Perioperative, functional, and oncologic outcomes after ablation or partial nephrectomy for solitary renal tumors: a systematic review and meta-analysis of comparative trials

doi:10.21203/rs.3.rs-2988681/v1

Download PDF

Research Article

Perioperative, functional, and oncologic outcomes after ablation or partial nephrectomy for solitary renal tumors: a systematic review and meta-analysis of comparative trials

https://doi.org/10.21203/rs.3.rs-2988681/v1

This work is licensed under a CC BY 4.0 License

Version 1

posted

You are reading this latest preprint version

Objectives

The perioperative, functional, and oncological outcomes of patients with solitary small renal tumors(SRMs) treated with ablation(AT) or partial nephrectomy(PN) remain controversial. The aim of this study was to compare the outcomes of these two surgical techniques.

Methods

In April 2023, we conducted a literature search in several widely used databases worldwide, including PubMed, Embase, and Google Scholar. Review Manager was used to compare various parameters. The study was registered with PROSPERO (CRD42022377157).

Results

Our final meta-analysis included 13 cohort studies with a total of 2,107 patients. Compared to partial nephrectomy (PN), ablation (AT) had shorter hospital stays (WMD − 2.37 days, 95% CI -3.05 to -1.69; p < 0.00001), shorter operating times (WMD − 57.06 min, 95% CI -88.92 to -25.19; p = 0.0004), less postoperative creatinine increases (WMD − 0.17 mg/dL, 95% CI -0.29 to -0.05; p = 0.006), less postoperative glomerular filtration rate decreases (WMD − 9.84 mL/min/1.73 m2, 95% CI -14.25 to -5.44; p < 0.0001), less postoperative new-onset chronic kidney disease (OR 0.33, 95% CI 0.16 to 0.71; p = 0.005), and less intraoperative blood loss (WMD − 285.92 ml, 95% CI -428.44 to -143.40; p < 0.0001). The transfusion rate was lower in the ablation group (OR 0.17, 95% CI 0.06 to 0.51; p = 0.001). The risk of local recurrence was higher in the ablation group (OR 2.96, 95% CI 1.27 to 6.89; p = 0.01), while the risk of distant metastasis was higher in the partial nephrectomy group (OR 2.81, 95% CI 1.28 to 6.18; p = 0.01). The intraoperative and postoperative complication rates were lower in the ablation group (OR 0.23, 95% CI 0.08 to 0.62; p = 0.004 and OR 0.21, 95% CI 0.11 to 0.38; p < 0.00001, respectively). However, overall survival, postoperative dialysis rate, and tumor-specific survival were not different between the two groups.

Conclusions

Our data suggest that ablation and partial nephrectomy are equally safe and effective in the treatment of small solitary kidney tumors and are better options for patients with poor preoperative physical condition or poor renal function.

Solitary kidney 1

Kidney cancer 2

Ablation 3

Nephrectomy 4

Sugery5

Kidney cancer accounts for 2%-3% of all cancers, with an estimated hundreds of thousands of new cases and tens of thousands of deaths worldwide each year¹. It is generally detected incidentally on non-invasive imaging, and most incidentally detected renal masses are usually small, with small renal masses (SRMs) measuring less than 4 cm (stage T1a) accounting for about half of all renal cancers². With technological advances, the surgical approach to renal cancer has evolved from a single previous open nephrectomy to multiple surgical options today, including partial nephrectomy, radiofrequency ablation, and cryoablation³. The European Association of Urology (EAU) refers to recommending partial nephrectomy as the standard surgical approach for small renal masses. However, small renal tumors of the solitary kidney are still a challenging treatment problem for urologists, and the choice of surgical approach remains controversial. For solitary renal tumors, renal function preservation must be considered because the patient has only one kidney. While partial nephrectomy, due to renal ischemia, can have a greater impact on renal function, patients with significant loss of renal function may develop chronic kidney disease (CKD), leading to increased risk of acute kidney injury (AKI) and mortality⁴. Additionally, partial nephrectomy has its own technical challenges, such as high complication rates and serious complications, such as blood loss and urinary leakage that require transfusion⁵. Ablation (AT) techniques involve using different energies to achieve tumor mass necrosis⁶. Minimally invasive treatments, which utilize heat- or cold-based energies, are of concern because they better preserve overall renal function⁷. The most widely used ablation therapies include radiofrequency ablation (RFA) and cryoablation (CA)⁸. The safety and efficacy of ablation techniques for solitary renal tumors were reported as early as 2003⁹. AT can be a good alternative to PN, particularly in patients with small solitary kidney tumors. This is because warm ischemia does not cause renal dysfunction, it maximally preserves renal function, reduces the risk of postoperative renal loss, and is less technically challenging. It does not require incision of the renal parenchyma, and it is more minimally invasive, with fewer complications¹⁰. Recent literature reports that several study groups have reported favorable outcomes with radiofrequency ablation of renal masses with 2–5 year follow-up^11,12,13. Mid-term follow-up results of patients treated with ablative techniques showed good local tumor control¹⁴. Cryoablation has also been documented to have fewer technical challenges, favorable oncologic outcomes, and shorter hospital stay¹⁵. Ablation (radiofrequency and cryoablation) is increasingly used in elderly patients and high-risk surgical patients. The guidelines consider AT as an alternative to PN in patients who are not candidates for surgery, particularly in patients with severe comorbidities who are not candidates for surgery, and in patients with urgent indications for nephron-sparing surgery¹⁶.

