Renal functional outcomes after robot-assisted partial nephrectomy and percutaneous cryoablation of clinical T1 renal cell carcinoma – A prospective study

INTRODUCTION

The incidence of renal cell carcinoma (RCC) has been increasing for decades, making RCC one of the most rapidly increasing cancer diagnoses in the developed world.^[1] The primary treatment for localized T1 RCC is surgery, and partial nephrectomy (PN) is the gold standard due to its nephron-sparing quality and similar oncological outcome to radical nephrectomy (RN).^[2,3]

RCC primarily occurs in the elderly, complicating treatment since elderly patients have abundant comorbidities, including renal functional impairment. Therefore, nephron-sparing treatment (NST) and minimally invasive treatments such as PN and thermal ablation (TA) are preferred to minimize the risk of the development or progression of chronic kidney disease (CKD).^[2-4] The long-term consequences of CKD include increased risk of cancer, cardiovascular events, hospitalization, and death.^[5] Over 25% of RCC patients have impaired renal function before treatment,^[6,7] and they are at risk of CKD progression following surgery or TA.^[8]

Robot-assisted PN (RAPN) and laparoscopic PN (LPN) are the preferred minimally invasive treatments with equal oncological outcomes.^[2,3,9,10] RAPN has a shorter warm ischemia time (WIT) and a lower conversion rate to RN.^[9] Renal functional outcome after different types of PN has been extensively studied.^[11-14]

TA is an increasingly prioritized minimally invasive treatment of T1 RCC offered to comorbid patients with no other treatment options. Studies have indicated a lower risk of complications after TA compared to PN.^[15,16] Furthermore, the 5-year RCC-specific survival in selected patients after TA to those treated with PN.^[16] However, renal functional outcome after TA has not been thoroughly investigated, especially the impact of percutaneous cryoablation (PCA).^[17,18]

This study investigated renal function after RAPN and PCA in clinical stage T1 (cT1) RCC and evaluated the relationship between baseline renal function and renal functional outcome.

MATERIAL AND METHODS

This non-randomized single-center prospective cohort study was approved by the Danish National Data Protection Agency (19/8784) and the Regional Committee on Health Research Ethics for Southern Denmark (S-20180080NA) with approval of an updated version in June 2020. Patients participated after informed written and oral consent.

Patient selection and data collection

Patients with cT1 RCC treated with RAPN or PCA at Odense University Hospital were prospectively and consecutively enrolled from Region of Southern Denmark between June 2019 and January 2021. Exclusion criteria were being under 18 years old at the time of treatment, presence of a benign tumor, conversion of RAPN to open surgery, conversion of RAPN to RN, salvage treatment within 6 months after primary treatment, missing baseline examinations, or multiple treatments in cases of multiple tumors [Figure 1].

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Figure 1:

Diagram of the inclusion process of patients undergoing nephron-sparing RCC treatment. RCC: Renal cell carcinoma, PCA: Percutaneous cryoablation, RAPN: Robot-assisted partial nephrectomy, OPN: Open partial nephrectomy, RN: Radical nephrectomy.

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The treatment options for individual patients were discussed in multidisciplinary team conferences with the participation of pathologists, radiologists, oncologists, and urologists. When NST was considered suitable, the final treatment decision was based on tumor characteristics, age, health status, renal function, and patient preference, following the principle of shared decision-making.^[19]

Data were collected from the picture archiving and communication systems (PACS) and electronic patient records and stored in a REDCap database. Findings were reported according to the “Strengthening the Reporting of Observational Studies in Epidemiology” guidelines.^[20]

RESULTS

A total of 56 patients were included in this study: 38 PCA and 18 RAPN [Figure 1]. We found a significantly higher age (68.5 vs. 57.5 years, P = 0.019) and CCI (3.0 vs. 2.0, P = 0.007) in patients undergoing PCA compared to RAPN [Table 1]. Three patients had a solitary kidney, and all underwent PCA. All patients with baseline CKD IIIa–IV underwent PCA. One patient underwent PCA of two tumors. Therefore, 57 tumors were assessed in this study. Tumor characteristics in patients undergoing RAPN and PCA did not differ significantly [Table 2]. Four tumors were downgraded from cT1b to pT1a, and one tumor was upgraded from cT1b to pT2.

[Supplementary Table 1] shows treatment characteristics for RAPN and PCA. In RAPN, WIT was ≤30 min in all cases, and in 17 of 18 patients (94%), WIT was ≤25 min.

