Although the management of sporadic renal tumors is challenging enough, dealing with those with bilateral, multifocal, and hereditary kidney cancer adds an additional level of complexity. A clinician managing this patient population must understand the hereditary syndromes and the genetic testing available. Treating physicians must be familiar with enucleative surgery, complex or multiple tumor partial nephrectomy, complex renal reconstruction, re-operative renal surgery, and active surveillance strategies. With proper management, most patients affected with bilateral, multifocal, or hereditary RCC can have a long life expectancy while maintaining adequate renal function.
The management of a localized renal cell carcinoma (RCC) continues to evolve with fewer radical surgeries and increase in nephron preservation. Reasons for this include recognition of the importance of renal preservation, the emergence of both partial nephrectomy and adrenal sparing, and a more minimally invasive surgical approach. The approach to a sporadic renal mass smaller than 7 cm can provide treatment dilemmas to clinicians, as the American Urologic Association suggests several acceptable management options for patients.
Dealing with patients with bilateral, multifocal, kidney cancer adds an additional layer of complexity. Clinicians should be familiar with these entities, as they will undoubtedly come across patients with multifocal bilateral renal masses. With this patient population, the clinician should consider a variety of factors, including hereditary predisposition, need to stage bilateral operations, which kidney to operate on first, prolonged ischemic times, how to define recurrence, how to manage recurrence in a previously operated renal unit, and the possibility of progression to end-stage renal failure.
Definitions of multifocality and bilaterality
Sporadic, unilateral renal tumors account for most patients with kidney cancer; however, patients with multiple renal masses are not uncommon, and clinicians who specialize in RCC will eventually be faced with the management of these patients. Multifocality in kidney cancer refers to having more than one renal tumor, which can further be divided into whether the additional tumors are ipsilateral or bilateral. Bilateral tumors refer to lesions on both kidneys and they can present in a synchronous manner (at the same time) or a metachronous fashion (at different times). Multifocality and bilaterality are entities frequently seen together; bilateral renal involvement is observed in 90% of those with multifocal disease and the converse is true that more than half of patients with bilateral tumors have multifocal RCC.
Several series have found that the incidence of bilateral, synchronous renal masses is approximately 2% of individuals who present with renal masses ; however, even among patients who had a sporadic, solitary renal mass, contralateral metachronous renal masses occur in about 1% to 2% of patients. It is important to recognize that multifocal tumors have been found in as many as 25% of patients in some studies, and many multifocal RCCs will be bilateral. Patients also may present with a unilateral multifocal tumor complicating surgical planning and possibly causing some urologists to shy away from a partial nephrectomy. These patients, however, are likely the most in need of nephron-sparing surgery, as they would have a high propensity to form additional tumors in the contralateral kidney.
The estimated incidence of multifocality widely varies based on how the series was performed. Some series estimate multifocality by preoperative imaging, yet cross-sectional imaging studies frequently miss these small satellite lesions in more than 75% of cases. Other series include unknown lesions seen at the time of surgery. Based on these different definitions, the incidence is reported to be between 3% and 11%. Other reports based on pathologic examination demonstrate multifocality to be as high as 25% of radical nephrectomy specimens based on the presence of microscopic satellite tumors. Although papillary RCC more commonly presents with multifocality, all histologic subtypes can have satellite tumors.
Description of hereditary renal syndrome phenotypes
Hereditary kidney cancer is believed to represent 1% to 4% of RCC cases. Of these patients, some may fit into well-characterized hereditary kidney cancer syndromes, whereas many more patients with RCC may have a genetic component that is not fully recognized or understood. Because of our current poor understanding of genetics and cancer susceptibility genes, the 1% to 4% estimate may be a gross underestimation. A generational study from Iceland (dating back 11 centuries) has aggregated nearly 60% of RCC to specific families. These data suggest that unknown germline mutations may account for a large number of these apparently sporadic cases of kidney cancer. The complexity of inherited susceptibility loci associated with RCC continues to be elucidated by genome-wide association studies.
