Treatment of early-stage RCC: excise

Kidney cancer. Principles and practice. Second edition. Primo N. Lara, Jr. Eric Jonasch (Editors). Springer International Publishing (2015)

Comparison of oncologic outcomes between radical nephrectomy and partial nephrectomy

The mainstay of treatment for RCC is surgical therapy due to its resistance to chemotherapy and radiation therapy. Recent advances in the development of targeted therapies for advanced RCC have resulted in longer survival for patients with metastatic RCC; however, treatment for localized RCC remains surgical extirpation. The management of RCC has been governed by Robson’s initial description in 1963 of a radical nephrectomy (RN) for the treatment of all renal tumors [50]. Utilizing a flank, subcostal, or midline incision, Robson’s description of an RN included the removal of the entire kidney, perirenal fat, surrounding Gerota’s fascia, overlying peritoneum, and adrenal gland [50]. This approach resulted in excellent oncologic outcomes [51]. In cases where surgical extirpation of the kidney would render a patient functionally or anatomically anaphoric, an “essential” partial nephrectomy (PN) was performed in these select patients to avoid the need for renal replacement therapy. As data on oncologic outcomes of patients who underwent an “essential” PN emerged, the use of PN for elective indications was gaining acceptance. During the past decade, the paradigm has shifted toward treating localized RCC with nephron-sparing surgery (NSS) as oncologic outcomes have proven to be equivalent to traditional RN (Table 9.1). In fact, in the recent AUA guidelines, which reviewed all the existing literature for oncologic outcomes for RN and PN, recurrence-free survival rates were equal at 98.0–99.2%, respectively [5].

In addition to oncologic equivalency, nephron preservation also results in improved renal functional outcomes after surgery [45, 46]. Furthermore, several recent studies have shown a defined benefit with PN compared to RN in terms of overall survival and reduced rates of cardiovascular events and non-cancer-related deaths [52–54]. Weight et al. published the Cleveland Clinic’s follow-up data comparing survival outcomes in patients undergoing RN or a PN for a cT1b renal mass. In this cohort of 1,004 patients, postoperative eGFR was an independent predictor of overall survival and cardiac-specific survival on multivariate analysis. Patients treated with PN had a statistically significant improved 5-year OS compared to patients treated with RN (85% vs. 78% (p = 0.01)) [52]. Interestingly, of the 175 deaths in this cohort, 48 were due to cardiovascular events and 19 were related to renal failure. Similar conclusions were reached by Thompson et al. and Huang et al. when examining the Mayo Clinic nephrectomy registry as well as the SEER cancer database. Their data demonstrated that in patients younger than 65 years old treated for a pT1a renal mass, RN was significantly associated with death from any cause (RR 2.16, p = 0.02) [53]. Also, a query of the SEER cancer registry showed a statistically significant increase in the risk of cardiovascular events (p < 0.05) and all-cause mortality (HR 1.46, p < 0.001) for patients treated with RN for a pT1a renal mass [54]. Furthermore, in a graded fashion, renal dysfunction has been shown to be associated with significantly increased cardiovascular risks, hospitalizations, and mortality [47]. Finally, when employed in elective situations, health-related quality of life scores were higher in the PN compared to RN group [55] with equivalent lengths of stay and direct hospital costs [56].

Despite oncologic equivalency and improved renal functional outcomes, NSS carries a higher risk of a major urologic complication that must be considered in the risk/benefit equation. In the recent AUA guidelines concerning the management of the clinical T1 renal mass, the complication rate for open PN ranges from 4.5 to 8.7% based on the results of 15 published studies [5]. Also, the recent EORTC trial comparing PN to RN in tumors less than 5 cm highlights this risk/benefit balance. In this prospective randomized study of 541 patients, PN was associated with a statistically significant increased risk of severe hemorrhage, defined as >1 L, and urinary fistulas (p < 0.001) [57]. Conversely, patients who underwent a PN had a statistically significant lower sCr at follow-up (p < 0.0001). Similarly, other studies have shown that as tumor size or tumor complexity increases, the incidence of technical adverse events increases too. Patard et al. compared morbidity in patients undergoing PN for tumors <4 cm and >4 cm. In this study, there was a statistically significant increase in the rates of blood transfusions (p = 0.001) and urinary fistula (p = 0.01) in patients undergoing PN for tumors >4 cm [58]. Clearly, the risks of chronic kidney disease and their attendant detrimental health effects need to be quantified and weighed against the more immediate and short-term surgical risks.

