Michael Grasso III and Demetrius H. Bagley (eds.)Upper Urinary Tract Urothelial Carcinoma10.1007/978-3-319-13869-5_5

5. Surgical Management of Upper Tract Urothelial Carcinoma– Open, Laparoscopic, and Robotic Approaches to Nephroureterectomy and Outcomes

Marc J. Mann¹, Costas D. Lallas¹ and Edouard J. Trabulsi²

(1)

Department of Urology, Thomas Jefferson University, 1025 Walnut Street, Philadelphia, PA 19107, USA

(2)

Department of Urology, Kimmel Cancer Center, Sidney Kimmel Medical College, Thomas Jefferson University, 1025 Walnut Street, Philadelphia, PA 19107, USA

Edouard J. Trabulsi

Email: Edouard.Trabulsi@jefferson.edu

5.1 Introduction

It is estimated that upper tract urothelial carcinoma (UTUC) is a rare disease making up only 5–6 % of all urothelial malignancies, and occurs in only 1–4 people per 100,000 with a peak incidence in the 6th and 7th decades occurring in men more frequently than women [1]. Perhaps due to the rarity of incidence limiting research knowledge and the relatively aggressive nature at times of UTUC, surgical management of UTUC tends to be more aggressive than that of the lower tract. In order to adequately stage the disease, there is a heavy reliance on radiographic and visual imaging via ureteroscopy. The reason for this reliance on imaging and direct visualization is primarily due to the problem of obtaining tissue biopsies to accurately gauge depth of invasion. There are severe size limitations on the biopsy forceps, as it must fit through an ureteroscope. As a result reliance has been on grading of the cellular atypia rather than the clinical T stage of the disease. Indeed, studies have shown direct correlation with tumor grade and degree of invasion on final pathologic analysis although under-grading occurs up to 25 % of the time [2]. Anatomically, there are relatively thinner layers of tissue between the surface of then urothelium to the surrounding adventitia for the development of locally advanced disease in the kidney and ureter, as compared to the urothelium in the bladder. This causes a higher risk of each lesion to progress. Furthermore, as opposed to cases of bladder cancer with superficial high-grade disease, where one has the options to treat with intravesical washings of chemotherapies and immunotherapies via a catheter, in UTUC it is necessary to use sedation or anesthesia to cystoscopically place a ureteral catheter or to percutaneously place a nephrostomy tube. Despite the invasive nature of applying the treatment, and limitations due to natural peristalsis, utilization of various methods of renal pelvic and ureteral irrigation with BCG is an option for select patients with CIS of the upper tracts [3, 4]. As organ-sparing options with intraluminal chemotherapies are limited, and the relatively thinner barriers for tumor progression compared to lower tract urothelial carcinoma (LTUC); the gold standard for treatment of UTUC continues to be radical nephroureterectomy (RNU). In this chapter we will discuss the surgical management of UTUC as well as innovations in the surgical approach and current controversies.

5.2 Indications for RNU or Partial Ureterectomy

Conservative management of UTUC via endoscopic laser ablation, or intraluminal chemotherapy, is indicated in cases of low-grade/low-volume tumor burden disease. However, in many cases, even when the tumor is low-grade, the volume or bulk of disease can overwhelm the ability to of intraluminal chemotherapy or laser ablation to manage, surgical management is indicated. Furthermore, if the tumor is high-grade surgical management is indicated [5]. This is true even if there are suspicious lymph nodes on imaging as well [6]. There is little evidence to support performing a RNU in the presence of proven metastatic lymph nodes, as survival is poor, however, after treatment response with neoadjuvant chemotherapy, it can be considered [6]. In instances of proven or metastatic disease chemotherapy and radiation should be encouraged. However, in clinically localized disease, the gold standard of surgical management consists of removal of the affected kidney and ureter en bloc with a bladder cuff around the ipsilateral ureteral orifice.

It is important to be cognizant that as a result of the loss of 50 % of a patient’s nephrons from the RNU, the choice of chemotherapeutics and need for substitution of treatments can decrease survival and limit the efficacy of chemotherapies. Radical removal of nephrons via nephrectomy has been proven to decrease overall survival in renal cell carcinoma [7]. In addition, renal failure as a result of renal surgery or otherwise, is associated with accelerated atherosclerosis and concomitant increase in cardiovascular morbidity [8, 9]. As a result, there is renewed interest in nephron-sparing surgical treatments for UTUC such as partial ureterectomy [10]. In addition, the development of minimally invasive surgical techniques of laparoscopy and robotic-assisted laparoscopic surgery have both made significant inroads in the treatment algorithm for UTUC and will be discussed as well in this chapter.