During the past 3 decades, more than a half-dozen hereditary cancer conditions have been described and linked to specific germline mutations. Alterations for these syndromes generally occur in tumor suppressor genes, however proto-oncogene alterations can be responsible as well. Because additional events are likely necessary for renal tumorigenesis, these syndromes have different penetrance of renal malignancy. Although these conditions often share a common manifestation of bilateral, multifocal kidney tumors, they differ in the tumor histology, coexistence with renal cysts, and additional clinical features. For patients without a previously diagnosed syndrome, an astute clinician with knowledge of these conditions may be the key to a successful diagnosis. Particular attention must focus on patients’ past medical history, including a thorough review of systems. A thorough family medical history must detail the health of both maternal and paternal family members. Although most patients are diagnosed based on the presentation and a known family history, new diagnosis is not uncommon, because some patients are unaware of family history, are adopted, or there is the possibility of a de novo mutation. If a clinician is going to be involved in the care of these patients, an awareness of the genetic basis and associated features of these syndromes is necessary to appropriately recognize who may benefit from genetic counseling.
Von Hippel-Lindau
Von Hippel-Lindau (VHL) is an autosomal dominant syndrome with an incidence of 1:35,000 individuals. The syndrome is characterized by the development of clear-cell RCC in addition to multiple tumor types, including retinal angiomas, spinal and cerebellar hemangioblastomas, pancreatic cysts and neuroendocrine tumors, pheochromocytomas, and epididymal cystadenomas. Linkage analyses from kindred with affected individuals determined the gene for VHL to be located at 3p. Later work located the VHL gene to 3p25.1 and determined it behaved like a classic tumor suppressor gene.
Patients with VHL are prone to the development of both renal cysts and clear-cell renal tumors. Approximately 25% to 60% of patients with VHL develop RCC and, when it occurs, it generally is bilateral and multifocal. Before the current screening recommendations, approximately a third of patients with VHL died from metastatic kidney cancer. With proper screening, patients at risk are identified when the lesions are small and treatment can prevent the development of metastatic disease.
Birt-Hogg-Dube
Birt-Hogg-Dube (BHD) is a hereditary cancer syndrome first discovered in the dermatologic literature when 3 physicians described a kindred of 70 patients with multiple fibrofolliculomas associated with trichodiscomas and acrochordons. Later, patients with BHD were found to have bilateral, multifocal RCC and pneumothoraces that were determined to be part of the syndrome. Linkage analysis of kindreds with BHD found the gene was located on 17p11.2. The gene for BHD was determined to be FLCN, which behaves like a classic tumor suppressor syndrome and is passed in an autosomal dominant fashion.
BHD is believed to be fairly rare, with an incidence estimated to be approximately 1:200,000. When evaluating these patients, a history of a pneumothorax or a thorough dermatologic evaluation may be a clue to the diagnosis. On imaging, renal cysts may occur with BHD, but when present, they are generally simple, unlike mixed lesions in VHL. Approximately 18% of patients with BHD develop renal tumors, and when they occur, they are generally multifocal and bilateral. Tumors can be multiple histologies, with hybrid oncocytic and chromophobe renal tumors the most common (50% and 35%, respectively). Clear-cell renal tumors associated with BHD are rare, but when they occur, they can be quite aggressive.
Hereditary Leiomyomatosis and Renal Cell Cancer
Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant syndrome first recognized more than 50 years ago as being responsible for familial, cutaneous leiomyomas. Later an association with uterine fibroids and RCC was identified. Familial linkage analysis identified the chromosomal region to 1p42.3–43 and later determined the responsible gene was fumarate hydratase, FH. This key enzyme is responsible for conversion of fumarate to malate in the Kreb’s cycle, and loss of the remaining wild-type copy leads to anaerobic respiration.
The renal tumors associated with HLRCC were first described to be papillary type II. Later reports in a larger subset of renal tumors demonstrated that these tumors may have other patterns besides a papillary configuration, but the unifying hallmark is the large eosinophilic nucleolus with a clear perinucleolar halo. Although most patients with hereditary kidney cancer syndromes frequently have bilateral, multifocal kidney tumors, the early experience with HLRCC did not show this phenotype, likely because of the aggressive nature of this disease. The first clinical series demonstrated that approximately half of patients presented with nodal or disseminated disease, even in the presence of small T1 renal masses. With early identification and screening, however, treatment before spread has now demonstrated the bilateral and multifocal nature of the disease.
