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The effect of surgical approach on performance of lymphadenectomy and perioperative morbidity for radical nephroureterectomy
Urologic Oncology: Seminars and Original Investigations 34 (2016) 121.e15–121.e21
Original article
The effect of surgical approach on performance of lymphadenectomy and perioperative morbidity for radical nephroureterectomy Shane M. Pearce, M.D.*, Joseph J. Pariser, M.D., Sanjay G. Patel, M.D., Gary D. Steinberg, M.D., Arieh L. Shalhav, M.D., Norm D. Smith, M.D. Section of Urology, Department of Surgery, University of Chicago, Chicago, IL Received 2 July 2015; received in revised form 13 September 2015; accepted 16 September 2015
Abstract Objectives: To examine the effect of surgical approach on regional lymphadenectomy (LND) performance and inpatient complications for radical nephroureterectomy (NU) using a national administrative database. Methods: The National Inpatient Sample (2009–2012) was used to identify patients who underwent NU for urothelial carcinoma. Cohorts were stratified by performance of LND. Covariates included patient demographics, comorbidity, hospital characteristics, hospital volume, performance of LND, surgical approach (open [ONU], laparoscopic [LNU], or robotic [RNU]), and complications. Multivariable logistic regression was used to identify factors associated with LND performance and complications. Results: A weighted population of 14,059 (85%) without LND and 2,560 (15%) with LND was identified. LND was more common in RNU (27%) compared with ONU (15%) and LNU (10%) (P o 0.01). On multivariable analysis, when compared with ONU, RNU was associated with increased odds of LND performance (odds ratio [OR] ¼ 1.9, 95% CI: [1.3–2.8]; P ¼ 0.001), whereas LNU was associated with decreased odds of LND performance (OR ¼ 0.6, 95% CI: [0.4–0.8]; P ¼ 0.004). Multivariable analysis of risk factors for complications demonstrated lower odds of complications with RNU (OR ¼ 0.6, 95% CI: [0.4–0.8]; P ¼ 0.001), whereas performance of LND increased the risk of complications (OR ¼ 1.3, 95% CI: [1.001–1.7]; P ¼ 0.049). Conclusions: When compared with ONU, RNU increased the odds of LND performance and had a lower inpatient complication rate, whereas LNU reduced the odds of LND performance and had no significant effect on inpatient complication rates. Performance of LND was independently associated with higher inpatient complication rates. r 2016 Elsevier Inc. All rights reserved.
Keywords: Urothelial carcinoma; Upper urinary tract; Lymph node excision; Complications; Treatment outcome; Patterns of care
1. Introduction Upper tract urothelial carcinoma (UTUC) is a relatively rare entity, with most of the tumors arising from the renal pelvis. As only 5% of urothelial neoplasms occur in the kidneys and the ureters, patterns of care and optimal management of UTUC are far less studied when compared with urothelial carcinoma of the bladder [1]. Multicenter studies of radical nephroureterectomy (NU) with regional lymph node dissection (LND) for UTUC indicate a 25% overall incidence of node-positive disease, with rates ranging from 6% to 35% depending on tumor stage and Corresponding author. Tel.: þ1-608-234-7401; fax: þ1-773-702-1001. E-mail address: [email protected] (S.M. Pearce). *
http://dx.doi.org/10.1016/j.urolonc.2015.09.008 1078-1439/r 2016 Elsevier Inc. All rights reserved.
grade [2,3]. Based on extrapolation of data from patients undergoing radical cystectomy for bladder cancer, it is logical that proper diagnosis and management of LN metastasis in UTUC could improve patient outcomes. However, the practice of LND during NU for invasive UTUC has not been consistently adopted by urologists, likely because of a lack of prospective evidence supporting a cancer-specific survival benefit for LND and incomplete understanding of the optimal LND template [4]. Over the last decade, interest in minimally invasive surgical techniques for UTUC has grown. Laparoscopic (LNU), and more recently robot-assisted laparoscopic (RNU), techniques have been described as alternatives to the traditional open approach (ONU) [5]. There are 2 metaanalyses comparing LNU and ONU have supported
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oncologic equivalence; however, definitive conclusions cannot be made because most studies included in analysis were limited by short follow-up (o5 y) [6,7]. Both LNU and RNU appear to improve postoperative convalescence when compared with ONU [8,9]. A recent matched analysis compared 22 patients who underwent RNU and 22 patients who underwent LNU at a single institution, finding that patients undergoing RNU were more likely to undergo an LND and, when performed, median LN yields were higher for the robotic approach [10]. National trends in adoption of LNU and RNU in comparison with ONU and the effect of the various approaches on practice patterns for performance of LND have not been examined. Using the National Inpatient Sample, we evaluated the effect of surgical approach on LND performance and complication rates.
2. Materials and methods The U.S. Healthcare Cost and Utilization Project (HCUP) Nationwide Inpatient Sample (NIS) database is the largest all-payer inpatient database in the United States, representing the inpatient experience of a 20% stratified probability sample of American nonmilitary, nonfederal hospitals [11]. The NIS was queried for patients who underwent NU for a renal pelvis or ureteral neoplasm between 2009 and 2012. A survey-weighted design allowed for population-level estimates of national trends and incidence rates. Institutional review board approval was not required, as the NIS does not include identifiable patient information. All patients with a primary diagnosis of renal pelvic or ureteral neoplasm who underwent NU were identified using International Classification of Disease Ninth revision (ICD-9) diagnostic and procedure codes (Supplementary Table S1). Patients with missing age (n ¼ 1), younger than 18 years (n ¼ 3), or with metastatic disease (n ¼ 13) were excluded. ICD-9 procedure codes for performance of regional LND and surgical approach (ONU, LNU, and RNU) allowed construction of cohorts. Demographic information included age, sex, race, and primary insurance type. Equally sized age tertiles were generated for intergroup comparison and logistic regression. Hospital setting (urban or rural), teaching status, and hospital volume were examined. Annual hospital NU volume (any approach) was determined and divided into tertiles (low: 1–2 cases/y, intermediate: 3–7 cases/y, and high: Z8 cases/y). Comorbidity was calculated using the Elixhauser method, which has been shown to compare favorably to other well-validated comorbidity scores [12]. The Elixhauser comorbidity score was also divided into tertiles. Outcomes assessed included length of stay, inpatient mortality, and complications, as described previously [13]. Hemorrhagic complications included the receipt of blood transfusion during the inpatient stay. Prolonged length of stay of Z7 days represented the 75th percentile
100%
6.5 18.0
75%
Proportion of 50% NU by Approach
12.2
13.6
17.3
16.3
22.0 12.3 RNU LNU
75.5
70.5
70.1
65.8
2009
2010
2011
2012
ONU
25%
0%
Fig. Surgical approach for radical nephroureterectomy from 2009 to 2012. Over time, there was an increase in the proportion of cases performed with robot assistance, with reductions in both laparoscopic and open cases (P o 0.001).
