Robot-assisted partial nephrectomy for renal cell carcinoma: A narrative review of different clinical scenarios

Abstract

Objective

Nowadays robot-assisted partial nephrectomy (RAPN) represents the standard of care for clinical T1 (cT1) renal masses, providing similar oncological outcomes when compared to open or laparoscopic PN with advantages in terms of functional outcomes and lower perioperative comorbidity, when compared to radical nephrectomy.

Methods

We performed an extensive literature review of studies regarding RAPN, its evolution, technical aspects and applications, and new technological tools using different combinations of Medical Subject Headings terms “RAPN”, “partial nephrectomy”, “robot-assisted”, “nephron-sparing surgery”, “renal cell carcinoma”, “complex renal masses”, “endophytic renal masses”, and “bilateral renal tumors”.

Results

A consistent body of evidence was selected, including original articles, systematic reviews, meta-analyses, and clinical trials having RAPN as the central focus in adult patients, with all its technical nuances. We started our narrative review with a background on PN and its evolution toward the robotic era with a special spotlight on the extending indications for PN in large and highly complex renal masses. Our review continued with an overview of nephron-sparing surgery in bilateral and recurrent masses. RAPN for bilateral synchronous renal masses represents a challenging scenario with no formal recommendations provided by international guidelines and controversial management and decision-making. Additionally, we reported evidence on redo RAPN which seems to be safe and effective. A final overview of the available technological tools, and in particular on three-dimensional reconstruction was provided.

Conclusion

RAPN has been established as the standard of care for cT1 renal masses with an expanding spectrum of applications in different scenarios, including large (cT2), highly complex, and bilateral renal masses, as well as the surgical treatment of local recurrences after nephron-sparing surgery with acknowledged advantages in terms of functional outcomes and perioperative risk profiles while maintaining similar oncological outcomes when compared to open or laparoscopic PN and radical treatment.

1. Introduction

Renal cell carcinoma (RCC) constitutes approximately 3% of all malignancies, with the highest incidence rates observed in Western countries [1,2]. In 2022, it was estimated that there were 431 288 new cases of RCC worldwide, with 138 611 of these occurring in Europe [3,4]. Over the past two decades, the therapeutic landscape for RCC has undergone significant advancements, enabling clinicians to personalize treatment strategies for patients across both localized and metastatic disease stages. In the context of localized RCC, partial nephrectomy (PN) has become the treatment of choice for clinical T1 (cT1) renal tumors [5], offering distinct benefits over radical nephrectomy (RN), particularly in preserving renal function while ensuring comparable oncological efficacy [[6], [7], [8]]. The advent and increasing utilization of robot-assisted techniques have further extended the applicability of PN to more complex cases and larger renal masses [[9], [10], [11]]. Moreover, PN has also gained the stage in a crucial clinical scenario such as bilateral and recurrent masses. This advancement demanded to optimize surgical outcomes by mitigating factors that affect renal function, such as ischemia induced by vascular clamping, excision of perilesional healthy tissue, and ischemia related to suturing. Under this light, several technological tools have also been incorporated within the robotic console to maximize the precision and case-tailoring before and during the surgical procedure. This review synthesizes the current literature on robot-assisted PN (RAPN) across various clinical scenarios, including complex and large renal masses, bilateral tumors, and local recurrence, and the incorporation of different technologies to enhance and support RAPN.

2. Materials and methods

An extensive literature search from PubMed, Scopus, and Web of Science was performed on April 20, 2024, gathering studies evaluating the evolution of RAPN, its technical aspects and applications, and new technological tools. The research was conducted without time or language filters using different combinations of the following Medical Subject Headings terms “RAPN”, “partial nephrectomy”, “robot-assisted”, “nephron-sparing surgery”, “renal cell carcinoma”, “complex renal masses”, “endophytic renal masses”, and “bilateral renal tumors”. Hand-bibliography research of included studies and previous reviews on the topic was also realized to implement additional relevant studies. We excluded a priori pre-clinical and animal studies. Two independent reviewers (Salamone V and Giudici S) completed this process independently and all disagreements were settled by a third author (Grosso AA).

