Introduction
Epidemiology and risk factors
Renal cell carcinoma (RCC) is the eighth most common malignancy in the world. According to the National Cancer Institute, in 2017 approximately 64,000 diagnoses were made in the United States and more than 330,000 worldwide. The incidence of RCC has been steadily increasing in the United States, but this may be caused by incidental detection from imaging studies. In the 1980s, approximately 40% of renal neoplasms were stage 1 (≤ 7 cm and confined to kidney), but now represent greater than 60% of RCC at presentation. , If the benign renal masses are included, an estimated 80,000 patients in the United States undergo renal mass evaluation on an annual basis.
Clear cell RCC (ccRCC) comprises greater than 75% of all RCC and papillary RCC is the next most common (predominantly seen in the end-stage renal disease [ESRD] population). The most common hereditary syndrome for RCC (specifically ccRCC) is the von Hippel-Lindau (VHL) disease, which accounts for a small proportion (2%–3%) of patients with RCC. Although only 1.6% of patients with ccRCC have VHL disease, the majority of those with VHL disease will develop ccRCC. The molecular biology and pathogenesis involves loss of VHL tumor suppressor function and persistent hypoxia-inducible factor activity, leading to apparent tissue “hypoxia” and resulting in activation of tumor pathways and promoting tumor growth. This gene mutation is also the most prevalent gene mutation (40%–80%) found in the general (including the sporadic) RCC population. ,
The incidence of RCC is greatest in the sixth to seventh decade with higher risk of RCC among men (1.6:1 male:female ratio) and those of African descent. Potentially modifiable risk factors include tobacco use, obesity, hypertension (HTN), diabetes mellitus (DM), cystic disease, and ESRD. Paradoxically, obese patients with RCC have lower mortality. In addition, unlike tobacco exposure, alcohol use is associated with lower risk of RCC, even though it is linked to other cancers. , Chronic kidney disease (stages 3–4 CKD and ESRD) also appears to increase risk for RCC to some degree and, reciprocally, RCC is associated with increased risk of CKD decline. , Those with small renal masses and CKD share the same risk factors (tobacco use, obesity, DM, and HTN) partially caused by the high burden of comorbid diseases and may explain this bidirectional relationship.
Chronic kidney disease and renal cell carcinoma risk
RCC risk among CKD patients is high. For the dialysis-dependent ESRD population, the risk of RCC escalates to 100-fold greater than the general population and incidence of RCC among ESRD patients range 1% to 7%. , RCC risk rises with longer duration of dialysis, potentially from dialysis-related inflammatory processes and the link to acquired cystic kidney disease (ACKD). Incidence of ACKD is particularly high among ESRD patients and when progression to RCC occurs, the histologic subtype of papillary RCC is more prominent than in the general population. One Japanese cohort examining the relationship between histologic subtype and dialysis duration found that those with dialysis duration less than 10 years were more likely to have ccRCC, and those on dialysis for longer than 10 years had ACKD-associated RCC (more papillary RCC). The proportion of ESRD patients (22%–37%) with papillary RCC is 4 to 5 times greater than that of the general population (5%–7%). , Incidence of ccRCC and papillary RCC varies according to population and confers some degree of prognosis, as shown in Table 28.1 . ,
| Subtype | Incidence (%) | Prognosis | Population |
| Clear cell carcinoma | 70–80 | Fair | General |
| Papillary carcinoma | 10–20 | Favorable | ESRD, acquired cystic kidney disease |
| Chromophobe | 5 | Favorable |
Among pre-ESRD CKD patients, risk of RCC is also high and appears to increase with worsening estimated glomerular filtration rate (eGFR). When a cohort of 1 million cancer-free subjects were stratified by CKD stage, RCC risk was 39%, 81% greater for stage 3a and 3b CKD, respectively, than the reference group, then approached twofold greater for those with stage 4 CKD. The potential relationship between RCC and kidney function was further explored among 202,195 transplant recipients. Incidence of RCC rose during periods of graft failure and fell during periods of kidney function. Furthermore, early signs of kidney dysfunction, such as albuminuria, have also been associated with RCC, further supporting the relationship of kidney pathology with RCC.