of the entire study cohort. No specific staging information is available in the NIS. Stata 13.1 (StataCorp, College Station, TX) was used for statistical analyses with survey weighting. The chi-square test with Rao-Scott correction was used for comparison of categorical variables [14]. Multivariate logistic regression was performed to identify patient, hospital, and surgical factors associated with performance of LND and to identify risk factors for any postoperative inpatient complications. A 2-sided P o 0.05 was considered significant for all statistical tests. 3. Results A total of 16,619 patients were included for analysis. The use of ONU, LNU, and RNU approaches evolved over time from 2009 to 2012, as shown in the Fig. Specifically, the use of RNU increased (6% of all cases in 2009 to 22% in 2012), whereas the use of ONU (76% to 66%) and LNU (18% to 12%) declined (P ¼ 0.001). Baseline patient demographics and hospital characteristics by performance of LND are shown in Table 1. The median age of the entire cohort was 72 years (interquartile range [IQR]: 64–80). Patients 67 years and younger were more likely to undergo LND (18%, n ¼ 998) when compared with patients 78 years and older (12%, n ¼ 620; P o 0.001). Hospital characteristics were significantly different between the groups, with LND dissection more common in teaching hospitals (19% vs. 8%, P o 0.001), intermediate-volume hospitals (16%), and high-volume hospitals (20% vs. 11% for low volume, P o 0.001). Patients undergoing RNU were more likely to undergo LND (27%) when compared with ONU (15%) and LNU (10%, P o 0.001). There were no trends in performance of LND over time (P ¼ 0.4). Inpatient outcomes by performance of LND are shown in Table 2. On univariate analysis, there was no difference in the rate of intraoperative complications (P ¼ 0.6) or
S.M. Pearce et al. / Urologic Oncology: Seminars and Original Investigations 34 (2016) 121.e15–121.e21 Table 1 Baseline characteristics of patients undergoing nephroureterectomy by performance of LND Characteristic, N (%)
No LND (n ¼ 14,059)
LND performed (n ¼ 2,560)
All (n ¼ 16,619)
14,059 (85)
2,560 (15)
Age tertiles r67 68–77 Z78
4,611 (82) 4,670 (83) 4,748 (88)
998 (18) 942 (17) 620 (12)
Sex Male Female
8,390 (84) 5,665 (86)
1,631 (16) 929 (14)
Race White Black Hispanic Other Unknown
0.126
0.364 10,918 518 677 660 1,286
(85) (88) (87) (84) (80)
1,941 68 102 126 323
(15) (12) (13) (16) (20)
Elixhauser comorbidity r1 2–3 Z4
5,477 (84) 5,881 (85) 2,700 (85)
1,024 (16) 1,055 (15) 482 (15)
Primary insurance Medicare Medicaid Private Other
9,985 378 3,198 479
1,607 127 721 100
Hospital location Urban Rural
9,796 (85) 580 (90)
1,677 (15) 62 (10)
Hospital teaching status Teaching Nonteaching
5,608 (81) 4,768 (92)
1,347 (19) 392 (8)
Hospital volume Low Intermediate High
5,664 (89) 3,876 (84) 4,520 (80)
665 (11) 758 (16) 1,137 (20)
Surgical approach Open Laparoscopic Robotic
9,998 (85) 2,386 (90) 1,675 (73)
1,697 (15) 252 (10) 611 (27)
Year 2009 2010 2011 2012
3,385 3,307 3,822 3,545
Table 2 Perioperative outcomes by performance of LND Characteristic, N (%)
P value
o0.001
0.918
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Intraoperative complication Yes No
No LND LND performed P value (n ¼ 14,059) (n ¼ 2,560) 0.623 529 (4) 13,530 (96)
111 (4) 2,449 (96)
Any postoperative complication Yes 3,825 (27) No 10,235 (73)
748 (29) 1,812 (71)
Complications by type Hemorrhagic Gastrointestinal Cardiac Urinary Othera
2,780 898 287 251 281
Length of stay, median (IQR) Prolonged LOS (Z7 d) Inpatient mortality
5 (3–7) 3,841 (27) 182 (1)
(20) (6) (2) (2) (2)
0.414
570 137 56 53 40
(22) (5) (2) (2) (2)
5 (3–7) 820 (32) 30 (1)
0.303 0.437 0.852 0.705 0.557 0.064 0.073 0.842
LOS ¼ length of stay. To comply with NIS guidelines preventing report of cell numbers r10, infection, vascular, respiratory, seroma, wound, and other complications were reported as other. a
0.006 (86) (75) (82) (83)
(14) (25) (18) (17) 0.123
o0.001
o0.001
o0.001
0.376 (86) (84) (87) (82)
554 652 574 780
(14) (16) (13) (18)
Cells not totaling n ¼ 14,059 for No LND or n ¼ 2,560 for LND performed represent missing data from the National Inpatient Sample.
