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Guideline Summary
Guideline Title
Guideline for management of the clinical stage 1 renal mass.
Bibliographic Source(s)
American Urological Association Education and Research, Inc. Guideline for management of the clinical stage 1 renal mass. Linthicum (MD): American Urological Association Education and Research, Inc.; 2009. 81 p. [182 references]
Guideline Status

This is the current release of the guideline.

Scope

Disease/Condition(s)

Clinical stage 1 renal mass

Guideline Category
Assessment of Therapeutic Effectiveness
Counseling
Diagnosis
Evaluation
Management
Risk Assessment
Treatment
Clinical Specialty
Internal Medicine
Nephrology
Oncology
Pathology
Surgery
Urology
Intended Users
Physicians
Guideline Objective(s)
  • To conduct a systematic literature review of the relevant scientific evidence
  • To identify descriptive information about samples and procedures relevant to interpreting existing evidence
  • To identify outcomes relevant to patients, families, and practitioners
  • To estimate outcome effect sizes for the most commonly used treatments and approaches
  • To complement the available evidence with expert opinion
  • To determine what additional evidence is needed to further evidence-based management of the clinically localized renal mass
  • To provide medical practitioners with a current understanding of the principles and strategies for the management of the clinical stage 1 renal mass
Target Population

Patients with the clinical stage 1 renal mass

Interventions and Practices Considered

Diagnosis/Evaluation/Counseling

  1. Computed tomography or magnetic resonance imaging with or without contrast
  2. Percutaneous renal mass core biopsy when indicated
  3. Discussing with patients available treatment options and their benefits and risks and counseling patients about potential advantages of nephron-sparing treatment approaches

Management/Treatment

  1. Partial nephrectomy (open or laparoscopic)
  2. Radical nephrectomy (open or laparoscopic)
  3. Thermal ablation (cryoablation or radiofrequency ablation)
  4. Active surveillance with no intervention or delayed intervention
Major Outcomes Considered
  • Major urological complications
  • Major nonurological complications
  • Perioperative events (conversions, transfusions, reinterventions)
  • Total recurrence-free survival (RFS)
  • Local RFS
  • Metastatic RFS
  • Cancer-specific survival
  • Overall survival

Methodology

Methods Used to Collect/Select the Evidence
Searches of Electronic Databases
Description of Methods Used to Collect/Select the Evidence

Literature Searches and Article Selection

Literature searches on English-language publications were performed using the MEDLINE database from January 1, 1996 to September 30, 2007 using the terms "renal carcinoma" and "renal mass" in conjunction with the interventions evaluated. Pediatric studies, studies with sample size less than five, editorials and reviews were eliminated. Studies that focused primarily on surgical techniques without detailed outcomes information and studies in which more than 50% of patients were dialysis patients, solitary kidney patients, patients with recurrent renal cell carcinoma (RCC) or patients with hereditary RCC syndromes were eliminated. Studies that reported descriptive or outcomes information collapsed across multiple interventions were also excluded. Multiple reports on the same patient group were carefully examined to ensure inclusion of only nonredundant outcomes data. For the survival analyses, studies had to meet the additional criteria that the diagnosis of RCC was validated pathologically and that survival outcomes for RCC patients were separable from outcomes for patients diagnosed with benign tumors. One exception was made to this rule: active surveillance (AS) patients were included in metastatic recurrence-free survival (RFS) analyses. This exception was made because of the clinical importance of estimating the probability of metastases in patients for whom no intervention was undertaken. All extracted articles used adult human subjects.

Number of Source Documents

A total of 114 articles met inclusion criteria and underwent data extraction. Table 1 in the original guideline document lists the total number of arms for each intervention and the number of studies of each type used to generate descriptive information and used in the meta-analyses.

Methods Used to Assess the Quality and Strength of the Evidence
Expert Consensus (Committee)
Rating Scheme for the Strength of the Evidence

Not applicable

Methods Used to Analyze the Evidence
Meta-Analysis of Observational Trials
Systematic Review with Evidence Tables
Description of the Methods Used to Analyze the Evidence

Data Extraction and Evidence Combination

Quantitative information about samples, procedures and outcomes was extracted by the methodologist into Excel spreadsheets. All entered data were double checked for accuracy.

