Is Extensive Parenchymal Resection During Robotic Partial Nephrectomy Justified? A Match-Paired Comparison of Two Extirpative Surgical Modalities for Treatment of a Complex Renal Neoplasm

Introduction

Partial nephrectomy (PN) is accepted as the standard treatment for clinical T1a (<4 cm) renal masses. ¹ The laparoscopic and robot-assisted PN has demonstrated to have comparable outcomes to the open approach, ^2,3 with the additional benefits of decreased blood loss, pain, convalescence time, and cosmetic outcomes.

In recent era, the robot-assisted approach has become the preferred method for PN of small renal masses, and owing to the wide range of movements that facilitate intracorporeal suturing, the three-dimensional vision and better ergonomics for the surgeon ^4,5 have allowed for a less pronounced learning curve during the early experience of the procedure. ⁶ All these features can be used to overcome the technical challenges of an extensive resection and reconstruction of the kidney when the tumor complexity demands it. However, it has been advocated that robotic PN (RPN) in such a setting might not provide any tangible benefit compared with radical nephrectomy (RN).

Our objective was to evaluate the outcomes of RPN in patients requiring an extensive volume resection and to compare them with the outcomes of similar patients that underwent laparoscopic RN (LRN), also a minimally invasive approach.

Patients and Methods

Patients undergoing RPN with extensive volume resection were identified from our prospectively maintained Institutional Review Board-approved RPN database from 2006 to 2014. The operating surgeon (J.H.K. or R.J.S.) determined the extension of resection subjectively at the time of nephron-sparing surgery (NSS) for all patients. Those with estimated parenchymal resection ≥30% were selected for imaging volume calculation, since it was the value previously defined as heminephrectomy for tumors. ^7,8

Pre- and postoperative cross-sectional imaging (CT or MRI)-based volumetric assessment of the operated kidney was performed to assess volume changes of the operated kidney postresection. Preoperative cross-sectional imaging was obtained within 1 month from the surgery, while postoperative cross-sectional imaging was obtained 4 to 6 months postoperatively. Volume was estimated from axial scans in the venous phase reconstructed at 3 mm intervals. EasyViz (Medical Insight, Krumtappen, Denmark) was used for image evaluation. Freehand scripting was used to define the kidney outline at each cross-sectional level (Fig. 1). The area was calculated at each axial section. The total volume was calculated by tallying the computed area at each 3 mm slice. Patients without pre- and postoperative cross-sectional imaging, patients with a solitary kidney, and patients with calculated volume preservation >70% were excluded from the analysis.

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FIG. 1.

(a) Cross-sectional CT image demonstrating a large 8.3 cm renal mass in the left kidney (R.E.N.A.L. score 11a). The blue line demarcates the functional renal parenchyma, and the red arrow indicates the left renal vein crossing the aorta; (b) cross-sectional CT image demonstrating the postoperative renal parenchyma remnant. In this example, 54% of the renal parenchyma was preserved; (c) cross-sectional CT image demonstrating a 5 cm renal mass in the left kidney (R.E.N.A.L. score 8p). The red arrow indicates the left renal artery; (d) cross-sectional CT image demonstrating the postoperative renal parenchyma remnant. In this other example, 60% was preserved.

To address the possible benefits of the NSS, we matched the RPN cohort (1:1 matching) to patients undergoing LRN, also a minimally invasive approach. The groups were matched based on tumor size, R.E.N.A.L. nephrometry score, age-adjusted Charlson comorbidity (ACCI) index, and preoperative estimated glomerular filtration rate (eGFR).

Demographic and clinical data evaluated included age, gender, race, body mass index (BMI), ACCI, preoperative eGFR (within 30 days before surgery), and tumor characteristics. Perioperative variables analyzed were operative duration, estimated blood loss (EBL), hospital length of stay (HLOS), pathologic specimen findings, and postoperative complications within 30 days of surgery using the Clavien–Dindo grading system. ⁹ Complications were further stratified into minor (Clavien I-II) and major (Clavien III-V). Follow-up data included eGFR at the last clinical office visit, recurrence, and metastasis status. The complexity of tumors was calculated using the R.E.N.A.L. nephrometry scoring system. ¹⁰ Pre- and postoperative eGFR was estimated using the Modification of Diet in Renal Disease equation. ¹¹ The chronic kidney disease (CKD) staging ¹² was assigned according to eGFR. The eGFR preservation was calculated as a proportion of postoperative eGFR measured at the last follow-up to preoperative eGFR, and the rates of CKD upstaging were evaluated (from class I-II to III-V, from class III to IV-V, and from class IV to V).