postoperative complications (P ¼ 0.4) between LND cohorts. Patients undergoing LND experienced a prolonged length of stay in 32% of cases vs. 27% when no LND was performed, P ¼ 0.073. Table 3 displays perioperative outcomes by surgical approach. There was no significant difference in the
rate of intraoperative complications by surgical approach (P ¼ 0.1). The rate of any postoperative complication was lowest for RNU (19%, n ¼ 426) and highest for ONU (30%, n ¼ 3,529 or, P o 0.001). Significant differences were seen in the rate of gastrointestinal (7%, 8%, and 3% for ONU, LNU, and RNU, respectively, P ¼ 0.008) and hemorrhagic complications (22%, 15%, and 15% for ONU, LNU, and RNU, respectively, P ¼ 0.003). A prolonged length of stay Z7 days was most likely after ONU (32%, n ¼ 3,736) when compared with LNU (22%, n ¼ 567) and RNU (16%, n ¼ 357; P o 0.001). The results of a multivariate logistic regression for predictors of LND performance during NU are shown in Table 4. Robotic approach independently increased the odds of LND (odds ratio [OR] ¼ 1.9, 95% CI: [1.3–1.8]; P ¼ 0.001), whereas laparoscopic approach decreased the odds of LND (OR ¼ 0.6, 95% CI: [0.4–0.8]; P ¼ 0.004). Other factors associated with performance of LND included Elixhauser score Z4 (OR ¼ 1.6, 95% CI: [1.1–2.3]; P ¼ 0.013), teaching hospital (OR ¼ 2.4, 95% CI: [1.6–3.7]; P o 0.001), intermediate-volume hospital (OR ¼ 1.5, 95% CI: [1.2–2.0]; P ¼ 0.003), and high-volume hospital (OR ¼ 2.4, 95% CI: [1.5–3.9]; P ¼ 0.001). Table 4 also displays multivariate logistic regression for risk factors for any postoperative complication. Robotic approach reduced the risk of complications (OR ¼ 0.6, 95% CI: [0.4–0.8]; P ¼ 0.001), whereas performance of LND increased the risk (OR ¼ 1.3, 95% CI: [1.001–1.7]; P ¼ 0.049). Other factors associated with complications included 78 years and older (OR ¼ 1.6, 95% CI: [1.2–2.1]; P ¼ 0.002), black race (OR ¼ 1.9, 95% CI: [1.2–3.1];
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Table 3 Perioperative outcomes by surgical approach Outcome, N (%)
ONU (n ¼ 11,698)
LNU (n ¼ 2,638)
RNU (n ¼ 2,286)
Intraoperative complication Yes No
479 (4) 11,220 (96)
117 (4) 2,521 (96)
44 (2) 2,243 (98)
Any postoperative complication Yes No
3,529 (30) 8,170 (70)
618 (23) 2,020 (77)
426 (19) 1,860 (81)
Complications by type Hemorrhagic Gastrointestinal Cardiac Urinary Othera
2,619 766 258 248 268
Length of stay, median (IQR) Prolonged LOS (Z7 d)
5 (4–7) 3,736 (32)
P value 0.121
o0.001
(22) (7) (2) (2) (2)
397 211 52 32 39
(15) (8) (2) (1) (1)
4 (3–6) 567 (22)
335 59 33 25 14
(15) (3) (1) (1) (1)
4 (3–5) 357 (16)
0.003 0.008 0.653 0.225 0.072 o0.001 o0.001
LOS ¼ length of stay. To comply with NIS guidelines preventing report of cell numbers r10, infection, vascular, respiratory, seroma, wound, and other complications were reported as other. a
P ¼ 0.007), other race (OR ¼ 2.0, 95% CI: [1.2–3.2]; P ¼ 0.006), Elixhauser comorbidity score 2 to 3 (OR ¼ 1.7, 95% CI: [1.4–2.1]; P o 0.001), comorbidity score Z4 (OR ¼ 3.3, 95% CI: [2.5–4.3]; P o 0.001), and private insurance (OR ¼ 0.7, 95% CI: [0.5–0.9]; P ¼ 0.010).
4. Comment Despite retrospective evidence indicating that a thorough regional LND can provide improved disease staging and potential therapeutic benefit in patients with limited nodal disease, the concept of meticulous LND for UTUC during NU has not been consistently adopted by urologists around the world [2,15]. The reasons for this are unclear, but single-center series have shown that surgeon-specific factors and surgical approach may independently predict performance of LND [10,16]. With the diffusion of laparoscopic and robotic techniques into urology, minimally invasive techniques have been increasingly used for NU [9]. Our goal was to examine the effect of hospital characteristics and surgical approach (ONU, LNU, and RNU) on performance of LND in a contemporary, national cohort of patients treated for UTUC. We also examined the effect of LND and surgical approach on in-hospital morbidity and mortality. The robotic approach for NU is being increasingly used in place of laparoscopic and open approaches. As of 2012, most of the NUs in the United States were still performed with an open approach (66%); however, robot assistance was used in 22% of cases compared with pure laparoscopic approach in just 12% of cases. This is consistent with the adoption of robotic surgery as a minimally invasive treatment alternative for many urologic malignancies. In 2009, robot-assisted prostatectomy supplanted the traditional open
approach as the most common technique for radical prostatectomy in the United States [17] with similar trends observed for partial nephrectomy [18]. Additionally, robot assistance is being increasingly used for radical cystectomy, as evidenced by use in 13% of cases from 2009 to 2011 in a national cohort [19]. In the current study's population-based cohort, LND was performed in 15% of cases overall. This is relatively lower that the LND rate of 36% to 60% in 2 recent multicenter case series from academic centers in the United States and Europe [20,21]. The rate of positive nodal disease among patients undergoing LND in these 2 series was 18% to 20%. Most retrospective series have highlighted the need for LND, particularly in patients with pT2–4 disease [4]. Furthermore, because preoperative imaging studies, urine cytology, and biopsy findings have limited reliability in disease staging and identification of LN involvement, it can be argued that LND should be performed in all patients treated with NU where accurate disease staging is desired [16]. Yet, controversy persists because of the lack of standardized LND templates and limited, retrospective data supporting the therapeutic role of LND in UTUC [4]. Clearly, patterns of LND vary depending on the practice setting, and better preoperative diagnostics are needed if selective LND is to be used effectively. We demonstrated that the robotic approach independently increased the odds of LND performance nearly 2-fold when compared with the open approach, whereas a laparoscopic approach reduced the odds of LND performance. In a study of 22 matched pairs (matched for pathologic stage and age), Ambani et al. [10] reported a discrepancy in LND performance between RNU and LNU, with LND performed in 59% of RNU compared with 27% of LNU. As this study was relatively small and limited to 3 surgeons at a single
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Table 4 Multivariate logistic regression for predictors of lymph node dissection performance and postoperative complications Factors
Outcome Lymph node dissection
Any complication
OR
95% CI
P value
OR
95% CI
P value
Surgical approach Open Laparoscopic Robotic
REF 0.55 1.88
– 0.37–0.83 1.28–2.76
– 0.004 0.001
REF 0.78 0.55
– 0.59–1.03 0.40–0.77
– 0.081 0.001
Lymph node dissection Not performed Performed
N/A N/A
N/A N/A
N/A N/A
REF 1.31
– 1.001–1.72
– 0.049
Age r67 68–77 Z78
REF 1.34 0.77
– 0.91–1.98 0.50–1.17
– 0.141 0.221
REF 1.25 1.59
– 0.92–1.70 1.18–2.13
– 0.155 0.002
Sex Male Female
REF 0.85
– 0.66–1.10
– 0.217
REF 1.19
– 0.97–1.46
– 0.090
Race White Black Hispanic Other Unknown
REF 0.54 0.69 0.81 1.24
– 0.24–1.22 0.34–1.44 0.38–1.72 0.77–1.99
– 0.138 0.329 0.586 0.369
REF 1.93 1.20 1.96 1.20
– 1.20–3.10 0.74–1.94 1.21–3.16 0.87–1.65
– 0.007 0.467 0.006 0.270
Elixhauser comorbidity r1 2–3 Z4
REF 1.09 1.61
– 0.83–1.42 1.10–2.34
– 0.544 0.013
REF 1.73 3.30
– 1.41–2.14 2.51–4.32
– o0.001 o0.001
Primary insurance Medicare Medicaid Private Other
REF 1.89 1.31 1.38
– 0.93–3.83 0.88–1.96 0.61–3.11
– 0.080 0.186 0.442
REF 0.72 0.65 0.92
– 0.35–1.48 0.47–0.90 0.51–1.67
– 0.372 0.010 0.790
Hospital teaching status Nonteaching Teaching
REF 2.44
– 1.60–3.71
– o0.001
REF 1.04
– 0.83–1.32
– 0.723
Hospital volume Low Intermediate High
REF 1.51 2.38
– 1.15–1.97 1.45–3.90
– 0.003 0.001
REF 1.06 0.95
– 0.85–1.33 0.67–1.35
– 0.614 0.789
N/A ¼ not applicable; REF ¼ reference.
