Renal cell carcinoma. Clinical management. Eric A. Klein (Editor). Springer (2013)
There will be an estimated 58,240 new cases and 13,040 deaths from kidney cancer in the USA in 2010. Compared to 1971, this represents a fivefold increase in the incidence and twofold increase in the mortality of renal cancer. Associated risk factors for kidney cancer include hypertension, obesity, and African American race. Epidemiological evidence suggests an increase in all stages of renal cancer, including the advanced and metastatic cases. It is now understood that renal cortical tumors are a family of distinct tumors with variable histology, cytogenetic defects, and metastatic potential. Approximately 90% of the tumors that metastasize are the conventional clear cell carcinoma; however, they account for only 54% of the total number of resected tumors. Approximately 30–40% of renal tumor patients will either present with or later develop metastatic disease. The widespread use of the modern abdominal imaging techniques (CT, MRI, and abdominal ultrasound) over the last two decades, usually ordered to evaluate nonspecific abdominal and musculoskeletal complaints or during unrelated cancer care, has changed the profile of the typical renal tumor patient from one with a massive, symptomatic tumor at presentation to one with a small, asymptomatic, renal mass (<4 cm) incidentally discovered in 70% of the cases. A survival rate of 90% or greater, depending on the tumor histology, is expected for these small tumors if partial (PN) or radical nephrectomy (RN) is performed.
RN was once considered the “gold standard” and utilized to treat all tumors, small and large, and even to solve diagnostic dilemmas when an uncertain renal mass was encountered. PN was only utilized in restricted conditions such as tumor in a solitary kidney or in patients with conditions which compromised renal function. New concerns that RN could cause or worsen preexisting chronic kidney disease (CKD) has lead to recommendations for more restricted use of RN, whether performed by open or minimally invasive techniques, for the resection of large renal tumors, including those which destroy the majority of the kidney, invade the renal sinus, invade branched or main renal veins or extend into the inferior vena cava, and/or are associated with regional adenopathy or metastatic disease. The increased treatment and cure of small, incidentally discovered renal tumors, most of which are nonlethal in nature, does not appear to offset the increased mortality caused by the advanced and metastatic tumors. This “treatment disconnect” may result from unaccounted etiological factors increasing the incidence of all renal cortical tumors and their virulence.
Radical nephrectomy: historical considerations
Successful attempts to surgically cure renal tumors were reported widely after World War 2 with surgical strategies designed to address the renal capsular and perinephric fat infiltration observed in up to 70% of the tumors. Using a thoracoabdominal incision, Mortensen reported the first radical nephrectomy, an operation that removed all of the contents of Gerota’s fascia. Radical nephrectomy was popularized in the 1960s by Robson who described this operation as the perifascial resection of the tumor-bearing kidney and perirenal fat, regional lymph nodes, and ipsilateral adrenal gland. In 1969 Robson reported RN results in a series of 88 patients and described a 65% survival for tumors confined within Gerota’s fascia (Robson stages 1 and 2), but the finding of regional nodal metastases led to less than 30% 5-year survival rate.
En bloc RN, ipsilateral adrenalectomy, and extensive regional lymphadenectomy, usually through large abdominal or transthoracic incisions, became the standard approach to the renal tumors for the next 20 years as major centers began reporting favorable results. In this era, the imaging studies used to diagnose a patient, who was generally symptomatic with a large renal tumor, was intravenous urograms, retrograde pyelograms, and arteriograms. These techniques were unable to detect small tumors and the incidental tumor detection rate was <5%. Despite this acceptance of RN by urologic surgeons, convincing data did not exist establishing the therapeutic impact of the component parts of the operation (i.e., the need for adrenalectomy or the need for and extent of lymph node dissection). Historical series were subjected to selection biases, and the virtues of randomized trials in clinical investigation to address the many questions in kidney tumor surgery were not yet realized. Although a subsequent report with longer follow-up from Robson in 1982 projected declining long-term survival rates in the range of 40%, there was no doubt that the surgical techniques associated with the safe removal of large renal tumors were established, well described, and reproducible making RN the only effective treatment for renal cortical tumors. Today, at major centers with a commitment to renal tumor surgery, despite the above-described imaging-induced stage and tumor size migration, RN is still required in approximately 20–30% of patients with renal tumors not amenable to kidney sparing approaches (Fig. 7.1).