Table 9.1. Oncologic outcomes in patients treated with radical nephrectomy compared to nephron-sparing surgery

__Kidney Cancer_ Principles and Practice-Springer International Publishing (2015) T 9.1

Table 9.2. Oncologic comparison between open and laparoscopic partial nephrectomy 5-year disease-free survival (%)

__Kidney Cancer_ Principles and Practice-Springer International Publishing (2015) T 9.2

Partial nephrectomy for pT2 renal masses

Extending the partial nephrectomy experience for pT1b tumors, newer series have demonstrated that PN for T2 renal masses has equivalent oncologic outcomes compared to RN with acceptable perioperative complication rates. Hansen et al. published a study examining the SEER database which compared 245 patients who underwent a PN and 8,602 patients who underwent an RN for a renal mass >7 cm. In their analysis, the cancerspecific mortality (CSM) for an RN was 5.7% and 17.7% at 2 and 5 years, respectively [59]. For PN, the CSM was 3.4 and 11.9% at the same time points which was not statistically significant different [59]. Breau et al. found that RCCspecific survival and OS were similar when their institution matched PN to RN for stage T2 tumors or greater. Local recurrence occurred in 4 (6%) patients, while distant spread occurred in 15 (22%) individuals [60].

Similarly, our institution performed an analysis of 49 renal tumors >7 cm that were treated by PN. The 5and 10-year RCC-specific survival was 94.5 and 70.9% [61]. In our series, 8.2% of patients required blood transfusions, and 12.2% developed urinary fistulas [61]. As previously mentioned, in a recent EORTC trial, 541 patients with cT1 renal masses =5 cm were randomized to PN or RN. PN was associated with a statistically significant increased risk of severe hemorrhage (defined as >1 L) and urinary fistula (p < 0.001) [57]. Conversely, patients who underwent a PN had a statistically significant lower serum creatinine at follow-up (p < 0.0001). Our study, among others, has shown that in the appropriate setting, PN for pT2 masses is oncologically sound with acceptable complications rates. Furthermore, as expected, PN is associated with better renal functional preservation. Urologists must weigh the risks and benefits of PN, including improved renal functional outcomes and improved cardiovascular status, with an increased risk of short-term morbidity in the setting of oncologic equivalence.

Comparison of open and minimally invasive techniques in the treatment of localized RCC

With the advent of minimally invasive surgery, laparoscopic techniques have been applied to the kidney. There was an initial reluctance to adopt laparoscopic renal surgery widely because of concerns for tumor seeding of the peritoneum. Also, maculation of specimens raised concerns for inadequate staging. Today, nephrectomy specimens are removed intact, and concerns over tumor seeding have not been substantiated. Indeed, although prospective randomized trials of open versus laparoscopic radical nephrectomy were never completed, long-term retrospective data suggest oncological equivalence between the two approaches [62–66] (Table 9.2). Today, given significantly lower intraoperative blood loss and shorter convalescence, laparoscopic RN is the standard of care for renal surgery that requires total removal of the kidney [62].

In 1990, the first laparoscopic radical nephrectomy (LRN) was performed by Clayman et al. for a 3 cm oncocytoma [67]. In that case report, each segmental artery was dissected and individually ligated, because the clips available at that time were not large enough to secure the main renal artery. Furthermore, a preoperative angioinfarction of the kidney was performed, and intraoperatively, a ureteral catheter was placed. Since that initial report, the laparoscopic renal surgery rapidly gained traction. Presently, at centers of excellence, the vast majority of nephrectomies are performed via a laparoscopic approach. Furthermore, surgery for large renal tumors and tumors with thrombi extending into the renal vein and even the vena cava is now being performed laparoscopically [68–70].

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Fig. 9.3. Usual port site arrangement for left transperitoneal robot-assisted partial nephrectomy. Two common arrangements are depicted. Blue circles indicate camera ports. Dashed circles indicate assistant ports. Larger circles represent 12 mm ports, while the smaller circles represent 5 mm ports. Green circles represent 8 mm ports that accommodate the robotic arms

Coincident with the growth of laparoscopy has been the increased detection of incidental SRMs during the last two decades, as cross-sectional imaging has become a routine diagnostic tool [1]. Thanks to the widespread acceptance of NSS and refinement of laparoscopic instrumentation, a patient can be offered a PN via laparoscopic approaches (with and without robotic assistance) utilizing only three or four small incisions, none measuring greater than 1.2 cm. A large multiinstitutional retrospective study comparing laparoscopic partial nephrectomy (LPN) with OPN provided evidence on multivariate analyses that LPN was associated with decreased blood loss and shorter operative times and hospital stays [71]. However, perioperative/postoperative complications, such as prolonged warm ischemia and renal hemorrhage, and re-exploration rates were notably higher in the LPN group, while oncologic control appeared to be equivalent in the two groups. The AUA systematic review published its guidelines on the treatment for stage I renal tumors identifying a nearly 50% increase in “major complications” in LPN compared to OPN [5]. Despite the increase in major urologic complications, cancer control for appropriately selected patients appears to be preserved [72].