center, this finding was attributed to surgeon practice pattern. The feasibility of performing LND during laparoscopy has been demonstrated previously [22], but LND remains somewhat underused during LNU. Capitanio et al. found that LND was performed in 42% and 24% of patients after ONU and LNU, respectively, in a large multicenter study spanning 3 continents. The findings in our study may highlight variation in surgeon practice patterns, or it could represent the manifestation of an inherent difference in the capability to perform LND between the various surgical techniques. Dissemination of minimally invasive surgical techniques and particularly robot-assistance technology has
had an evolving effect on the training, case experience, and comfort level of surgeons with various surgical approaches. As a surgeon's experience with robotic technology increases, his or her comfort, willingness, and ability to perform an LND may also improve. Robot assistance has been shown to aid performance of other complex urologic procedures and may facilitate LND and increase its use as a component of NU. The population-based nature of our study, with adjustment for hospital teaching status, volume, and location, may lend support to this latter hypothesis. However, definitive conclusions regarding the cause for the association between a surgical approach and LND
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performance cannot be made without detailed patient staging information and surgeon-specific factors such as subspecialization and fellowship training. Increased hospital volume was independently associated with performance of LND. Although this relationship has not been studied in patients undergoing NU for UTUC, Prasad et al. [23] demonstrated that high-volume surgeons were more likely to perform pelvic LND during radical prostatectomy when controlling for patient comorbidity and tumor characteristics. Lower-volume surgeons, presumably in lower-volume hospitals, may opt to forego LND because of concern for increased complication rates or longer operative times. We also found that LND was more likely to be performed at teaching hospitals and in patients with comorbidities. Referral bias could explain some of these results; with highly comorbid patients more likely to be referred to either tertiary care centers or experienced surgeons, who may be more likely to perform LND as part of NU. It is also possible that patients at increased risk for nodal involvement based on preoperative staging are preferentially referred to higher-volume facilities and teaching hospitals. Multivariate analysis controlling for patient and hospital characteristics revealed that patients undergoing LND were 30% more likely to experience any postoperative complication. Although the unadjusted rate of intraoperative or postoperative complications did not vary based on performance of LND, there was a marginally higher rate of hemorrhagic complications, which included receipt of blood transfusion, after LND performance (22% vs. 20%). Lymph node excision near the great vessels may put patients at an increased risk for postoperative complications, particularly related to bleeding; however, this was not statistically significant. In our data set, RNU was protective for postoperative complications compared with ONU, although LNU had no significant effect on postoperative complications. Specifically, we observed lower rates of hemorrhagic and gastrointestinal complications with RNU. Both LNU and RNU were also associated with a reduced incidence of prolonged hospitalization when compared with ONU. A previous NIS study found that LNU independently reduced the risk of intraoperative complications, blood transfusions, and prolonged length of stay when compared with ONU, but it did not reduce the odds of postoperative complications overall [8]. However, that study did not examine the effect of robot assistance. We also confirmed several known risk factors for postoperative complications including increased age, race (black or other), and comorbidity. Our study has multiple important strengths. To our knowledge, this is the first study to report trends in use of the 3 major surgical approaches for NU (ONU, LNU, and RNU) in a contemporary national cohort. Using the NIS, we were able to provide the first detailed analysis of national practice patterns in performance of LND during NU. We also provided important benchmarks related to morbidity,
length of stay, and mortality after NU while identifying risk factors for complications. This study has limitations, which must be noted. The NIS does not provide detailed information regarding tumor characteristics (size, grade, and location), preoperative staging, and other surgical details such as bladder-cuff management, extent of LND, and node yield. These variables likely influence selection of surgical approach and subsequent perioperative morbidity. It is certainly possible that more complex cases are preferentially performed in an open fashion, which would create a selection bias and explain some of the observed differences in complication rates between approaches. However, this does not fully explain the differential rate of LND performance. It is also unknown which cases of RNU and LNU were converted to open procedures. This missing information could lead to overestimation of the use of RNU and LNU and subsequent alteration of LND performance and complication rates. NIS data are limited to the inpatient hospitalization, and therefore, analysis of readmission rates, late complications, and mortality after discharge is not possible. Because of this, morbidity and mortality rates may have been underestimated. The NIS also does not effectively capture individual surgeon volume. This may affect the selection of surgical approach, performance of LND, and complication rates. All retrospective studies from large, claims-based data sets, such as the NIS, are limited by coding errors, potential underreporting of complications, and unmeasured confounding variables. 5. Conclusions LND is performed in a minority of NU cases, and its use has been stable over time. Use of robot assistance during NU in the United States is increasing relative to laparoscopic and open approaches. RNU is associated with an increased likelihood of LND performance and a reduced risk of postoperative complications. Other factors associated with LND performance include hospital teaching status and increased hospital volume. LND increases the risk of postoperative complications independent of surgical approach in this data set. Appendix A. Supplementary Information Supplementary data associated with this article can be found in the online version at http://dx.doi.org/10.1016/ j.urolonc.2015.09.008.