Radical nephrectomy: patient selection and preoperative evaluation
To a large extent, the modern imaging studies of CT, ultrasound, and MRI that have been so effective in creating the era of the “incidentaloma” and the associated tumor size and stage migration also provide the surgeon with an accurate description of the extent of disease prior to operation. At MSKCC, tumors routinely selected for RN include those large and centrally localized tumors that have effectively replaced the majority of the normal renal parenchyma, often associated with regional adenopathy, inferior vena cava, or right atrial extension, none of which are amenable to a PN. In addition, RN is performed on patients with metastatic disease referred by medical oncology for cytoreductive nephrectomy prior to the initiation of systemic therapy. Patients with extensive metastatic disease and a poor Karnofsky performance status are advised to undergo percutaneous needle biopsy of the primary tumor or a metastatic site and subsequently referred for systemic therapy. Patients with small incidentally discovered or exophytic tumors amenable to PN are asked to also sign consent for radical nephrectomy if operative findings or technical problems arise making PN unsafe or unwise. Over the last 3 years at our center, 1,030 surgical nephrectomies have been performed with 21% RN and 79% PN, reflecting our center’s commitment to kidney sparing approaches whenever possible.
Fig. 7.1. CT of the abdomen of a 44-year-old male with massive left renal tumor (21 cm × 15 cm × 12 cm) completely replacing the kidney. He subsequently underwent left radical nephrectomy, regional lymph node dissection,and ipsilateral adrenalectomy
Prior to operation, routine serum chemistries, coagulation profile, type and cross match (or autologous blood donation), and chest X-ray are obtained. Routine brain imaging and bone scanning are not performed unless site-specific abnormalities in the history, physical, or routine preoperative laboratory examination are discovered. For patients with significant comorbid conditions, particularly cardiac and pulmonary related, appropriate consultations are obtained with an effort made to optimize patients for operation whenever possible. Patients with significant coronary or carotid artery disease may require revascularization prior to RN. For patients with compromised pulmonary status, consultation with anesthesiology is requested for consideration of epidural postoperative analgesia.
Open radical nephrectomy: surgical anatomy, choice of incisions, and operative considerations
The kidneys are retroperitoneal organs located in the lumbar fossa. They are covered with a variable amount of perinephric fat and Gerota’s fascia and lay in proximity to the psoas major and quadratus lumborum muscles, and diaphragm. The right kidney abuts the right adrenal gland; liver, hepatic flexure of the colon, and second portion of the duodenum cover the renal hilum. The left kidney is in proximity to the left adrenal whose main vein drains into the left renal vein, pancreatic tail, and spleen superiorly and the left colon medially. Depending on the surgeon’s preference, relating mainly to patient’s body habitus, the tumor size and location, the RN can be performed through an eleventh rib flank incision, a transperitoneal midline or subcostal incision, or a transthoracic incision or a miniflank supra eleventh rib incision rib miniflank incision. The “miniflank incision” (Fig. 7.2) has the advantage of speedy entry into the retroperitoneum and avoidance of the rib resection with a decreased likelihood (<5%) of subsequent atony of the flank muscles and bulge. For large tumors with any question of liver, pancreatic, splenic, or IVC extension optimum exposure with bilateral subcostal (chevron) or thoracoabdominal incision is preferred and leaves options open for gaining control over the renal hilum particularly when there is regional adenopathy and parasitic veins to contend with. In the retroperitoneal approach to RN, the peritoneum and pleura are dissected off Gerota’s fascia exposing the kidney and ipsilateral great vessel.