In recent years, numerous studies have been published attempting to explore whether TA is an effective and safe alternative for the treatment of SRMs in solitary kidneys. However, the results have been inconsistent^17–29. Additionally, the sample size at single centers was small, and no credible conclusions could be drawn. Therefore, this systematic review and meta-analysis compared perioperative, functional, and oncologic outcomes between the two surgical modalities.

This study adhered to the standards specifed in PRISMA³⁰((Preferred Reporting Items for Systematic Reviews and Meta-Analysis) and was prospectively registered in the PROSPERO database (CRD42023 411427). Articles included in the systematic review were investigated independently by two reviewers (WZ and WL). The data obtained from the literature were before April 1, 2023. Extensive literature searches were conducted using MEDLINE, EMBASE, and Google Scholar databases. The search was limited to English language papers. Medical Subject Headings (MeSH) terms and keywords, such as " Solitary Kidney*", " Ablation*" OR "Cryoablation*", " Partial Nephrectomy". In addition, we manually searched and reviewed relevant references to avoid any omission.

Selection criteria

The inclusion and exclusion criteria for the studies were determined using the PICOS method. The inclusion criteria consisted of solitary renal tumors undergoing ablation in the experimental group and partial nephrectomy in the control group. The primary outcome measures of this study were changes in creatinine and estimated glomerular filtration rate, new onset of chronic kidney disease after surgery, postoperative dialysis rate (percentage of patients requiring dialysis after treatment), local recurrence, and postoperative metastasis. Secondary outcome measures included length of hospital stay, operation time, complications (intraoperative complications, postoperative complications, major complications), intraoperative blood loss, blood transfusion, overall survival, and cancer-specific survival. Cohort studies, case-control studies, and randomized controlled trials (RCT) were eligible for inclusion. Non-comparative studies, editorial comments, conference abstracts, case reports, unpublished studies or comments, articles published in non-English language, and studies with no data available were excluded. Data extraction was performed independently by two reviewers and included general information such as the first author, publication year, and demographic characteristics such as age, sex, follow-up time, tumor size, and perioperative outcomes such as operative time, length of hospital stay, and intraoperative complications.

Study screening and selection

Two independent authors (WZ and WL) manually screened all retrieved records. When consensus could not be reached between the two authors, it was resolved by consultation with a third author (LY). Retrospective, prospective, non-randomized, and randomized studies were included according to PICOS criteria. Reviews, conference abstracts, case reports, letters to editors, and editorials were excluded. Papers were selected for screening by reading the full text if found to be relevant to the objectives of this study.

