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Patient and Caregiver Knowledge and Utilization of Partial Versus Radical Nephrectomy: Results of a National Kidney Foundation Survey to Assess Educational Needs of Kidney Cancer Patients and Caregivers
Original Investigation Patient and Caregiver Knowledge and Utilization of Partial Versus Radical Nephrectomy: Results of a National Kidney Foundation Survey to Assess Educational Needs of Kidney Cancer Patients and Caregivers Paul Russo, MD,1 Lynda A. Szczech, MD, MSCE,2 Gail S. Torres, MS, RD, RN,3 and Marilyn D. Swartz, MSN, RN3 Background: In response to requests from patients, caregivers, and physicians for information on kidney cancer, the National Kidney Foundation (NKF) conducted a survey to assess the educational needs of the kidney cancer community. Key areas of assessment were patient and caregiver knowledge of risk factors for chronic kidney disease (CKD), including kidney cancer and nephrectomy, and of kidney-sparing surgical options. Study Design: Survey to assess educational needs of patients with kidney cancer and caregivers. Setting & Participants: Respondents were invited through physician referrals and online sources and included 365 adult patients with kidney cancer and 52 caregivers. Predictor: Age, geographic region, and cancer stages 1-2 versus 3-4. Outcomes & Measurements: Survey responses were descriptively analyzed, with data compared and weighted to the population age and geographic characteristics of the general kidney cancer population. Results: 83% of 181 early-stage patients, 92% of 123 late-stage patients, and 86% of 113 patients who did not know their stage received radical nephrectomy. Although 62% agreed that radical nephrectomy for cancer treatment is a risk factor for CKD, only 40% agreed that losing part or all of 1 kidney from injury or a disease other than cancer is a risk factor for CKD. 56% agreed that kidney cancer can be related to CKD. Limitations: We did not have patient medical records to validate responses and we do not know the number of people who were invited to take the survey but declined. Conclusions: There is a lack of patient awareness that kidney cancer and radical nephrectomy are risk factors for CKD. Only a minority of patients underwent partial nephrectomy or were given it as an option for their early-stage kidney cancer. This suggests a knowledge deficit among physicians, surgeons, patients, and caregivers alike that there is a bidirectional relationship between kidney cancer and CKD and that kidneysparing surgery is preferable when feasible. Am J Kidney Dis. 61(6):939-946. © 2013 by the National Kidney Foundation, Inc. INDEX WORDS: Chronic kidney disease; kidney cancer; partial nephrectomy; patient and caregiver knowledge; radical nephrectomy.
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he National Kidney Foundation (NKF) receives many requests for information from patients, caregivers, and physicians regarding kidney cancer in general and specifically with respect to the impact of treatment on overall kidney health. In response, the NKF commissioned a survey of patients and caregivers to assess their knowledge about risk factors and treatment options for kidney cancer and chronic kidney disease (CKD). The ultimate goal of the survey was to identify educational opportunities that address knowledge deficits found in the kidney cancer community. Although many elements related to the care of patients with kidney tumor were explored in the survey, including the role of caregivers, the nature of information resources used, and health maintenance strategies used by patients living with a solitary kidney, the focus of this report is on patient and caregiver knowledge regarding surgical options for disease management and their impact on overall kidney health. We focused on this topic because of clear clinical evidence that radical nephrectomy is grossly overused in the management of small renal masses despite the Am J Kidney Dis. 2013;61(6):939-946
accumulating evidence that kidney-sparing surgery provides oncologic control equivalent to radical nephrectomy while concurrently preserving kidney function and preventing CKD. An estimated 64,770 new cases and 13,570 deaths from kidney cancer occurred in the United States in 2011.1 Compared with 1971, this shows a 5-fold increase in incidence and 2-fold increase in mortality. Epidemiologic evidence indicates an increase in all
From the 1Memorial Sloan Kettering Cancer Center, Weill School of Medicine, Cornell School of Medicine, New York, NY; 2 Pharmaceutical Product Development, Research Triangle Park, NC; and 3National Kidney Foundation, New York, NY. Received May 17, 2012. Accepted in revised form January 29, 2013. Originally published online March 25, 2013. Address correspondence to Paul Russo, MD, Memorial Sloan Kettering Cancer Center, Weill School of Medicine, Cornell School of Medicine, 1275 York Ave, New York, NY 10065. E-mail: [email protected] © 2013 by the National Kidney Foundation, Inc. 0272-6386/$36.00 http://dx.doi.org/10.1053/j.ajkd.2013.01.028 939
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stages of renal cancer, including advanced and metastatic stages.2 In ⬃30% of patients with kidney tumor, metastatic disease will either be seen at presentation or develop later. After World War II, radical surgical resection of the kidney, perinephric soft tissues, ipsilateral adrenal gland, and regional lymph nodes, termed radical nephrectomy, was introduced and popularized. This operation is still used today, whether by open or minimally invasive approaches, for the resection of massive tumors that are locally advanced or metastatic as part of the strategy of cytoreduction prior to the administration of systemic therapy.3-6 Extensive use of the modern cross-sectional imaging techniques of the abdomen (computed tomography, magnetic resonance imaging, and ultrasonography) during the last 20 years, typically ordered to assess nonspecific abdominal and musculoskeletal symptoms or during unrelated cancer care, has altered the profile of the patient with kidney tumor from one with a massive symptomatic tumor at presentation to one with a small asymptomatic mass. Approximately 70% of surgically resected kidney tumors today are spotted incidentally, with a median tumor size ⬍4 cm.7 This imaging-induced tumor size and stage migration has created a new pool of patients with small renal masses (T1, ⬍7 cm) with a generally favorable prognosis after surgical resection by either radical or partial nephrectomy. In the last 15 years, a significant transition from radical nephrectomy for all kidney tumors to the expanded use of partial nephrectomy has occurred.8 The basis of this transition has been enhanced understanding of the variable oncologic threats provided in the family of renal cortical tumors, an appreciation for the oncologic equivalency of partial and radical nephrectomy for T1 (⬍7-cm) tumors, and increasing concerns regarding the causation of CKD by radical nephrectomy and its associated cardiovascular morbidity and potential mortality. Despite the accumulating knowledge that partial and radical nephrectomy provide comparable oncologic outcomes for small renal masses and that partial nephrectomy has the advantage of preventing or delaying the onset of postsurgical CKD, radical nephrectomy remains grossly overused in the United States.9 Despite the increasing elucidation of the complex interplay between kidney cancer surgery and CKD, a knowledge deficit in both physicians and patients may be responsible for this continued overuse of radical nephrectomy.
METHODS Survey Development Survey questions were developed by the following people: oncologist (n ⫽ 1), oncologic urologic surgeons (n ⫽ 2), nephrologists (n ⫽ 2), oncologic nurse (n ⫽ 1), patient with kidney cancer 940
(n ⫽ 1), and health education experts from the NKF (n ⫽ 2). There were 50 questions (46 close ended and 4 open ended). Survey pretests with 5 members of the target audience (3 patients and 2 caregivers) were conducted on December 17, 2010, at the Harris Interactive New York City office and were 60 minutes long. The final survey questions can be found in Item S1 (provided as online supplementary material).