Most studies examined one treatment group; some studies compared two treatment groups. All intervention groups were treated as single arms that estimated the outcome or other variable in the population of interest, regardless of the number of groups in a particular study. This approach maximized statistical power and the use of available information. Table 1 in the original guideline document lists the total number of arms for each intervention and the number of studies of each type used to generate descriptive information and used in the meta-analyses.

The effect size calculated was a point estimate with 95% confidence intervals. The point estimate for a given outcome includes all study arms that reported that particular outcome. Most of the data involved the occurrence of an event (i.e., a complication, a recurrence, a death), resulting in point estimates that are estimates of the event rate for a particular outcome in the population of interest bounded by 95% confidence intervals. In the tables, the event rates are expressed as percentages.

Statistical Model

A random effects model was used to calculate the effect size for each study and to generate the overall effect sizes for particular interventions. (Note: All effect size calculations and analyses were run using Comprehensive Meta-Analysis [CMA] software, version 2.0 [Biostat, Inc.]). This model assumes that the true effect could legitimately vary from study to study following a normal distribution and that some variability across studies is variability in true effect that is not error. This model produces conservative estimates of effect sizes and is the most appropriate given the type of data available.

Limitations of Available Data

Limitations of study design: The overwhelming majority of studies available to the Panel were observational, retrospective, reported findings on samples of convenience that were not randomized to treatments and involved only one treatment group. There are inherent, unknown and unquantifiable biases within each study because of the lack of randomization. The Panel weighed this issue carefully in its deliberations and concluded that meta-analysis was valuable to describe the existing literature and to determine what types of information are needed to further evidence-based management of the clinical stage 1 renal mass.

Confounding variables: Interpreting statistically significant differences in outcomes across interventions requires thorough consideration of other variables that could account for differences. Three confounding variables that differed across interventions were focused on in detail: patient age, tumor size, and follow-up duration. For most outcomes, the influence of confounding variables could not be separated from possible intervention effects, making interpretation of statistically significant differences difficult. For this reason, only comparisons for which confounding variables appear to exert minimal influence are presented. The possible impact of these factors must be weighed carefully in interpreting the point estimates.

Refer to the original guideline document for more information.

Methods Used to Formulate the Recommendations
Expert Consensus
Description of Methods Used to Formulate the Recommendations

The supporting systematic literature review and data analysis and the drafting of this document were conducted by the Renal Mass Guideline Panel created in 2006 by the American Urological Association Education and Research, Inc. (AUA). The Practice Guidelines Committee (PGC) of the AUA selected the Panel chair who in turn appointed the Panel facilitator and members; all Panel members were urologists with specific expertise in this disease. The mission of the Panel was to develop either analysis- or consensus-based recommendations, depending on the type of evidence available, to support optimal clinical practices in the management of the clinical stage 1 renal mass.

The Panel developed the guideline statements from the findings of the systematic review, a careful assessment of the meta-analysis, the use of expert opinion when data were lacking or incomplete, and panel consensus.

Rating Scheme for the Strength of the Recommendations

The guideline statements are graded with respect to the degree of flexibility in application. A "standard" is the most rigid treatment policy. A "recommendation" has significantly less rigidity, and an "option" has the largest amount of flexibility. These terms are defined as follows:

Standard: A guideline statement is a standard if: (1) the health outcomes of the alternative interventions are sufficiently well known to permit meaningful decisions, and (2) there is virtual unanimity about which intervention is preferred.

Recommendation: A guideline statement is a recommendation if: (1) the health outcomes of the alternative interventions are sufficiently well known to permit meaningful decisions, and (2) an appreciable, but not unanimous majority agrees on which intervention is preferred.

Option: A guideline statement is an option if: (1) the health outcomes of the interventions are not sufficiently well known to permit meaningful decisions, or (2) preferences are unknown or equivocal.

Cost Analysis

A formal cost analysis was not performed and published cost analyses were not reviewed.

Method of Guideline Validation
External Peer Review
Internal Peer Review
Description of Method of Guideline Validation

The draft of the guideline was sent to 69 peer reviewers of whom 35 provided comments; the Panel revised the document based on the comments received. The guideline was submitted first for approval to the Practice Guidelines Committee (PGC) of the American Urological Association Education and Research, Inc. (AUA) and then forwarded to the AUA Board of Directors for final approval.