During transabdominal RN, the colon is reflected medially along the white line of Toldt. We commonly employ self-retaining retractors to provide maximum exposure with care taken to pad organs prone to iatrogenic injury such as the spleen, liver, and pancreas. On the right side, mobilization of the duodenum (Kocher maneuver) medially provides clear exposure of the inferior vena cava and renal hilum. Peritoneal attachments to the liver and ligamentous attachments to the spleen are carefully divided with care taken not to tear liver and splenic capsules. Inferiorly, the ureter is identified, ligated, and divided. The gonadal vessels are identified coursing through the retroperitoneal soft tissues entering either the left renal vein or inferior vena cava on the right where it is ligated and divided. Split and roll techniques are used along the ipsilateral great vessel until the renal vein is identified. All lymphatic attachments overlying the renal vein are carefully divided. On the left side, the adrenal and gonadal veins are identified as they drain into the renal vein, ligated and divided. Using blunt dissection, a vessel loop is placed around the renal vein allowing for upward traction and identification of the renal artery. Care is taken not to tear a posterior lumbar vein which often also drains into the renal vein. The renal vein should be palpated and inspected to exclude the possibility of a tumor thrombus. As soon as is possible, the renal artery is identified beneath the renal vein at its aortic ostium, ligated, suture ligated, and divided. The arterial decompression that ensues renders the kidney more mobile and deflates the many fragile and distended parasitic vessels along the surface of the kidney that often bleed during this mobilization process. Lack of renal vein decompression indicates an accessory renal artery often emanating from the aorta either superior or inferior to the level of the renal vein. The surgeon should avoid the renal vein ligation prior to complete arterial decompression which will cause marked venous congestion and hemorrhage from the tumor and parasitic vessels.
Fig. 7.2 Miniflank surgical incision is a quick and effective approach to the retroperitoneum and kidney and can be utilized both for partial and radical nephrectomy
It is our practice to perform ipsilateral adrenalectomy and regional node dissection to maximize local tumor control, decrease the chance of local recurrence if these tissues are harboring micrometastatic disease, and provide maximum pathological staging to allow entry into ongoing adjuvant clinical trials. Little evidence currently exists that the resection of tumor-bearing lymph nodes or ipsilateral adrenal gland provides a therapeutic effect. Care is taken not to traumatize the tail of the pancreas or the splenic vein during this portion of the dissection. Dissection continues along the aorta clipping and ligating arterial and venous supply to the adrenal. Following removal of the kidney and surrounding perinephric soft tissues and adrenal, the operative bed is thoroughly irrigated and inspected for any bleeding vessels. The spleen and pancreas are thoroughly inspected. Drains are not used unless a laceration of the pancreas is suspected or documented.
Once the tumor resection is accomplished, postoperative nomograms are available that incorporate clinical presentation, tumor histological subtype, size, and stage to provide and provide a clinical prognosis. Results for our center indicate 5-year survival rates following resection of non-metastatic tumors ranging from 30% to 98% depending on the above-mentioned clinical and pathological features. These postoperative nomograms have been extremely useful in patient counseling, tailoring cost-effective follow-up strategies, and designing clinical trials.