Study Design The study design was a cross-sectional quantitative survey administered online by Harris Interactive Inc between January 3, 2011, and May 27, 2011. The target populations were patients with kidney cancer and caregivers of patients with kidney cancer (parents, siblings, friends, and other family members or professional caregivers such as nurses or aides). Qualified participants were US residents, older than 18 years, and either had a diagnosis of kidney cancer, were a caregiver for someone with a diagnosis of kidney cancer, or were a caregiver for someone with a diagnosis of kidney cancer within the last year. The goal number of respondents was 500, a sufficient number to demonstrate significance when comparing responses among different stages of kidney cancer (stage 1: tumor ⬍7 cm; stage 2: tumor ⬎7 cm; stage 3: the tumor, regardless of size, has spread beyond the kidney to nearby tissues or blood vessels or has spread to a nearby lymph node; stage 4: the tumor, regardless of size, has spread to distant sites, has invaded directly beyond the local area, or involves ⬎1 lymph node). The survey was self-administered and required approximately 30 minutes to complete. Patients and caregivers were recruited from 3 sources: 1. The Harris Interactive Chronic Illness Panel who selfreported that they either had a diagnosis of cancer or were living in a household in which someone had a diagnosis of cancer. 2. Oncologists, nephrologists, and urologists who were randomly sampled from the American Medical Association Master File and asked to refer their patients with kidney cancer/caregivers to the survey. After qualifying through a brief screen, physicians were mailed up to 30 postcards to use for referring patients/caregivers. 3. NKF-referred partners and the Association of Cancer Online Resources (www.ACOR.org) recruited participants through their listservs; any recipient of this invitation had to request an identification number and password directly from Harris in order to participate. Because all participants had a unique identification number and password, they were prevented from completing the survey more than once. All respondents and physicians received an honorarium for participating and for referring patients, respectively. Ninetynine physicians referred patients and caregivers to the survey, generating 278 completed surveys. There were 85 responses from the Harris Interactive Chronic Illness panel, 40 from the Association of Cancer Online Resources kidney cancer listserv, and 14 from the NKF-referred caregiver listserv. The total number of invitations is unknown because neither the number of referrals from each physician nor the number of e-mail recipients on the listservs can be determined. Kidney cancer stages were designated as early (stages 1 and 2; n ⫽ 181) and late (stages 3 and 4; n ⫽ 123). Throughout the study, participants who did not know answers to specific queries, such as what stage they had (n ⫽ 113), were designated as the “don’t-know” group. Precise medical, surgical, and pathologic data for individual patients were not available for any of the patients and hence the answers to the survey could not be confirmed. Similarly, we do not have information regarding the office discussions between physicians and patients, the suitability of an individual patient for a Am J Kidney Dis. 2013;61(6):939-946
Knowledge Deficits and Partial Nephrectomy Table 1. Patient Characteristics According to Stage of Kidney Cancer Early Stage Patient Characteristic
No. of patients Age (y)a Male sex Female sex Diagnosed with CKD Time since diagnosis of kidney cancer (y) Metastatic kidney cancer Urologist is primary provider Radical nephrectomy
Stage 1
Stage 2
60.3 ⫾ 10.6
62.5 ⫾ 11.3
5.0 ⫾ 5.0
5.6 ⫾ 5.8
Late Stage Stages 1-2
181 (43.4) 61 43% 57% 14% 5.3
Stage 3
Stage 4
57.9 ⫾ 11.6
58.8 ⫾ 9.1
4.1 ⫾ 5.1
5.7 ⫾ 4.4
3% 56% 83%
Stages 3-4
Don’t Know Stage
123 (29.5) 58 46% 54% 27% 4.9
113 (27.1) 66.9 ⫾ 9.1 46% 54% 22% 7.3 ⫾ 9.0
52% 18% 92%
16% 51% 86%
Note: All kidney cancer staging information was provided by the respondents and is defined as follows: stage 1, tumor ⬍7 cm; stage 2, tumor ⬎7 cm; stage 3, the tumor regardless of size has spread beyond the kidney to nearby tissues or blood vessels or has spread to a nearby lymph node; and stage 4, the tumor regardless of size has spread to distant sites, has invaded directly beyond the local area, or involves more than 1 lymph node. Values for continuous variables are given as mean or mean ⫾ standard deviation. Abbreviation: CKD, chronic kidney disease. a Range was 26-87 years.
partial nephrectomy, whether referrals to tertiary centers were made, or the degree of surgical expertise or surgical volume of individual surgeons. Although there were respondents, we do not have the denominator of potential respondents who were invited to do the survey but later declined.
Statistical Analysis Descriptive statistics were used to tabulate response rates and final data were compared and weighted to population age and geographic characteristics of the general kidney cancer population in the United States, which are outlined in the Centers for Disease Control and Prevention Behavioral Factor Surveillance System Study. A standard t test of column proportions and means was applied, tests were 2 tailed, an infinite population was assumed, and samples were considered to be independent. To adjust for overlap of respondents between columns, overlap formulas were applied.
RESULTS Survey Participants A total of 417 respondents (365 patients and 52 caregivers) participated. Caregivers answered the same questions as patients, but in a format that made reference to the patient they cared for, so that all factual information regarding the patient’s medical history and treatments is reflective of the total number of respondents. Questions on knowledge, such as awareness of risk factors for CKD, were reflective of both caregivers and patients as a combined group. Caregivers answered additional questions pertaining only to themselves, such as their age and sex. Patients were aged 26-87 (average, 60) years, and 55% were women. Caregivers were aged 30-91 (average, 53) years, and 81% of these respondents were women. Am J Kidney Dis. 2013;61(6):939-946
Patient Characteristics by Kidney Cancer Stage Patient characteristics according to stage of kidney cancer are listed in Table 1. Forty-three percent of patients had early-stage cancer, 30% had late-stage cancer, and 27% did not know their stage. Radical nephrectomy was the predominant surgical treatment for each group: ⬃83% in the early-stage group, 92% in the late-stage group, and 86% in the don’t-know group. The don’t-know group had had a diagnosis for a significantly longer time (⬃2 years) than the earlyand late-stage groups. More than one-fourth of respondents did not know what stage of kidney cancer that they or their patient had. Characteristics of Tumor at Diagnosis Table 2 highlights characteristics of patients’ tumors at diagnosis. More than half the respondents did Table 2. Characteristics of Tumor at Diagnosis Percentage of Respondents
Size of tumor at diagnosis ⬍4 cm 4-7 cm ⬎7 cm Don’t know or were not told
15 30 22 33
Type of tumor at diagnosis Benign Indolent with limited metastatic potential Clear cell Don’t know or were not told
11 27 7 55
Note: N ⫽ 417. 941
Russo et al Table 3. Patient Surgical History Percentage of Respondents
Type of surgery Radical nephrectomy Radical nephrectomy (laparoscopic) Partial nephrectomy Surgery for removal of metastases Respondent does not remember type of surgery Time of surgery ⬍1 y ago 1-3 y ago ⬎3 y ago Physician discussed candidacy for partial nephrectomy Yes, but still recommended radical nephrectomy No Yes, but was told patient not a candidate Respondent does not remember if discussed Respondent does not understand the differences in surgeries enough to comment
67 19 18 6 3
20 32 48
38 25 24 8 5
Note: n ⫽ 363. Total response rate is 113% due to multiple responses.
not remember or were not told what type of kidney tumor they or their patient had and 33% did not know or were not told how large the tumor was. Of respondents who knew the tumor size, 45% had tumors ⱕ7 cm (T1), 11% had benign tumors, and 27% knew they had the more indolent papillary or chromophobe tumors, which have limited metastatic potential. Patient History Surgical Treatment Of 417 patients described by respondents, 363 (87%) underwent some form of surgical treatment for kidney cancer. Table 3 lists the distribution of surgery type, timing of surgery in relation to taking the survey, and whether a physician discussed candidacy for partial nephrectomy. Among patients who underwent radical nephrectomy, 25% reported that they were not aware of the option of partial nephrectomy, and 38% were told about partial nephrectomy, but their surgeons recommended against it. Even for patients with early-stage kidney cancer, only 18% underwent partial nephrectomy. CKD Diagnosis and Type of Nephrectomy
Of 81 patients (19%) who were given a diagnosis of CKD, 40% were given the diagnosis prior to their kidney cancer diagnosis; 53%, after; and 7% did not 942
remember when they were given the diagnosis. Table 4 lists nephrectomy type in relation to the time of CKD and kidney cancer diagnoses. CKD was diagnosed in 29 patients before they underwent an operation and 23 of them (79%) underwent radical nephrectomy even though loss of kidney function had been determined prior to surgery; the majority did not receive kidney-sparing surgery. Participant Knowledge of Kidney Cancer and Kidney Health Table 5 summarizes participants’ knowledge of risk factors for developing CKD and their understanding of the relationship between CKD and kidney cancer. Only 56% of patients thought that kidney cancer and CKD were somehow related, and only 40% thought that losing part or all of 1 kidney due to an injury or a disease other than cancer is a risk factor for developing CKD. The majority of respondents (81%) thought that there are not enough informational resources available for kidney cancer, and less than one-third were satisfied with current resources.