Statistical analysis

This study used Review Manager V5.4.1 software (Cochrane Collaboration, Oxford, UK) for statistical analysis. Results are presented as 95% confidence intervals (CI) and odds ratios (OR) for dichotomous variables and weighted mean difference (WMD) for continuous variables. Data from some studies reporting only medians, quartiles, or extreme value ranges were converted to means and standard deviations (SDs) using data conversion tables provided by McGrath³¹. Meta-analysis was performed using the Mantel-Haenszel method for dichotomous variables and the inverse variance method for continuous variables. For survival data, because some articles do not give survival curves, we analyze survival data in the form of binary variables, the simplest way is to collect them directly from the original article, and if the data are provided only in the form of survival curves, we extract survival rates from some designated times. We used a random-effects model for all analyses due to the predictable significance of heterogeneity across trials. Study heterogeneity was calculated using the I² statistic, with 0–40% defined as mild heterogeneity; 40% – 60% as moderate heterogeneity; 60–75% as large heterogeneity; and 75–100% as high heterogeneity³². Values of p < 0.05 were considered statistically significant.

Bias risk assessment

We included articles that were all cohort studies and no randomized cohort studies were identified. The risk of bias was assessed using the Newcastle-Ottawa Scale (NOS) and the quality of the literaturetative evaluation was evaluated using a semiquantistar system, which consisted of 9 stars.

Sensitivity Analysis

We used the leave-one-out method to exclude studies from the pooled effect one at a time to assess the robustness of the estimates. Furthermore, we evaluated the robustness based on the study cohort size (excluding studies with < 100 patients), which may contribute to heterogeneity. However, we cannot perform sensitivity analyses comparing three or fewer studies.

Publication Bias

Funnel plots were used to screen for potential publication bias.

Baseline characteristics

The initial literature search retrieved 53 articles. After removing nine duplicates, 44 studies remained for screening. Fifteen of these papers were excluded from title and abstract screening as they were not relevant to the objectives of this study. The full texts of the remaining 29 studies were screened, and 16 papers lacking data specificity, wrong interventions, etc., were further excluded. Finally, 13 studies involving 2107 patients were accepted and included in the meta-analysis. Table 1 summarizes the baseline characteristics and preoperative variables of the included patients (sample size, age, body mass index (BMI), preoperative creatinine, preoperative glomerular filtration rate, preoperative follow-up time, number of patients with preoperative chronic kidney disease, tumor size, preoperative American Society of Anesthesiologists (ASA) score). Table 2 summarizes the surgical, complication, functional, and oncologic findings, and it can be seen from Table 3 that the relevant characteristics and variables of this study are comparable. There were no significant differences between the groups in age (P = 0.09), male sex (P = 0.16), BMI (P = 0.57), and follow-up time (P = 0.79), but there were some differences in baseline tumor size (P = 0.002), indicating that tumors were smaller in the ablation (AT) group than in the partial nephrectomy (PN) group. The same preoperative creatinine baseline (P < 0.00001) showed some differences, indicating worse preoperative renal function in the AT group. Table 4 summarizes the overall and cancer-specific survival of the included patients. Figure 1 shows the flow diagram of the PRISMA process.