Hereditary Papillary Renal Cell Carcinoma
Hereditary papillary renal cell carcinoma (HPRC) was first recognized almost 20 years ago in a family with 3 generations of papillary RCC that did not appear linked to chromosome 3p. Besides the occurrence of kidney cancer, no other clinical manifestations have been found. The gene was linked to 7q31 and the gene, MET, was found to be an important receptor tyrosine kinase. Trisomy 7 is common in HPRC and it preferentially amplifies the mutant copy. Unlike the other hereditary kidney cancer syndromes associated with germline mutations, MET is a proto-oncogene.
HPRC is a rare syndrome with fewer than 20 families described with this entity. It is passed in an autosomal dominant fashion and is highly penetrant. Nearly 70% of carriers develop renal tumors; however, the mean age of tumor occurrence is nearly 50, older than observed with the other hereditary syndromes.
A recent trial performed at the National Cancer Institute (NCI) evaluating small molecules targeting MET receptors has shown excellent tumor response in patients with HPRC. Such targeted approaches (presently being tested in other hereditary renal cancers) may in the future delay the need for surgical intervention or perhaps avoid a need for surgery altogether.
Succinate Dehydrogenase B Deficiency
Several syndromes are associated with hereditary causes of pheochromocytoma and paraganglioma. Many of these patients have been found with germline mutations in subunits of the succinate dehydrogenase (SDH) enzyme, an inner mitochondrial membrane enzyme critical to both the Kreb’s cycle and the electron transport chain. In 2001, the SDHB gene was found mutated in families with hereditary pheochromocytoma and paraganglioma, and this gene is passed in an autosomal dominant fashion. Several years later, a family with a known SDHB mutation was found to contain 2 individuals with early-onset RCC. Screening of RCC families without a known mutation has demonstrated that nearly 5% have SDHB mutations. Patients with SDHB can present with early-onset and bilateral renal tumors. The distinctive morphology of SDHB renal tumors is still being elucidated; however, a recent report mentions these tumors contained indistinct cell borders, cytoplasmic inclusions, and eosinophilic cytoplasm.
Tuberous Sclerosis 1 and 2
Tuberous sclerosis complex (TSC) is an autosomal dominant condition that is characterized by tumors in the brain, skin, and kidney. Germline mutations can be found in 2 related genes, TSC1 and TSC2, both of which act like classic tumor suppressor genes. TSC1 and TSC2 encode for hamartin (located on 9q34) and tuberin (located on 16p13.3), respectively. Renal manifestations occur early and are highly penetrant. These features include angiomyolipomas, cysts, and clear-cell RCC. Patients can progress to renal failure, possibly attributable to these lesions or to other factors currently poorly understood. Although considered benign, angiomyolipomas can grow and cause significant morbidity related to pain and risk of hemorrhage. TSC-related clear-cell RCC can behave quite aggressively, with many patients dying from their disease. Genetic analysis of these renal tumors demonstrates that loss of 3p and VHL mutations are uncommon with these tumors.
Familial Renal Oncocytoma/Bilateral Multifocal Oncocytoma
Oncocytomas are benign tumors that account for roughly 10% of enhancing renal masses. Oncocytomas are bilateral or multifocal in 5% and 13% of cases, respectively. Patients with multifocal renal lesions with a known history of oncocytoma (either in the setting of a synchronous, contralateral oncocytoma or a new metachronous tumor) demonstrate pathologic concordance in more than 70% of cases. The pathologic term, oncocytomatosis (later called oncocytosis), has been used to describe the constellation of findings including multiple microscopic, oncocytic nodules and oncocytic changes in the non-neoplastic tubules. For unclear reasons, these patients appear to have renal insufficiency, with many progressing to end-stage renal disease. A familial form has been named familial renal oncocytoma (FRO) and affected individuals develop bilateral and multifocal oncocytomas. The gene for FRO has not been described, but research efforts are currently ongoing.
