Trifecta Outcomes in Multifocal Tumors: A Comparison Between Robotic and Open Partial Nephrectomy

Abstract

Objectives:

To report a comparative analysis of outcomes in patients who underwent multiple excisions for unilateral synchronous multifocal renal tumors using both open and robotic approaches.

Methods:

We retrospectively reviewed 110 patients who underwent robotic and open partial nephrectomy and had multiple tumor excisions in an ipsilateral kidney. “Trifecta” was defined as negative surgical margins, no urologic complications, and a glomerular filtration rate (GFR) preservation of ≥90% at last follow-up. Inverse probability of treatment weighting (IPTW) was applied to equilibrate treatment groups, minimize selection bias, and optimize inference on the basis of each patient's clinicodemographic characteristics.

Results:

Sixty-eight robotic and 42 open patient approaches had sufficient data for IPTW. After weighting, there were no statistical differences in baseline characteristics between the two groups. On adjusted analyses, robotic partial nephrectomy achieved equivalent rates of trifecta to open surgery (16.3% vs 16.5%, p = 0.99), which persisted on subgroup analyses of patients with two (20.1% vs 23.7%, p = 0.82) or more than two tumors (6.8% vs 7.4%, p = 0.95). There were no differences between robotic and open cohorts for negative margin rates, absence of complications, or GFR ≥90%. The robotic cohort had a shorter mean length of stay (3.4 vs 4.9 days, p < 0.001).

Conclusions:

Surgical resection remains the mainstay for patients with unilateral, synchronous, and multifocal renal tumors. Our analysis found that both open and robotic approaches to partial nephrectomy are equally likely to achieve the “trifecta” outcome in an equilibrated high-risk group of patients. The robotic approach for these complex patients may be safe and feasible for a carefully selected group of patients.

Introduction

Partial nephrectomy is the gold standard treatment for T1a renal tumors, allowing for excellent oncologic results and improved functional results compared with radical nephrectomy.^1,2 Partial nephrectomy also has become the surgery of choice for select patients with synchronous multifocal renal tumors. The incidence of unilateral, synchronous, and multifocal renal tumors has been reported to be 4.8%–25%.^3

–8 Several studies have shown that open partial nephrectomy for unilateral, synchronous, and multifocal renal tumors is associated with acceptable recurrence rates and with equivalent cancer-specific survival and complication rates compared with radical nephrectomy.^9

–12 More recently, surgical management of unilateral, synchronous, and multifocal renal tumors with laparoscopic^13

–16 and robotic partial nephrectomy^17

–21 has been described in one-armed case reports and feasibility studies with excellent functional and oncologic outcomes.²² There have been no studies, however, that have compared minimally invasive and open partial nephrectomy approaches in this patient population.

Recently, the concept of the “trifecta” outcome has been introduced in the partial nephrectomy patient population as a marker of surgical proficiency.^23,24 With regard to partial nephrectomy, the trifecta outcome includes negative surgical margins, no major urologic complications, and good renal function recovery postoperatively. We aim to report the trifecta outcome in patients who underwent multiple excisions for unilateral, synchronous, and multifocal renal tumors using either an open or robotic approach.

Materials and Methods

We retrospectively reviewed our institutional review board-approved single institution partial nephrectomy database for consecutive cases between 2009 and 2016 performed for clinically localized multifocal renal cell carcinoma. The final cohort included 42 open (38.2%) and 68 robotic (61.8%) cases with multiple excisions performed in a single kidney. Fourteen surgeons (9 open, 4 robotic, and 1 both), all fellowship trained or with at least 1-year staff experience, were included in the study. The surgical technique for open and robotic multifocal partial nephrectomy at our institution has previously been described.^19,25 Cases were performed under either zero, cold, or warm ischemia, per surgeon preference. Zero ischemia was reserved for exophytic tumors with minimal cortical involvement (n = 12, 11.1%). In cases with ischemia, both artery and vein were clamped.

Owing to an improved understanding of the more limited role of warm ischemia in determining ultimate renal functional preservation,²⁶ the definition for trifecta²⁷ was modified to the composite outcome of negative margins, no Clavien grade ≥1 complications, and a glomerular filtration rate (GFR) preservation of ≥90% at last follow-up. Each of these was individually assessed as secondary outcomes, as was length of stay. Margins were considered positive if they involved either parenchymal or sinus tissue. Complications were scored according to the Clavien–Dindo grading system and included both intraoperative and postoperative complications within 30 days. Creatinine was measured preoperatively within 1 month of partial nephrectomy and again each postoperative day during the duration of the patient's stay and at 3- or 6-month intervals thereafter. GFR was estimated from serum creatinine using the modification of diet in renal disease formula. GFR-P was defined as 100*maximum GFR at last follow-up/preoperative GFR.