Table 1

Baselines characteristics of included studies
Reference	§	Type	N*	Age	Male	BMI kg/m²)	Preoperative renal function			Pathology	Tumor Size(cm)	ASA	Follow-up^#
							Creatinine	eGFR	CKD(%)	Be/Ma/Un
Beksac 2022	I	CA	43	68 (61, 73)	31	28 (26, 33)	NA	56 (45, 66)	30 (70%)	10/23/10	2.00(0.80–3.8)	34(83%)	70 (43–112)
		PN	31	59 (56, 66)	17	31 (28, 35)	NA	58 (46, 74)	16 (52%)	3/28/0	2.80,(1.3-4.0)	25(83%)	40 (15–61)
Bhindi 2018	I	CA	54	65 (54–75)	39	NA	NA	56 (48–69)	NA	NA	3.5 (2.3–6.5)	NA	NA
		PN	64	63 (58–67)	47	NA	NA	56 (47–77)	NA	NA	3.7 (2.0–5.0)	NA	NA
Goyal 2011	R	CA	23	68.4 (39.8–79.4)	13	NA	1.3 ± 0.4	54.6 ± 16.5	15(65%)	5/18/0	2.5 (1–4)	NA	31.2 (0.6–153)
		PN	15	65.2 (47.2–85.3)	13	NA	1.5 ± 0.7	55.07 ± 22.2	9(60%)	3/12/0	3.4 (1-5.5)	NA	30.8 (0.1-113.5)
Haber 2012		CA	30	60.9 ± 11.4	22	31.5 ± 5.8	1.5 ± 0.5	53.8 ± 19.0	NA	5/25/0	2.6 ± 1.08	NA	60.2 ± 46.3
		LPN	48	60.6 ± 13.7	25	30.1 ± 6.2	1.2 ± 0.3	61.6 ± 18.6	NA	12/36/0	3.2 ± 1.33	NA	42.7 ± 30.8
Mitchell 2011	R	AT	50	63 (27–83)	33	NA	1.3 (0.8–2.6)	53.3 ± 12.3	34(68%)	NA	2.5 (1.2–7.3)	38(76%)	NA
		PN	62	69 (49–89)	49	NA	1.5 (0.7–3.3)	56.2 ± 22.3	44(72%)	NA	3.5 (0.7–13.0)	39(63%)	NA
Mues 2012	R	AT	98	64 (38–86)	64	NA	1.4	59		6/69/23	2.5(1–4.4)	NA	31
		PN	100	64 (35–92)	64	NA	1.4	59	NA	97/3/0	3.9 (1–10)	NA	24
Olweny 2012	I	PFA	37	63.8 (56.3–69.1)	24	NA	NA	NA	NA	37/0/0	2.1 (1.8–2.8)	NA	6.5 (5.8–7.1)
		PN	37	54.8 (47.8–59.1)	20	NA	NA	NA	NA	37/0/0	2.5 (1.7–3.1)	NA	6.1 (5.4–7.3)
Pandolfo 2022	I	AT	119	66.1 ± 12.6	NA	29.6 ± 6.1	1.43 ± 0.53	53.7 ± 17.4	79(66%)	NA	2.5 ± 1.3	81(66%)	46 ± 39.4
		PAPN	50	65.5 ± 9.0	NA	26.6 ± 4.2	1.2 ± 0.32	63.9 ± 24.6	28(56%)	NA	2.8 ± 1.1	22(44%)	37 ± 30
Panuma 2013	I	CA	43	64 (57–72)	35	29 (26–32)	1.3 (1.2–1.5)	57 ± 9.2	30(70%)	13/25/5	2.2 (1.6–3.2)	36 (83%)	41 (26–59)
		PN	33	60 (51–69)	22	29.1 (26–32)	1.2 (1-1.4)	62 ± 17.	14(42%)	9/24/0	2.9 (1.8–4.2)	17 (59%)	17 (5–62)
Raman 2010	I	PFA	47	65.9 (16.7)	33	NA	NA	46.5 (15.9–91.6)	40(85%)	5/40/8	2.7 (1.5–6.5)	NA	18.1 (6–66)
		OPN	42	59.6 (12.8)	26	NA	NA	55.9 (30.5–89.7)	22(52%)	9/37/0	3.5 (1.3–5.5)	NA	30.0 (11–83)
Turna 2009	R	RFA^a	29	60.7 ± 14.3	18	30.0 ± 7.5	1.4 ± 0.5	53.2 ± 16.2	17(59%)	5/24/0	2.6 ± 1.0	20(69%)	14.0(1–44)
		CA^b	36	64.1 ± 11.1	23	31.3 ± 5.7	1.4 ± 0.5	52.3 ± 19.7	26(72%)	8/22/6	2.5 ± 1.1	28(78%)	24.0(1–84)
		LPN	36	60.3 ± 15.5	21	30.5 ± 7.1	1.2 ± 0.4	65 ± 23.5	23(64%)	12/23/1	3.7 ± 1.9	24(67%)	42.5(7–81)
Xiaobing 2017	R	RFA	16	59.6(36–79)	11	NA	94.9(66–113)	NA	NA	0/14/2	3.4(1.5–6.0)	NA	33.7 ± 22.9
		PN	20	62.1(41–83)	15	NA	91.4(53–174)	NA	NA	2/18/0	3.6(1.5–6.0)	NA	26.1 ± 16.2
Yasuda 2022	I	CA	102	67 (58–73)	69	31 (27–35)	NA	53 (40–65)	NA	NA	2.3(1.6–3.1)	NA	31.2 (6.8–114.9)
		PN	842	64 (55–70)	535	29 (25–33)	NA	57 (44–71)	NA	NA	3.9(2.8–5.3)	NA	57.4 (47.2–71.1)
CA:cryoablation; AT:ablation therapy; RFA:radiofrequency ablation; PN:partial nephrectomy; RAPN:robot-assisted partial nephrectomy; OPN:open partial nephrectomy; LPN:laparoscopic partial nephrectomy;ASA:Percent of patients with American society of anesthesiologists (ASA) score 3 or 4; CKD: chronic kidney disease,;BMI: body mass index༛GFR: glomerular filtration rate༛NA:not applicable.;CKD:GFR＜60 ml/min/1.73m2;M(SD);Be/Ma/Un = benigh/malignant/unknown; #:Follow up duration in months;§:Data a (b-c) are presented as quartiles or extreme values and d ± e as mean ± standard deviation in the table;N*:Number of Patients༛Type:Surgical method༛I: interquartile range༛R:Rang.