Minimally invasive radical nephrectomy
Following its introduction in 1991 by Clayman et al., laparoscopic radical nephrectomy (LRN) offered a minimally invasive alternative to the classical open RN with dividends of less wound pain and morbidity, decreased analgesic requirement, decreased hospitalization, more rapid convalescence, and faster return to normal activities. Survival rates were directly comparable to those achieved with open RN. At the time of its introduction, RN in general was the preferred treatment for all renal masses and PN was largely reserved for only essential cases where RN would put a patient at risk for dialysis. The choice of which procedure to offer the patient with the small renal tumor, LRN or open PN, posed a dilemma for surgical groups possessing both capabilities as the literature in each respective field developed in parallel over the last decade. A 9-year experience compared LRN (N = 61) to open RN (N = 33) for suspected renal cancer and found advantages for the laparoscopic operation which included less estimated blood loss (172 ml vs.451 ml), shorter hospital stay (3.4 days vs. 5.2 days), and quicker return to normal activity (3.6 weeks vs.8.1 weeks), but disadvantages for the laparoscopic operation were longer operating time (5.5 h vs. 2.8 h) and greater costs ($15,816 vs. $13,672.45). Interestingly, 23% of patients in the LRN group had benign disease versus 9% for the ORN group perhaps indicating a willingness of both surgeon and patient to accept a minimally invasive solution to a renal mass of uncertain nature.
Other centers also described their initial experiences in similar terms and readily concluded that LRN should supplant ORN particularly in cases with small renal tumors which remained well within the technical capabilities of the early laparoscopic surgeons. Many of the initial laparoscopic studies described renal cortical tumors in a historical context as a single tumor type (renal cell carcinoma) with a single metastatic potential and did not utilize the 1997 Heidelberg classification of renal tumors, did not discuss the uncertainties of preoperative radiological diagnosis, and did not discuss the deleterious impact of RN (by whatever means) on renal function. Often patients who underwent LRN and were found to have benign conditions were not included in the outcomes analysis. These articles argued strongly that LRN should be the new “gold standard” for all small, T1 renal tumors.
A study comparing open PN (N = 82) and LRN (N = 35) for small T1a renal tumors (<4 cm) discussed similar advantages of LRN described in other papers but noted a deleterious impact on renal function in the patients undergoing LRN. In this study too, 20% of the patients in each treatment group had lesions that were not renal cell carcinoma. The question beginning to face the urology community was this; was the price of a future of renal insufficiency for a speedy recovery, lesser surgical incisions, and faster return to normal activities after LRN potentially too great?
Evidence for intra-institutional differences in the treatment of small renal masses since the availability of laparoscopy was reported in a series of 194 patients Cornell Medical Center. Of the operations performed, 63 (33%, mean tumor size 3.6 cm) were open partial nephrectomies, 51 (26%, mean tumor size 7.6 cm) were ORN, and 80 (41%, mean tumor size 4.6 cm) were LRN. When analyzed over time, in the latter half of 2000, 89% of the LRN were performed on tumors of 4 cm or less. In 2002, the number of LRN performed for tumors 4 cm or less had decreased to 42%. The experience with OPN during the same time frame was more consistent; 30% for tumors of 4 cm or greater from 1997 to 2000 and 26% from 2000 to 2002. For OPN tumors of 4 cm or less, 70% from the years 1997–2000 and 73% from 2000 to 2002 were performed. During the same period, the number of ORN performed for tumors of 4 cm or less continued to decrease to 2.9% in 2001 and 0% in 2002. A recent study demonstrated the negative impact of LRN vs. LPN on renal function. The investigators compared 93 patients undergoing an LPN to 171 patients undergoing an LRN for a unilateral, sporadic renal tumor with a normal contra lateral
kidney and a serum creatinine <1.5 mg/dl. Tumors treated by LPN were smaller than LRN (2.4 cm vs. 5.4 cm), whereas age, BMI, serum creatinine, gender, and tumor location were similar between the two groups. The mean 6-month serum creatinine was greater in the LRN group vs. the LPN group (1.4 mg/dl vs. 1.0 mg/dl) and 36% of the LRN developed renal insufficiency (defined as serum creatinine >1.5 mg/dl) vs. 0% of the patients undergoing LPN.