Bilateral/Multifocal and Familial Renal Cancer of Unknown Etiology
Patients with a first-degree or second-degree relative with kidney cancer are considered to have familial renal cancer (FRC). Even after genetic counseling, many patients will not have an identifiable gene mutation; however, this does not rule out a genetic component involved in their familial predisposition. The number of known germline cancer syndromes continues to rise and, with time, many of these families could have a predisposing genetic factor identified. Many patients with FRC will present with bilateral and multifocal RCC.
The management of these patients is often dependent on the number of lesions and the size of the largest lesion. In most instances, these patients are recommended to undergo a percutaneous biopsy of the largest or most accessible lesion (occasionally more than one). This often allows for preoperative planning, a possible need for a resection of a wider margin or lymph node dissection, or additional imaging studies. In some instances, percutaneous biopsy of these patients allows for avoidance of surgical intervention if bilateral multifocal oncocytomas are diagnosed. Should surgery be planned, these patients are treated with partial nephrectomy whenever possible, as they can be prone to future development of new renal lesions. Enucleation can also be performed with these patients, especially in those with multifocal tumors, as they are likely to develop de novo lesions. Observation of small renal lesions until the largest lesion measures 3 cm may also be a feasible option.
Description of hereditary renal syndrome phenotypes
Hereditary kidney cancer is believed to represent 1% to 4% of RCC cases. Of these patients, some may fit into well-characterized hereditary kidney cancer syndromes, whereas many more patients with RCC may have a genetic component that is not fully recognized or understood. Because of our current poor understanding of genetics and cancer susceptibility genes, the 1% to 4% estimate may be a gross underestimation. A generational study from Iceland (dating back 11 centuries) has aggregated nearly 60% of RCC to specific families. These data suggest that unknown germline mutations may account for a large number of these apparently sporadic cases of kidney cancer. The complexity of inherited susceptibility loci associated with RCC continues to be elucidated by genome-wide association studies.
During the past 3 decades, more than a half-dozen hereditary cancer conditions have been described and linked to specific germline mutations. Alterations for these syndromes generally occur in tumor suppressor genes, however proto-oncogene alterations can be responsible as well. Because additional events are likely necessary for renal tumorigenesis, these syndromes have different penetrance of renal malignancy. Although these conditions often share a common manifestation of bilateral, multifocal kidney tumors, they differ in the tumor histology, coexistence with renal cysts, and additional clinical features. For patients without a previously diagnosed syndrome, an astute clinician with knowledge of these conditions may be the key to a successful diagnosis. Particular attention must focus on patients’ past medical history, including a thorough review of systems. A thorough family medical history must detail the health of both maternal and paternal family members. Although most patients are diagnosed based on the presentation and a known family history, new diagnosis is not uncommon, because some patients are unaware of family history, are adopted, or there is the possibility of a de novo mutation. If a clinician is going to be involved in the care of these patients, an awareness of the genetic basis and associated features of these syndromes is necessary to appropriately recognize who may benefit from genetic counseling.
Von Hippel-Lindau
Von Hippel-Lindau (VHL) is an autosomal dominant syndrome with an incidence of 1:35,000 individuals. The syndrome is characterized by the development of clear-cell RCC in addition to multiple tumor types, including retinal angiomas, spinal and cerebellar hemangioblastomas, pancreatic cysts and neuroendocrine tumors, pheochromocytomas, and epididymal cystadenomas. Linkage analyses from kindred with affected individuals determined the gene for VHL to be located at 3p. Later work located the VHL gene to 3p25.1 and determined it behaved like a classic tumor suppressor gene.
Patients with VHL are prone to the development of both renal cysts and clear-cell renal tumors. Approximately 25% to 60% of patients with VHL develop RCC and, when it occurs, it generally is bilateral and multifocal. Before the current screening recommendations, approximately a third of patients with VHL died from metastatic kidney cancer. With proper screening, patients at risk are identified when the lesions are small and treatment can prevent the development of metastatic disease.
Birt-Hogg-Dube
Birt-Hogg-Dube (BHD) is a hereditary cancer syndrome first discovered in the dermatologic literature when 3 physicians described a kindred of 70 patients with multiple fibrofolliculomas associated with trichodiscomas and acrochordons. Later, patients with BHD were found to have bilateral, multifocal RCC and pneumothoraces that were determined to be part of the syndrome. Linkage analysis of kindreds with BHD found the gene was located on 17p11.2. The gene for BHD was determined to be FLCN, which behaves like a classic tumor suppressor syndrome and is passed in an autosomal dominant fashion.