Despite the adverse relationship between CKD and RCC risk, prognosis of RCC among those with ESRD appears to be better than in the general population, , , – with a 5-year cancer-specific survival of 90.1% for the ESRD population and 69% for the general population. The lower mortality among those with ESRD may be explained by more favorable demographic and tumor characteristics and potentially earlier diagnosis. , , A French cohort of ESRD patients was more functional and was diagnosed with RCC at a younger age (fifth vs. sixth decade) than in the general population. Detection appears to be earlier and asymptomatic potentially because of higher frequency of imaging among ESRD patients. The ESRD group had smaller tumor size, lower stage, lower grade, and was less likely to have nodal invasion or metastases. Furthermore, the predominant tumor subtype of papillary RCC tends to have a milder clinical course.
Cystic disease
The close association of RCC and ESRD has often been explained by the predominance of ACKD among ESRD patients, with an annual incidence among dialysis patients (0.15%–0.34%) of up to 40 times that of the general population (0.008%). In ESRD, ACKD prevalence ranges 10% to 44% soon after dialysis initiation but exceeds 90% as dialysis vintage reaches 5 to 10 years. In addition to long dialysis duration, male sex and younger age appear to be associated with ACKD. ESRD and male sex are risk factors common to RCC. ACKD is also reported in pre-ESRD CKD (7%–22%) and transplant (23%) populations. Although ACKD prevalence for these groups also far exceeds that of the general population, ACKD remains less common among these groups compared with dialysis patients. , , ,
Cysts appear to accumulate because of chronic hypoxia and acid-base dysregulation and possibly in response to growth factors. , , The acquired cysts open into the tubules and retain functional capacity to some degree, which is suggested by higher cyst fluid creatinine concentration than serum content and the regression of these cysts after renal transplantation. ,
The cystic lesions of ACKD are thought to be precursors of RCC that progress in the setting of prolonged lack of kidney function. The cystic lesions share common pathologic characteristics with RCC. The most prominent subtype of RCC among ESRD patients is papillary RCC, not the clear cell carcinoma usually seen in the general population. The RCC associated with ESRD has similar immunohistochemical patterns as with ACKD. ,
Cystic diseases other than ACKD have not been closely associated with RCC. The incidence of RCC in polycystic kidney disease is no different from that of the general population.
Screening for renal cell carcinoma
Even with the higher incidence of RCC among ESRD patients, routine screening for RCC is not recommended. Decision analysis performed of ACKD screening did not demonstrate a clear benefit to survival in the ESRD population. However, young individuals who are healthy with longer expected lifespan are suggested to be reasonable candidates for screening. , Debate continues regarding screening among potential transplant recipients who have an equally high rate of RCC as the ESRD population (3.5%). , However, transplant recipients diagnosed with RCC have good prognosis with tumor detection at a younger age, earlier stage, smaller tumor size, and favorable RCC subtype of papillary RCC. Presence of RCC does not adversely affect graft survival. Ten-year cancer-specific survival (∼90%) in transplant recipients is higher than for both the general (75%) and ESRD populations (77%). ,
Presentation
Renal cancers present as either solid renal masses or complex cystic renal masses (see Diagnosis later). The majority of renal masses and cancers are diagnosed incidentally and present without overt signs or symptoms. This reflects both the changing epidemiology of renal cancers—in which small, clinically localized renal masses now represent at least 50% of incident tumors—and the widespread use of axial imaging. , The “classic triad” of symptoms associated with a malignant renal mass include hematuria, flank pain, and abdominal mass. Symptoms associated with RCC are often a result of local tumor growth, hemorrhage, paraneoplastic symptoms, or metastatic disease, and are uncommon in patients with clinically localized disease. In fact, less than 10% of patients in contemporary series present with these symptoms and greater than 50% of renal masses are diagnosed incidentally. ,
Diagnosis
Physical examination
Physical examination has a limited role in the diagnosis of clinically localized disease and is most useful in distinguishing the signs and symptoms of advanced disease. For many years, RCC was known as the internists’ tumor , reflecting the variety of systemic symptoms and more common presentation at advanced stage. For instance, paraneoplastic syndromes (i.e., hypertension, polycythemia, hypercalcemia, abnormal liver function) are present in approximately 10% to 20% of patients with metastatic RCC. , In the contemporary era where most patients are diagnosed with clinically localized, early stage disease, physical examination may reveal medical conditions that influence management decisions, including body habitus, prior abdominal scars, stigmata of CKD, and so on.