Considerable effort was spent in the urology literature introducing and evaluating laparoscopic techniques for RN and comparing these approaches to historical surgical approaches (i.e., thoracoabdominal, chevron, or rib resecting flank incisions from the 1960s and 1970s) but not to the recently described min-flank surgical incisions which do not require rib resection and can be widely adopted and practiced without elaborate laparoscopic training. Not discussed in the laparoscopic literature was the role of adrenalectomy and regional node dissections or issues related to training or learning curves. Laparoscopic studies focused on comparing oncological outcomes to open RN (no apparent differences), length of stay (LOS) in the hospital, analgesic requirements, time to return to work and normal activities (better than open RN), and complications. At the same time, improvements in perioperative care and the use of clinical pathways were reducing LOS for all urological procedures, including open and laparoscopic kidney surgery. Other reports detailing technical concerns such as surgical approach (transperitoneal vs. retroperitoneal vs. hand assisted), intact tumor extraction vs. morcellation, the impact of prior operations, and concerns for LRN in obese and comorbidly ill patients were published. It would appear that morcellation procedures are rarely done today due to loss of pathological clarity and concerns for intra-abdominal contamination during the morcellation process. Descriptions of laparoscopic extraction incisions would indicate that they did not adversely affect LOS and patient recovery. These extraction incisions were in the range of 7 cm, not much smaller than the described miniflank incisions (8–10 cm), raising the question, as in other laparoscopic procedures such as cholecystectomy, whether patient expectations play a significant role in many of the laparoscopic outcomes. Surgeons have also used robotic-assisted techniques to perform RN, and the recent literature has compared outcomes to classical laparoscopic techniques with similar perioperative outcomes such as EBL and complications but not surprisingly, at the front end of any new approach, operating time and costs were significantly greater in the robotic-assisted cases.
Complications of radical nephrectomy
In a review of 688 RN from 1995 to 2002, 112 patients (16%) experienced a perioperative complication. Complications were graded using a five-tiered scale based on the severity of impact or the intensity of treatment required to address the complication. There were 21 (3%) complications that were directly attributed to the procedure (procedure related) including three patients with acute renal failure, one patient with a retroperitoneal hemorrhage, seven patients with an adjacent organ injury, four patients with a bowel obstruction, and six patients with a pneumothorax. Four patients required surgical re-exploration, three for decompression of bowel obstruction, and one for delayed splenic rupture (grade 4, N = 3). There were three postoperative deaths (grade 5), two due to myocardial infarction, and one due to pulmonary embolism. The remainder of the complications was grade 1–3 and was managed by oral medication or bedside care (grade 1, N = 78), intravenous therapy or thoracostomy tube (grade 2, N = 43), or intubation, interventional radiology, endoscopy, or reoperation (grade 3, N = 11). The grading scale employed correlated with mean hospital LOS as follows: no complications, 5.2 days; grade 1 complications, 6.8 days; grade 2 complications, 7.4 days; and grades 3–5 complications, 9.3 days. Grading complications provide an effective means of describing the severity of complications although its current use in the literature is limited.
Complications unique to LRN in particular and laparoscopy in general have been reported from individual centers and are more likely to occur earlier in a center’s experience (initial 50 cases). In one series, when the initial 50 LRN cases are compared to the subsequent 50 cases, surgical time decreased from 2.9 to 2.7 h while the mean tumor size increased from 4.8 to 5.4 cm. Major complications were 14%, minor complications were 11%, and two patients required open conversion in one series. Intra-operative events occur in approximately 4% of cases and include adjacent organ injury (spleen, bowel), vascular stapler malfunction with open conversion occurring in approximately 1–2% of cases. Minimally invasive surgical (MIS) training has gradually been integrated into more residency training programs, and, despite this, a stable complication rate over the last 5 years in centers with a major commitment to MIS has been observed which is attributed by some to the passage of more relatively inexperienced surgeons through the learning curve.