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[13] Joudi FN, Allareddy V, Kane CJ, Konety BR. Analysis of complications following partial and total nephrectomy for renal cancer in a population based sample. J Urol 2007;177:1709–14. [14] Rao JNK, Scott AJ. On chi-squared tests for multiway contingency tables with cell proportions estimated from survey data. Ann Stat 1984;12:46–60. [15] Brausi MA, Gavioli M, De Luca G, Verrini G, Peracchia G, Simonini G, et al. Retroperitoneal lymph node dissection (RPLD) in conjunction with nephroureterectomy in the treatment of infiltrative transitional cell carcinoma (TCC) of the upper urinary tract: impact on survival. Eur Urol. 2007;52:1414–20. [16] Secin FP, Koppie TM, Salamanca JIM, Bokhari S, Raj GV, Olgac S, et al. Evaluation of regional lymph node dissection in patients with upper urinary tract urothelial cancer. Int J Urol 2007;14:26–32. [17] Sammon JD, Karakiewicz PI, Sun M, Sukumar S, Ravi P, Ghani KR, et al. Robot-assisted versus open radical prostatectomy: the differential effect of regionalization, procedure volume and operative approach. J Urol 2013;189:1289–94. [18] Sammon JD, Karakiewicz PI, Sun M, Ravi P, Ghani KR, Jeong W, et al. Robot-assisted vs. laparoscopic partial nephrectomy: utilization rates and perioperative outcomes. Int Braz J Urol 2013;39:377–86. [19] Monn MF, Cary KC, Kaimakliotis HZ, Flack CK, Koch MO. National trends in the utilization of robotic-assisted radical cystectomy: an analysis using the Nationwide Inpatient Sample. Urol Oncol 2014;32:785–90. [20] Ouzzane A, Colin P, Ghoneim TP, Zerbib M, De La Taille A, Audenet F, et al. The impact of lymph node status and features on oncological outcomes in urothelial carcinoma of the upper urinary tract (UTUC) treated by nephroureterectomy. World J Urol 2013;31:189–97. [21] Raman JD, Lin YK, Kaag M, Atkinson T, Crispen P, Wille M, et al. High rates of advanced disease, complications, and decline of renal function after radical nephroureterectomy 47. Urol Oncol 2014;32:e9–14. [22] Busby JE, Brown GA, Matin SF. Comparing lymphadenectomy during radical nephroureterectomy: open versus laparoscopic. Urology 2008; 71:413–6. [23] Prasad SM, Keating NL, Wang Q, Pashos CL, Lipsitz S, Richie JP, et al. Variations in surgeon volume and use of pelvic lymph node dissection with open and minimally invasive radical prostatectomy. Urology 2008;72:647–52. [discussion 652–3].
Original article
The effect of surgical approach on performance of lymphadenectomy and perioperative morbidity for radical nephroureterectomy Shane M. Pearce, M.D.*, Joseph J. Pariser, M.D., Sanjay G. Patel, M.D., Gary D. Steinberg, M.D., Arieh L. Shalhav, M.D., Norm D. Smith, M.D. Section of Urology, Department of Surgery, University of Chicago, Chicago, IL Received 2 July 2015; received in revised form 13 September 2015; accepted 16 September 2015
Abstract Objectives: To examine the effect of surgical approach on regional lymphadenectomy (LND) performance and inpatient complications for radical nephroureterectomy (NU) using a national administrative database. Methods: The National Inpatient Sample (2009–2012) was used to identify patients who underwent NU for urothelial carcinoma. Cohorts were stratified by performance of LND. Covariates included patient demographics, comorbidity, hospital characteristics, hospital volume, performance of LND, surgical approach (open [ONU], laparoscopic [LNU], or robotic [RNU]), and complications. Multivariable logistic regression was used to identify factors associated with LND performance and complications. Results: A weighted population of 14,059 (85%) without LND and 2,560 (15%) with LND was identified. LND was more common in RNU (27%) compared with ONU (15%) and LNU (10%) (P o 0.01). On multivariable analysis, when compared with ONU, RNU was associated with increased odds of LND performance (odds ratio [OR] ¼ 1.9, 95% CI: [1.3–2.8]; P ¼ 0.001), whereas LNU was associated with decreased odds of LND performance (OR ¼ 0.6, 95% CI: [0.4–0.8]; P ¼ 0.004). Multivariable analysis of risk factors for complications demonstrated lower odds of complications with RNU (OR ¼ 0.6, 95% CI: [0.4–0.8]; P ¼ 0.001), whereas performance of LND increased the risk of complications (OR ¼ 1.3, 95% CI: [1.001–1.7]; P ¼ 0.049). Conclusions: When compared with ONU, RNU increased the odds of LND performance and had a lower inpatient complication rate, whereas LNU reduced the odds of LND performance and had no significant effect on inpatient complication rates. Performance of LND was independently associated with higher inpatient complication rates. r 2016 Elsevier Inc. All rights reserved.
Keywords: Urothelial carcinoma; Upper urinary tract; Lymph node excision; Complications; Treatment outcome; Patterns of care
1. Introduction Upper tract urothelial carcinoma (UTUC) is a relatively rare entity, with most of the tumors arising from the renal pelvis. As only 5% of urothelial neoplasms occur in the kidneys and the ureters, patterns of care and optimal management of UTUC are far less studied when compared with urothelial carcinoma of the bladder [1]. Multicenter studies of radical nephroureterectomy (NU) with regional lymph node dissection (LND) for UTUC indicate a 25% overall incidence of node-positive disease, with rates ranging from 6% to 35% depending on tumor stage and Corresponding author. Tel.: þ1-608-234-7401; fax: þ1-773-702-1001. E-mail address: [email protected] (S.M. Pearce). *
http://dx.doi.org/10.1016/j.urolonc.2015.09.008 1078-1439/r 2016 Elsevier Inc. All rights reserved.
grade [2,3]. Based on extrapolation of data from patients undergoing radical cystectomy for bladder cancer, it is logical that proper diagnosis and management of LN metastasis in UTUC could improve patient outcomes. However, the practice of LND during NU for invasive UTUC has not been consistently adopted by urologists, likely because of a lack of prospective evidence supporting a cancer-specific survival benefit for LND and incomplete understanding of the optimal LND template [4]. Over the last decade, interest in minimally invasive surgical techniques for UTUC has grown. Laparoscopic (LNU), and more recently robot-assisted laparoscopic (RNU), techniques have been described as alternatives to the traditional open approach (ONU) [5]. There are 2 metaanalyses comparing LNU and ONU have supported
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oncologic equivalence; however, definitive conclusions cannot be made because most studies included in analysis were limited by short follow-up (o5 y) [6,7]. Both LNU and RNU appear to improve postoperative convalescence when compared with ONU [8,9]. A recent matched analysis compared 22 patients who underwent RNU and 22 patients who underwent LNU at a single institution, finding that patients undergoing RNU were more likely to undergo an LND and, when performed, median LN yields were higher for the robotic approach [10]. National trends in adoption of LNU and RNU in comparison with ONU and the effect of the various approaches on practice patterns for performance of LND have not been examined. Using the National Inpatient Sample, we evaluated the effect of surgical approach on LND performance and complication rates.