Descriptive statistics were used to describe the patient population according to treatment status. Differences between cohorts for categorical baseline characteristics were compared using the χ ² test. Continuous variables were described by median and interquartile range, and the Wilcoxon rank-sum test was used to compare differences.

Inverse probability of treatment weighting (IPTW) was applied to equilibrate treatment groups with regard to clinicodemographic characteristics.²⁸ To minimize bias and maximize precision of the propensity score model,²⁹ all variables that might affect the primary outcome based on a priori hypotheses were included. Variables that could be influenced by treatment choice were explicitly excluded. This left us with the following: age, gender, Charlson comorbidity index, body mass index (BMI, kg/m²), preoperative chronic kidney disease (CKD) ≥3, solitary kidney, R.E.N.A.L. score (4–6: low, 7–9: moderate, 10–12: high), maximum tumor dimension (averaged across tumors), malignant histology on final pathology analysis, number of tumor excisions, and year of surgery (2009–2013: early and 2014–2016: late). Chi-squared tests, standardized differences, and propensity score histograms were used to compare treatment groups pre- and postweighting. Propensity weight-adjusted logistic regressions with robust standard errors were employed to determine the relationship between the treatment group and primary and secondary outcomes. Subgroup analyses were performed on patients with two tumors and patients with more than two tumors.

All statistical testing was two sided, and a p value of <0.05 was considered statistically significant. STATA 13 software (STATA, College Station, TX) was used for all statistical analyses.

Results

A total of 272 tumors were excised during 110 partial nephrectomies for a period of 7 years. This included 109 excisions in 42 patients in the open cohort (mean = 2.59) and 163 excisions in 68 patients in the robotic cohort (mean = 2.40). At baseline, the open group was more likely to have CKD stage ≥3 (p = 0.02), solitary kidneys (p = 0.03), higher R.E.N.A.L. scores (p = 0.02), and surgery in the early years (p = 0.03). After IPTW, both cohorts were evenly matched (Table 1 and Supplementary Fig. S1; Supplementary Data are available online at www.liebertpub.com/end). In the cohort at large, 15.5% achieved trifecta, with 77.2% of patients (or 92.3% of tumors) achieving negative margins, 65.4% having no complications, and 37.3% achieving GFR preservation ≥90%.

Table 1.

Baseline Characteristics and Propensity-Weighted Adjustment

	Unadjusted				Adjusted (propensity weighted) ^a
Variables	Open (n = 42)	Robotic (n = 68)	p value	Open (n = 42)	Robotic (n = 68)	SD ^b	p value
Age category (%)			0.13			0.03	0.91
<50	14.3	20.6		23.3	21.6
50–64	45.2	52.9		47.8	49.0
65+	40.5	26.5		28.9	29.4
Gender, male (%)	73.8	63.2	0.25	80.7	67.9	−0.27	0.18
CCI^c (%)			0.09			−0.02	0.95
0	23.8	39.7		28.5	29.2
>1	76.2	60.3		71.5	70.8
Body mass index, kg/m² (%)			0.36			0.10	0.76
<25	9.5	14.7		11.9	8.9
25–29	42.9	33.8		38.1	38.3
30–34	38.1	22.1		30.9	30.8
35+	9.5	29.4		19.1	22.0
≥3 Preoperative CKD (%)	52.3	29.4	0.02	48.7	42.1	−0.14	0.63
Solitary kidney (%)	23.8	8.8	0.03	15.3	19.3	0.11	0.67
R.E.N.A.L score (%)			0.02			0.03	0.90
Low (4–6)	28.6	45.9		48.8	43.8
Moderate (7–9)	40.5	41.0		33.7	41.4
High (10+)	30.9	13.1		17.5	14.8
Tumor average maximum dimension, cm (median, IQR)	2.3 (1.8–3.4)	2.1 (1.8–2.8)	0.15	2.1 (1.8–2.9)	2.1 (1.8–2.8)	−0.04	0.81
Renal cell carcinoma (%)	83.3	85.3	0.78	89.2	88.1	−0.03	0.86
No of excisions (median, IQR)	2.0 (2.0–3.0)	2 (2.0–2.5)	0.40	2.0 (2.0–3.0)	2.0 (2.0–3.0)	−0.13	0.56
Year of surgery			0.03			−0.04	0.88
2009–2013	71.4	50.0		57.2	59.2
2014–2016	28.6	50.0		42.8	40.7

Propensity weighting performed using inverse probability treatment weights adjusting for all baseline characteristics.