5.3 Open Radical Nephroureterectomy and Treatment of the Bladder Cuff

Open RNU is the radical removal of the kidney, ureter, and bladder cuff and is the gold standard for treatment for clinically localized high grade UTUC [11]. The decision tree of the type of procedure begins with approach of open, laparoscopic or robotic-assisted laparoscopic. In this segment, we will describe the outcomes and considerations of the open approach. The next decision point is the application of a lymphadenectomy and/or extent of it. The application and utility of lymphadenectomy will be described in a separate section below. Finally, we will discuss here the various approaches to the removal of the bladder cuff around the insertion of the ureter into the bladder urothelium.

There are a number of incisions that can be made for a RNU can. One can perform a two-incision technique, whereupon the kidney is dissected free from the vascular hilum and the upper ureter via a flank incision and a subsequent Gibson incision for freeing the rest of the ureter up to the bladder enabling the completion of the entire procedure in an extraperitoneal fashion. Alternatively, one can perform the same procedure completely from a pubic to sternum midline incision violating the peritoneum, but allowing for fantastic exposure and access to all major vessels after incising along the white line of Toldt and reflecting the colon (and duodenum if on the right side). Choice of incision tends to be surgeon preference and comfort with considerations for the particular surgical history and tumor anatomy of the individual patient.

Conversely, the decision of the approach to the bladder cuff does have significant oncological implications. In a retrospective Canadian study pooling results from 10 institutions, 5-year survival for RNU has been shown to be 46–30 % varying primarily with the approach to the bladder cuff removed with the specimen [12]. There are three approaches that can be taken to the distal ureter. It can be removed intravesically whereupon an extraperitoneal open incision is made in the anterior bladder after the kidney and ureter have been dissected free and the ureteral orifice (UO) is incised from inside the bladder until free altogether. The intravesical resection of the bladder cuff was associated with the best disease-free survival of 46.3 % at 5 years. There is also the extravesical approach whereupon the ureter is dissected free through the detrusor until completely free, this approach was found to have a disease-free survival (DFS) of 38.5 % at 5 years. Finally, there is the endoscopic approach, whereupon after freeing the kidney and ureter up to the detrusor the ureteral orifice is then incised with a Collins knife or an electrocautery knife or resected with a loop and then closed from within the peritoneal cavity. The distal ureter has been described as closed using an endoloop to prevent tumor seeding. This approach was found to have an 11.9 % disease-free survival at 5 years. This data is consistent with older literature using the SEER database and other retrospective reviews, as there have been no randomized studies performed to date. The evidence seems to support intravesical or extravesical approaches to the bladder cuff in open RNU [13–16].

Since up to 34 % of patients can recur after RNU with tumors in the bladder, studies have analyzed perioperative treatment of the bladder with chemotherapeutic washing at time of RNU [17]. The OMDIT-C British trial published in 2011 of patients with UTUC randomized to instillation of one dose of Mitomycin C for prevention of bladder tumor recurrence after RNU, found a decreased incidence of bladder recurrence in analysis by treatment of 16 % (compared to 27 %) at 1 year follow up [18]. While it is not by any means standard of care, it is an option to strongly consider for tumor recurrences in the bladder after RNU.

5.4 Laparoscopic Nephroureterectomy

The indications for performance of a laparoscopic RNU (LRNU) are the same as that for open RNU, however, the patient must be able to tolerate 15 mmHg pneumoperitoneum from a cardiopulmonary anesthesia stand-point. The benefits of minimally invasive surgery are much the same here in terms of decreased blood loss, cosmesis of smaller incisions and quicker convalescence, much as they are in comparison of open and laparoscopic radical nephrectomy. The positioning and port placement for LRNU can be the same as that for a laparoscopic radical nephrectomy with or without a hand-port or an additional 12-mm port in either the right or left lower quadrant to assist in the dissection of the distal ureter. There are various iterations of positioning and port placement for laparoscopic radical nephrectomy. We place the patient in a modified flank position with a 10-pound sand bag underneath the ipsilateral flank and the patient secured to the bed with straps loosely over the legs (which are elevated on pillows) and tightly across the hips and chest. For trocar placement, we prefer the use of a medial 12 mm camera port placement approximately 2 cm superior to the umbilicus and 2 cm lateral to midline or just lateral to rectus abdominus with two working ports in the mid clavicular line approximately 12 cm apart centered on the camera port with the superior port being a 5 mm and the inferior port being a 12 mm. An additional 5 mm port may be placed for liver retraction as well. A hand port can either be placed in the midline infra-umbilically or via an ipsilateral Gibson incision. If intention is for a purely laparoscopic approach, after the kidney and the ureter is dissected down past the superior vesicle artery, the bladder can then be opened at the dome and the ureteral orifice is ligated and then dissected free with a bladder cuff intravesically (or extravesically) until completely freed. The specimen is always removed in a bag to prevent tumor seeding [19]. Alternatively, some may prefer to combine laparoscopic dissection of the kidney and bladder with an extraperitoneal/intravesical bladder cuff to reduce the theoretically risk of peritoneal tumor seeding.