DISCUSSION In this study, 417 patients and caregivers responded to a questionnaire designed to determine if there were any unmet educational and informational needs in the kidney cancer population. The interaction between surgical therapies proposed and delivered and the new and emerging concerns for CKD as perceived by the recipients of kidney cancer surgical care also were carefully studied. The survey results suggest key areas in which enhanced education, for both patients and physicians, could be beneficial. Of patients with earlystage renal tumors, radical nephrectomy was used in the vast majority. Although a small minority of patients (18%) underwent partial nephrectomy, 38% were told about partial nephrectomy but were advised against it, and 25% of patients did not hear of the option of partial nephrectomy. Despite this large proTable 4. Nephrectomy Type in Relation to Time of CKD and Kidney Cancer Diagnoses
Nephrectomy Type
CKD Diagnosed Before Kidney Cancer (n ⴝ 29)
CKD Diagnosed After Kidney Cancer (n ⴝ 50)
Don’t Remember When CKD Diagnosed (n ⴝ 2)
Partial Radical
6 (21) 23 (79)
9 (18) 41 (82)
0 (0) 2 (100)
Note: Only 19% (n ⫽ 81) of patients were given a diagnosis of CKD. Values are given as number (percentage). Abbreviation: CKD, chronic kidney disease. Am J Kidney Dis. 2013;61(6):939-946
Knowledge Deficits and Partial Nephrectomy Table 5. Participant Knowledge Regarding Kidney Cancer and CKD Percentage of Participants with Knowledge
Risk factor for CKD Loss of a kidney due to an injury or a disease other than cancer Radical nephrectomy for cancer treatment Medications that cause kidney damage High blood pressure Diabetes Family history of kidney disease Older than 60 y Having urinary obstructions Repeated urinary infections Heart and blood vessel disease Racial/ethnic background that is African American, Hispanic American, Asian American, Pacific Islander, or American Indian Relationship between CKD and kidney cancer Agree that kidney cancer and CKD can be related Agree that it is possible to get CKD in remaining kidney after nephrectomy for kidney cancer Agree that kidney health protection after nephrectomy is important Agree that a person with kidney cancer can take steps to reduce the risk for CKD
40 62 68 66 66 60 52 49 45 42 31
56 71
94 75
Note: N ⫽ 417. Abbreviation: CKD, chronic kidney disease.
portion of patients undergoing nephrectomy (either radical or partial nephrectomy), most patients had a limited understanding of the risk factors for CKD. The knowledge and educational deficits revealed in our survey may be due to lack of communication between health care professionals and patients and also to lack of knowledge on the part of physicians and surgeons, especially in regard to the problem of overuse of radical nephrectomy and its impact on the development of CKD. Accordingly, CKD was diagnosed in only 19% of patients in our study, which seems low considering that all patients had kidney cancer and the majority also underwent radical nephrectomy. This may suggest a lack of awareness about the need for CKD testing and education in this population. The large proportion of patients who did not know their stage of kidney cancer (27%), tumor size (33%), or tumor type (55%) may indicate that they did not receive this information from their physicians and thus could not make informed decisions about the type of treatment they should receive, including kidney-sparing surgery. Notably, the group of Am J Kidney Dis. 2013;61(6):939-946
patients who did not know their stage of kidney cancer had had the diagnosis for a significantly longer time compared with the early- and late-stage groups. Although there was apparently more time for these patients to learn about their disease, they were still uninformed. Although more than half the respondents understood that radical nephrectomy for cancer treatment can lead to CKD (62%), fewer knew that losing a kidney for any other reason is also a risk (40%); it appears that they do not understand the association between nephron loss and the development of CKD. It may be that they only recognize an association between the general diagnosis of cancer and CKD, especially because only 56% think that a relationship exists specifically between kidney cancer and CKD. They appear not to understand the bidirectional nature of kidney cancer and CKD. Although a majority of respondents thought it is possible to get CKD in the remaining kidney after nephrectomy for kidney cancer (71%), one cannot know if they interpret this as CKD being just another independent disease state that can occur in anyone at any time or as a direct result of radical nephrectomy. That most patients who were given a diagnosis of CKD prior to their kidney cancer diagnosis still underwent radical nephrectomy (79%) also suggests that surgeons may not recognize the importance of kidney-sparing surgery, even in those already given a diagnosis of CKD. During the last decade, well-done clinical studies have fortified the case for partial nephrectomy when possible based on 3 basic points.10-14 First, the pathology of resected renal tumors indicates that up to 20% are completely benign (angiomyolipoma, renal oncocytoma, and metanephric adenoma) with no metastatic potential, 25% are indolent cancers (papillary and chromophobe) with limited metastatic potential, and for the majority of T1 cancers that are the more malignant conventional clear cell carcinoma (54%), long-term cancer-specific survival rates after resection are ⱖ90%.15 Second, oncologic results for patients with T1 tumors are equivalent whether partial or radical nephrectomy is done. This is in keeping with the evolution of surgical oncology from the Halstedian radical surgical resection of all tumors (sarcoma and breast cancer) toward limb- and organ-preservation operations that yield similar oncologic outcomes.16 Third, the finding that CKD is a pre-existing condition in ⬃26% of patients with a normal serum creatinine level prior to surgical resection and that radical nephrectomy is a risk factor for the creation of CKD or the worsening of pre-existing CKD makes the casual use of radical nephrectomy for a small renal mass a potentially toxic event.10 The well-known association of CKD and cardiovascular morbidity and 943
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mortality in the general population now is being observed in the renal tumor population. Epidemiologic evidence suggests that when radical nephrectomy is used instead of partial nephrectomy for small renal masses, there are more subsequent cardiovascular events and worse overall survival.17-20 Many patients with kidney cancer also have significant and common preexisting medical morbidities predisposing them to CKD, including diabetes, hypertension, and vascular disease. CKD now is also being directly implicated in the evolution of kidney cancer by as yet uncertain mechanisms.21-23 Appeals to the urology community to perform partial nephrectomy when possible for the treatment of a small renal mass were published in 200924 and after the exacting work of the American Urological Association guidelines committee later that year.25 CKD is an increasing public health problem in the United States and now is considered an independent risk factor for the development of cardiovascular morbidity and mortality.26-29 It also is recognized that patients with kidney cancer have a higher rate of CKD than the general population that is not related entirely to radical nephrectomy.23 Launay-Vacher et al30 evaluated 4,684 patients with cancer and reported that 12% and 20% had an estimated glomerular filtration rate ⬍60 mL/min/1.73 m2 by the Modification of Diet in Renal Disease (MDRD) Study and Cockcroft-Gault equations, respectively. Canter et al31 reported the prevalence of baseline CKD in 1,114 patients presenting with solid renal tumors. Twentytwo percent had stage 3 CKD or greater despite 88% having a serum creatinine level within normal limits (⬍1.4 mg/dL). In a subgroup of 282 patients 70 years or older, 113 (40%) had CKD stage 3.31 These results are similar to those first reported by Memorial Sloan Kettering Cancer Center investigators that demonstrated a 26% rate of CKD in 662 patients with small renal tumors and a serum creatinine level within normal limits.10 In the non-neoplastic kidney at the time of nephrectomy, extensive nephropathologic findings are observed in the vast majority of patients. It is not clear if these changes are a direct cause of renal neoplasia or a result of medical comorbid conditions that are prevalent in patients with kidney tumor.32-34 Although partial nephrectomy leads to equal survival outcomes and oncologic results compared with radical nephrectomy while also maximally preserving kidney function and inhibiting or delaying the onset of CKD and its late cardiovascular morbidity and mortality, radical nephrectomy remains overused in the United States and abroad. Strong epidemiologic evidence from national databases, such as the National Inpatient Sample, Surveillance Epidemiology and End Results (SEER) database, and the SEER database linked to Medicare claims, indicates that approximately 70%-80% of patients with tumors ⬍4 cm still 944
undergo radical nephrectomy.18,19,35,36 For reasons that are unclear, women and elderly patients are more likely to be treated with radical nephrectomy.37 A lot of urologists believe a “quick” radical nephrectomy in an elderly patient would result in the patient being exposed to fewer postoperative complications than would a partial nephrectomy, but this is the very patient population in greatest need for kidney preservation. In 1,712 patients with kidney tumors, Memorial Sloan Kettering Cancer Center investigators assessed age and type of procedure and found that statistical evidence for risk of complications associated with partial nephrectomy increasing with advancing age was lacking. In addition, no evidence linking age to estimated blood loss or surgical time was reported. The authors concluded that because of the advantages of preservation in kidney function, elderly patients, if fit, should be wholly eligible for partial nephrectomy.38 Although this study did not provide information on nonsurgical management (active surveillance) of kidney tumors, particularly in elderly (⬎75 years) and medically unfit patients, this approach increasingly is viewed as an acceptable alternative in carefully selected patients, with death from medical illnesses far superseding disease progression from kidney cancer.39-42 In such carefully selected patients, active surveillance is another means of maximizing kidney function and avoiding iatrogenic CKD. Our study is limited because we do not have specific clinical information regarding the kidney cancers being treated or the surgical and medical capabilities of the treating physicians. We also have no insight about why a surgeon would mention partial nephrectomy but urge the patient to undergo radical nephrectomy. Clinical characteristics of the tumor and surgical skill of the surgeon also were not known. This lack of clinical data precludes more complex statistical analysis. However, we would expect patient-relayed inaccuracies to be evenly distributed among those filling out the survey and the perception of early- and late-stage disease to be reliable. In conclusion, the present study provides data indicating that a minority of patients underwent partial nephrectomy or were given partial nephrectomy as a potential option for the management of their earlystage kidney cancer. This result is not surprising given the data described from national databases indicating overuse of radical nephrectomy for the treatment of small renal masses. From the patient’s and caregiver’s vantage points, educational resources (including web based) describing treatment options for patients with small renal tumors may allow for more informed dialogues between patients and their physicians or inspire second opinions and referral to tertiary centers, where partial nephrectomy and all other options Am J Kidney Dis. 2013;61(6):939-946
Knowledge Deficits and Partial Nephrectomy
for kidney cancer are readily available. General awareness of the interplay between kidney functional concerns and potential unfavorable consequences of overly aggressive surgical treatments need to be clearly defined. A working knowledge of the bidirectional relationship of CKD and the surgical management of kidney cancer is now essential for all urologists. Educational programs for surgeons and patients alike are required to promote the benefits of kidney-sparing approaches when possible.