Recommendations

Major Recommendations

Grades of the guideline statements (Standard, Recommendation, Option) are defined at the end of the "Major Recommendations" field.

Panel Consensus Regarding Treatment Modalities

Despite limitations of the literature, the Panel was able to reach the following consensus about the various treatment modalities:

  • Nephron-sparing surgery (NSS) should be considered in all patients with a clinical T1 renal mass as an overriding principle, presuming adequate oncologic control can be achieved, based on compelling data demonstrating an increased risk of chronic kidney disease (CKD) associated with radical nephrectomy (RN) and a direct correlation between CKD and morbid cardiovascular events and mortality on a longitudinal basis. RN is still a viable option when necessary based on tumor size, location or radiographic appearance if the surgeon judges that NSS is not feasible or advisable. A laparoscopic approach to RN is now an established standard and should be considered if this procedure is required as it is associated with a more rapid recovery.
  • Active surveillance (AS) is a reasonable option for the management of localized renal masses that should be discussed with all patients and should be a primary consideration for patients with decreased life expectancy or extensive comorbidities that would make them high risk for intervention. For patients who are candidates for intervention, counseling about AS should include a balanced discussion of the small but real risk of cancer progression, lack of curative salvage therapies if metastases develop, possible loss of window of opportunity for NSS and substantial limitations of the current AS literature. Larger tumors (> 3 to 4 cm) and those with aggressive appearance, such as infiltrative growth pattern, may be associated with increased risk and should be managed in a proactive manner, if possible.
  • Thermal ablation (cryoablation or radiofrequency ablation [RFA]), either percutaneous or laparoscopic, is an available treatment option for the patient at high surgical risk who wants active treatment and accepts the need for long-term radiographic surveillance after treatment. Tumor biopsy (core biopsy is recommended for better diagnostic accuracy) should always be performed prior to treatment to define histology and should also be considered after treatment, particularly if there is any suspicion of recurrence. Counseling about thermal ablation should include a balanced discussion of the increased risk of local recurrence when compared to surgical excision, potential need for reintervention, lack of well-proven radiographic parameters for success, potential for difficult surgical salvage if tumor progression is found and the substantial limitations of the current thermal ablation literature. Larger tumors (> 3.5 cm) and those with irregular shape or infiltrative appearance may be associated with increased risk of recurrence when managed with thermal ablation.
  • Surgical excision by partial nephrectomy (PN) is a reference standard for the management of clinical T1 renal masses, whether for imperative or elective indications, given the importance of preservation of renal parenchyma and avoidance of CKD. This treatment modality is greatly underutilized. PN has well established longitudinal oncologic outcomes data comparable to RN. Adequate expertise and careful patient selection are important. A laparoscopic approach can provide more rapid convalescence, but has been associated with an increased risk of major urologic complications and longer warm ischemia times when compared to traditional open partial nephrectomy (OPN). In general, OPN is preferred for complex cases such as tumor in the renal hilum, tumor in a solitary kidney, or multiple tumors.

Treatment Guideline Statements

The Panel developed the following guideline statements from a careful assessment of the meta-analysis, the use of expert opinion when data were lacking or incomplete, and panel consensus. These statements apply to the treatment of patients with clinical T1 renal masses. Inherent in these guideline statements is the importance of individualizing patient diagnostic evaluation and therapy. In an attempt to recognize commonly encountered clinical variations, each guideline statement addresses a specific patient.

For All Index Patients

  • Standard: Physicians should obtain a high-quality cross-sectional imaging study (computed tomography [CT] or magnetic resonance imaging [MRI]) with and without contrast (in the presence of adequate renal function) to assess contrast enhancement, exclude angiomyolipoma, assess for locally invasive features, define the relevant anatomy and evaluate the status of the contralateral kidney and its vasculature. [Based on Panel consensus]
  • Standard: Physicians should discuss with the patient the current understanding of the natural history of clinical stage 1 renal masses, the relative risks of benign versus malignant pathology and the potential role of active surveillance. [Based on Panel consensus]
  • Standard: Percutaneous renal mass core biopsy with or without fine needle aspiration should be performed in all patients undergoing thermal ablation and in patients for whom it might impact management, particularly patients with clinical or radiographic findings suggestive of lymphoma, abscess or metastasis. [Based on Panel consensus]
  • Standard: Physicians should review with the patient the available treatment options and the attendant benefits and risks, including oncologic considerations, renal functional considerations and potential morbidities. [Based on Panel consensus]
  • Standard: Physicians should counsel the patient about the potential advantages of a nephron-sparing treatment approach in the imperative and elective settings. These advantages include avoidance of the need for dialysis and a reduced risk of developing chronic kidney disease with the attendant morbidity and mortality. [Based on Panel consensus]

