 77,78 and patient age.
There are a variety of nomograms or scoring systems described in the literature that combine various clinical, pathologic and even molecular markers purported to be prognostic in localized, locally advanced and metastatic renal cell carcinoma. Instead, the TNM pathologic stage, grade, nodal involvement and margin status remain the primary utilized factors to assess risk of local and distant recurrence following curative surgery.
In regards to the timing of failure, most studies note that the majority of disease relapses occur within the first three years following surgery. After that, additional failures are less common but have been reported to occur as late as 20 years following surgery. Therefore, surveillance guidelines are tailored to account for this disease biology, with more rigorous follow-up during the first three years following surgery and then decreasing the frequency of surveillance in subsequent years to reflect the decrease in recurrence risk over time following surgical resection.
Although the aforementioned algorithms assess prognosis using more clinical features, the current and past literature that provide guidance on surveillance regimens primarily depend on stage; however, grade is included in some risk stratification tools, such as UISS, SSIGN and MSKCC. Although grade is a risk factor considered in existing stratification tools, based on the meta-analysis conducted, including only cohorts of patients with localized disease, a consistent overall estimate was not feasible at this point using these prognostic factors.
Only stage was consistently analyzed in the recurrence data and thus serves as the key risk stratifier. See Appendix C for corresponding forest plots. Low risk is defined as organ-confined tumors pT1, N0 or Nx with negative or radiographically normal lymph nodes. A baseline abdominal scanning CT or MRI rather than US within three to twelve months after nephron-sparing surgery is useful for several reasons.
Following a partial nephrectomy and alteration of the kidney architecture, this imaging serves as a comparison point for possible future evaluations. In addition, imaging may be clinically indicated to monitor for post-operative complications and for patient symptomatology. For those undergoing a radical nephrectomy for low risk cT1 tumors a baseline postoperative US may suffice. Although during this time frame the risk of metastasis and metachronous cancer is low, this imaging does allow monitoring of the contralateral kidney as well. In patients at higher risk for local recurrence related to aberrant histology or positive margins, or those with bilateral or multifocal disease, such as the case of heredity or papillary cancer types, more frequent imaging may be indicated.
Option; Evidence Strength: Grade C. Abdominal imaging US, CT or MRI beyond the baseline post-operative evaluation is optional, as the risk of local recurrence in the renal remnant or the renal fossa and visceral or nodal metastatic progression is low. Patients with familial renal cell carcinoma syndromes represent a unique clinical situation that warrants more intensive and serial monitoring for the development of future renal tumors. Abdominal imaging US, CT or MRI beyond this baseline post-operative evaluation for low risk patients pT1, N0, Nx is optional as the risk of local recurrence in the renal remnant or the renal fossa and visceral or nodal metastatic progression is low.
With increasing awareness of the consequences of chronic kidney disease, 93 there has been an expanded utilization of partial nephrectomy for Clinical T1b and higher renal masses, which may be associated with a higher recurrence rate; therefore, careful attention and close follow-up should be conducted in patients with higher risk characteristics for recurrence imperative indications, clinical T1b and above, positive margins, higher tumor grade or aberrant histology or in patients who have perioperative adverse events such as a urinary leak, urinary fistula, AV fistula or ureteral stricture, and may warrant further imaging until the issue s is are resolved.
Pulmonary metastases are the most common site of renal cancer recurrence and are associated with more favorable outcome with appropriate treatment when identified as the sole site of recurrence. Based on the projected risk of progression, rates and sites of recurrence, thoracic imaging for the purpose of detecting pulmonary metastasis at least annually for three years is recommended.
CXR may be preferable to CT scan of the chest given the propensity of false positive CT imaging in the detection of benign radiographic findings that may then mandate invasive workups, such as intrapulmonary lymph nodes and granulomas. The choice of imaging modality should be weighed against the level of clinical suspicion. In the patient with low risk pT1, N0, Nx disease, it is reasonable to perform a CXR annually for at least three years.