Table 2

Perioperative outcomes
Reference	Type	N*	hospital stay	operating time	Post operative SCr(mg/dL)	SCr increase (mg/dL)	Post operative eGFR (mL/min/1.73m2)	Percent eGFR decrease after surgery (%)	New onset CKD	Blood loss in cc	T	D	L	Me	I	P	M
Beksac 2022	CA	43	NA						4	NA		0	11	6	NA	NA	1
	PN	31							6			1	1	1		NA	2
Bhindi 2018	CA	54							NA			NA	NA	NA		NA	NA
	PN	64							NA			NA	NA	NA		NA
Goyal 2011	CA	23	2.6 ± 2.0	NA	1.33 ± 0.4	NA	51.9 ± 16.5	4.7 ± 15.9	2	87 ± 105.7	0	1	1	2		2
	PN	15	6.7 ± 3.7	NA	1.9 ± 0.7	NA	43.5 ± 18	17.7 ± 26.7	2	316 ± 528.3	1	2	2	1		8
Haber 2012	CA	30	2.4 ± 2.2	197.4 ± 52.6	1.7 ± 0.6	0.2 ± 0.3	47.5 ± 14.8	11.0 ± 16.1	NA	162.4 ± 163.2	1	0	4	4	1	2
	LPN	48	4.6 ± 2.9	227.7 ± 73.1	1.7 ± 0.9	0.4 ± 0.5	47.5 ± 18.4	21.4 ± 21.9	NA	391.3 ± 692.0	8	3	0	1	4	11
Mitchell 2011	AT	50	NA		NA	0.1 ± 0.4	50.6 ± 16.5	3.4 ± 18	2	NA	NA	0	NA
	PN	62	NA		NA	0.1 ± 0.6	51.9 ± 19.4	7 ± 25	5	NA	NA	1	NA
Mues 2012	AT	98	2.0 ± 1.4	158.3 ± 46.3	NA				NA	67.3 ± 79.2	0	NA	7	2	1	9	4
	PN	100	4.8 ± 4.0	169 ± 40.4					NA	575.4 ± 775.4	4		3	1	6	18	8
Olweny 2012	PFA	37	NA						NA	NA	NA		3	1	NA
	PN	37	NA						NA	NA			3	3	NA
Pandolfo 2022	AT	119	2.7 ± 3.2	83 ± 75					NA	NA			NA	NA	2	6	1
	PAPN	50	4.7 ± 2	200 ± 92					NA	NA			NA	NA	2	5	1
Panuma 2013	CA	43	1 ± 0	178.1 ± 51.3					3	60.9 ± 23.7	1	2	12	6	0	3	1
	PN	33	4 ± 1.5	238.2 ± 96.8					8	250 ± 232.4	7	0	0	2	5	13	6
Raman 2010	PFA	47	NA		NA			10.4 ± 16	0	NA	NA	2	5	NA	NA	NA	NA
	OPN	42	NA		NA			24.5 ± 26	7	NA	NA	1	3	NA		NA
Turna 2009	RFA^a	29	NA	NA	1.5 ± 0.8	0.1 ± 0.4	52 ± 15	13.2 ± 28.3	NA	NA	1	0	13	4		2
	CA^b	36	1.8 ± 1.3	181 ± 69	1.6 ± 0.7	0.2 ± 0.3	51 ± 27		NA	151 ± 171		0	6	3		5
	LPN	36	3.3 ± 2.6	223 ± 81	1.6 ± 0.6	0.4 ± 0.5	48 ± 17	27.7 ± 27.7	NA	408 ± 800	0	3	0	0		21
Xiaobing 2017	RFA	16	13.6 ± 6.2	148.3 ± 59.3	NA						NA	NA	1	1	1	2
	PN	20	19.5 ± 8.8	214.7 ± 101.6							NA		3	0	5	4
Yasuda 2022	CA	102	NA	173.3 ± 63.1							0		7	NA	NA	NA	6
	PN	842	NA	250.8 ± 68.3							53		31	NA	NA	NA	69
I:Intra-operative complication;P:Post-operative complication;M:Major complications;T:Transfusion ;L:Local recurrence;D:Dialysis༛Me:Metastasis