3. Results and discussion

3.1. RAPN: changing paradigms of the surgical management for RCC

PN has emerged as the standard of care for managing small renal masses, offering superior long-term functional outcomes and comparable oncological results to RN. Although Wells [12] first reported the feasibility of PN in 1884, its initial modern applications were confined to imperative indications such as bilateral renal masses or tumors in a functionally or anatomically solitary kidney. Historically, traditional open surgery was predominantly employed for the management of most renal tumors for many years. However, with increasing emphasis on minimally invasive surgery, the robotic approach has gained prominence, demonstrating significant reductions in perioperative morbidity, including blood loss, hospitalization time, and complication rates [13,14]. Over the years, surgical techniques have also evolved from more extensive resections (wide resection) to precise techniques such as pure enucleation, aiming to preserve as much healthy parenchyma as possible [15]. Numerous studies have validated the safety of enucleation in minimizing surgical margins [16], while optimizing renal function preservation and surgical tolerability [17,18]. Moreover, the techniques have been improved in different aspects including the spread of the retroperitoneal approach, which showed to have been feasible in posterior masses [19], the evolution of the renography technique [20], and in some cases the omission of the abdominal drain [21]. Collectively, this evidence has expanded the indications for RAPN to include select candidates, such as frail, comorbid, and obese patients [22,23].

3.2. RAPN for cT2 renal masses

In recent years, renal surgery has undergone a significant paradigm shift concerning cT2 renal masses [24]. In 2017, Mir et al. [25] conducted a meta-analysis of four studies comparing PN and RN, revealing that the PN group exhibited a lower recurrence rate and cancer-specific mortality without impacting all-cause mortality. A multicenter series involving 8664 patients by Janssen et al. [26] identified 123 patients who underwent PN and 105 who underwent RN for tumors ≥7 cm in an elective setting. This study demonstrated that nephron-sparing surgery (NSS) for cT2 clear-cell RCC was technically feasible with acceptable complication rates in centers with highly skilled surgeons [26]. In 2018, the “ROSULA” collaborative group presented a large series of RAPN for cT2 renal masses. In this project, “Trifecta”, defined as negative surgical margins, no perioperative complications, and warm ischemia time (WIT) of <25 min, served as a surrogate marker of surgical quality. Trifecta was achieved in 49% of the population, with major complications occurring in 5% of cases. Although there was a significant decline in renal function at discharge, it remained stable over time at the 1-year follow-up [27]. Additionally, the ROSULA group compared 216 cases of RAPN to 432 cases of minimally invasive RN cases within this clinical setting, demonstrating a similar perioperative risk profile, including comparable readmission and complication rates. The study found similar overall survival and disease-free survival rates at the 3-year and 5-year follow-ups; however, the RAPN group had a higher rate (91.6%) of 5-year freedom from de novo estimated glomerular filtration rate of <45 mL/min/1.73 m² compared to the RN group (68.9%) (p<0.001) [28].