Radical nephrectomy: adverse renal medical impact
A historical misconception exists that RN can cause a permanent rise in serum creatinine due to the sacrifice of normal renal parenchyma not involved by tumor but will not cause serious long-term side effects as long as the patient has a normal contralateral kidney. The renal transplant literature is cited as the clinical evidence to support this view since patients undergoing donor nephrectomy have not been reported to have higher rates of kidney failure requiring dialysis or death. However, distinct differences between kidney donors and kidney tumor patients exist. Donors tend to be carefully screened for medical comorbidities and are generally young (age 45 or less). In contrast, renal tumor patients are not screened, are older (mean age 61 years), and many have significant comorbidities affecting baseline kidney function including metabolic syndrome, hypertension, coronary artery disease, obesity, vascular disease, and diabetes. In addition, as patients age, particularly beyond 60 years, nephrons atrophy and glomerular filtration rate progressively decreases. A study of 110 nephrectomy specimens in which the nontumor-bearing kidney was examined demonstrated extensive and unsuspected underlying renal disease including vascular sclerosis, diabetic nephropathy, glomerular hypertrophy, mesangial expansion, and diffuse glomerulosclerosis. Only 10% of patients had completely normal renal tissue adjacent to the tumor.
Evidence that RN could cause a significant rise in the serum creatinine when compared to PN in patients with renal cortical tumors of 4 cm or less was published by investigators from Mayo Clinic and MSKCC in 2000 and 2002, respectively. RN patients were more likely to have elevated serum creatinine levels to >2.0 ng/ml and proteinuria (Mayo Study), a persistent finding even when study patients were carefully matched for associated risk factors (MSKCC study) including diabetes, smoking history, preoperative serum creatinine, and ASA score. In both studies, oncological outcomes were highly favorable (>90% survival rates) whether PN or RN was done.
CKD, defined as an estimated glomerular filtration rate (eGFR) of less than 60 min/ min/1.73 m2, is increasingly viewed as a major public health problem in the USA and since 2003 is considered an independent cardiovascular risk factor. An estimated 19 million adults in the USA have CKD, and by the year 2030, two million will be in need of chronic dialysis or renal transplantation. Traditional risk factors for CKD include age greater than 60, hypertension, diabetes, cardiovascular disease, and family history of renal disease, factors also common in the population of patients that develop renal cortical tumors. A study involving 1,120,295 patients demonstrated a direct correlation between CKD and rates of hospitalization, cardiovascular events, and death, which occurred before overt renal failure requiring dialysis or renal transplantation. As kidney function deteriorated, the percentage of patients with two associated cardiovascular risk factors increased from 34.7% (stages 1 and 2 CKD) to 83.6% (for stage 3) to 100% for stages 4 and 5 subjects. Patients with CKD are more likely to require medical interventions to treat cardiovascular disease than those with normal renal function. The low prevalence of patients with stage 4 or 5 CKD is attributable to their 5-year survival rates of only 30%.
A concern that the overzealous use of RN, particularly in patients with small renal masses and common comorbidities that can affect renal function, could be causing or worsening preexisting CKD became a focus of intense research. MSKCC investigators used a widely available formula, the Modification in Diet and Renal Disease (MDRD) equation (http://www. nephron.com/MDRD_GFR.cgi), to estimate the glomerular filtration rate (eGFR) in a retrospective cohort study of 662 patients with a normal serum creatinine and two healthy kidneys that underwent either elective PN or RN for an RCT 4 cm or less in diameter. To their surprise, 171 patients (26%) had preexisting CKD (GFR <60) prior to operation. Data were analyzed using two threshold definitions of CKD, a GFR < 60 ml/ min/1.73 m2 or a GFR < 45 ml/min/1.73 m2. After surgery, the 3-year probability of freedom from new onset of GFR < 60 was 80% after PN but only 35% after RN. Corresponding values for 3-year probability of freedom from a GFR < 45, a more severe level of CKD, was 95% for PN and 64% for RN. Multivariable analysis indicated that RN was an independent risk factor for the development of new onset CKD (Fig. 7.3 ). Mayo Clinic investigators identified 648 patients from 1989 to 2003 treated with RN or PN for a solitary renal tumor less than or equal to 4 cm with a normal contralateral kidney. In 327 patients younger than 