ACKNOWLEDGEMENTS The survey was conducted by Harris Interactive Inc. Support: This survey was funded by Pfizer. The sponsor participated in study design and the decision to submit this report for publication. Financial Disclosure: Dr Russo is a consultant for Wilex AG. Dr Szczech is an employee of Pharmaceutical Product Development. The other authors declare that they have no other relevant financial interests.
SUPPLEMENTARY MATERIAL Item S1: Final survey questions. Note: The supplementary material accompanying this article (http://dx.doi.org/10.1053/j.ajkd.2013.01.028) is available at www.ajkd.org.
REFERENCES 1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62(1):10-29. 2. Ljungberg B, Campbell SC, Cho HY, et al. The epidemiology of renal cell carcinoma. Eur Urol. 2011; 60(4):615-621. 3. Robson CJ, Churchill BM, Andersen W. The results of radical nephrectomy for renal cell carcinoma. J Urol. 1969;101(3):297. 4. Skinner DG, Colvin RB, Vermillion CD, Pfister RC, Leadbetter WF. Diagnosis and management of renal cell carcinoma: a clinical and pathological study of 309 cases. Cancer. 1971;28(5): 1165-1177. 5. Russo P. Open radical nephrectomy for localized renal cell carcinoma. In: Vogelzang N, Nicholas J, eds. Genitourinary Oncology. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2006:725-731. 6. Russo P. Multi-modal treatment for metastatic renal cancer— the role of surgery. World J Urol. 2010;28(3):295-230. 7. Russo P. Renal cell carcinoma: presentation, staging, and surgical treatment. Semin Oncol. 2000;27(2):160-176. 8. Han JS, Huang WC. Impact of kidney cancer surgery on oncologic and kidney functional outcomes. Am J Kidney Dis. 2011;58(5):846-854. 9. Russo P. The role of surgery in the management of early-stage renal cancer. Hematol Oncol Clin North Am. 2011;25(4):737-752. 10. Huang WC, Levey AS, Serio AM, et al. Chronic kidney disease after nephrectomy in patients with renal cortical tumors: a retrospective cohort study. Lancet Oncol. 2006;7(9):735-740. 11. Russo P, Jang T, Eggener S, Pettus J, Karellas M, O’Brien F. Survival rates after resection for localized kidney cancer 19892004. Cancer. 2008;113(1):84-96. 12. Kattan MW, Reuter V, Motzer RJ, Katz J, Russo P. A postoperative prognostic nomogram for renal cell. J Urol. 2001;166(1):63-67. 13. Russo P. Partial nephrectomy for renal cancer (I). BJU Int. 2010;105(9):1206-1220. Am J Kidney Dis. 2013;61(6):939-946
14. Teloken PE, Thompson RH, Tickoo SK, et al. Prognostic impact of histological subtype in patients with surgically treated localized renal cell carcinoma. J Urol. 2009;182(5):2132-2136. 15. Snyder ME, Bach A, Kattan MW, Raj GV, Reuter VE, Russo P. Incidence of benign lesions for clinically localized renal masses ⬍7cm in radiological diameter: influence of sex. J Urol. 2006;176(6):2391-2396. 16. Thompson RH, Siddiqui S, Lohse CM, Leibovich BC, Russo P, Blute ML. Partial versus radical nephrectomy for 4 to 7 cm renal cortical tumors. J Urol. 2009;182(6):2601-2606. 17. Thompson HR, Boorjian SA, Lohse CM, et al. Radical nephrectomy for pT1a renal masses may be associated with decreased overall survival compared to partial nephrectomy. J Urol. 2008;179(2):468-473. 18. Huang WC, Elkin EB, Levey AS, Jang TL, Russo P. Partial nephrectomy versus radical nephrectomy in patients with small renal tumors—is there a difference in mortality and cardiovascular outcomes. J Urol. 2009;181(1):55-62. 19. Tan HJ, Norton EC, Ye Z, Hafez K, Gore JL, Miller DC. Long-term survival following partial vs radical nephrectomy among older patients with early-stage kidney cancer. JAMA. 2012;307(15):16291635. 20. Kim SP, Thompson H, Boorjian SA, et al. Comparative effectiveness for survival and renal function of partial and radical nephrectomy for localized renal tumors: a systematic review and meta-analysis. J Urol. 2012;18(1):51-57. 21. Weng PH, Hung KY, Huang HL, Chen JH, Sung PK, Huang KC. Cancer-specific mortality in chronic kidney disease: longitudinal follow-up of a large cohort. Clin J Am Soc Nephrol. 2011;6(5): 1121-1128. 22. Wong G, Hayen A, Chapman JR, et al. Association of CKD and cancer risk in older people. J Am Soc Nephrol. 2009;20(6):1341-1350. 23. Russo P. End stage and chronic kidney disease: associations with renal cancer. Front Oncol. 2012; 2:1-7. 24. Lane BR, Poggio ED, Herts BR, Novick AC, Campbell SC. Renal function assessment in the era of chronic kidney disease: renewed emphasis on renal function centered patient care. J Urol. 2009;182(2):436-444. 25. Campbell SC, Novick AC, Belldegrun A, et al. Guideline for management of the clinical T1 renal mass. J Urol. 2009;182(4): 1271-1279. 26. Foley RN, Wang C, Collins AJ. Cardiovascular risk factor profiles and kidney function stage in the US general population: the NHANES 3 study. Mayo Clin Proc. 2005;80(10):1270-1277. 27. Stevens LA, Li S, Wang C, et al. Prevalence of CKD and comorbid illness in elderly patients in the United State: results from the Kidney Early Evaluation Program (KEEP). Am J Kidney Dis. 2010;55(3)(suppl 2):S23-S33 28. Stenvinkel P. Chronic kidney disease: a public health priority and harbinger of premature cardiovascular disease. J Int Med. 2010;268(5):456-467. 29. Go AS, Chertow GM, Fan D, et al. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004;35(13):1296-1305. 30. Launay-Vacher V, Oudard S, Janus N, et al. Prevalence of renal insufficiency in cancer patients and implications for anticancer drug management. The Renal Insufficiency and Anticancer Medications Study (IRMA). Cancer. 2007;110(6):1376-1384. 31. Canter D, Kutikov A, Sirohi M, et al. Prevalence of baseline CKD in patients presenting with solid renal tumors. Urology. 2011;77(4):781-785. 32. Bijol V, Mendez GP, Hurwitz S, Renneke HG, Nose V. Evaluation of the nonneoplastic pathology in tumor nephrectomy specimens. Am J Surg Pathol. 2006;30(5):575. 33. Henriksen KJ, Meehan SM, Chang A. Nonneoplastic kidney diseases in adult tumor nephrectomy and nephroureterectomy 945
Russo et al specimens: common, harmful, yet underappreciated. Arch Pathol Lab Med. 2009;133(7):1012-1025. 34. Bonsib SM, Pei Y. The non-neoplastic kidney in tumor nephrectomy specimens: what can it show and what is important? Adv Anat Pathol. 2010;17(4):235-250. 35. Hollenback BK, Tash DA, Miller DC, et al. National utilization trends of partial nephrectomy for renal cell carcinoma: a case of underutilization? Urology. 2006; 67(2):254-259. 36. Miller DC, Hollingsworth JM, Hafez KS, et al. Partial nephrectomy for small renal masses. An emerging quality of care concern? J Urol. 2006;175(3):853-857. 37. Dulabon LM, Lowrance WT, Russo P, Huang WC. Trends in renal tumor surgery delivery within the United States. Cancer. 2010;116(10):2316-2321.