Standardized differences.

Charlson comorbidity index.

Bold values indicate statistical significance.

CKD = chronic kidney disease.

On adjusted analyses, robotic partial nephrectomy achieved equivalent rates of trifecta to open surgery (14.7% vs 17.0%, p = 0.83), which persisted on subgroup analyses of patients with two (20.8% vs 23.9%, p = 0.84) or more than two tumors (4.3% vs 7.0%, p = 0.74) (Fig. 1). The individual outcomes comprising trifecta were also assessed on adjusted analyses. There were no differences between robotic and open cohorts for negative margin rates (80.0% vs 79.4%, p = 0.95), absence of complications (67.6% vs 62.8%, p = 0.70), or GFR ≥90% (27.4% vs 38.1%, p = 0.36) (Fig. 2).

FIG. 1.

Results stratified by number of tumors after inverse probability of treatment weight-adjusted analyses, with adjustment for age, gender, Charlson comorbidity index, BMI, stage ≥3 preoperative CKD, solitary kidney status, tumor maximum dimension, R.E.N.A.L. score, RCC (%), number of excisions, and year of surgery. BMI = body mass index; CKD = chronic kidney disease.

FIG. 2.

Results stratified by trifecta outcomes after inverse probability of treatment weight-adjusted analyses, with adjustment for age, gender, Charlson comorbidity index, BMI, stage ≥3 preoperative CKD, solitary kidney status, tumor maximum dimension, renal cell carcinoma (%), R.E.N.A.L. score, number of excisions, and year of surgery GFR goal = GFR preservation ≥90% at last follow-up. GFR = glomerular filtration rate.

On adjusted analyses, the robotic cohort had a shorter mean length of stay (3.7 vs 5.0 days, p < 0.001). Estimated blood loss (EBL; 280 vs 357 mL, p = 0.33) and operative time (224 vs 221 minutes, p = 0.86) were similar between the robotic and open cohorts. Two out of 68 patients (2.9%) recurred in the robotic arm, whereas 3 out of 42 patients (7.1%) recurred in the open arm. Median functional data (creatinine) follow-up was 9.8 months (interquartile range, IQR, 1.2–24.8). Dividing this follow-up by surgical technique, median functional data follow-up was 7.5 months (IQR, 0.8–19.8) for the robotic arm and 22.1 months (IQR, 1.9–35.4) for the open arm.

Discussion

Partial nephrectomy aims to balance oncologic effectiveness with renal functional optimization and limited perioperative morbidity.²³ Given its functional advantages, partial nephrectomy is more commonly used for the management of complex renal masses.^9,12,14 Multifocal synchronous tumors present a unique challenge; there is, however, significant evidence for the role of partial nephrectomy in this cohort of patients.

Blute and colleagues were some of the first to report on their experience with multifocal tumors treated by partial and radical nephrectomy.⁹ Given the poor pathologic concordance of lesions in their study, the authors concluded that all suspicious lesions should be resected at time of surgery. In a more contemporary series by Simhan et al., the authors reported on 76 patients with a total of 241 unilateral synchronous multifocal renal masses who underwent partial nephrectomy.¹² In their study, malignant concordance rate was 77.2% and the benign concordance rate was 48.6%. Given their results, the authors concluded that all lesions be resected and that partial nephrectomy allows for acceptable oncologic and functional outcomes for these patients. In another recent study by Mano and colleagues, the authors compared 128 patients with unilateral, synchronous, and multifocal renal tumors who underwent surgical resection through either radical or partial nephrectomy.¹¹ They reported a recurrence-free survival of 98% for partial nephrectomy and 85% for radical nephrectomy, with no difference in overall survival in the two cohorts, providing further evidence for the use of partial nephrectomy for patients with multifocal renal tumors.

Initially, minimally invasive renal surgery was used for relatively straightforward cases, reserving complex cases for open surgery. However, for the past 2 decades, minimally invasive renal surgery has expanded to more complex cases, ushering in the area of robotic surgery for multifocal tumors.¹⁵ We initially described our robotic surgical experience and demonstrated its feasibility with ipsilateral multifocal renal tumors in 2012.¹⁹ In our initial study, we reported on eight patients with a total of 19 tumors resected (mean of 2.4 tumors per patient). Mean ischemia time was 21 minutes (10–35) and mean EBL was 250 mL (100–500). No intraoperative complications were reported and mean hospital stay was 4.2 days.