Renal function was assessed in 56 patients and decreased significantly after both treatment types regarding median p-creatinine, eGFR, eGFR-CKD, and DTPA, but not in DTPA-CKD [Table 2].

Total renal volume change in patients was significant in patients who underwent PCA but not RAPN. Both treatment groups had a significant reduction in the ipsilateral volume but not a corresponding increase in the contralateral volume. The ipsilateral renal area decreased significantly in both treatment groups. The contralateral renal area also significantly decreased 6 months after PCA, but no significant change was found after RAPN. The split renal function of the ipsilateral kidney decreased significantly in both groups [Tables 3, and 4]. No patients developed end-stage renal disease or required dialysis within 6 months of follow-up.

Baseline CKD IIIb–IV leads to a significantly greater reduction in renal volume at 6 months after treatment compared to patients with baseline normal renal function CKD I–II (P = 0.003; [Supplementary Table 2a]). In addition, median total renal volume and area were slightly lower at baseline and 6 months after PCA with a higher range compared to RAPN [Figure 2]. Median eGFR and DTPA-GFR were lower and their range was higher at both baseline and 6 months after PCA compared to RAPN [Figure 2]. Changes in median DTPA-GFR and eGFR are illustrated with the baseline CKD group and treatment type [Figure 3]. Median GFR was stable or decreased, except for patients with baseline DTPA-CKD IIIb in whom GFR increased at the 6-month follow-up [Figure 3]. Nevertheless, changes in renal function after PCA were not significantly different from those after RAPN with any of the measured parameters [Supplementary Table 2b].

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Figure 2:

Boxplots of renal functional change from baseline to 6 months after RAPN and PCA. (a) Total renal volume. (b) Renal area of the tumor-bearing (ipsilateral) and non-tumor bearing (contralateral) kidneys as determined by renography. (c) eGFR. (d) DTPA-GFR. RAPN: Robotic-assisted partial nephrectomy, PCA: Percutaneous cryoablation, eGFR: Estimated glomerular filtration rate (CKD-EPI), mL/min/1.73m², DTPA-GFR: Tc-99m-diethylenetriamine pentaacetic acid clearance, mL/min/1.73m². Black dots are outliers. Gray box: Box plot of the total renal function.

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Figure 3:

Illustrations of the change in median GFR from baseline to 6 months post-treatment. Color represents renal function baseline CKD-group. CKD stages defined according to KDIGO guidelines:^[26] CKD I (GFR: ³90 mL/min/1.73 m²), CKD II (GFR: 60–89 mL/min/1.73 m²), CKD IIIa (GFR: 45–59 mL/min/1.73 m²), CKD IIIb (GFR: 30–44 mL/min/1.73 m²), CKD IV (GFR: 15–29 mL/min/1.73 m²), CKD V (GFR: <15 mL/min/1.73 m²). (a) Change in DTPA GFR in patients treated with RAPN. Blue: Baseline CKD I (9 patients); red; baseline CKD II (5 patients). (b) Change in eGFR in patients treated with RAPN. Blue: Baseline CKD I (10 patients); red: Baseline CKD II (8 patients). (c) Change in DTPA GFR in patients treated with PCA. Blue: Baseline CKD I (8 patients); red: Baseline CKD II (12 patients); green: Baseline CKD IIIa (4 patients); yellow: Baseline CKD IIIb (2 patients); gray: baseline CKD IV (1 patient). (d) Change in eGFR in patients treated with PCA. Blue: Baseline CKD I (13 patients); red: Baseline CKD II (18 patients); green: Baseline CKD IIIa (2 patients); yellow: Baseline CKD IIIb (2 patients); gray: Baseline CKD IV (3 patients). GFR: Glomerular filtration rate, eGFR: Estimated glomerular filtration rate, CKD: Chronic kidney disease, DTPA GFR: Tc-99m-diethylenetriamine pentaacetic acid clearance, RAPN: Robot-assisted partial nephrectomy, PCA: Percutaneous cryoablation.

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DISCUSSION

This study found that renal function significantly decreased 6 months after RAPN and PCA of cT1 RCC, reflected in multiple renal function parameters. Pre-existing CKD IIIb–IV was predictive of a significantly greater reduction in total renal volume after PCA compared to patients with a normal baseline renal function. This reduction was not accompanied by significant decreases in eGFR, DTPA, or split renal function. Despite significant differences in baseline health and renal function between patients who underwent RAPN and PCA, the change in renal function was comparable in both treatment groups.