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38. Lowrance WT, Yee DS, Savage C, et al. Complications after radical and partial nephrectomy as a function of age. J Urol. 2010;183(5):1725-1730. 39. Lane BR, Abouassaly R, Gao T, et al. Active treatment of localized renal tumors may not impact overall survival in patients aged 75 years or older. Cancer. 2010;116(13):3080-3083. 40. Wehle MJ, Thiel DD, Petrou SP, et al. Conservative management of incidental contrast-enhancing renal masses as safe alternative to invasive therapy. Urology. 2004;64(1):49-52. 41. Volpe A. Jewett MA. The role of surveillance for small renal masses. Nat Clin Pract Urol. 2007;4(1):2-3. 42. Kunkle DA, Egleston BL, Uzzo RG. Excise, ablate, or observe: the small renal mass dilemma—a meta-analysis and review. J Urol. 2008;179(4):1277.
Am J Kidney Dis. 2013;61(6):939-946
T
he National Kidney Foundation (NKF) receives many requests for information from patients, caregivers, and physicians regarding kidney cancer in general and specifically with respect to the impact of treatment on overall kidney health. In response, the NKF commissioned a survey of patients and caregivers to assess their knowledge about risk factors and treatment options for kidney cancer and chronic kidney disease (CKD). The ultimate goal of the survey was to identify educational opportunities that address knowledge deficits found in the kidney cancer community. Although many elements related to the care of patients with kidney tumor were explored in the survey, including the role of caregivers, the nature of information resources used, and health maintenance strategies used by patients living with a solitary kidney, the focus of this report is on patient and caregiver knowledge regarding surgical options for disease management and their impact on overall kidney health. We focused on this topic because of clear clinical evidence that radical nephrectomy is grossly overused in the management of small renal masses despite the Am J Kidney Dis. 2013;61(6):939-946
accumulating evidence that kidney-sparing surgery provides oncologic control equivalent to radical nephrectomy while concurrently preserving kidney function and preventing CKD. An estimated 64,770 new cases and 13,570 deaths from kidney cancer occurred in the United States in 2011.1 Compared with 1971, this shows a 5-fold increase in incidence and 2-fold increase in mortality. Epidemiologic evidence indicates an increase in all
From the 1Memorial Sloan Kettering Cancer Center, Weill School of Medicine, Cornell School of Medicine, New York, NY; 2 Pharmaceutical Product Development, Research Triangle Park, NC; and 3National Kidney Foundation, New York, NY. Received May 17, 2012. Accepted in revised form January 29, 2013. Originally published online March 25, 2013. Address correspondence to Paul Russo, MD, Memorial Sloan Kettering Cancer Center, Weill School of Medicine, Cornell School of Medicine, 1275 York Ave, New York, NY 10065. E-mail: [email protected] © 2013 by the National Kidney Foundation, Inc. 0272-6386/$36.00 http://dx.doi.org/10.1053/j.ajkd.2013.01.028 939
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stages of renal cancer, including advanced and metastatic stages.2 In ⬃30% of patients with kidney tumor, metastatic disease will either be seen at presentation or develop later. After World War II, radical surgical resection of the kidney, perinephric soft tissues, ipsilateral adrenal gland, and regional lymph nodes, termed radical nephrectomy, was introduced and popularized. This operation is still used today, whether by open or minimally invasive approaches, for the resection of massive tumors that are locally advanced or metastatic as part of the strategy of cytoreduction prior to the administration of systemic therapy.3-6 Extensive use of the modern cross-sectional imaging techniques of the abdomen (computed tomography, magnetic resonance imaging, and ultrasonography) during the last 20 years, typically ordered to assess nonspecific abdominal and musculoskeletal symptoms or during unrelated cancer care, has altered the profile of the patient with kidney tumor from one with a massive symptomatic tumor at presentation to one with a small asymptomatic mass. Approximately 70% of surgically resected kidney tumors today are spotted incidentally, with a median tumor size ⬍4 cm.7 This imaging-induced tumor size and stage migration has created a new pool of patients with small renal masses (T1, ⬍7 cm) with a generally favorable prognosis after surgical resection by either radical or partial nephrectomy. In the last 15 years, a significant transition from radical nephrectomy for all kidney tumors to the expanded use of partial nephrectomy has occurred.8 The basis of this transition has been enhanced understanding of the variable oncologic threats provided in the family of renal cortical tumors, an appreciation for the oncologic equivalency of partial and radical nephrectomy for T1 (⬍7-cm) tumors, and increasing concerns regarding the causation of CKD by radical nephrectomy and its associated cardiovascular morbidity and potential mortality. Despite the accumulating knowledge that partial and radical nephrectomy provide comparable oncologic outcomes for small renal masses and that partial nephrectomy has the advantage of preventing or delaying the onset of postsurgical CKD, radical nephrectomy remains grossly overused in the United States.9 Despite the increasing elucidation of the complex interplay between kidney cancer surgery and CKD, a knowledge deficit in both physicians and patients may be responsible for this continued overuse of radical nephrectomy.
METHODS Survey Development Survey questions were developed by the following people: oncologist (n ⫽ 1), oncologic urologic surgeons (n ⫽ 2), nephrologists (n ⫽ 2), oncologic nurse (n ⫽ 1), patient with kidney cancer 940
(n ⫽ 1), and health education experts from the NKF (n ⫽ 2). There were 50 questions (46 close ended and 4 open ended). Survey pretests with 5 members of the target audience (3 patients and 2 caregivers) were conducted on December 17, 2010, at the Harris Interactive New York City office and were 60 minutes long. The final survey questions can be found in Item S1 (provided as online supplementary material).
Study Design The study design was a cross-sectional quantitative survey administered online by Harris Interactive Inc between January 3, 2011, and May 27, 2011. The target populations were patients with kidney cancer and caregivers of patients with kidney cancer (parents, siblings, friends, and other family members or professional caregivers such as nurses or aides). Qualified participants were US residents, older than 18 years, and either had a diagnosis of kidney cancer, were a caregiver for someone with a diagnosis of kidney cancer, or were a caregiver for someone with a diagnosis of kidney cancer within the last year. The goal number of respondents was 500, a sufficient number to demonstrate significance when comparing responses among different stages of kidney cancer (stage 1: tumor ⬍7 cm; stage 2: tumor ⬎7 cm; stage 3: the tumor, regardless of size, has spread beyond the kidney to nearby tissues or blood vessels or has spread to a nearby lymph node; stage 4: the tumor, regardless of size, has spread to distant sites, has invaded directly beyond the local area, or involves ⬎1 lymph node). The survey was self-administered and required approximately 30 minutes to complete. Patients and caregivers were recruited from 3 sources: 1. The Harris Interactive Chronic Illness Panel who selfreported that they either had a diagnosis of cancer or were living in a household in which someone had a diagnosis of cancer. 2. Oncologists, nephrologists, and urologists who were randomly sampled from the American Medical Association Master File and asked to refer their patients with kidney cancer/caregivers to the survey. After qualifying through a brief screen, physicians were mailed up to 30 postcards to use for referring patients/caregivers. 3. NKF-referred partners and the Association of Cancer Online Resources (www.ACOR.org) recruited participants through their listservs; any recipient of this invitation had to request an identification number and password directly from Harris in order to participate. Because all participants had a unique identification number and password, they were prevented from completing the survey more than once. All respondents and physicians received an honorarium for participating and for referring patients, respectively. Ninetynine physicians referred patients and caregivers to the survey, generating 278 completed surveys. There were 85 responses from the Harris Interactive Chronic Illness panel, 40 from the Association of Cancer Online Resources kidney cancer listserv, and 14 from the NKF-referred caregiver listserv. The total number of invitations is unknown because neither the number of referrals from each physician nor the number of e-mail recipients on the listservs can be determined. Kidney cancer stages were designated as early (stages 1 and 2; n ⫽ 181) and late (stages 3 and 4; n ⫽ 123). Throughout the study, participants who did not know answers to specific queries, such as what stage they had (n ⫽ 113), were designated as the “don’t-know” group. Precise medical, surgical, and pathologic data for individual patients were not available for any of the patients and hence the answers to the survey could not be confirmed. Similarly, we do not have information regarding the office discussions between physicians and patients, the suitability of an individual patient for a Am J Kidney Dis. 2013;61(6):939-946
Knowledge Deficits and Partial Nephrectomy Table 1. Patient Characteristics According to Stage of Kidney Cancer Early Stage Patient Characteristic
No. of patients Age (y)a Male sex Female sex Diagnosed with CKD Time since diagnosis of kidney cancer (y) Metastatic kidney cancer Urologist is primary provider Radical nephrectomy
Stage 1
Stage 2
60.3 ⫾ 10.6
62.5 ⫾ 11.3
5.0 ⫾ 5.0
5.6 ⫾ 5.8
Late Stage Stages 1-2
181 (43.4) 61 43% 57% 14% 5.3
Stage 3
Stage 4
57.9 ⫾ 11.6
58.8 ⫾ 9.1
4.1 ⫾ 5.1
5.7 ⫾ 4.4
3% 56% 83%
Stages 3-4
Don’t Know Stage
123 (29.5) 58 46% 54% 27% 4.9
113 (27.1) 66.9 ⫾ 9.1 46% 54% 22% 7.3 ⫾ 9.0
52% 18% 92%
16% 51% 86%
Note: All kidney cancer staging information was provided by the respondents and is defined as follows: stage 1, tumor ⬍7 cm; stage 2, tumor ⬎7 cm; stage 3, the tumor regardless of size has spread beyond the kidney to nearby tissues or blood vessels or has spread to a nearby lymph node; and stage 4, the tumor regardless of size has spread to distant sites, has invaded directly beyond the local area, or involves more than 1 lymph node. Values for continuous variables are given as mean or mean ⫾ standard deviation. Abbreviation: CKD, chronic kidney disease. a Range was 26-87 years.