2. Materials and methods The U.S. Healthcare Cost and Utilization Project (HCUP) Nationwide Inpatient Sample (NIS) database is the largest all-payer inpatient database in the United States, representing the inpatient experience of a 20% stratified probability sample of American nonmilitary, nonfederal hospitals [11]. The NIS was queried for patients who underwent NU for a renal pelvis or ureteral neoplasm between 2009 and 2012. A survey-weighted design allowed for population-level estimates of national trends and incidence rates. Institutional review board approval was not required, as the NIS does not include identifiable patient information. All patients with a primary diagnosis of renal pelvic or ureteral neoplasm who underwent NU were identified using International Classification of Disease Ninth revision (ICD-9) diagnostic and procedure codes (Supplementary Table S1). Patients with missing age (n ¼ 1), younger than 18 years (n ¼ 3), or with metastatic disease (n ¼ 13) were excluded. ICD-9 procedure codes for performance of regional LND and surgical approach (ONU, LNU, and RNU) allowed construction of cohorts. Demographic information included age, sex, race, and primary insurance type. Equally sized age tertiles were generated for intergroup comparison and logistic regression. Hospital setting (urban or rural), teaching status, and hospital volume were examined. Annual hospital NU volume (any approach) was determined and divided into tertiles (low: 1–2 cases/y, intermediate: 3–7 cases/y, and high: Z8 cases/y). Comorbidity was calculated using the Elixhauser method, which has been shown to compare favorably to other well-validated comorbidity scores [12]. The Elixhauser comorbidity score was also divided into tertiles. Outcomes assessed included length of stay, inpatient mortality, and complications, as described previously [13]. Hemorrhagic complications included the receipt of blood transfusion during the inpatient stay. Prolonged length of stay of Z7 days represented the 75th percentile
100%
6.5 18.0
75%
Proportion of 50% NU by Approach
12.2
13.6
17.3
16.3
22.0 12.3 RNU LNU
75.5
70.5
70.1
65.8
2009
2010
2011
2012
ONU
25%
0%
Fig. Surgical approach for radical nephroureterectomy from 2009 to 2012. Over time, there was an increase in the proportion of cases performed with robot assistance, with reductions in both laparoscopic and open cases (P o 0.001).
of the entire study cohort. No specific staging information is available in the NIS. Stata 13.1 (StataCorp, College Station, TX) was used for statistical analyses with survey weighting. The chi-square test with Rao-Scott correction was used for comparison of categorical variables [14]. Multivariate logistic regression was performed to identify patient, hospital, and surgical factors associated with performance of LND and to identify risk factors for any postoperative inpatient complications. A 2-sided P o 0.05 was considered significant for all statistical tests. 3. Results A total of 16,619 patients were included for analysis. The use of ONU, LNU, and RNU approaches evolved over time from 2009 to 2012, as shown in the Fig. Specifically, the use of RNU increased (6% of all cases in 2009 to 22% in 2012), whereas the use of ONU (76% to 66%) and LNU (18% to 12%) declined (P ¼ 0.001). Baseline patient demographics and hospital characteristics by performance of LND are shown in Table 1. The median age of the entire cohort was 72 years (interquartile range [IQR]: 64–80). Patients 67 years and younger were more likely to undergo LND (18%, n ¼ 998) when compared with patients 78 years and older (12%, n ¼ 620; P o 0.001). Hospital characteristics were significantly different between the groups, with LND dissection more common in teaching hospitals (19% vs. 8%, P o 0.001), intermediate-volume hospitals (16%), and high-volume hospitals (20% vs. 11% for low volume, P o 0.001). Patients undergoing RNU were more likely to undergo LND (27%) when compared with ONU (15%) and LNU (10%, P o 0.001). There were no trends in performance of LND over time (P ¼ 0.4). Inpatient outcomes by performance of LND are shown in Table 2. On univariate analysis, there was no difference in the rate of intraoperative complications (P ¼ 0.6) or
S.M. Pearce et al. / Urologic Oncology: Seminars and Original Investigations 34 (2016) 121.e15–121.e21 Table 1 Baseline characteristics of patients undergoing nephroureterectomy by performance of LND Characteristic, N (%)
No LND (n ¼ 14,059)
LND performed (n ¼ 2,560)
All (n ¼ 16,619)
14,059 (85)
2,560 (15)
Age tertiles r67 68–77 Z78
4,611 (82) 4,670 (83) 4,748 (88)
998 (18) 942 (17) 620 (12)
Sex Male Female
8,390 (84) 5,665 (86)
1,631 (16) 929 (14)
Race White Black Hispanic Other Unknown
0.126
0.364 10,918 518 677 660 1,286
(85) (88) (87) (84) (80)
1,941 68 102 126 323
(15) (12) (13) (16) (20)
Elixhauser comorbidity r1 2–3 Z4
5,477 (84) 5,881 (85) 2,700 (85)
1,024 (16) 1,055 (15) 482 (15)
Primary insurance Medicare Medicaid Private Other
9,985 378 3,198 479
1,607 127 721 100
Hospital location Urban Rural
9,796 (85) 580 (90)
1,677 (15) 62 (10)
Hospital teaching status Teaching Nonteaching
5,608 (81) 4,768 (92)
1,347 (19) 392 (8)
Hospital volume Low Intermediate High
5,664 (89) 3,876 (84) 4,520 (80)
665 (11) 758 (16) 1,137 (20)
Surgical approach Open Laparoscopic Robotic
9,998 (85) 2,386 (90) 1,675 (73)
1,697 (15) 252 (10) 611 (27)
Year 2009 2010 2011 2012
3,385 3,307 3,822 3,545
Table 2 Perioperative outcomes by performance of LND Characteristic, N (%)
P value
o0.001
0.918
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Intraoperative complication Yes No
No LND LND performed P value (n ¼ 14,059) (n ¼ 2,560) 0.623 529 (4) 13,530 (96)
111 (4) 2,449 (96)
Any postoperative complication Yes 3,825 (27) No 10,235 (73)
748 (29) 1,812 (71)
Complications by type Hemorrhagic Gastrointestinal Cardiac Urinary Othera
2,780 898 287 251 281
Length of stay, median (IQR) Prolonged LOS (Z7 d) Inpatient mortality
5 (3–7) 3,841 (27) 182 (1)
(20) (6) (2) (2) (2)
0.414
570 137 56 53 40
(22) (5) (2) (2) (2)
5 (3–7) 820 (32) 30 (1)
0.303 0.437 0.852 0.705 0.557 0.064 0.073 0.842
LOS ¼ length of stay. To comply with NIS guidelines preventing report of cell numbers r10, infection, vascular, respiratory, seroma, wound, and other complications were reported as other. a
0.006 (86) (75) (82) (83)
(14) (25) (18) (17) 0.123
o0.001
o0.001
o0.001
0.376 (86) (84) (87) (82)
554 652 574 780
(14) (16) (13) (18)
Cells not totaling n ¼ 14,059 for No LND or n ¼ 2,560 for LND performed represent missing data from the National Inpatient Sample.