More recently, robotic-assisted laparoscopy has emerged as another tool in the armamentarium for treatment of localized kidney cancer (Fig. 9.3). As urologists have become more familiar with robotic techniques, the usage of robotics has broadened to include NSS. Robotic assistance enables the surgeon to perform more efficient intracorporeal suturing and thus safely resect larger, more anatomically complex lesions. Furthermore, the learning curve for robotically assisted laparoscopic partial nephrectomy (RALPN) may be less steep than LPN, based on equivalent same surgeon results when comparing initial RALPN versus vast LPN experience [73]. Sitting at the console, the robotic user can rotate one’s wrists 180° and pass suture from virtually any angle. Renal reconstruction can be performed in 3-D, and the passing of suture through the kidney is easier than with pure laparoscopic technique due to the wrist motions of the robot.

Many small series have been published showing that a RALPN is technically feasible without increasing patient morbidity [74–77] (Table 9.3). These series do not have long enough follow-up to show equivalent oncologic control as the open or laparoscopic approaches; however, currently, there is no suspicion that the technique is inferior [74–76]. The largest recent series concluded that RALPN is an oncologically sound approach with acceptable immediate nephron-sparing outcomes [77].

Table 9.3. Short-term outcomes of published robotic-assisted partial nephrectomy series

__Kidney Cancer_ Principles and Practice-Springer International Publishing (2015) T 9.3

Finally, due to its location, the kidney can be accessed via a pure retroperitoneal approach (Fig. 9.4), and retroperitoneoscopic renal surgery was first described in the early 1990s. This approach offers rapid and direct access to the hilum [78].

However, the retroperitoneoscopic approach is unfamiliar to some urologists, and the small working space can make the operation difficult and tedious, especially in patient with copious retroperitoneal fat, which can impede visualization. Finally, the retroperitoneum, especially in the presence of copious fat, lacks reliable landmarks that a transperitoneal approach offers. This absence of predictable anatomical cues contributes to a steep learning curve and may lead to catastrophic complications in inexperienced hands. In one multi-institutional report, the IVC was transected in two patients with a stapling device, because it was mistaken for the main right renal vein [79]. Nonetheless, there are clinical scenarios where this approach may be more advantageous. In morbidly obese patients and those with prior extensive abdominal surgery or radiation, a retroperitoneal approach can be safely performed without significant increases in morbidity, blood loss, or operative time [80]. In prior series looking at head-to-head comparisons between transperitoneoscopic and retroperitoneoscopic LPN, reported clinical outcomes were comparable in terms of blood loss, operative times, and convalescence [81]. Despite these favorable results, this technique does require an additional level of expertise.

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Fig. 9.4. Usual port site arrangement for right retroperitoneal laparoscopic radical nephrectomy. Blue circle indicates camera port. Larger circle represents 12 mm port, while the smaller circles represent 5 mm ports

As indications expand and surgical skills become more refined, the pendulum has gradually swung away from open and toward MIS for kidney cancer, especially at centers of excellence. Due to the stage migration associated with RCC in recent years, the historic standard of open radical nephrectomy is unwarranted, and the associated CKD is preventable and potentially harmful [82]. Assuming equivalent oncologic outcomes and renal preservation, minimally invasive techniques should be employed to minimize patient morbidity [5].

Role of lymph node dissection in low-risk RCC

The role of a lymph node dissection (LND) in RCC, especially low-risk RCC, is unproven. EORTC 30881 was a large prospective phase 3 trial that randomized 772 patients with cTanyN0M0 to RN +/LND. Seventy percent of these patients had pT1-2 disease [83]. There were no statistical differences between RN with LND versus RN alone with respect to morbidity, progression-free survival, time to progression, and overall survival [83]. Importantly, only 1% of these patients had pathologic node positive disease which was non-palpable at surgery and not evident on preoperative imaging. Conclusions of this study show that patients with low-risk RCC (cT1-2N0M0) most likely do not benefit from LND [83]. However, this study may have been underpowered to detect a significant difference in oncologic outcomes in patients with lowrisk RCC.

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