partial nephrectomy, whether referrals to tertiary centers were made, or the degree of surgical expertise or surgical volume of individual surgeons. Although there were respondents, we do not have the denominator of potential respondents who were invited to do the survey but later declined.
Statistical Analysis Descriptive statistics were used to tabulate response rates and final data were compared and weighted to population age and geographic characteristics of the general kidney cancer population in the United States, which are outlined in the Centers for Disease Control and Prevention Behavioral Factor Surveillance System Study. A standard t test of column proportions and means was applied, tests were 2 tailed, an infinite population was assumed, and samples were considered to be independent. To adjust for overlap of respondents between columns, overlap formulas were applied.
RESULTS Survey Participants A total of 417 respondents (365 patients and 52 caregivers) participated. Caregivers answered the same questions as patients, but in a format that made reference to the patient they cared for, so that all factual information regarding the patient’s medical history and treatments is reflective of the total number of respondents. Questions on knowledge, such as awareness of risk factors for CKD, were reflective of both caregivers and patients as a combined group. Caregivers answered additional questions pertaining only to themselves, such as their age and sex. Patients were aged 26-87 (average, 60) years, and 55% were women. Caregivers were aged 30-91 (average, 53) years, and 81% of these respondents were women. Am J Kidney Dis. 2013;61(6):939-946
Patient Characteristics by Kidney Cancer Stage Patient characteristics according to stage of kidney cancer are listed in Table 1. Forty-three percent of patients had early-stage cancer, 30% had late-stage cancer, and 27% did not know their stage. Radical nephrectomy was the predominant surgical treatment for each group: ⬃83% in the early-stage group, 92% in the late-stage group, and 86% in the don’t-know group. The don’t-know group had had a diagnosis for a significantly longer time (⬃2 years) than the earlyand late-stage groups. More than one-fourth of respondents did not know what stage of kidney cancer that they or their patient had. Characteristics of Tumor at Diagnosis Table 2 highlights characteristics of patients’ tumors at diagnosis. More than half the respondents did Table 2. Characteristics of Tumor at Diagnosis Percentage of Respondents
Size of tumor at diagnosis ⬍4 cm 4-7 cm ⬎7 cm Don’t know or were not told
15 30 22 33
Type of tumor at diagnosis Benign Indolent with limited metastatic potential Clear cell Don’t know or were not told
11 27 7 55
Note: N ⫽ 417. 941
Russo et al Table 3. Patient Surgical History Percentage of Respondents
Type of surgery Radical nephrectomy Radical nephrectomy (laparoscopic) Partial nephrectomy Surgery for removal of metastases Respondent does not remember type of surgery Time of surgery ⬍1 y ago 1-3 y ago ⬎3 y ago Physician discussed candidacy for partial nephrectomy Yes, but still recommended radical nephrectomy No Yes, but was told patient not a candidate Respondent does not remember if discussed Respondent does not understand the differences in surgeries enough to comment
67 19 18 6 3
20 32 48
38 25 24 8 5
Note: n ⫽ 363. Total response rate is 113% due to multiple responses.
not remember or were not told what type of kidney tumor they or their patient had and 33% did not know or were not told how large the tumor was. Of respondents who knew the tumor size, 45% had tumors ⱕ7 cm (T1), 11% had benign tumors, and 27% knew they had the more indolent papillary or chromophobe tumors, which have limited metastatic potential. Patient History Surgical Treatment Of 417 patients described by respondents, 363 (87%) underwent some form of surgical treatment for kidney cancer. Table 3 lists the distribution of surgery type, timing of surgery in relation to taking the survey, and whether a physician discussed candidacy for partial nephrectomy. Among patients who underwent radical nephrectomy, 25% reported that they were not aware of the option of partial nephrectomy, and 38% were told about partial nephrectomy, but their surgeons recommended against it. Even for patients with early-stage kidney cancer, only 18% underwent partial nephrectomy. CKD Diagnosis and Type of Nephrectomy
Of 81 patients (19%) who were given a diagnosis of CKD, 40% were given the diagnosis prior to their kidney cancer diagnosis; 53%, after; and 7% did not 942
remember when they were given the diagnosis. Table 4 lists nephrectomy type in relation to the time of CKD and kidney cancer diagnoses. CKD was diagnosed in 29 patients before they underwent an operation and 23 of them (79%) underwent radical nephrectomy even though loss of kidney function had been determined prior to surgery; the majority did not receive kidney-sparing surgery. Participant Knowledge of Kidney Cancer and Kidney Health Table 5 summarizes participants’ knowledge of risk factors for developing CKD and their understanding of the relationship between CKD and kidney cancer. Only 56% of patients thought that kidney cancer and CKD were somehow related, and only 40% thought that losing part or all of 1 kidney due to an injury or a disease other than cancer is a risk factor for developing CKD. The majority of respondents (81%) thought that there are not enough informational resources available for kidney cancer, and less than one-third were satisfied with current resources.
DISCUSSION In this study, 417 patients and caregivers responded to a questionnaire designed to determine if there were any unmet educational and informational needs in the kidney cancer population. The interaction between surgical therapies proposed and delivered and the new and emerging concerns for CKD as perceived by the recipients of kidney cancer surgical care also were carefully studied. The survey results suggest key areas in which enhanced education, for both patients and physicians, could be beneficial. Of patients with earlystage renal tumors, radical nephrectomy was used in the vast majority. Although a small minority of patients (18%) underwent partial nephrectomy, 38% were told about partial nephrectomy but were advised against it, and 25% of patients did not hear of the option of partial nephrectomy. Despite this large proTable 4. Nephrectomy Type in Relation to Time of CKD and Kidney Cancer Diagnoses
Nephrectomy Type
CKD Diagnosed Before Kidney Cancer (n ⴝ 29)
CKD Diagnosed After Kidney Cancer (n ⴝ 50)
Don’t Remember When CKD Diagnosed (n ⴝ 2)
Partial Radical
6 (21) 23 (79)
9 (18) 41 (82)
0 (0) 2 (100)
Note: Only 19% (n ⫽ 81) of patients were given a diagnosis of CKD. Values are given as number (percentage). Abbreviation: CKD, chronic kidney disease. Am J Kidney Dis. 2013;61(6):939-946
Knowledge Deficits and Partial Nephrectomy Table 5. Participant Knowledge Regarding Kidney Cancer and CKD Percentage of Participants with Knowledge
Risk factor for CKD Loss of a kidney due to an injury or a disease other than cancer Radical nephrectomy for cancer treatment Medications that cause kidney damage High blood pressure Diabetes Family history of kidney disease Older than 60 y Having urinary obstructions Repeated urinary infections Heart and blood vessel disease Racial/ethnic background that is African American, Hispanic American, Asian American, Pacific Islander, or American Indian Relationship between CKD and kidney cancer Agree that kidney cancer and CKD can be related Agree that it is possible to get CKD in remaining kidney after nephrectomy for kidney cancer Agree that kidney health protection after nephrectomy is important Agree that a person with kidney cancer can take steps to reduce the risk for CKD
40 62 68 66 66 60 52 49 45 42 31
56 71
94 75
Note: N ⫽ 417. Abbreviation: CKD, chronic kidney disease.