BHD is believed to be fairly rare, with an incidence estimated to be approximately 1:200,000. When evaluating these patients, a history of a pneumothorax or a thorough dermatologic evaluation may be a clue to the diagnosis. On imaging, renal cysts may occur with BHD, but when present, they are generally simple, unlike mixed lesions in VHL. Approximately 18% of patients with BHD develop renal tumors, and when they occur, they are generally multifocal and bilateral. Tumors can be multiple histologies, with hybrid oncocytic and chromophobe renal tumors the most common (50% and 35%, respectively). Clear-cell renal tumors associated with BHD are rare, but when they occur, they can be quite aggressive.
Hereditary Leiomyomatosis and Renal Cell Cancer
Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant syndrome first recognized more than 50 years ago as being responsible for familial, cutaneous leiomyomas. Later an association with uterine fibroids and RCC was identified. Familial linkage analysis identified the chromosomal region to 1p42.3–43 and later determined the responsible gene was fumarate hydratase, FH. This key enzyme is responsible for conversion of fumarate to malate in the Kreb’s cycle, and loss of the remaining wild-type copy leads to anaerobic respiration.
The renal tumors associated with HLRCC were first described to be papillary type II. Later reports in a larger subset of renal tumors demonstrated that these tumors may have other patterns besides a papillary configuration, but the unifying hallmark is the large eosinophilic nucleolus with a clear perinucleolar halo. Although most patients with hereditary kidney cancer syndromes frequently have bilateral, multifocal kidney tumors, the early experience with HLRCC did not show this phenotype, likely because of the aggressive nature of this disease. The first clinical series demonstrated that approximately half of patients presented with nodal or disseminated disease, even in the presence of small T1 renal masses. With early identification and screening, however, treatment before spread has now demonstrated the bilateral and multifocal nature of the disease.
Hereditary Papillary Renal Cell Carcinoma
Hereditary papillary renal cell carcinoma (HPRC) was first recognized almost 20 years ago in a family with 3 generations of papillary RCC that did not appear linked to chromosome 3p. Besides the occurrence of kidney cancer, no other clinical manifestations have been found. The gene was linked to 7q31 and the gene, MET, was found to be an important receptor tyrosine kinase. Trisomy 7 is common in HPRC and it preferentially amplifies the mutant copy. Unlike the other hereditary kidney cancer syndromes associated with germline mutations, MET is a proto-oncogene.
HPRC is a rare syndrome with fewer than 20 families described with this entity. It is passed in an autosomal dominant fashion and is highly penetrant. Nearly 70% of carriers develop renal tumors; however, the mean age of tumor occurrence is nearly 50, older than observed with the other hereditary syndromes.
A recent trial performed at the National Cancer Institute (NCI) evaluating small molecules targeting MET receptors has shown excellent tumor response in patients with HPRC. Such targeted approaches (presently being tested in other hereditary renal cancers) may in the future delay the need for surgical intervention or perhaps avoid a need for surgery altogether.
Succinate Dehydrogenase B Deficiency
Several syndromes are associated with hereditary causes of pheochromocytoma and paraganglioma. Many of these patients have been found with germline mutations in subunits of the succinate dehydrogenase (SDH) enzyme, an inner mitochondrial membrane enzyme critical to both the Kreb’s cycle and the electron transport chain. In 2001, the SDHB gene was found mutated in families with hereditary pheochromocytoma and paraganglioma, and this gene is passed in an autosomal dominant fashion. Several years later, a family with a known SDHB mutation was found to contain 2 individuals with early-onset RCC. Screening of RCC families without a known mutation has demonstrated that nearly 5% have SDHB mutations. Patients with SDHB can present with early-onset and bilateral renal tumors. The distinctive morphology of SDHB renal tumors is still being elucidated; however, a recent report mentions these tumors contained indistinct cell borders, cytoplasmic inclusions, and eosinophilic cytoplasm.