If chest imaging is negative for three years post-surgery, then imaging beyond that point should only be done as clinically indicated. Therefore, for patients who are candidates for further therapy to treat a local or metastatic disease recurrence, an increased frequency of examinations is recommended. Based on the known rates and sites of recurrence, both chest CXR or chest CT and abdominal imaging US, CT or MRI is recommended every six months for at least three years and annually to year five following baseline imaging.
As pulmonary metastases are the most common site of renal cancer recurrence, timely detection of recurrent disease in the chest is optimized by a chest CT, which can be performed at the same time as the abdominal imaging. Occasionally, patients will present with symptoms that could be attributed to metastatic disease. These symptoms may include, but are not limited to, new onset bone pain, weight loss, anorexia, abdominal discomfort, asthenia, fatigue, gross hematuria and lower extremity edema. When patients present with symptoms that could be attributed to disease recurrence or metastasis, site-specific imaging should be obtained, and the modality of imaging CT, MRI, US, bone scan, plain films should be tailored to the specific presenting symptom.
The type of abdominal imaging utilized should be based on clinical factors and physician discretion keeping in mind the limitations of US over cross-sectional imaging with MRI or CT in visualizing a recurrence, the radiation exposures over time and the limitations based on contrast allergies or renal function.
Please refer to the radiologic imaging benefits and risks section for additional details. Cross-sectional imaging seems prudent for the first postoperative baseline scan due to the higher accuracy and detail provided over ultrasound.
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Most studies with five years of follow-up note that disease relapse usually occurs within the first three years with additional failures decreasing in frequency after three years. Therefore, surveillance guidelines are tailored to account for disease biology with more rigorous follow-up during the first three years following surgery and then decreasing the frequency of surveillance in subsequent years to reflect the decreased risk of recurrence over time following surgical resection.
Studies in the literature support continued imaging up to five years from the date of surgery; 95 however, there is a paucity of data to direct the frequency of imaging US, CT or MRI beyond five years. Articles providing rates for 10 years, 80, mainly for cancer-specific survival, do it for stages or risk groups from the available tools in a non-overlapping manner, so overall estimates as those obtained for five years cannot be calculated at this point.
Still, these studies and those that enumerate the occurrence of metastases in terms of their location and timing show that 1 metastases to the lung are the most common ones and can occur at any time during follow-up between 10 and 20 years after surgery, , either solitary or in combination with other sites, 2 the contralateral kidney, bones and brain are other common metastatic sites during the period between 10 and 15 years after surgery, 3 even individuals with pT1a disease can experience distant metastases beyond 5 years, 79, and 4 metastases have been reported to occur beyond years after nephrectomy.
There are no data in the literature to support the use of PET scanning in the evaluation or surveillance of patients with renal tumors due to the lack of data on the specificity and sensitivity. Its use is discouraged in these circumstances. Future roles may exist for PET with newer imaging agents, such as G, which are currently being studied.
The follow-up protocol for patients who have been selected for active surveillance is based on the AUA small renal mass treatment guidelines criteria, where definitive treatment has been deferred, and involves unique considerations. It is assumed that the patient who has been chosen for active surveillance is one who would undergo intervention if, in the course of active surveillance, changes occur in the primary tumor for which intervention would normally be indicated.
In the patient for whom no surgical or minimally invasive intervention i. For a complete definition of the patient criteria for whom active surveillance is indicated, please refer to Appendix D. Follow-up protocols may vary depending on whether the patient has undergone a biopsy of the renal mass. The Panel considered clinical scenarios including biopsy-proven, untreated, clinically localized renal cancers; biopsies yielding low-malignant potential neoplasms or normal renal parenchyma; and renal lesions radiographically suspicious for neoplasm that either have not been biopsied or have indeterminate biopsy results.
Alternatively, a strategy of observation with delayed intervention as indicated may be elected in order to determine the growth rate or to obtain alternative diagnostic imaging. Potential triggers for intervention while on active surveillance primarily involve absolute tumor size, tumor growth rate or a change in patient preference.
The meta-analysis by Chawla and colleagues focused on estimating the yearly tumor growth rate of enhancing renal masses among multiple small series. The development of these metastases could not be associated with tumor growth or neoplasm size at presentation. Among these studies, the mean metastasis-free survival rate was