Laboratory evaluation
There are no biomarkers or routine laboratory tests used to routinely diagnose renal malignancies. As such, laboratory tests are useful in assessment of renal function (glomerular filtration rate) and metastatic evaluation. Routine laboratory tests for renal mass evaluation include complete blood count, basic or complete metabolic panel, and urinalysis. Serum creatinine and urinalysis for protein are recommended before any intervention and, if abnormal, used to classify CKD stage.
Imaging techniques
Contrast-enhanced axial imaging, either computed tomography (CT) or magnetic resonance imaging (MRI), is the ideal imaging technique for the diagnosis and staging of clinically localized renal masses. Masses initially diagnosed by ultrasound or intravenous pyelography should be confirmed with contrast-enhanced imaging. Contrast-enhanced abdominal imaging (CT or MRI) best characterizes the mass, provides information regarding renal morphology (of the affected and unaffected kidney), assesses extrarenal tumor spread (venous invasion or regional lymphadenopathy), and evaluates the adrenal glands and other abdominal organs for visceral metastases. Enhancement of greater than 15 to 20 Houndsfield units on CT or 20% enhancement on MRI is indicative of RCC, but does not preclude benign tumors. ,
Imaging readily distinguishes solid from cystic renal masses. Solid masses are more often presumed malignant whereas cystic renal masses are characterized as simple or complex based on the Bosniak Classification system. The Bosniak system was developed using CT criteria that segregate cystic lesions into categories that define the likelihood of malignancy. , Bosniak 1 lesions are simple cysts: thin-walled fluid-filled structures with zero risk of malignancy that do not require follow-up. Bosniak 2 lesions are minimally complex with a minimal risk (< 3%) of malignancy. These include nonenhancing septated cysts, cysts with calcifications, infected cysts, and hyperdense cysts. Bosniak 2F cysts include cysts with “perceived” enhancement and hyperdense lesions greater than 3 cm. These cysts have a 3% to 10% risk of malignancy and 15% risk of radiographic progression to a more complex cyst. Complex cystic renal masses that have thickened irregular walls or septa on enhancement are classified as Bosniak 3. Approximately 50% of such lesions prove to be malignant on final pathology. Bosniak 4 complex cystic lesions are very suspicious for malignancy because they contain enhancing nodular soft tissue components and about 75% to 90% of such lesions prove to be RCC on final pathology. Of note, the majority of cystic renal masses are low-grade cystic RCC and behave in an indolent fashion.
Patients with CKD should receive contrast with caution as iodinated contrast agents can transiently or permanently affect GFR (contrast induced nephropathy) and gadolinium-based MRI contrast agents can lead to nephrogenic systemic fibrosis—a devastating and potentially fatal condition. Noncontrast CT or MRI and ultrasound can be used to best characterize renal masses in patients who cannot receive intravenous contrast. Contrast-enhanced ultrasonography (CEUS) uses microbubbles in lieu of contrast agents and early data are promising for the characterization and assessment of enhancement of renal masses. CEUS may play an important role in patients with CKD or those patients who cannot receive typical contrast agents in the future.
In patients with RCC or suspicion of RCC, complete staging is finalized with chest radiography (x-ray). Chest CT scan should be obtained selectively, primarily for patients with pulmonary symptoms or an abnormal chest x-ray. , Bone scans and brain imaging should be reserved primarily for patients with bone pain, elevated alkaline phosphatase, or neurologic symptoms, respectively. Positron emission tomography scan has no role in the routine evaluation or staging of RCC.