Tuberous Sclerosis 1 and 2
Tuberous sclerosis complex (TSC) is an autosomal dominant condition that is characterized by tumors in the brain, skin, and kidney. Germline mutations can be found in 2 related genes, TSC1 and TSC2, both of which act like classic tumor suppressor genes. TSC1 and TSC2 encode for hamartin (located on 9q34) and tuberin (located on 16p13.3), respectively. Renal manifestations occur early and are highly penetrant. These features include angiomyolipomas, cysts, and clear-cell RCC. Patients can progress to renal failure, possibly attributable to these lesions or to other factors currently poorly understood. Although considered benign, angiomyolipomas can grow and cause significant morbidity related to pain and risk of hemorrhage. TSC-related clear-cell RCC can behave quite aggressively, with many patients dying from their disease. Genetic analysis of these renal tumors demonstrates that loss of 3p and VHL mutations are uncommon with these tumors.
Familial Renal Oncocytoma/Bilateral Multifocal Oncocytoma
Oncocytomas are benign tumors that account for roughly 10% of enhancing renal masses. Oncocytomas are bilateral or multifocal in 5% and 13% of cases, respectively. Patients with multifocal renal lesions with a known history of oncocytoma (either in the setting of a synchronous, contralateral oncocytoma or a new metachronous tumor) demonstrate pathologic concordance in more than 70% of cases. The pathologic term, oncocytomatosis (later called oncocytosis), has been used to describe the constellation of findings including multiple microscopic, oncocytic nodules and oncocytic changes in the non-neoplastic tubules. For unclear reasons, these patients appear to have renal insufficiency, with many progressing to end-stage renal disease. A familial form has been named familial renal oncocytoma (FRO) and affected individuals develop bilateral and multifocal oncocytomas. The gene for FRO has not been described, but research efforts are currently ongoing.
Bilateral/Multifocal and Familial Renal Cancer of Unknown Etiology
Patients with a first-degree or second-degree relative with kidney cancer are considered to have familial renal cancer (FRC). Even after genetic counseling, many patients will not have an identifiable gene mutation; however, this does not rule out a genetic component involved in their familial predisposition. The number of known germline cancer syndromes continues to rise and, with time, many of these families could have a predisposing genetic factor identified. Many patients with FRC will present with bilateral and multifocal RCC.
The management of these patients is often dependent on the number of lesions and the size of the largest lesion. In most instances, these patients are recommended to undergo a percutaneous biopsy of the largest or most accessible lesion (occasionally more than one). This often allows for preoperative planning, a possible need for a resection of a wider margin or lymph node dissection, or additional imaging studies. In some instances, percutaneous biopsy of these patients allows for avoidance of surgical intervention if bilateral multifocal oncocytomas are diagnosed. Should surgery be planned, these patients are treated with partial nephrectomy whenever possible, as they can be prone to future development of new renal lesions. Enucleation can also be performed with these patients, especially in those with multifocal tumors, as they are likely to develop de novo lesions. Observation of small renal lesions until the largest lesion measures 3 cm may also be a feasible option.
Principles and goals of surgical management
For patients with sporadic, solitary renal tumors, the goal of therapy is cancer cure while maximizing renal function. With sporadic patients, a single surgery is likely to be sufficient, with surveillance most commonly aimed at identification of cancer dissemination. In the sporadic population, RCC usually presents in patients in their 60s, and although not ideal, a radiographically normal-appearing contralateral kidney gives the clinician the option of sacrificing an affected kidney in the setting of a large tumor requiring a complex partial nephrectomy. For patients with bilateral, multifocal, and hereditary renal tumors, the goal of therapy is much different. These patients generally present with tumors at a younger age and the clinician has to be forward thinking, not just worrying about the current tumors, but what may develop in the future. The goal of therapy in this population is to prevent cancer dissemination, while maximizing renal function, limiting the number of renal surgeries, and minimizing the amount of surgical morbidity when possible.
Historical Management
Traditional management of synchronous, bilateral renal masses included bilateral radical nephrectomy to prevent dissemination and death from kidney cancer and dialysis. With this approach, patients could receive either concomitant or delayed renal transplantation. For patients with VHL disease, this was a common approach in some centers. Fortunately, this approach is no longer widely accepted with the advent and increasing acceptance of partial nephrectomy.