For Index Patient No. 1: A healthy patient with a clinical T1a ( < 4.0 cm) enhancing renal mass

  • Standard: Complete surgical excision by partial nephrectomy is a standard of care and should be strongly considered. [Based on review of the data and Panel consensus]
  • Standard: Radical nephrectomy should be discussed as an alternate standard of care which can be performed if a partial nephrectomy is not technically feasible as determined by the urologic surgeon. [Based on review of the data and Panel consensus]
  • Option: Thermal ablation, such as cryoablation or radiofrequency ablation, should be discussed as a less-invasive treatment option, but local tumor recurrence is more likely than with surgical excision, measures of success are not well defined, and surgical salvage may be difficult. [Based on review of the data and Panel consensus]
  • Option: Active surveillance with delayed intervention should be discussed as an option for patients wishing to avoid treatment and willing to assume oncologic risk. [Based on review of the data and Panel consensus]

For Index Patient No. 2: A patient with major comorbidities/increased surgical risk and a clinical T1a (< 4.0 cm) enhancing renal mass

  • Standard: Complete surgical excision by partial nephrectomy should be discussed as a standard of care with increased surgical risk in this patient. [Based on review of the data and Panel consensus]
  • Standard: Radical nephrectomy should be discussed as a standard of care with an increased risk of surgical complications and chronic kidney disease in this patient. [Based on review of the data and Panel consensus]
  • Recommendation: Thermal ablation should be discussed as a less-invasive treatment option which may be advantageous in this high surgical risk patient, acknowledging the increased risk of local tumor recurrence compared to surgical excision. [Based on review of the data and Panel consensus]
  • Recommendation: Active surveillance should be offered as an acceptable approach which can delay or avoid the need for intervention in this high-risk patient. [Based on review of the data and Panel consensus]

For Index Patient No. 3: A healthy patient with a clinical T1b (> 4.0 cm to < 7.0 cm), enhancing renal mass

  • Standard: Radical nephrectomy should be discussed as a standard of care for patients with a normal contralateral kidney. [Based on review of data and Panel consensus]
  • Standard: Complete surgical excision by partial nephrectomy should be discussed as an alternative standard of care, particularly when there is a need to preserve renal function. [Based on review of data and panel consensus]
  • Option: Thermal ablation can/may be discussed as a treatment option which is less effective due to an increased risk of local recurrence. [Based on Panel consensus]
  • Option: Active surveillance with delayed intervention can/may be discussed as an option in patients who want to avoid surgery and are willing to accept an increased risk of tumor progression compared to partial nephrectomy or radical nephrectomy. [Based on review of the data and Panel consensus]

For Index Patient No. 4: A patient with major comorbidities/increased surgical risk and a clinical T1b (> 4.0 cm to < 7.0 cm), enhancing renal mass

  • Standard: Radical nephrectomy should be discussed as a standard of care for patients with a normal contralateral kidney, although it can be associated with surgical morbidity and an increased risk of chronic kidney disease. [Based on review of the data and Panel consensus]
  • Recommendation: Complete surgical excision by partial nephrectomy should be discussed as a recommended modality when there is a need to preserve renal function, although it can be associated with increased urologic morbidity. [Based on review of the data and Panel consensus]
  • Recommendation: Active surveillance should be discussed with patients who want to avoid surgery or who are considered high risk for surgical therapy. [Based on review of the data and Panel consensus]
  • Option: Thermal ablation can/may be discussed as treatment option which is less effective due to an increased risk of local recurrence. [Based on Panel consensus]

Definitions:

Grades of Guideline Statements

The guideline statements are graded with respect to the degree of flexibility in application. A "standard" is the most rigid treatment policy. A "recommendation" has significantly less rigidity, and an "option" has the largest amount of flexibility. These terms are defined as follows:

Standard: A guideline statement is a standard if: (1) the health outcomes of the alternative interventions are sufficiently well known to permit meaningful decisions, and (2) there is virtual unanimity about which intervention is preferred.