Clinical diagnosis and risk stratification of renal masses
Depending on tumor size, 20% to 30% of clinically localized renal masses may be benign. , As stated earlier, solid renal masses and complex cystic lesions (Bosniak 3 and 4) are considered malignant at diagnosis. However, patient and tumor characteristics can indicate populations more or less likely to harbor benign or malignant disease. For instance, women with smaller tumors have a higher likelihood of having benign tumors. However, with the exception of fat-containing angiomyolipoma, none of the current imaging modalities or laboratory tests can reliably distinguish between benign and malignant solid tumors, or between indolent and aggressive tumor biology. A number of predictive clinical models exist for the prediction of RCC; however, these models perform with modest concordance indices of 0.55 to 0.65. , The best predictors of malignancy are male sex and increasing tumor size, where men have a nearly threefold increased risk of malignancy (effect size 2.71, 95% confidence interval [CI], 2.39–3.02) compared with women and likelihood of malignancy increases per cm of tumor diameter (effect size 1.3 per cm increase in diameter, 95% CI, 1.22–1.43).
Renal mass biopsy
Renal mass biopsy (RMB) currently has an adjunctive role in the diagnosis and risk stratification of patients with renal masses suspicious for RCC and is therefore recommended to be used in a utility-based approach. RMB, or fine needle aspiration (FNA), traditionally was reserved for patients suspected of having metastasis of another primary to the kidney, abscess, or lymphoma, or when needed to establish a pathologic diagnosis of RCC in occasional patients presenting with disseminated metastases or unresectable primary tumors.
The role of RMB for clinically localized RCC has evolved considerably over the past few decades with an increasing use and considerable variance in practice patterns. RMB is demonstrated to be a safe procedure with low rates of hematoma (4.9%), hemorrhage requiring transfusion (0.4%), and no reports of tumor seeding with contemporary techniques. A biopsy indicating RCC is highly reliable with a specificity of 96% and positive predictive value of 99.8%. A significant nondiagnostic rate (14%), negative predictive value (67%), and poor ability to discriminate high-grade cancers (60%–80%) limit the widespread utility in patients in whom a histologic diagnosis would not change management. , Core biopsy is preferred to FNA, given lower diagnostic yield with the latter; however, the American Society of Cytopathology endorses rapid on-site evaluation, which can optimize specimen quality for pathologic evaluation by obtaining real-time assessment of FNA or touch imprints of core biopsies to confirm specimen adequacy.
Pathologic considerations
For the pathologic evaluation of renal mass resection specimens, the College of American Pathologists requires that the following 14 parameters are always reported for RCC ( Fig. 28.1 ): procedure type; laterality; tumor size; tumor focality (single vs. multiple); macroscopic extent of tumor; histologic type and grade; presence/absence of sarcomatoid features; presence/absence of rhabdoid features; tumor necrosis; microscopic tumor extension; margin status; pathologic stage; and nonneoplastic parenchyma. Historically, the evaluation has centered around the RCC, and evaluation of the nonneoplastic parenchyma was optional before 2010 and largely ignored. The importance of nonneoplastic renal diseases and its association with RCC has only been recently recognized. Several studies have observed that nonneoplastic renal diseases, such as diabetic nephropathy ( Fig. 28.2 ) and focal segmental glomerulosclerosis, can be identified in 10% to 15% of specimens.
Given that preservation of renal function has become an important objective for low-stage RCC, early detection of a nonneoplastic renal disease, such as diabetic nephropathy, provides an opportunity for medical intervention that can delay the progression of CKD and ESRD. There are many opportunities for improved coordinated care of the kidney cancer patients between urologists, oncologists, nephrologists, and pathologists.
Approximately 25% of renal masses may be benign (e.g., angiomyolipoma, oncocytoma) and synoptic reporting is typically not used for benign neoplasms. In such instances, the proper evaluation of the nonneoplastic parenchyma would be the most important aspect of the pathologic evaluation.
Renal cell carcinoma treatment
Preoperative management
Consideration of kidney function given the higher risk of CKD should be made for most patients requiring treatment of RCC with surgical or ablative therapies. Among those with localized RCC, particularly for those with small renal masses (≤ 4 cm), cancer-specific survival approaches nearly 100%; therefore, complications related to CKD and related comorbidities, such as cardiovascular mortality, are more likely to determine morbidity and mortality.