3.3. Robot-assisted NSS for highly complex renal masses

Complexity in PN can be assessed from multiple perspectives, including tumor characteristics, patient factors, and surgical setting features. Focusing on tumor characteristics, several nephrometric scores have been developed to objectively quantify the difficulty of PN [29]. One of the most significant factors influencing complexity is the endophytic rate of the mass. Traditionally, highly complex cases (Preoperative Aspects and Dimensions Used for an Anatomical [PADUA] score of >10) have been approached using open surgery. However, as robotic surgical capabilities have advanced, there has been a paradigm shift towards minimally invasive surgery. This shift is supported by the inherent benefits of robotic technology, such as magnified visibility, enhanced ergonomics, and the use of EndoWrist instruments. These features enable surgeons to perform precise tissue dissection and tumor excision, and facilitate an easier reconstruction phase. Autorino et al. [30] compared endophytic, mesophytic, and exophytic masses, demonstrating that the safety and feasibility of RAPN for endophytic renal masses were comparable to those in the general RAPN population. In one of the largest multicenter analyses, Carbonara et al. [31] confirmed that RAPN for completely endophytic renal masses can be performed with acceptable outcomes in centers with significant robotic expertise. However, there is an increased risk of prolonged ischemia time and overall complications compared to exophytic and mesophytic masses. Complex masses also include those located at the renal hilum. The NEPRAH study, published in 2024, compared the outcomes of hilar to non-hilar masses [32]. It found longer WIT and operative time, along with a higher risk of postoperative complications (odds ratio 1.33; p=0.05) in the hilar group, though no significant differences in recurrence-free survival, cancer-specific survival, or overall survival were observed [32]. Careful planning and a tailored approach are essential in this context. Specifically, selecting the optimal resection strategy and technique [33], as well as implementing a customized renorrhaphy, significantly enhances the chances of success, reduces margin rates, and improves functional preservation [6,[34], [35], [36]].

3.4. Imperative indication in NSS: RAPN in bilateral tumors

Bilateral synchronous renal masses present a complex clinical challenge with no established guidelines from international bodies and contentious management strategies. Nevertheless, when technically feasible, NSS is recommended to preserve renal function and reduce cardiovascular morbidity [4]. Striking a balance between oncological outcomes, renal function preservation, and minimizing complications is crucial and demands considerable expertise from the surgeon while being vital for patient outcomes. Key determinants for achieving these goals include precise preoperative planning, surgeon's proficiency, volume of the center, and tumor characteristics. Unfortunately, due to scenario complexity, there is a paucity of data and only a limited number of series on patients undergoing RAPN for bilateral renal masses, leaving many questions unanswered [37,38].

Gallo et al. [38] analyzed data from a prospectively maintained multi-institutional database of patients undergoing simultaneous RAPN. They found that 27 patients underwent simultaneous bilateral RAPN with an acceptable complication rate (25.9%, primarily Clavien-Dindo grade 2 events), comparable to complications reported for elective unilateral RAPN. These findings indicate that in selected patients and with experienced surgeons, simultaneous bilateral RAPN can be safe and feasible without significant impact on renal function. Additionally, Di Maida et al. [37] reported on patients with bilateral synchronous masses undergoing PN. They retrospectively reviewed data from 41 patients who underwent various combinations of robotic and open approaches, either in a single or staged procedure. Of these, 37 (90.2%) patients received bilateral PN; three (7.3%) had PN plus RN; and one (2.4%) underwent bilateral RN. A double robotic approach was utilized in 26 (63.4%) patients, a combined robotic and open approach in two (4.9%) patients, and a bilateral open approach in 13 (31.7%) patients. There were no conversions from robotic to open surgery. The authors concluded that despite limited evidence and lack of international recommendations, a simultaneous or staged surgical approach is feasible in selected patients to optimize renal function preservation and oncological outcomes.

3.5. PN for local recurrence after NSS

Local recurrence after PN is defined as relapse on tumor resection bed or in the ipsilateral kidney. It may be due to an incomplete resection or a de novo metachronous neoformation. The disease recurrence rate after RAPN varies among studies and has been estimated to be between 4% and 13% [39]. Most of them are observed within 5 years, yet late relapse may occur even decades after primary treatment. Management of local RCC recurrence after NSS includes non-surgical and surgical options: in the first case, ablative therapy (cryoablation and radiofrequency ablation); in the second case, salvage (redo) radical and PN [40].