postoperative complications (P ¼ 0.4) between LND cohorts. Patients undergoing LND experienced a prolonged length of stay in 32% of cases vs. 27% when no LND was performed, P ¼ 0.073. Table 3 displays perioperative outcomes by surgical approach. There was no significant difference in the
rate of intraoperative complications by surgical approach (P ¼ 0.1). The rate of any postoperative complication was lowest for RNU (19%, n ¼ 426) and highest for ONU (30%, n ¼ 3,529 or, P o 0.001). Significant differences were seen in the rate of gastrointestinal (7%, 8%, and 3% for ONU, LNU, and RNU, respectively, P ¼ 0.008) and hemorrhagic complications (22%, 15%, and 15% for ONU, LNU, and RNU, respectively, P ¼ 0.003). A prolonged length of stay Z7 days was most likely after ONU (32%, n ¼ 3,736) when compared with LNU (22%, n ¼ 567) and RNU (16%, n ¼ 357; P o 0.001). The results of a multivariate logistic regression for predictors of LND performance during NU are shown in Table 4. Robotic approach independently increased the odds of LND (odds ratio [OR] ¼ 1.9, 95% CI: [1.3–1.8]; P ¼ 0.001), whereas laparoscopic approach decreased the odds of LND (OR ¼ 0.6, 95% CI: [0.4–0.8]; P ¼ 0.004). Other factors associated with performance of LND included Elixhauser score Z4 (OR ¼ 1.6, 95% CI: [1.1–2.3]; P ¼ 0.013), teaching hospital (OR ¼ 2.4, 95% CI: [1.6–3.7]; P o 0.001), intermediate-volume hospital (OR ¼ 1.5, 95% CI: [1.2–2.0]; P ¼ 0.003), and high-volume hospital (OR ¼ 2.4, 95% CI: [1.5–3.9]; P ¼ 0.001). Table 4 also displays multivariate logistic regression for risk factors for any postoperative complication. Robotic approach reduced the risk of complications (OR ¼ 0.6, 95% CI: [0.4–0.8]; P ¼ 0.001), whereas performance of LND increased the risk (OR ¼ 1.3, 95% CI: [1.001–1.7]; P ¼ 0.049). Other factors associated with complications included 78 years and older (OR ¼ 1.6, 95% CI: [1.2–2.1]; P ¼ 0.002), black race (OR ¼ 1.9, 95% CI: [1.2–3.1];
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Table 3 Perioperative outcomes by surgical approach Outcome, N (%)
ONU (n ¼ 11,698)
LNU (n ¼ 2,638)
RNU (n ¼ 2,286)
Intraoperative complication Yes No
479 (4) 11,220 (96)
117 (4) 2,521 (96)
44 (2) 2,243 (98)
Any postoperative complication Yes No
3,529 (30) 8,170 (70)
618 (23) 2,020 (77)
426 (19) 1,860 (81)
Complications by type Hemorrhagic Gastrointestinal Cardiac Urinary Othera
2,619 766 258 248 268
Length of stay, median (IQR) Prolonged LOS (Z7 d)
5 (4–7) 3,736 (32)
P value 0.121
o0.001
(22) (7) (2) (2) (2)
397 211 52 32 39
(15) (8) (2) (1) (1)
4 (3–6) 567 (22)
335 59 33 25 14
(15) (3) (1) (1) (1)
4 (3–5) 357 (16)
0.003 0.008 0.653 0.225 0.072 o0.001 o0.001
LOS ¼ length of stay. To comply with NIS guidelines preventing report of cell numbers r10, infection, vascular, respiratory, seroma, wound, and other complications were reported as other. a
P ¼ 0.007), other race (OR ¼ 2.0, 95% CI: [1.2–3.2]; P ¼ 0.006), Elixhauser comorbidity score 2 to 3 (OR ¼ 1.7, 95% CI: [1.4–2.1]; P o 0.001), comorbidity score Z4 (OR ¼ 3.3, 95% CI: [2.5–4.3]; P o 0.001), and private insurance (OR ¼ 0.7, 95% CI: [0.5–0.9]; P ¼ 0.010).
4. Comment Despite retrospective evidence indicating that a thorough regional LND can provide improved disease staging and potential therapeutic benefit in patients with limited nodal disease, the concept of meticulous LND for UTUC during NU has not been consistently adopted by urologists around the world [2,15]. The reasons for this are unclear, but single-center series have shown that surgeon-specific factors and surgical approach may independently predict performance of LND [10,16]. With the diffusion of laparoscopic and robotic techniques into urology, minimally invasive techniques have been increasingly used for NU [9]. Our goal was to examine the effect of hospital characteristics and surgical approach (ONU, LNU, and RNU) on performance of LND in a contemporary, national cohort of patients treated for UTUC. We also examined the effect of LND and surgical approach on in-hospital morbidity and mortality. The robotic approach for NU is being increasingly used in place of laparoscopic and open approaches. As of 2012, most of the NUs in the United States were still performed with an open approach (66%); however, robot assistance was used in 22% of cases compared with pure laparoscopic approach in just 12% of cases. This is consistent with the adoption of robotic surgery as a minimally invasive treatment alternative for many urologic malignancies. In 2009, robot-assisted prostatectomy supplanted the traditional open
approach as the most common technique for radical prostatectomy in the United States [17] with similar trends observed for partial nephrectomy [18]. Additionally, robot assistance is being increasingly used for radical cystectomy, as evidenced by use in 13% of cases from 2009 to 2011 in a national cohort [19]. In the current study's population-based cohort, LND was performed in 15% of cases overall. This is relatively lower that the LND rate of 36% to 60% in 2 recent multicenter case series from academic centers in the United States and Europe [20,21]. The rate of positive nodal disease among patients undergoing LND in these 2 series was 18% to 20%. Most retrospective series have highlighted the need for LND, particularly in patients with pT2–4 disease [4]. Furthermore, because preoperative imaging studies, urine cytology, and biopsy findings have limited reliability in disease staging and identification of LN involvement, it can be argued that LND should be performed in all patients treated with NU where accurate disease staging is desired [16]. Yet, controversy persists because of the lack of standardized LND templates and limited, retrospective data supporting the therapeutic role of LND in UTUC [4]. Clearly, patterns of LND vary depending on the practice setting, and better preoperative diagnostics are needed if selective LND is to be used effectively. We demonstrated that the robotic approach independently increased the odds of LND performance nearly 2-fold when compared with the open approach, whereas a laparoscopic approach reduced the odds of LND performance. In a study of 22 matched pairs (matched for pathologic stage and age), Ambani et al. [10] reported a discrepancy in LND performance between RNU and LNU, with LND performed in 59% of RNU compared with 27% of LNU. As this study was relatively small and limited to 3 surgeons at a single
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Table 4 Multivariate logistic regression for predictors of lymph node dissection performance and postoperative complications Factors
Outcome Lymph node dissection
Any complication
OR
95% CI
P value
OR
95% CI
P value
Surgical approach Open Laparoscopic Robotic
REF 0.55 1.88
– 0.37–0.83 1.28–2.76
– 0.004 0.001
REF 0.78 0.55
– 0.59–1.03 0.40–0.77
– 0.081 0.001
Lymph node dissection Not performed Performed
N/A N/A
N/A N/A
N/A N/A
REF 1.31
– 1.001–1.72
– 0.049
Age r67 68–77 Z78
REF 1.34 0.77
– 0.91–1.98 0.50–1.17
– 0.141 0.221
REF 1.25 1.59
– 0.92–1.70 1.18–2.13
– 0.155 0.002
Sex Male Female
REF 0.85
– 0.66–1.10
– 0.217
REF 1.19
– 0.97–1.46
– 0.090
Race White Black Hispanic Other Unknown
REF 0.54 0.69 0.81 1.24
– 0.24–1.22 0.34–1.44 0.38–1.72 0.77–1.99
– 0.138 0.329 0.586 0.369
REF 1.93 1.20 1.96 1.20
– 1.20–3.10 0.74–1.94 1.21–3.16 0.87–1.65
– 0.007 0.467 0.006 0.270
Elixhauser comorbidity r1 2–3 Z4
REF 1.09 1.61
– 0.83–1.42 1.10–2.34
– 0.544 0.013
REF 1.73 3.30
– 1.41–2.14 2.51–4.32
– o0.001 o0.001
Primary insurance Medicare Medicaid Private Other
REF 1.89 1.31 1.38
– 0.93–3.83 0.88–1.96 0.61–3.11
– 0.080 0.186 0.442
REF 0.72 0.65 0.92
– 0.35–1.48 0.47–0.90 0.51–1.67
– 0.372 0.010 0.790
Hospital teaching status Nonteaching Teaching
REF 2.44
– 1.60–3.71
– o0.001
REF 1.04
– 0.83–1.32
– 0.723
Hospital volume Low Intermediate High
REF 1.51 2.38
– 1.15–1.97 1.45–3.90
– 0.003 0.001
REF 1.06 0.95
– 0.85–1.33 0.67–1.35
– 0.614 0.789
N/A ¼ not applicable; REF ¼ reference.