Baseline evaluation of kidney function with measurement of serum creatinine and estimation of GFR will allow for better understanding of the underlying risks of CKD with nephrectomy. A specific creatinine or eGFR threshold for increased postoperative CKD risk has not been clearly defined; however, Lane et al. demonstrated that among those with known CKD (eGFR < 60 mL/min/1.73 m 2 ), postoperative rapid decline (> 50% decline in eGFR or dialysis) in kidney function was 2.33 times more likely than those without CKD. Probability of rapid kidney function decline rose with each increasing CKD stage. A creatinine threshold of greater than 1.5 mg/dL has been associated with higher morbidity and mortality in general, including higher mean postoperative creatinine and risk of dialysis dependence. , Urinalysis including presence of proteinuria (as measured as albuminuria by urine dipstick analysis, urine albumin to creatinine ratio, or urine protein to creatinine ratio) will identify those with early signs of renal parenchymal damage. Proper blood pressure management and glycemic control before surgery are strategies to reduce risk of eGFR decline. Review and avoidance of nephrotoxic medications, intravenous contrast, and intraoperative hypotension may further lower acute kidney injury (AKI) risk. Nuclear scintigraphy measuring differential kidney function provides some insight to potential postoperative outcomes. These studies tend to underestimate GFR, because they do not account for the usual hypertrophy and hyperfiltration that occurs after nephron mass loss. Surgical factors including larger tumor size (R 2 =0.39) and increased clamp time (R 2 =0.17) were most determinant of the postoperative proportional eGFR decline.
Treatment of small renal masses
American urological association guidelines and principles of management
The American Urological Association (AUA) released updated Guidelines for Renal Mass and Localized Renal Cancer in 2017. The AUA recommends that a urologist lead the counseling process for patients with renal masses and should include nephrologists, pathologists, interventional radiologists, medical oncologists, and genetic counselors when appropriate. This recommendation is based on the familiarity of urologists with the disease process, risk-stratification paradigms (mentioned earlier), surgical management of the disease, the ability to engage other specialists, and to coordinate multidisciplinary care and follow-up.
The data supporting the AUA guidelines were systematically reviewed by the Agency for Healthcare Research and Quality, which made a number of important conclusions regarding the principles of management of renal masses suspicious for RCC. The four, well-recognized management strategies for renal masses suspicious of clinically localized RCC include partial nephrectomy (PN), radical nephrectomy (RN), thermal ablation (TA), and active surveillance (AS). The first principle of management is that oncologic outcomes (cancer-specific and metastasis-free survival) are determined by tumor size and stage regardless of management strategy used. Second, overall survival outcomes are determined by competing risks of death, because most patients with clinically localized RCC die of other causes. Therefore distinguishing features of management strategies include influence on renal functional outcomes, perioperative outcomes, and potential harms, and are discussed later.
Partial nephrectomy
PN is the preferred management strategy for small renal masses (stage T1a, ≤ 4.0 cm) whenever feasible and is a reasonable option for larger tumors with risk factors for progressive CKD or ESRD. PN is preferred given long-term data demonstrating equivalent oncologic outcomes to RN and a greater appreciation for the deleterious effects of CKD. Surgical principles of PN include preservation of normal renal parenchyma and minimization of prolonged warm ischemia. PN is associated with the highest risk of perioperative complications, including bleeding, urine leak, and other urologic complications (i.e., ureteral injury).
Radical nephrectomy
RN is recommended if a tumor indicates increased oncologic potential (larger tumor size, infiltrative growth pattern, aggressive histology on RMB, etc.), if PN would be challenging in expert hands, if there is no preexisting CKD, and if the risk of new eGFR less than 45 mL/min/1.73 m 2 is sufficiently low. RN is associated with low perioperative risks given the high proportion of surgeries performed laparoscopically. RN is associated with the greatest decrease in eGFR (average decrease 10.5 mL/min/1.73 m 2 ) and new onset CKD stage 3 or worse (relative risk, 2.56; 95% CI, 1.97–3.32) compared with all other management strategies.
Of note, the European Organization for Research and Treatment of Cancer (EORTC) 30904 trial randomized 541 patients with 5 cm (or smaller) renal tumors to PN or RN. The trial demonstrated no difference in oncologic outcomes among surgeries and a small but significant worse renal function in patients undergoing RN. , This trial is discussed in greater detail in the subsequent section, Renal Cell Carcinoma Treatment Modality and Chronic Kidney Disease Risk ; however, the trial is criticized because most patients were healthy with a normal contralateral kidney and unlikely to see the renal functional detriments of RN in the allotted follow-up.