Studying the predictors of local recurrence after NSS, Zhang et al. [41] showed how positive surgical margins (PSMs), higher Fuhrman grade, higher pathological stage, and large tumor size were significantly associated with recurrence risk while age, sex, and surgical approach had no effect on recurrence after NSS. Regarding highly complex (PADUA score of ≥10) masses, Mari et al. [42] found a strong association between PSMs, higher Fuhrman grade, pathological T3a (pT3a) upstaging, and risk of recurrence.

Most recently, Di Maida et al. [43] presented their experience with salvage PN after NSS. Data from 26 patients treated with robotic redo PN for locally recurrent RCC after previous NSS were gathered and analyzed. The median clinical diameter was 3.5 (interquartile range [IQR] 2.2–4.9) cm and the median PADUA score was 8 (IQR 7–9). In 14 (53.8%) cases, the recurrence was found at the level of the previous tumor resection bed, and four (15.4%) patients had a PSM reported at the time of primary tumor resection. The median operative time was 177 (IQR 148–200) min, and hilar clamping was performed in 14 (53.8%) cases with a median WIT of 16 (14.5–22) min. Pure enucleation (surface-intermediate-base [SIB] score 0–1), hybrid enucleation (SIB score 2), and pure enucleoresection (SIB score 3) were recorded in 13 (50.0%), eight (30.8%), and five (19.2%) cases, respectively. Intraoperative complications were recorded in two (7.7%) cases: one pancreatic and the other vascular pedicle injury. No conversions to RN occurred. The median length of hospitalization was 5 (IQR 4–6) days. pT1a, pT1b, pT2, and pT3a were recorded in 18 (69.2%), five (19.2%), one (3.8%), and two (7.7%) cases, respectively. No major (Clavien-Dindo grade of ≥3) complications occurred. The most common histotype was clear cell RCC and in 24 (92.3%) cases, there was a concordance in the histotype of primary and relapsing tumors. This study highlighted the feasibility and safety of redo PN for the treatment of locally recurrent RCCs after NSS, either on the previous tumor resection bed or elsewhere in the kidney. Moreover, it reinforces the concept of sparing nephrons whenever possible, since also in advanced and recurrent disease stages, renal function represents a mainstay for further systemic therapies [44,45].

3.6. New technologies in robot-assisted renal surgery

Over the last years, technology has tremendously expanded, covering many aspects of healthcare, from diagnosis to treatment to follow-up [46,47]. Robotics found a very fertile ground in this field since the integration of the surgical system with technological tools has been progressively adopted in various procedures [[48], [49], [50]]. Innovative imaging technologies have been explored in NSS, such as highly accurate three-dimensional (3D) virtual models that have the goal to facilitate the anatomical characterization of the tumor and surrounding vasculature to tailor the best surgical plan to the patient, especially for highly complex renal masses or imperative indications for NSS (solitary kidney and bilateral tumors).

In 2017, von Rundstedt et al. [51] reported the first study evaluating the validity of a renal model for pre-surgical simulation of robot-assisted laparoscopic PN: a patient-specific 3D digital model was obtained based on CT scan or MRI and then converted into a silicone soft-tissue model. RAPN was rehearsed for all patients using the 3D model with the da Vinci Si platform before performing the RAPN on each patient. The study demonstrated similarity in tumor resection time, resected tumor volume, and morphology for these models when compared to the patient's actual resected tumor, suggesting that this system might be valuable for surgical planning and RAPN training with some uncertainties with regard to endophytic tumors, especially to the exact tumor contour and a certain degree of discordance with respect to tumor volume.

At the end of next year, Porpiglia et al. [52] introduced the hyperaccuracy 3D (HA3D) reconstruction during RAPN and assessed its efficacy in sponsoring selective clamping of renal arterial branches for complex renal masses. The authors demonstrated that 43% of patients in the HA3D group received selective clamping of secondary-order arterial branches of the renal artery significantly reducing the rate of patients undergoing global ischemia (80.6% in the no HA3D group vs. 23.8% in the HA3D group, p<0.01). Moreover, a lower rate of opening of the collecting system was recorded in the HA3D group when compared to the counterpart (14.3% vs. 41.9%, p=0.05) [52].