center, this finding was attributed to surgeon practice pattern. The feasibility of performing LND during laparoscopy has been demonstrated previously [22], but LND remains somewhat underused during LNU. Capitanio et al. found that LND was performed in 42% and 24% of patients after ONU and LNU, respectively, in a large multicenter study spanning 3 continents. The findings in our study may highlight variation in surgeon practice patterns, or it could represent the manifestation of an inherent difference in the capability to perform LND between the various surgical techniques. Dissemination of minimally invasive surgical techniques and particularly robot-assistance technology has
had an evolving effect on the training, case experience, and comfort level of surgeons with various surgical approaches. As a surgeon's experience with robotic technology increases, his or her comfort, willingness, and ability to perform an LND may also improve. Robot assistance has been shown to aid performance of other complex urologic procedures and may facilitate LND and increase its use as a component of NU. The population-based nature of our study, with adjustment for hospital teaching status, volume, and location, may lend support to this latter hypothesis. However, definitive conclusions regarding the cause for the association between a surgical approach and LND
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performance cannot be made without detailed patient staging information and surgeon-specific factors such as subspecialization and fellowship training. Increased hospital volume was independently associated with performance of LND. Although this relationship has not been studied in patients undergoing NU for UTUC, Prasad et al. [23] demonstrated that high-volume surgeons were more likely to perform pelvic LND during radical prostatectomy when controlling for patient comorbidity and tumor characteristics. Lower-volume surgeons, presumably in lower-volume hospitals, may opt to forego LND because of concern for increased complication rates or longer operative times. We also found that LND was more likely to be performed at teaching hospitals and in patients with comorbidities. Referral bias could explain some of these results; with highly comorbid patients more likely to be referred to either tertiary care centers or experienced surgeons, who may be more likely to perform LND as part of NU. It is also possible that patients at increased risk for nodal involvement based on preoperative staging are preferentially referred to higher-volume facilities and teaching hospitals. Multivariate analysis controlling for patient and hospital characteristics revealed that patients undergoing LND were 30% more likely to experience any postoperative complication. Although the unadjusted rate of intraoperative or postoperative complications did not vary based on performance of LND, there was a marginally higher rate of hemorrhagic complications, which included receipt of blood transfusion, after LND performance (22% vs. 20%). Lymph node excision near the great vessels may put patients at an increased risk for postoperative complications, particularly related to bleeding; however, this was not statistically significant. In our data set, RNU was protective for postoperative complications compared with ONU, although LNU had no significant effect on postoperative complications. Specifically, we observed lower rates of hemorrhagic and gastrointestinal complications with RNU. Both LNU and RNU were also associated with a reduced incidence of prolonged hospitalization when compared with ONU. A previous NIS study found that LNU independently reduced the risk of intraoperative complications, blood transfusions, and prolonged length of stay when compared with ONU, but it did not reduce the odds of postoperative complications overall [8]. However, that study did not examine the effect of robot assistance. We also confirmed several known risk factors for postoperative complications including increased age, race (black or other), and comorbidity. Our study has multiple important strengths. To our knowledge, this is the first study to report trends in use of the 3 major surgical approaches for NU (ONU, LNU, and RNU) in a contemporary national cohort. Using the NIS, we were able to provide the first detailed analysis of national practice patterns in performance of LND during NU. We also provided important benchmarks related to morbidity,
length of stay, and mortality after NU while identifying risk factors for complications. This study has limitations, which must be noted. The NIS does not provide detailed information regarding tumor characteristics (size, grade, and location), preoperative staging, and other surgical details such as bladder-cuff management, extent of LND, and node yield. These variables likely influence selection of surgical approach and subsequent perioperative morbidity. It is certainly possible that more complex cases are preferentially performed in an open fashion, which would create a selection bias and explain some of the observed differences in complication rates between approaches. However, this does not fully explain the differential rate of LND performance. It is also unknown which cases of RNU and LNU were converted to open procedures. This missing information could lead to overestimation of the use of RNU and LNU and subsequent alteration of LND performance and complication rates. NIS data are limited to the inpatient hospitalization, and therefore, analysis of readmission rates, late complications, and mortality after discharge is not possible. Because of this, morbidity and mortality rates may have been underestimated. The NIS also does not effectively capture individual surgeon volume. This may affect the selection of surgical approach, performance of LND, and complication rates. All retrospective studies from large, claims-based data sets, such as the NIS, are limited by coding errors, potential underreporting of complications, and unmeasured confounding variables. 5. Conclusions LND is performed in a minority of NU cases, and its use has been stable over time. Use of robot assistance during NU in the United States is increasing relative to laparoscopic and open approaches. RNU is associated with an increased likelihood of LND performance and a reduced risk of postoperative complications. Other factors associated with LND performance include hospital teaching status and increased hospital volume. LND increases the risk of postoperative complications independent of surgical approach in this data set. Appendix A. Supplementary Information Supplementary data associated with this article can be found in the online version at http://dx.doi.org/10.1016/ j.urolonc.2015.09.008.
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