portion of patients undergoing nephrectomy (either radical or partial nephrectomy), most patients had a limited understanding of the risk factors for CKD. The knowledge and educational deficits revealed in our survey may be due to lack of communication between health care professionals and patients and also to lack of knowledge on the part of physicians and surgeons, especially in regard to the problem of overuse of radical nephrectomy and its impact on the development of CKD. Accordingly, CKD was diagnosed in only 19% of patients in our study, which seems low considering that all patients had kidney cancer and the majority also underwent radical nephrectomy. This may suggest a lack of awareness about the need for CKD testing and education in this population. The large proportion of patients who did not know their stage of kidney cancer (27%), tumor size (33%), or tumor type (55%) may indicate that they did not receive this information from their physicians and thus could not make informed decisions about the type of treatment they should receive, including kidney-sparing surgery. Notably, the group of Am J Kidney Dis. 2013;61(6):939-946
patients who did not know their stage of kidney cancer had had the diagnosis for a significantly longer time compared with the early- and late-stage groups. Although there was apparently more time for these patients to learn about their disease, they were still uninformed. Although more than half the respondents understood that radical nephrectomy for cancer treatment can lead to CKD (62%), fewer knew that losing a kidney for any other reason is also a risk (40%); it appears that they do not understand the association between nephron loss and the development of CKD. It may be that they only recognize an association between the general diagnosis of cancer and CKD, especially because only 56% think that a relationship exists specifically between kidney cancer and CKD. They appear not to understand the bidirectional nature of kidney cancer and CKD. Although a majority of respondents thought it is possible to get CKD in the remaining kidney after nephrectomy for kidney cancer (71%), one cannot know if they interpret this as CKD being just another independent disease state that can occur in anyone at any time or as a direct result of radical nephrectomy. That most patients who were given a diagnosis of CKD prior to their kidney cancer diagnosis still underwent radical nephrectomy (79%) also suggests that surgeons may not recognize the importance of kidney-sparing surgery, even in those already given a diagnosis of CKD. During the last decade, well-done clinical studies have fortified the case for partial nephrectomy when possible based on 3 basic points.10-14 First, the pathology of resected renal tumors indicates that up to 20% are completely benign (angiomyolipoma, renal oncocytoma, and metanephric adenoma) with no metastatic potential, 25% are indolent cancers (papillary and chromophobe) with limited metastatic potential, and for the majority of T1 cancers that are the more malignant conventional clear cell carcinoma (54%), long-term cancer-specific survival rates after resection are ⱖ90%.15 Second, oncologic results for patients with T1 tumors are equivalent whether partial or radical nephrectomy is done. This is in keeping with the evolution of surgical oncology from the Halstedian radical surgical resection of all tumors (sarcoma and breast cancer) toward limb- and organ-preservation operations that yield similar oncologic outcomes.16 Third, the finding that CKD is a pre-existing condition in ⬃26% of patients with a normal serum creatinine level prior to surgical resection and that radical nephrectomy is a risk factor for the creation of CKD or the worsening of pre-existing CKD makes the casual use of radical nephrectomy for a small renal mass a potentially toxic event.10 The well-known association of CKD and cardiovascular morbidity and 943
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mortality in the general population now is being observed in the renal tumor population. Epidemiologic evidence suggests that when radical nephrectomy is used instead of partial nephrectomy for small renal masses, there are more subsequent cardiovascular events and worse overall survival.17-20 Many patients with kidney cancer also have significant and common preexisting medical morbidities predisposing them to CKD, including diabetes, hypertension, and vascular disease. CKD now is also being directly implicated in the evolution of kidney cancer by as yet uncertain mechanisms.21-23 Appeals to the urology community to perform partial nephrectomy when possible for the treatment of a small renal mass were published in 200924 and after the exacting work of the American Urological Association guidelines committee later that year.25 CKD is an increasing public health problem in the United States and now is considered an independent risk factor for the development of cardiovascular morbidity and mortality.26-29 It also is recognized that patients with kidney cancer have a higher rate of CKD than the general population that is not related entirely to radical nephrectomy.23 Launay-Vacher et al30 evaluated 4,684 patients with cancer and reported that 12% and 20% had an estimated glomerular filtration rate ⬍60 mL/min/1.73 m2 by the Modification of Diet in Renal Disease (MDRD) Study and Cockcroft-Gault equations, respectively. Canter et al31 reported the prevalence of baseline CKD in 1,114 patients presenting with solid renal tumors. Twentytwo percent had stage 3 CKD or greater despite 88% having a serum creatinine level within normal limits (⬍1.4 mg/dL). In a subgroup of 282 patients 70 years or older, 113 (40%) had CKD stage 3.31 These results are similar to those first reported by Memorial Sloan Kettering Cancer Center investigators that demonstrated a 26% rate of CKD in 662 patients with small renal tumors and a serum creatinine level within normal limits.10 In the non-neoplastic kidney at the time of nephrectomy, extensive nephropathologic findings are observed in the vast majority of patients. It is not clear if these changes are a direct cause of renal neoplasia or a result of medical comorbid conditions that are prevalent in patients with kidney tumor.32-34 Although partial nephrectomy leads to equal survival outcomes and oncologic results compared with radical nephrectomy while also maximally preserving kidney function and inhibiting or delaying the onset of CKD and its late cardiovascular morbidity and mortality, radical nephrectomy remains overused in the United States and abroad. Strong epidemiologic evidence from national databases, such as the National Inpatient Sample, Surveillance Epidemiology and End Results (SEER) database, and the SEER database linked to Medicare claims, indicates that approximately 70%-80% of patients with tumors ⬍4 cm still 944
undergo radical nephrectomy.18,19,35,36 For reasons that are unclear, women and elderly patients are more likely to be treated with radical nephrectomy.37 A lot of urologists believe a “quick” radical nephrectomy in an elderly patient would result in the patient being exposed to fewer postoperative complications than would a partial nephrectomy, but this is the very patient population in greatest need for kidney preservation. In 1,712 patients with kidney tumors, Memorial Sloan Kettering Cancer Center investigators assessed age and type of procedure and found that statistical evidence for risk of complications associated with partial nephrectomy increasing with advancing age was lacking. In addition, no evidence linking age to estimated blood loss or surgical time was reported. The authors concluded that because of the advantages of preservation in kidney function, elderly patients, if fit, should be wholly eligible for partial nephrectomy.38 Although this study did not provide information on nonsurgical management (active surveillance) of kidney tumors, particularly in elderly (⬎75 years) and medically unfit patients, this approach increasingly is viewed as an acceptable alternative in carefully selected patients, with death from medical illnesses far superseding disease progression from kidney cancer.39-42 In such carefully selected patients, active surveillance is another means of maximizing kidney function and avoiding iatrogenic CKD. Our study is limited because we do not have specific clinical information regarding the kidney cancers being treated or the surgical and medical capabilities of the treating physicians. We also have no insight about why a surgeon would mention partial nephrectomy but urge the patient to undergo radical nephrectomy. Clinical characteristics of the tumor and surgical skill of the surgeon also were not known. This lack of clinical data precludes more complex statistical analysis. However, we would expect patient-relayed inaccuracies to be evenly distributed among those filling out the survey and the perception of early- and late-stage disease to be reliable. In conclusion, the present study provides data indicating that a minority of patients underwent partial nephrectomy or were given partial nephrectomy as a potential option for the management of their earlystage kidney cancer. This result is not surprising given the data described from national databases indicating overuse of radical nephrectomy for the treatment of small renal masses. From the patient’s and caregiver’s vantage points, educational resources (including web based) describing treatment options for patients with small renal tumors may allow for more informed dialogues between patients and their physicians or inspire second opinions and referral to tertiary centers, where partial nephrectomy and all other options Am J Kidney Dis. 2013;61(6):939-946
Knowledge Deficits and Partial Nephrectomy
for kidney cancer are readily available. General awareness of the interplay between kidney functional concerns and potential unfavorable consequences of overly aggressive surgical treatments need to be clearly defined. A working knowledge of the bidirectional relationship of CKD and the surgical management of kidney cancer is now essential for all urologists. Educational programs for surgeons and patients alike are required to promote the benefits of kidney-sparing approaches when possible.