65, it was found that RN was significantly associated with an increased risk of death which persisted after adjusting for year of surgery, diabetes, Charlson–Romano index, and tumor histology. Using the surveillance, epidemiology and end results (SEER) cancer registry data linked with Medicare claims, MSKCC investigators studied 2,991 patients older than 65 years for resected renal tumors of 4 cm or less from 1995 to 2002. A total of 254 patients (81%) underwent RN and 556 patients underwent PN. During a median follow-up of 4 years, 609 patients experienced a cardiovascular event and 892 patients died. After adjusting for preoperative demographic and comorbidity variables, RN was associated with a 1.38 times increased risk of overall mortality and a 1.4 times greater number of cardiovascular events (Fig. 7.4 ). Tan and colleagues recently confirmed these findings in an updated report which utilized the same SEER linked with Medicare data between 1992 and 2007 in 7,138 patients of whom 1,925 (27%) patients underwent PN and 5,213 (73%) underwent RN for T1a renal tumors. In this study, patients undergoing PN had a significantly decreased risk of all cause mortality compared to those undergoing RN (HR 0.54), whereas no significant difference was noted in kidney cancer-specific survival. A recent pooled analysis of 51 studies involving 31,728 patients from the world’s literature was published by Kim and colleagues. The authors reported that PN was associated with a 19% risk reduction in all cause mortality, a 29% risk reduction in cancer-specific mortality, and a 61% risk reduction in severe CKD. Despite these findings, the authors pointed out that the data obtained were observational and subject to selection biases and statistical heterogeneity. Similar results were reported in patients undergoing laparoscopic RN and PN.
Fig. 7.3. Impact of radical vs. partial nephrectomy on renal function after management of T1a renal tumors. Radical nephrectomy is associated with a 3-year probability of freedom from new onset of GFR <60 ml/min/1.73 m2 of only 35% (vs. 80% after PN) and a 3-year probability of freedom from a GFR <45 ml/min/1.73 m2, a more severe level of CKD, of 64% (vs. 95% for PN)
Fig. 7.4. Data from the SEER linked to Medicare database indicates that radical nephrectomy is associated with a 1.38 times increased risk of overall mortality and a 1.4 times greater number of cardiovascular events when comparedto partial nephrectomy
Confusing matters to some extent was a recently published randomized clinical trial from Europe comparing PN (N = 268) to RN (N = 273) for tumors of 5 cm or less (T1a, T1b) operated upon from 1992 to 2003. After a median followup of 9.3 years, oncologic events were uncommon with only 12 of 117 deaths due to RCC (8 in the PN group, 4 in the RN group). Tumor progression was also uncommon (12 in the PN group, 9 in the RN group). In this study the PN patients did not experience better overall survival (76% vs. 81% in the RN group). The most common cause of death was cardiovascular, but again there was no advantage for PN (25 cardiovascular deaths in the PN group vs. 20 in the RN group). This study had significant limitations, including accrual difficulties leading to premature closure, inclusion of some tumors >4 cm, the fact that some patients (10.2%) switched treatment groups after randomization, the fact that the trial was conducted at many centers and occurred during a treatment era when elective PN was not common, and the oncological efficacy was questioned by many. Despite these factors, the study was randomized and raises the possibility that within the contemporary pool of patients undergoing PN or RN for T1 renal tumors, other preexisting medical factors, including those that could adversely affect renal function such as diabetes and hypertension, could be to some extent responsible for the apparent advantage to PN in the more vulnerable patient, whereas patients with excellent baseline renal function my not suffer the same ill consequence of RN despite a reduced eGFR. Also unknown is to what degree the solitary healthy kidney can recover and compensate follow RN. Further investigation to clarify this important issue is ongoing. The effect of these reports has made urologists increasingly aware that preexisting CKD can be significantly worsened by the liberal use of RN for the treatment of the small renal mass. Short-term end points, including length of hospital stay, analgesic requirements, and cosmetic elements viewed by many as the reason to elect laparoscopic RN over the more challenging PN, must now be tempered by these new concerns regarding CKD and overall survival. The most recent AUA guidelines for the management of the small renal tumor emphasize these points and strongly support the use of PN whenever technically feasible.