In the interim, we have greatly increased our experience, and herein, we report on our outcomes on a total of 110 patients (68 robotic), with 272 tumors excised. Mean number of excisions in the open cohort was 2.59 and that in the robotic cohort was 2.40. Patients with CKD stage 3 or higher, solitary kidneys, or more complex R.E.N.A.L scoring were noted to be more prevalent in the open cohort than in the robotic cohort before matching (p = 0.02), suggesting that historical practices of preferring open surgery on complex tumors and patients were evident in our database. However, after matching both groups, trifecta rates were similar in both robotic cohorts and open cohorts. Interestingly, this persisted regardless of the number of tumors excised, indicating complexity had no effect on the outcomes. Upon further analysis, both open and robotic groups had similar rates of negative margins, absence of complications, and goal postoperative GFRs. Our series is further evidence of the ability to safely and effectively use the robotic platform for the treatment of carefully selected patients with synchronous multifocal renal tumors.

Although without robust functional outcomes, similar studies earlier in the literature showed feasibility of the robotic approach for multifocal tumors.^17,22 Rogers and colleagues described one of the initial series of robotic partial nephrectomies for complex renal tumors. The authors concluded that this approach was both safe and feasible for complex patients, including those with multifocal tumors.²⁰ Later, Hankins et al. published their full experience of 54 patients at the National Cancer Institute with multifocal tumors.¹⁸ Although a majority of their patients had hereditary tumor syndromes (mean number of tumors excised was 8.63), their experience provides another example of the effective use of the robotic platform to treat carefully selected complex patients.

Limitations of our study include the retrospective design, experience from a single institution, and notable referral bias since the cases were done at our high-volume institution. Hereditary cases were included in our analysis, further limiting the applicability of the study to the general population. In addition, we matched the cohorts based on measured covariates; however, covariates that were unmeasured could have biased our study. Lastly, the median creatinine follow-up in months was shorter in the robotic arm; this is likely because the majority of patients who underwent robotic partial nephrectomy were concentrated at the latter end of the study period. Longer follow-up of these patients may result in a slight decrease in GFR. Given the unique analysis in comparing outcomes for open and robotic techniques, we believe there is significant utility in our study. Although groups have reported on the use of robotic surgery for multifocal tumors, we believe this is the first study comparing outcomes between open and robotic approaches in the literature. Although beyond the scope of this study, it is important to note that despite these comparable outcomes, the cost differences between the robotic and open surgical approaches may be significant. Still, our analysis shows that success can be achieved in these complex cases with robotic surgery. Nevertheless, a prospective study could provide further evidence to support the equivalency of both surgical approaches.

Conclusions

Our large comparative series showed in a matched series of patients with synchronous multifocal renal tumors, both open and robotic approaches were able to achieve equivalent rates of the trifecta outcome. This trend was demonstrated regardless of the number of tumor excisions, validating the equivalency of the robotic approach. Overall, this report adds to the growing body of literature supporting the use of the robotic platform for patients with complex or multifocal renal tumors.

Footnotes

Author Disclosure Statement

Jihad H. Kaouk certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the article (e.g., employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Endocare, Inc., Intuitive. - J.H. Kaouk (consultant). Remaining authors certify that they have no conflicts of interest.

Abbreviations Used

References

Campbell

, Novick

, Belldegrun

, et al. Guideline for management of the clinical T1 renal mass. J Urol, 2009; 182:1271–1279.

Mir

, Derweesh

, Porpiglia

, et al. Partial nephrectomy versus radical nephrectomy for clinical T1b and T2 renal tumors: A systematic review and meta-analysis of comparative studies. Eur Urol, 2017; 71:606–617.

Jacqmin

, Saussine

, Roca

, et al. Multiple tumors in the same kidney: Incidence and therapeutic implications. Eur Urol, 1992; 21:32–34.

Karayiannis

, Varkarakis

, Chort

, et al. Multifocality of renal cell tumors is a factor to consider before performing a partial nephrectomy. Anticancer Res, 2002; 22:3103–3107.

Richstone

, Scherr

, Reuter

, et al. Multifocal renal cortical tumors: Frequency, associated clinicopathological features and impact on survival. J Urol, 2004; 171:615–620.

Steinbach

, Stockle

, Griesinger

, et al. Multifocal renal cell tumors: A retrospective analysis of 56 patients treated with radical nephrectomy. J Urol, 1994; 152(5 Pt 1):1393–1396.

Tsivian

, Moreira

, Caso

, et al. Predicting occult multifocality of renal cell carcinoma. Eur Urol, 2010; 58:118–126.