For variables with normal distribution, data are presented as mean ± SD and the respective groups were compared using the Student's t test. For variables with non-normal distribution, data are presented as median (interquartile range [IQR]) and the groups were compared using Mann–Whitney U test. Categoric variables were compared using the chi-squared test. Multivariable analysis of factors predicting CKD upstaging (surgery type, CCI, tumor size, R.E.N.A.L. score, and preoperative eGFR) was conducted using a logistic regression model. Significance was set at p-value <0.05. Analyses were performed using SPSS v21 software (IBM SPSS Statistics; IBM Corp., Armonk, NY).

Results

From 809 RPNs performed during the study period, 79 patients met our inclusion criteria, however, only 52 could be matched to the LRN group. The median R.E.N.A.L. score for both groups was 9 (IQR 9–10). Demographics and preoperative clinical variables were comparable between the groups (Table 1). The median renal volume preservation in the RPN group was 57.0% (IQR 47.2–67.2) with a median warm ischemia time of 27.5 (IQR 21.0–34.0) minutes. No patient had an off-clamp RPN in this cohort.

The operative duration (220 ± 59 minutes vs 154 ± 56 minutes; p < 0.001) and the EBL (250 [100–650] mL vs 150 [100–250] mL; p < 0.001) were higher in the RPN group (Table 2). The HLOS was shorter in the RPN group (4 [3–4] days vs 5 [4–6] days; p = 0.009). The rates of overall and major complications were comparable between RPN and LRN (38.5% vs 42.3%; p = 0.62 and 11.5% vs 5.8%; p = 0.48, respectively), and no statistic difference was found when comparing specific complications such as blood transfusion (7 vs 1; p = 0.06), urine leak (3 vs 0; p = 0.24), and surgical site complication (2 vs 5; p = 0.43).

On histopathology evaluation, the number of renal-cell carcinomas and positive margins was comparable between RPN and LRN groups (48 [92.3%] vs 47 [90.4%]; p = 0.72 and 2 [3.8%] vs 0; p = 0.49, respectively). Local staging (pT stage) distribution is shown in Table 3.

The RPN group had higher overall glomerular filtration rate (GFR) preservation (75.8% vs 68.5%; p = 0.01) and a lower rate of CKD upstaging (26.9% vs 50.6%; p = 0.001). On multivariable analysis, assessing factors predicting CKD upstaging (surgery type, ACCI, R.E.N.A.L. score, and preoperative eGFR), LRN, and baseline eGFR were significant predictors of CKD upstaging (OR 4.26; 95% CI [1.80–10.12]; p = 0.001 and OR 0.98; 95% CI [0.96–0.99]; p = 0.03, respectively; Table 4).

During the median follow-up time of 21 (IQR 9–36) months, metastasis incidence (5.8% vs 1.9%; p = 0.62) and cancer-specific and overall survival (96.2% vs 98.1%; p = 1.0 and 92.3% vs 82.7%; p = 0.23, respectively) were comparable between RPN and LRN, respectively. No patient presented with local recurrence during the follow-up.

Regarding the 27 patients not included in the analysis, the preoperative (age, BMI, ACCI, R.E.N.A.L. score, preoperative eGFR) and postoperative characteristics (renal volume preservation, GFR preservation, overall and major complications, renal-cell carcinoma [RCC] rate, pathologic T-stage distribution) were comparable to the 52 RPN cases analyzed. In this cohort, no metastasis was detected and one local recurrence was observed during the period of follow-up. One patient died from an unrelated cause, and no patient died from their renal cancer. Moreover, the preoperative clinical and demographic characteristics of the 52 RPN cases in this study are comparable to the remaining 757 cases, except for tumor size (5.1 [4.4–6.2] cm vs 2.8 [2.0–3.9] cm; p < 0.001) and R.E.N.A.L. score (9 [9–10] vs 7 [6–9]; p < 0.001).