Preservation of Renal Function
In patients with bilateral, multifocal, and hereditary kidney tumors, preservation of renal function is one of the most important aspects of therapy. Whenever feasible, a partial nephrectomy should be considered if there is potential to avoid dialysis. Because of the significant cardiovascular morbidity and mortality associated with renal replacement therapy, the overall risk on dialysis is often greater than the risk from renal malignancy. The 5-year overall survival on dialysis of 33% is far worse than the survival for nearly all stages of localized disease. Although survival on dialysis is poor in general, in patients with RCC, survival may actually be worse. Although patients with RCC placed on dialysis may be transplant candidates, many will die waiting for an organ because of the shortage of available donors and the 2-year cancer-free interval suggested by the American Society of Transplantation.
Workup and management
Patients presenting with bilateral, multifocal, and possibly hereditary renal tumors present management dilemmas. Decisions on timing of genetic testing, role of biopsy, likelihood of pathologic concordance, order of surgery, sequence of tumor removal, optimal methods of nephron preservation, and surveillance for de novo lesions are unique to this patient population. Management of these patients is largely based on more than 20 years of NCI experience with excellent oncologic outcomes. We discuss our experience on the workup and management of these patients.
Preoperative Testing: Percutaneous Biopsy, Renogram
We suggest an algorithm for the workup and management of patients with bilateral, multifocal, and known or suspected hereditary syndromes ( Fig. 1 ). For those without a known condition, genetic testing can be very helpful if a syndrome is identified. When there is no preliminary evidence of a hereditary syndrome, preoperative biopsy of the largest lesion(s) often guides histology-directed genetic testing. This strategy could also reduce the expense associated with genetic counseling by narrowing down the candidate syndromes.
Nuclear scintigraphy with a Mag-3 renogram is useful for preoperative imaging in patients with bilateral renal tumors. This test serves as a baseline to better delineate split renal function. Information gained from the nuclear scan may help with surgical planning or alter surgical approach. For a staged approach, it is useful to assess how the prior renal unit has recovered from the surgery, as resection of dozens of tumors may have to be performed in a single setting. In the setting of a large decrease in renal function, delaying surgery to allow additional recovery may be warranted. If the kidney demonstrates very poor function (<15% split function), functionally the patient is considered to have a solitary kidney. In this situation, the surgeons may consider an open surgical approach over laparoscopic technique if they feel it will minimize total ischemia or warm ischemia time.
For synchronous, bilateral renal tumors that require intervention, the timing of surgery is open to debate. Three main surgical options exist for patients with synchronous, bilateral renal masses that require intervention, and include (1) concomitant, bilateral partial nephrectomy, (2) staged partial nephrectomy with the larger/more complex side first, and (3) staged partial nephrectomy with the smaller/less complex side first. Although some centers feel comfortable performing concomitant renal surgery, many surgeons prefer a staged approach because of concerns for potential complications, such as postoperative renal failure from bilateral renal surgery.
Deciding on the approach deserves much thought in each unique case, as arguments can be made for all 3 circumstances ( Fig. 2 ). The bilateral renal surgery approach allows surgery to be performed in a single setting; however, if problems occur on the first side there is a risk that the second side would need to be aborted. Performing a bilateral laparoscopic partial nephrectomy is difficult owing to patient positioning changes and is often not feasible. Should the concomitant, bilateral approach be chosen it often requires a midline/chevron incision, but may result in having a need to manage bilateral complications simultaneously. For a staged approach in the absence of metastatic disease, it may be prudent to operate on the larger tumor first, as it may pose a greater threat for dissemination. In the setting of surgeries that have different complexities, it may be preferable to do the less complex side first in case the more challenging tumor necessitates a radical nephrectomy. If done in the opposite order and a radical nephrectomy was required, prolonged clamping of a solitary kidney could place the patient at risk for significant renal complications. At the NCI, the typical approach is via staged procedures performed through the flank retroperitoneal approaches.
Related posts:
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Approach to the Small Renal Mass: to Treat or Not to Treat
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