Outcomes from LRNU with and without hand-assistance have been well documented. Berger published in 2008 outcomes for LRNU including up to 7 years of median follow up with 50 % overall survival (OAS) 72 % cancer-specific survival (CSS) and 36 % recurrence-free survival (RFS) [20]. This data is consistent with other long-term data published previously in open and laparoscopic surgeries [21, 22]. However, in regards to higher stage disease, outcomes data comparing open to laparoscopic procedures remain conflicting [14, 15, 23–25]. At this point in time it is safe to declare that LRNU has similar outcomes to the open approach in lower stage disease, and this may be true for locally advanced as well, however, further study is necessary to elucidate that point.

5.5 Robotic Nephroureterectomy

Indications for robotic-assisted laparoscopic RNU (RALNU) are the same as for LRNU. The trifecta combination of limited work-hours on residents and the time intensity of laparoscopic training with increased mobility of the DaVinci Xi Robotic surgical platform has led to our expectation that the application of robotic technology to nephroureterectomy will increase in popularity. We expect this confluence of factors to cause a relative increase in the numbers of procedures performed due to both surgeon skill set as well as by patient demand in the near future. In fact, even prior to the development of the DaVinci Xi platform, using the older DaVinci systems, RALNU had already been described first by Nanigian and then altered by Park to alleviate the need for repositioning for the bladder cuff [26]. The benefits of robotic surgery over laparoscopic surgery for UTUC remain primarily in the 7° of freedom, 90° of articulation with motion scaling and tremor reduction that the robotic system offers and relatively lower threshold of training for surgeons to obtain for competency. Port placement has yet to be standardized, and is likely to change as the DaVinci Xi system becomes more popular as the camera and arms can be interchangeably placed through ports, but for the Si and earlier models, the ports are arranged the same as for a Nephrectomy with an extra infraumbilical midline 12 mm port for the 8 mm robotic arm trocar to get placed into for the bladder cuff.

Outcomes data is still young for outcomes of RALNU, however, perioperative outcomes appear to be on par with outcomes of LRNU [27, 28]. A retrospective review of 11 patients underwent RALNU and after a mean follow-up of 30 months, only 1 patient had a recurrence for a RFS of 91 % at 2.5 years [29]. While the very limited available evidence is encouraging, studies with significantly greater numbers and longer follow up must be performed before any conclusions can be made about this very exciting area of innovation.

5.6 Partial Ureterectomy

As a result of the earlier mentioned concern about loss of nephrons leading to a higher risk of mortality from cardiovascular complications, there has been increased pressure to apply more renal-preserving treatment approaches with increased volumes of lower-grade disease treated with intraluminal therapies as well as endoscopic laser ablations. In addition, more interest in distal or partial ureterectomy has occurred. Indications for partial or distal ureterectomy include functionally solitary or solitary kidney, and bilateral disease. In cases where the tumor is localized to a single segment, especially the distal segment. Segmental ureterectomy can also be considered when there is a significant likelihood of higher T-stage disease and adjuvant or salvage chemotherapy is likely to require nephron-sparing treatment. The procedure can be performed open, laparoscopic or robotically [30, 31]. Depending on the area excised, the drainage can be reconstructed with a Boari Flap and or a Psoas hitch, an end to end spatulated ureteroureterostomy, a ureteroneocystostomy, appendiceal substitution, autotransplantation as well as others [32–34].

Outcomes of a study reviewing SEER data of 569 patients who underwent partial ureterectomy compared to 1,222 patients who underwent RNU with a bladder cuff showed no significant differences in the 77.6 % 5-year CSS in multivariate analysis by surgical modality [35]. These results are consistent when compared to multinstitutional data on RNU, as well as in more recent comparisons of partial ureterectomy [36–38]. The current available literature all consists of retrospective reviews again likely including a patient selection bias, indicating that in select cases this can be an excellent treatment option.

5.7 Lymphadenectomy During RNU

The evaluation of regional and distant lymph nodes (LNs) is imperative in the staging of cancers. This is often performed clinically pre-operatively with radiographic imaging. However, when performing a RNU or segmental ureterectomy for UTUC, the evaluation of the evaluation of the LNs is critical as it is estimated that 20–40 % will develop LN involvement due to the relatively thin walls and variable copious lymphatic drainage [37, 39–42]. It has been well documented that in patients with muscle invasive urothelial cell carcinoma of the bladder performance of a lympadenectomy (LAD) leads to identification of more positive nodes in patients with positive nodes. While it is unclear if there is any survival benefit, but rather just a “Roy Rogers Phenomenon,” where the high risk patients do worse as their positive LNs are identified and up-staged, and the LN negative patients are down-staged. This question is currently being answered by a Phase III randomized clinical trial for bladder cancer [43].

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