Discussion

PN was initially the preferred option only for absolute indications such as tumors in a solitary kidney, bilateral tumors, and chronic renal insufficiency. The technique and patient outcomes have increasingly improved, making this approach the standard treatment for clinical T1a (<4 cm) renal masses in the last decade. ¹ It has been shown that PN is associated with better renal function preservation, reduced incidence of CKD, ^{13 –15} and consequently, reduced incidence in cardiovascular events. ¹⁶ Even though PN is still relatively underutilized, in recent years we have witnessed an upward trend toward its utility. ^17,18

Despite technical challenges, the minimally invasive PN has increased in number and has achieved comparable outcomes to the open technique for selected tumors. ^2,3 With the growing experience in RPN, the complexities of cases are also increasing ^2,19 at times involving extensive resection of renal volume. It has been proposed that PN in such a setting might not provide any tangible benefit compared with RN in terms of GFR preservation, postoperative complication rate, and oncologic outcomes. Our objective was to compare the outcomes of RPN to RN in patients where NSS mandated a large amount of renal volume resection.

The groups were matched based on patients and tumor features using Charlson index, preoperative eGFR, tumor size, and R.E.N.A.L. nephrometry score. Both groups were comparable and comprised patients with moderate comorbidity load and relative large tumors, with moderate to high complexity. The operative duration and the EBL were higher in the NSS group, as anticipated given the more challenging technique; however, this group showed a shorter length of hospital stay and comparable rates of overall and major complications. The frequency of postoperative complications in our cohort was similar to previous studies of robotic PN for complex tumors. ^2,19

Song and associates ²⁰ and Mir and associates ²¹ have demonstrated that late renal function after PN is associated to parenchymal volume preservation; however, in their cohort, the median volume preserved was high (80% and 83%, respectively). The median renal volume preserved in our RPN cohort was 57.0% (47.2–67.2), confirming the extensive parenchymal resection and reconstruction performed. However, despite this large volume loss in the RPN group, a higher proportion of GFR preservation and a lower rate of CKD upstaging were observed when compared to the LRN group. When controlling for all variables contributing to CKD upstaging, baseline eGFR and specially RPN were significant protector factors against CKD upstaging.

RCCs were identified in 92.3% of RPN cases and presented 3.8% of positive margins; however, none of the two patients presented local recurrence or metastasis on the follow-up period of 6 and 35 months after RPN. These results are comparable to previous larger RPN cohorts ^22,23 and support the idea that PN did not compromise the oncologic outcomes even when extensive parenchymal resection was required.

Other findings that corroborate for the oncologic safety of this approach are the comparable rates of cancer recurrence and metastasis between the RPN and LRN groups (0 vs 0 and 3 vs 1; p = 0.62, respectively). The four patients who presented with distant metastasis had pT3a tumors with negative margins. This suggests that tumor aggressive behavior rather than surgical approach is responsible for the oncologic outcome. Despite better renal functional outcomes, we did not observe any difference in cancer-specific and overall survival (96.2% vs 98.1%; p = 1.0 and 92.3% vs 82.7%; p = 0.23) between RPN and LRN, respectively. However, longer follow-up times are required to assess this.

The present study has some limitations, including the retrospective design with a relatively small sample size. In addition, the higher observed rate of pT3 tumors in the LRN group is likely due to a selection bias for the RN approach in such aggressive tumors. Finally, the follow-up times are relatively short, and long-term data are required to assess the impact of renal function on overall mortality rate in our cohorts.

Conclusions

RPN, in cases with extensive volume resection, provides renal functional preservation without increasing the surgical complications or compromising short-term oncologic outcomes when compared with RN. Even when relatively large parenchymal resection is anticipated, NSS might be worthy of consideration in carefully selected cases where technical expertise is available.