Thermal ablation
TA is most commonly achieved through radiofrequency or cryoablation and is considered an established alternative to PN for nephron-sparing surgery. TA has the most favorable perioperative outcome profile (low risk of urologic and nonurologic complications) given the high proportion of patients undergoing percutaneous approaches. TA is associated with the highest rates of local recurrence or persistence after a single treatment; this difference is alleviated when multiple treatment episodes are allowed for TA. , TA is preferred for peripheral, exophytic masses 3 cm or smaller given decreased oncologic efficacy and higher complication rates for larger, central tumors.
Active surveillance
AS is supported as an initial management strategy for patients with small renal masses (cT1a, ≤ 4 cm), especially those less than 2 cm. This endorsement is based on an improved understanding of the high rate of benign disease, low malignant potential of RCC, slow growth rates, and low rates of metastatic progression while on AS. , , – A large body of retrospective data and growing prospective data indicate growth rates on the order of 1 mm per year and exceedingly low rates of metastatic progression. Principles of AS include serial imaging (typically every 6–12 months) to establish growth parameters and facilitate timely intervention to preserve oncologic outcomes and nephron-sparing treatment options. Historically, a growth rate of more than 0.5 cm per year was believed to be indicative of adverse biology; however, more recent data indicate that growth rate may be highly variable and does not reliably predict adverse pathologic features or death from RCC.
Chronic kidney disease risk factors in renal cell carcinoma
Baseline chronic kidney disease risk in renal cell carcinoma population
Older age, tobacco exposure, obesity, DM, and HTN are overlapping risk factors for RCC and CKD, which may explain the high prevalence of CKD with RCC (10%–30%) generally, and increases to a range of 10% to 52% among those with small renal masses when compared with controls without cancer. Among the most frequent causes of CKD, DM (9%–22%) and HTN (23%–59%) are also commonly seen with RCC. , , , , DM and HTN in an RCC cohort were double that seen in a case-matched non-RCC control group. Furthermore, when those with RCC were categorized by age, older subgroups had twofold greater CKD than the younger group and those with CKD were more likely to have DM and HTN than those with RCC who did not have CKD. , The older age and high comorbidity burden predispose the RCC population to kidney function decline after nephron mass loss because of tumor resection.
Postoperative chronic kidney disease risk
Localized tumors treated with nephrectomy or ablative therapies decrease functional nephron units and therefore can lower GFR, particularly for those with CKD or CKD risk factors who inadequately hypertrophy or lack the capacity for compensatory hyperfiltration. Postnephrectomy CKD risk is dependent on medical factors including preexisting CKD, nutritional factors (hypoalbuminemia), and underlying comorbid diseases (HTN, DM, and obesity). For example, those with DM had 20% greater postoperative CKD than the nondiabetic RCC cohort, and only 47% of the diabetic group remained free from CKD after 2 years compared with 76% of their nondiabetic counterpart. Just as importantly, surgical determinants, such as tumor size, warm ischemia time, hypotension, and AKI also influence CKD risk. , , , – Nephron mass loss from surgical resection results in nearly doubling of CKD prevalence from 10% to 24% to 16% to 52% in observational cohort studies. GFR decline after resection was estimated to be 13 mL/min/m 2 (30% reduction) with a corresponding reduction of kidney size of 36% in one RCC cohort undergoing PN.
The United States Renal Data System lists RCC as a cause of ESRD for 0.5% of 360,000 dialysis patients. ESRD incidence rate over 10 years among 2940 RCC patients (4.05%) was 5.6-fold that of a comparative control group (23,520 patients) without RCC (0.68%) in an incident Taiwanese cohort.
Renal cell carcinoma treatment modality and chronic kidney disease risk
RCC treatment can result in eGFR reduction and CKD as discussed previously. For generations, RN has been the primary mode of RCC treatment regardless of tumor size. However, with the recognition that cancer-specific survival approaches 100% among those with small renal masses, less aggressive resection with PN is increasingly performed. PN should be considered standard therapy for T1a tumors according to the AUA guidelines. RN continues to be performed for more advanced stage and surgically complicated tumors.