ACKNOWLEDGEMENTS The survey was conducted by Harris Interactive Inc. Support: This survey was funded by Pfizer. The sponsor participated in study design and the decision to submit this report for publication. Financial Disclosure: Dr Russo is a consultant for Wilex AG. Dr Szczech is an employee of Pharmaceutical Product Development. The other authors declare that they have no other relevant financial interests.
SUPPLEMENTARY MATERIAL Item S1: Final survey questions. Note: The supplementary material accompanying this article (http://dx.doi.org/10.1053/j.ajkd.2013.01.028) is available at www.ajkd.org.
REFERENCES 1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62(1):10-29. 2. Ljungberg B, Campbell SC, Cho HY, et al. The epidemiology of renal cell carcinoma. Eur Urol. 2011; 60(4):615-621. 3. Robson CJ, Churchill BM, Andersen W. The results of radical nephrectomy for renal cell carcinoma. J Urol. 1969;101(3):297. 4. Skinner DG, Colvin RB, Vermillion CD, Pfister RC, Leadbetter WF. Diagnosis and management of renal cell carcinoma: a clinical and pathological study of 309 cases. Cancer. 1971;28(5): 1165-1177. 5. Russo P. Open radical nephrectomy for localized renal cell carcinoma. In: Vogelzang N, Nicholas J, eds. Genitourinary Oncology. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2006:725-731. 6. Russo P. Multi-modal treatment for metastatic renal cancer— the role of surgery. World J Urol. 2010;28(3):295-230. 7. Russo P. Renal cell carcinoma: presentation, staging, and surgical treatment. Semin Oncol. 2000;27(2):160-176. 8. Han JS, Huang WC. Impact of kidney cancer surgery on oncologic and kidney functional outcomes. Am J Kidney Dis. 2011;58(5):846-854. 9. Russo P. The role of surgery in the management of early-stage renal cancer. Hematol Oncol Clin North Am. 2011;25(4):737-752. 10. Huang WC, Levey AS, Serio AM, et al. Chronic kidney disease after nephrectomy in patients with renal cortical tumors: a retrospective cohort study. Lancet Oncol. 2006;7(9):735-740. 11. Russo P, Jang T, Eggener S, Pettus J, Karellas M, O’Brien F. Survival rates after resection for localized kidney cancer 19892004. Cancer. 2008;113(1):84-96. 12. Kattan MW, Reuter V, Motzer RJ, Katz J, Russo P. A postoperative prognostic nomogram for renal cell. J Urol. 2001;166(1):63-67. 13. Russo P. Partial nephrectomy for renal cancer (I). BJU Int. 2010;105(9):1206-1220. Am J Kidney Dis. 2013;61(6):939-946
14. Teloken PE, Thompson RH, Tickoo SK, et al. Prognostic impact of histological subtype in patients with surgically treated localized renal cell carcinoma. J Urol. 2009;182(5):2132-2136. 15. Snyder ME, Bach A, Kattan MW, Raj GV, Reuter VE, Russo P. Incidence of benign lesions for clinically localized renal masses ⬍7cm in radiological diameter: influence of sex. J Urol. 2006;176(6):2391-2396. 16. Thompson RH, Siddiqui S, Lohse CM, Leibovich BC, Russo P, Blute ML. Partial versus radical nephrectomy for 4 to 7 cm renal cortical tumors. J Urol. 2009;182(6):2601-2606. 17. Thompson HR, Boorjian SA, Lohse CM, et al. Radical nephrectomy for pT1a renal masses may be associated with decreased overall survival compared to partial nephrectomy. J Urol. 2008;179(2):468-473. 18. Huang WC, Elkin EB, Levey AS, Jang TL, Russo P. Partial nephrectomy versus radical nephrectomy in patients with small renal tumors—is there a difference in mortality and cardiovascular outcomes. J Urol. 2009;181(1):55-62. 19. Tan HJ, Norton EC, Ye Z, Hafez K, Gore JL, Miller DC. Long-term survival following partial vs radical nephrectomy among older patients with early-stage kidney cancer. JAMA. 2012;307(15):16291635. 20. Kim SP, Thompson H, Boorjian SA, et al. Comparative effectiveness for survival and renal function of partial and radical nephrectomy for localized renal tumors: a systematic review and meta-analysis. J Urol. 2012;18(1):51-57. 21. Weng PH, Hung KY, Huang HL, Chen JH, Sung PK, Huang KC. Cancer-specific mortality in chronic kidney disease: longitudinal follow-up of a large cohort. Clin J Am Soc Nephrol. 2011;6(5): 1121-1128. 22. Wong G, Hayen A, Chapman JR, et al. Association of CKD and cancer risk in older people. J Am Soc Nephrol. 2009;20(6):1341-1350. 23. Russo P. End stage and chronic kidney disease: associations with renal cancer. Front Oncol. 2012; 2:1-7. 24. Lane BR, Poggio ED, Herts BR, Novick AC, Campbell SC. Renal function assessment in the era of chronic kidney disease: renewed emphasis on renal function centered patient care. J Urol. 2009;182(2):436-444. 25. Campbell SC, Novick AC, Belldegrun A, et al. Guideline for management of the clinical T1 renal mass. J Urol. 2009;182(4): 1271-1279. 26. Foley RN, Wang C, Collins AJ. Cardiovascular risk factor profiles and kidney function stage in the US general population: the NHANES 3 study. Mayo Clin Proc. 2005;80(10):1270-1277. 27. Stevens LA, Li S, Wang C, et al. Prevalence of CKD and comorbid illness in elderly patients in the United State: results from the Kidney Early Evaluation Program (KEEP). Am J Kidney Dis. 2010;55(3)(suppl 2):S23-S33 28. Stenvinkel P. Chronic kidney disease: a public health priority and harbinger of premature cardiovascular disease. J Int Med. 2010;268(5):456-467. 29. Go AS, Chertow GM, Fan D, et al. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004;35(13):1296-1305. 30. Launay-Vacher V, Oudard S, Janus N, et al. Prevalence of renal insufficiency in cancer patients and implications for anticancer drug management. The Renal Insufficiency and Anticancer Medications Study (IRMA). Cancer. 2007;110(6):1376-1384. 31. Canter D, Kutikov A, Sirohi M, et al. Prevalence of baseline CKD in patients presenting with solid renal tumors. Urology. 2011;77(4):781-785. 32. Bijol V, Mendez GP, Hurwitz S, Renneke HG, Nose V. Evaluation of the nonneoplastic pathology in tumor nephrectomy specimens. Am J Surg Pathol. 2006;30(5):575. 33. Henriksen KJ, Meehan SM, Chang A. Nonneoplastic kidney diseases in adult tumor nephrectomy and nephroureterectomy 945
Russo et al specimens: common, harmful, yet underappreciated. Arch Pathol Lab Med. 2009;133(7):1012-1025. 34. Bonsib SM, Pei Y. The non-neoplastic kidney in tumor nephrectomy specimens: what can it show and what is important? Adv Anat Pathol. 2010;17(4):235-250. 35. Hollenback BK, Tash DA, Miller DC, et al. National utilization trends of partial nephrectomy for renal cell carcinoma: a case of underutilization? Urology. 2006; 67(2):254-259. 36. Miller DC, Hollingsworth JM, Hafez KS, et al. Partial nephrectomy for small renal masses. An emerging quality of care concern? J Urol. 2006;175(3):853-857. 37. Dulabon LM, Lowrance WT, Russo P, Huang WC. Trends in renal tumor surgery delivery within the United States. Cancer. 2010;116(10):2316-2321.
946
38. Lowrance WT, Yee DS, Savage C, et al. Complications after radical and partial nephrectomy as a function of age. J Urol. 2010;183(5):1725-1730. 39. Lane BR, Abouassaly R, Gao T, et al. Active treatment of localized renal tumors may not impact overall survival in patients aged 75 years or older. Cancer. 2010;116(13):3080-3083. 40. Wehle MJ, Thiel DD, Petrou SP, et al. Conservative management of incidental contrast-enhancing renal masses as safe alternative to invasive therapy. Urology. 2004;64(1):49-52. 41. Volpe A. Jewett MA. The role of surveillance for small renal masses. Nat Clin Pract Urol. 2007;4(1):2-3. 42. Kunkle DA, Egleston BL, Uzzo RG. Excise, ablate, or observe: the small renal mass dilemma—a meta-analysis and review. J Urol. 2008;179(4):1277.
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