Recommendation: A guideline statement is a recommendation if: (1) the health outcomes of the alternative interventions are sufficiently well known to permit meaningful decisions, and (2) an appreciable, but not unanimous majority agrees on which intervention is preferred.

Option: A guideline statement is an option if: (1) the health outcomes of the interventions are not sufficiently well known to permit meaningful decisions, or (2) preferences are unknown or equivocal.

Clinical Algorithm(s)

A treatment algorithm for the four index patients is provided in the original guideline document.

Evidence Supporting the Recommendations

Type of Evidence Supporting the Recommendations

The recommendations were based on a systematic review of the peer-reviewed published scientific literature on this topic and on expert opinion and consensus when evidence was lacking.

Benefits/Harms of Implementing the Guideline Recommendations

Potential Benefits

Appropriate management of the clinical stage 1 renal mass

Potential Harms

Renal Mass Biopsy

A review of studies since 2001 demonstrates that the false-negative rate with renal mass biopsy is now only 1%, and the incidence of symptomatic complications is relatively low, with only a very small percentage (< 2%) requiring any form of intervention. Needle-tract seeding also appears to be exceedingly rare, assuming appropriate patient selection.

Surgical Procedures

  • Major urologic complications of surgical procedures include postoperative hemorrhage requiring transfusion or other intervention, urinary leak or fistula, abscess, unanticipated loss of renal function or other local complications potentially related to the procedure.
  • Radical nephrectomy (RN) can lead to an increased risk of chronic kidney disease (CKD), which is associated with increased risk of morbid cardiac events and death according to population-based studies.
  • Partial nephrectomy (PN) is associated with an increased risk of perioperative morbidity (e.g., hemorrhage, warm ischemia, urine leak) when compared to RN.
  • Laparoscopic partial nephrectomy (LPN) has been associated with increased warm ischemic times and an increased risk of urological complications including postoperative hemorrhage and urinary fistula.
  • Thermal ablation is associated with a substantially increased risk of local recurrence.

Active Surveillance

Active surveillance is associated with increased risk of tumor progression that could preclude nephron-sparing approaches or lead to unsalvageable systemic metastases.

Refer to Table 14 in the original guideline document for classification of major and minor urologic and nonurologic complications listed in the literature.

Qualifying Statements

Qualifying Statements

Limitations of the Literature

The Panel identified major limitations of the available literature. Suboptimal study design was the predominant limitation across all studies, with a near absence of prospective or randomized data. Selection bias (e.g., differences in patient ages and tumor sizes) is evident across all interventions. Widely divergent duration of follow-up for the various modalities is another major confounding factor. Additional weaknesses include lack of standardized reporting and substantial variability in applied techniques, definitions of success, reporting of complications and other related outcomes. Complications were reported in variable ways or sometimes were completely omitted. Renal function was typically reported as pre and posttreatment serum creatinine values as opposed to estimated glomerular filtration rate (eGFR) or creatinine clearance as determined by a 24-hour urinary collection. Many of the active surveillance (AS) and ablative studies lacked pathologic data as did some surgical studies.

The nomenclature for renal mass anatomy is also highly variable among studies, limiting the ability to compare outcomes among different institutions. Reporting and publication biases probably also exist; studies with higher complication rates, recurrences or other inferior outcomes tend not to be published.

Refer to the original guideline document for more information on limitations of the literature.

Implementation of the Guideline

Description of Implementation Strategy

An implementation strategy was not provided.

Implementation Tools
Clinical Algorithm
For information about availability, see the Availability of Companion Documents and Patient Resources fields below.

Institute of Medicine (IOM) National Healthcare Quality Report Categories

IOM Care Need
Getting Better
Living with Illness
IOM Domain
Effectiveness
Patient-centeredness

Identifying Information and Availability

Bibliographic Source(s)
American Urological Association Education and Research, Inc. Guideline for management of the clinical stage 1 renal mass. Linthicum (MD): American Urological Association Education and Research, Inc.; 2009. 81 p. [182 references]
Adaptation

Not applicable: The guideline was not adapted from another source.