Preservation of renal parenchyma to minimize loss of kidney function is increasingly being prioritized for small renal masses given the equivalent oncologic outcomes, and comparable overall survival, which may likely be determined by nononcologic factors, such as CKD complications or cardiovascular disease. A systematic review and metaanalysis of 40,000 patients with localized RCC had 61% lower risk for CKD (hazard ration [HR], 0.39; CI, 0.33–0.47) with PN as compared with RN. All-cause mortality (HR, 0.81; CI, 0.76–0.87) and cancer-specific mortality (HR, 0.71; CI, 0.59–0.85) were also lower for the PN group. Comparable findings were observed in another metaanalysis, with a 2.56-fold greater risk of stage 3 CKD for RN than PN. Pooled eGFR decline was found to be 10.5 mL/min/1.73 m 2 lower for those undergoing PN versus RN. Risk of AKI, however, was no different between the two surgical procedures. However, of those with localized tumors, the subgroup with T1a tumors had slightly higher AKI risk (HR, 1.37; CI, 1.13–1.66) with RN. Nonsurgical nephron-sparing therapies (TA and AS) were additionally considered, revealing similar benefit over RN for preservation of kidney function. However, only two AS studies were included for analysis (one study population with age > 75 years), which may limit the interpretation of these findings. No clear differences were seen between treatment with either TA or PN.
ESRD risk has been found to be similarly higher with RN according to a large systematic review and metaanalysis. ESRD outcomes have also varied according to time period of treatment in a Canadian cohort of 11,937 patients using a multivariable proportional hazards model. During the earlier epoch (1995–2010), ESRD risk was not different between PN and RN groups; however, ESRD was less likely when PN was done rather than RN in a contemporary cohort (2003–2010) (HR, 0.44; 95% CI, 0.25–0.95). Furthermore, those with PN were less likely to develop new CKD (HR, 0.48; 95% CI, 0.41–0.57).
In the one randomized controlled trial, the EORTC study involving 541 patients with small renal masses (≤ 5 cm), risk of CKD was retrospectively examined. Postoperative eGFR was higher with PN (67 mL/min/1.73 m 2 ) versus RN (53 mL/min/1.73 m 2 ) even though 10-year survival was not proven to be better with PN. PN was most likely to lower the risk of CKD progression to mild CKD (stage 3) by 21% but did not reduce risk of progression to clinically more meaningful and more advanced stages of CKD (stage 4 and 5).
CKD from surgical resection may not lead to the same degree of progressive CKD decline seen in the corresponding stage of medically induced CKD. In a retrospective study examining patients with CKD from surgical resection, preexisting CKD with also surgically induced CKD, and with CKD caused by medical pathology alone, those with any medically induced CKD were more likely to progress to ESRD. Patients with medically induced CKD were older and had greater comorbidity, which likely explains the more rapid decline of CKD among these groups.
In addition, the lower mortality associated with PN for those with localized renal masses may be mediated by alteration of CKD related cardiovascular disease. Cardiovascular disease risk rises with and is independently associated with falling eGFR. Cardiovascular disease related death was associated with CKD among 1004 case-matched patients with localized tumors (T1b, 4–7 cm). eGFR decline and mortality was greater for those who had RN. For each eGFR decline of 7 mL/min/1.73 m 2 , risk of cardiovascular disease rose by 25% and risk of death increased by 17%.
In addition to usual surveillance for RCC after treatment, eGFR and proteinuria assessment and regular blood pressure monitoring may be reasonably performed particularly among those with higher risk of CKD progression (with comorbid diseases) and certainly for those with preexisting CKD ( Table 28.2 ). Like renal transplant donors, initial hyperfiltration and hypertrophy allows for compensatory increase in GFR; but in the RCC population who often have multiple comorbid diseases, these initial responses will often increase risk for proteinuria and nephrosclerosis long-term, leading to decline in kidney function. , A multidisciplinary team including the nephrologist, urologist, and pathologist would allow for proper diagnosis of CKD pathology and longitudinal management of the kidney cancer and the renal complications related to kidney cancer.
Related posts:
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