Whang

, O'Toole

, Bixon

, et al. The incidence of multifocal renal cell carcinoma in patients who are candidates for partial nephrectomy. J Urol, 1995; 154:968–970. discussion:70–71.

Blute

, Thibault

, Leibovich

, et al. Multiple ipsilateral renal tumors discovered at planned nephron sparing surgery: Importance of tumor histology and risk of metachronous recurrence. J Urol, 2003; 170:760–763.

10.

Krambeck

, Iwaszko

, Leibovich

, et al. Long-term outcome of multiple ipsilateral renal tumours found at the time of planned nephron-sparing surgery. BJU Int, 2008; 101:1375–1379.

11.

Mano

, Kent

, Larish

, et al. Partial and radical nephrectomy for unilateral synchronous multifocal renal cortical tumors. Urology, 2015; 85:1404–1410.

12.

Simhan

, Canter

, Sterious

, et al. Pathological concordance and surgical outcomes of sporadic synchronous unilateral multifocal renal masses treated with partial nephrectomy. J Urol, 2013; 189:43–47.

13.

Flum

, Wolf

Jr.

Laparoscopic partial nephrectomy for multiple ipsilateral renal tumors using a tailored surgical approach. J Endourol, 2010; 24:557–561.

14.

Lin

, Turna

, Frota

, et al. Laparoscopic partial nephrectomy versus laparoscopic cryoablation for multiple ipsilateral renal tumors. Eur Urol, 2008; 53:1210–1216.

15.

Steinberg

, Kilciler

, Abreu

, et al. Laparoscopic nephron-sparing surgery for two or more ipsilateral renal tumors. Urology, 2004; 64:255–258.

16.

Tsivian

, Tsivian

, Benjamin

, et al. Laparoscopic partial nephrectomy for multiple tumours: Feasibility and analysis of perioperative outcomes. BJU Int, 2011; 108:1330–1334.

17.

Boris

, Proano

, Linehan

, et al. Initial experience with robot assisted partial nephrectomy for multiple renal masses. J Urol, 2009; 182:1280–1286.

18.

Hankins

, Walton-Diaz

, Truong

, et al. Renal functional outcomes after robotic multiplex partial nephrectomy: The National Cancer Institute experience with robotic partial nephrectomy for 3 or more tumors in a single kidney. Int Urol Nephrol, 2016; 48:1817–1821.

19.

Laydner

, Autorino

, Spana

, et al. Robot-assisted partial nephrectomy for sporadic ipsilateral multifocal renal tumours. BJU Int, 2012; 109:274–280.

20.

Rogers

, Singh

, Blatt

, et al. Robotic partial nephrectomy for complex renal tumors: Surgical technique. Eur Urol, 2008; 53:514–521.

21.

Volpe

, Garrou

, Amparore

, et al. Perioperative and renal functional outcomes of elective robot-assisted partial nephrectomy (RAPN) for renal tumours with high surgical complexity. BJU Int, 2014; 114:903–909.

22.

Ginzburg

, Uzzo

, Kutikov

. The role of minimally invasive surgery in multifocal renal cell carcinoma. Curr Urol Rep, 2012; 13:202–210.

23.

Hung

, Cai

, Simmons

, et al.. “Trifecta” in partial nephrectomy. J Urol, 2013; 189:36–42.

24.

Zargar

, Allaf

, Bhayani

, et al. Trifecta and optimal perioperative outcomes of robotic and laparoscopic partial nephrectomy in surgical treatment of small renal masses: A multi-institutional study. BJU Int, 2015; 116:407–414.

25.

Novick

. Nephron-sparing surgery for renal cell carcinoma. Br J Urol, 1998; 82:321–324.

26.

Mir

, Ercole

, Takagi

, et al. Decline in renal function after partial nephrectomy: Etiology and prevention. J Urol, 2015; 193:1889–1898.

27.

Khalifeh

, Autorino

, Hillyer

, et al. Comparative outcomes and assessment of trifecta in 500 robotic and laparoscopic partial nephrectomy cases: A single surgeon experience. J Urol, 2013; 189:1236–1242.

28.

Curtis

, Hammill

, Eisenstein

, et al. Using inverse probability-weighted estimators in comparative effectiveness analyses with observational databases. Med Care, 2007; 45(10 Suppl 2):S103–S107.

29.

Brookhart

, Wyss

, Layton

, et al. Propensity score methods for confounding control in nonexperimental research. Circ Cardiovasc Qual Outcomes, 2013; 6:604–611.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.07 MB