Within the same field of interest, between 2021 and 2024 the Florentine school presented its experience in RAPN with 3D preoperative surgical planning [[53], [54], [55], [56], [57]]. The authors found that 3D reconstruction led to the downgrading of tumor complexity (by the PADUA score and PADUA risk-category) and increased the chance of NSS. The impact of 3D reconstruction was tested on functional outcomes as compared to a control group [57]. A significant preservation of renal function at 1-year follow-up emerged only in highly-complex (PADUA score of ≥10) masses [57]. A meta-analysis conducted by the European Association of Urology Young Academic Urologists and the European Section of Uro-Technology on this topic confirmed these results [58]. In particular, the authors showed how such technology may be beneficial in reducing the global ischemia rate (odd ratio [OR] 0.22, 95% confidence interval [CI] 0.07–0.76; p=0.02), transfusion rate (OR 0.20, 95% CI 0.07–0.56; p<0.01), blood loss (median decrease 23.1 mL, 95% CI 31.8–14.4 mL; p<0.01), events like opening of the collecting system (OR 0.36, 95% CI 0.15–0.89; p=0.03), while facilitating enucleation (OR 2.54, 95% CI 1.36–4.74; p<0.01). No significant differences emerged in rates of conversion to RN, minor and major complications, or surgical margins (all p>0.05).

The latest advance in the robotic urological field is represented by the da Vinci Single Port® (SP) system (Intuitive Surgical Inc., Sunnyvale, CA, USA). Its development aims to minimize skin incisions and facilitating work in a smaller working space while preserving the advantages of robotic instruments. Initial experiences with SP RAPN have demonstrated safety and feasibility, both through transperitoneal and retroperitoneal approaches [59]. Initial comparative studies suggest that SP RAPN can offer similar peri- and postoperative outcomes compared to multiport RAPN, with potential benefits such as lower opioid use and improved cosmetic results [60]. One of the main features of this novel technology is that it allows the expansion of the role of retroperitoneal kidney surgery. This can translate into faster postoperative recovery, which could ultimately lead to the implementation of outpatient surgery [61]. To date, SP RAPN has been used mostly for low to intermediate-complexity tumors; however, maturing experience will extend its indications to more complex cases.

4. Conclusion

PN has become the standard of care for managing small renal masses, with a notable paradigm shift towards its indication even for cT2 renal masses. RAPN has progressively substituted open and laparoscopic approaches providing comparable oncological outcomes with benefits in terms of functional outcomes, reduced perioperative morbidity, and shorter hospital stay for both small and highly complex renal masses. This review analyzed data on the adoption of RAPN across different clinical scenarios, providing updated information and valuable surgical insights. In particular, RAPN emerged as a preferred approach in case of a bilateral tumor either as single- or two-stage surgery, and in experienced hands should represent a valuable approach for local recurrent cases whenever technically feasible. The latest technological innovations further favor the adoption of RAPN since they can be integrated into the robotic console. Future research should aim to uncover innovative conclusions that could significantly contribute to the urological community's understanding of the RAPN's role in treating RCC.

Author contributions

Conception and Design: Antonio Andrea Grosso, Andrea Minervini.

Data acquisition: Antonio Andrea Grosso, Vincenzo Salamone, Sofia Giudici, Luca Lambertini, Francesco Lupo Conte, Luca Mazzola, Agostino Tuccio, Rino Oriti, Alfonso Crisci, Gianni Vittori, Mara Bacchiani, Anna Cadenar, Riccardo Fantechi.

Data Analysis: Antonio Andrea Grosso, Vincenzo Salamone, Fabrizio Di Maida.

Drafting of Manuscript: Antonio Andrea Grosso, Vincenzo Salamone.

Critical revision of the Manuscript: Andrea Mari, Andrea Minervini.

Conflicts of interest

The authors declare no conflict of interest.