Evaluating renal function after RCC treatment is important because the RCC population is typically elderly with abundant comorbidities.^[6,7] In addition, all-cause mortality for patients with pre existing CKD is significantly higher than for patients with normal renal function.^[5] In living kidney donors, neither postoperative GFR nor CKD development is associated with reduced survival compared to patients with impaired renal function due to medical conditions.^[13] This lack of association is likely explained by the remaining parenchyma taking over the surgically removed nephrons and compensatory mechanisms in healthy kidneys.^[27] In this study, patients treated with PCA were significantly older, prone to other renal diseases, and had significantly higher CCI compared to those who underwent RAPN. Furthermore, all patients with pre-existing CKD were treated with PCA. The contralateral renal volume in patients who underwent PCA did not increase sufficiently to preserve the total renal volume, as opposed to patients who underwent RAPN. This finding can be explained by the presence of preexisting impaired renal function reducing the regenerative mechanisms of the non-malignant renal parenchyma, indicating that the quantity and quality of the remaining renal tissue are crucial factors for preserving renal function.^[27,28]

A statistically significant change in eGFR-CKD was found in patients treated with PCA and RAPN with a net worsening in the CKD stage. In patients undergoing PCA, a fluctuation in eGFR-CKD and DTPA-CKD stages was observed, with some patients upstaging and others downstaging after treatment. A similar inconsistency in CKD stage changes was found by Wehrenberg-Klee et al., who retrospectively studied a small group of patients with baseline CKD III–V undergoing radiofrequency ablation (RFA) and PCA of RCC.^[28] Despite changes in CKD stage, they found no significant change in eGFR 1-year post-treatment with RFA or PCA. Consequently, CKD changes could indicate significant changes in renal function that cannot be detected with other variables. Therefore, the role of baseline CKD on renal functional outcome after RCC NST remains unclear and should not be considered of high value without other renal functional parameters.

WIT was found to be crucial for renal functional outcomes after PN.^[29] In a systematic review comparing LPN and RAPN, a lower WIT and a favorable postoperative eGFR rate were found after RAPN.^[9] A WIT cutoff of 20–25 min has been proposed to be an important predictor of adverse renal outcomes for all levels of baseline renal function.^[29] In this study, ischemic time was minimal, with a median WIT of 17.5 min, and no patients had WIT >30 min. Six months after treatment, no RAPN patients had new-onset CKD IIIb–V. Therefore, the shorter WIT used here is beneficial for renal functional outcomes. However, it should be noted that all patients treated with RAPN in this study had normal baseline renal function (eGFR ≥60 mL/min/1.73 m²; CKD I-II).

This study found a significant reduction in renal function after both RAPN and PCA and no significant differences between RAPN and PCA. Bhindi et al. evaluated eGFR changes in 118 patients with a solitary kidney undergoing PN or PCA of RCC,^[10] finding no significant difference in eGFR drop from baseline to 3 months post-treatment between PCA and PN. Similarly, in a systematic literature review, Uhlig et al. found that PN, PCA, RFA, and microwave ablation of renal tumors were all associated with a net decrease in renal function.^[18] However, no significant differences between PN and PCA were observed.

The findings of this study are limited by several factors. For example, as a single-center study with no randomization, it is sensitive to selection bias in the recruitment process. The majority of patients did not wish to participate in the study. This could be explained by the fact that treatment was performed in a fast-track setting at a highly specialized hospital with a large uptake area. Patients should attend the hospital for baseline DTPA examination in the short time frame from diagnosis to treatment. Furthermore, the inclusion period of the study was during the COVID-19 pandemic, and research examinations were temporarily shutdown. The small sample size introduces a degree of uncertainty to its statistical findings and the conclusions based on them. Moreover, because patients were recruited from a large geographical area, many refused to participate due to supplementary examinations requiring an additional hospital visit within the short period between diagnosis and treatment. Finally, its use of a single post-treatment renal function measurement will miss longitudinal fluctuations in changes in renal function. Because CKD is defined as a permanent decrease in renal function after 90 days,^[26] a 6-month follow-up was chosen to mitigate the potential impact of longitudinal variability on the data collected.

CONCLUSION

This study found a decrease in renal function 6 months after both RAPN and PCA. Patients with CKD IIIb–IV, all treated with PCA, showed a greater decline in renal volume than patients with baseline normal renal function. The renal functional changes were similar for RAPN and PCA patients.