Radical nephrectomy is overutilized
Despite the above well-described oncological and medical arguments in the contemporary literature supporting PN as an ideal treatment for such small renal masses, the urological oncology community continues to use RN as the predominant treatment of the T1a renal mass. A crosssectional view of clinical practice using the Nationwide Inpatient Sample revealed that only 7.5% of kidney tumor operations in the USA from 1988 to 2002 were PN. Using the SEER database, investigators from the University of Michigan reported from 2001, only 20% of all renal cortical tumors between 2 and 4 cm were treated by PN and using the SEER database linked with Medicare claims, Huang and colleagues from MSKCC reported a utilization rate of only 19% for T1a tumors (4 cm or less). Interestingly and for uncertain reasons, women and elderly patients are more likely to be treated with RN. Many urologists believe that a “quick” RN in an elderly patient would expose the patient to fewer postoperative complications than would a PN. However, MSKCC investigators evaluated age and type of procedure performed in 1,712 patients with kidney tumors found the interactive term was not significant indicating a lack of statistical evidence that the risk of complications associated with PN increased with advancing age. Furthermore, no evidence was reported linking age with estimated blood loss or operative time. Given the advantages of renal functional preservation, the authors concluded that elderly patients should be perfectly eligible for PN.
Although the urology literature has many great articles written concerning the use of laparoscopic techniques to resect kidney tumors, the penetrence of laparoscopic RN according to the National Inpatient Sample from 1991 to 2003 was only 4.6% with a peak incidence of 16% in 2003. These data indicate that the bulk of “kidney wasting operations” are being done by traditional open surgical approaches. In England, a similar under-utilization of PN was reported in 2002 with only 108 (4%) PN out of 2,671 nephrectomies performed. Investigators at MSKCC tracked nephrectomy use in 1,533 patients between 2000 and 2007 excluding patients with bilateral tumors and tumors in a solitary kidney and including only patients with an eGFR of greater than 45 ml/min/1.73 m2. Overall 854 (56%) patients underwent PN and 679 (44%) underwent RN. In the 820 patients with a renal tumor of 4 cm or less, the frequency of PN increased from 69% in 2000 to 89% in 2007. In the 365 patients with a renal tumor from 4 to 7 cm, the frequency of PN increased from 20% in 2000 to 60% in 2007. Despite a commitment to kidney sparing operations during this time frame by the MSKCC group, multivariate analysis indicated that PN was a significantly favored approach for males, younger patients, smaller tumors, and open surgeons.
Modern imaging capabilities has created a renal tumor stage and size migration with approximately 70% of patients today detected incidentally with a median tumor size of 4 cm or less. In addition, our current understanding indicates that renal cortical tumors are a family of neoplasms with distinct histopathological and cytogenetic features and variable metastatic potential. The conventional clear cell tumor has a malignant potential and accounts for only 54% of the total renal cortical tumors but 90% of those that metastasize. RN nephrectomy, whether performed by open or MIS technique, plays an important role in the management of massive renal tumors that have replaced the normal renal parenchyma, invade the renal vein, and have associated regional lymphadenopathy or metastatic disease. For patients with smaller tumors amenable to PN, RN should not be performed since it is associated with the causation or worsening of preexisting CKD which may cause an increased likelihood of cardiovascular morbidity and mortality. Despite a wealth of evidence supporting the more restricted indications for RN, strong evidence exists that it remains overutilized in the USA. Widespread education and training in kidney preserving surgical strategies is essential going forward.