Date Released
2009
Guideline Developer(s)
American Urological Association Education and Research, Inc. - Medical Specialty Society
Source(s) of Funding

American Urological Association Education and Research, Inc. (AUA)

Guideline Committee

Small Renal Mass Guideline Panel

Composition of Group That Authored the Guideline

Panel Members: Andrew C. Novick, MD, Chair, Cleveland Clinic Foundation, Cleveland, Ohio; Steven Charles Campbell, MD, PhD, Co-Chair, Cleveland Clinic Foundation, Cleveland, Ohio; Raymond J. Leveillee, MD, FRCS-G, PGC Representative, University of Miami School of Medicine, Miami, Florida; Arie Belldegrun, MD, UCLA School of Medicine, Los Angeles, California; Michael L. Blute, MD, Mayo Clinic, Rochester, Minnesota; George Kuoche Chow, MD, Mayo Clinic, Rochester, Minnesota; Ithaar H. Derweesh, MD, University of Tennessee, Memphis, Tennessee; Jihad H. Kaouk, MD, Cleveland Clinic Foundation, Cleveland, Ohio; Surena Fazeli Matin, MD, MD Anderson Cancer Center, Houston, Texas; Paul Russo, MD, Memorial Sloan-Kettering Cancer Center, New York, New York; Robert G. Uzzo, MD, Fox Chase Cancer Center, Philadelphia, Pennsylvania

Consultants: Martha M. Faraday, PhD; Linda E. Whetter, PhD, DVM; Michael Marberger, MD

American Urological Association Education and Research, Inc. (AUA) Staff: Heddy Hubbard, PhD, FAAN; Edith Budd; Michael Folmer; Katherine Moore; Kadiatu Kebe

Financial Disclosures/Conflicts of Interest

All panel members completed Conflict of Interest disclosures. Those marked with (C) indicate that compensation was received; relationships designated by (U) indicate no compensation was received.

Consultant or Advisor: Paul Russo, Wilex AG (C); Arie Belldegrun, Galil Medical (C), Wilex AG (C), Bayer (C), Pfizer (C), ROEI Medical (C); Surena Matin, Johnson & Johnson Wound Management (C); Michael Marberger, GSK (C), R. Wolf (U), GP-Pharma Barcelona (C), MSD (C); Steven C. Campbell, Pfizer (C), Sanofi Aventis (C)

Investigator: Arie Belldegrun, Pfizer (C), Amgen (C); Steven C. Campbell, Pfizer (U), Novartis (U)

Scientific Study or Trial: Raymond J. Leveillee, Pluromed (U), LMA Urology-Suisse (U), Boston Scientific (U); Michael Marberger, MDS (U), GSK (U), Focus Surgery (U)

Meeting Participant or Lecturer: Jihad Kaouk, Endocare (C); Steven C. Campbell, Sanofi Aventis (C); Robert G. Uzzo, Pfizer (C), Bayer (C); Raymond J. Leveillee, ACMI (C), Applied Medical (C), ValleyLab (C), Ethicon (U); Michael Marberger, GSK (C), MSD (C)

Board Member, Officer, Trustee: Arie Belldegrun, Agensys (C), Hana Biosciences (C), Cougar Biotechnology (C)

Other: Jihad Kaouk, Intuitive Surgical (C); Steven C. Campbell, Aventis Pharmaceuticals (C); Raymond J. Leveillee, ACMI (U), Ethicon (U), Intuitive Surgical (C); Linda Whetter, Zola Associates (C)

Guideline Status

This is the current release of the guideline.

Guideline Availability

Electronic copies: Available in Portable Document Format (PDF) from the American Urological Association, Inc. (AUA) Web site External Web Site Policy.

Availability of Companion Documents

None available

Patient Resources

None available

NGC Status

This NGC summary was completed by ECRI Institute on February 26, 2010. The information was verified by the guideline developer on March 25, 2010.

Copyright Statement

This NGC summary is based on the original guideline, which is copyrighted by the American Urological Association Education and Research, Inc. (AUA).

Disclaimer

NGC Disclaimer

The National Guideline Clearinghouse™ (NGC) does not develop, produce, approve, or endorse the guidelines represented on this site.

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