Table 3

The demographics of the studies
Variable	Number of studies with available data	WMD/OR	95% CI	p value
Age (years)	14	1.96	--4.58	0.09
BMI (kg/m2)	6	0.41	− 1- 1.82	0.57
Male (n)	13	1.21	0.93–1.59	0.16
Stone size (mm)	14	--0.65	-1.07-0.23	0.002
GFR	1 1	--5.59	-7.79–3.4	0.0001
follow-up	1 1	1.19	-7.73-10.12	0.79
WMD:weighted mean diference, OR odds ratio, Cl confdence interval

Table 4

the overall and cancer-specific survival
Reference		Overall survival(year)			cancer-specific survival(year)
	Follow-up number	1	3	5	1	3	5
Beksac 2022	33	32	26	NA	NA
	28	25	17	NA
Goyal 2011	23	21	17	11
	15	13	12	12
Haber 2012	30	30	28	26	NA	28	28
	48	44	44	44	NA	44	44
Olweny 2012	37	36	33	33	36	33	33
	37	37	37	34	37	37	34
Turna 2009	24	24	16	NA	23	16	NA
	22	21	16	NA	21	16
	23	21	16	NA	21	16

Table 5.Study quality of case-control studies based on the NWewcastle-Ottawa scale
NOS	Selection				Comparability	Outcome			Overall score
ID	1	2	3	4	5	6	7	8
Beksac 2022	★	★	★	★	★	★	★	★	8
Bhindi 2018	★	★	★	★	★	★	★	★	8
Goyal 2011		★	★	★	★	★	★	★	7
Haber 2012		★	★	★	★	★	★	★	7
Mitchell 2011		★	★	★	★	★	★	★	7
Mues 2012		★	★	★	★	★	★	★	7
Olweny 2012		★		★	★	★	★	★	6
Pandolfo 2022	★	★	★	★	★	★	★	★	8
Panumatrassamee 2013		★		★	★	★	★	★	6
Raman 2010		★		★	★		★	★	5
Turna 2009		★		★	★	★	★	★	6
Xiaobing 2017	★	★	★	★	★	★	★	★	8
Yasuda 2022	★	★	★	★	★	★	★	★	8
1:Representativeness of the exposed cohor;2: Selection of the nonexposed cohort 3: Assessment of exposure ;4:Demonstration that outcome of interest was not present at start of study 5:Comparability of cohorts on the basis of the design or analysis ;6: Ascertainment of outcome ;7:Long enough follow-up for outcomes to occur;8: Adequacy of follow-up of cohorts

Assessment of quality

All articles were cohort studies, and therefore the Newcastle-Ottawa Scale (NOS) was used for quality evaluation of the literature. Studies defined literature NOS ≥ 6 stars as high-quality literature. A total of 12 of the 13 studies were of high quality, but Raman provided experiments that were of low quality. Table 5 shows the details of the quality assessment of the cohort studies.

Meta-analysis of Perioperative outcomes

There were 13 studies, but Turna provided data that could be divided into radiofrequency ablation (RFA) and cryoablation (CA) as well as partial nephrectomy (PN) for comparison, which we labeled Turna a and Turna b. Seven studies provided details of hospital stay and operation time. Compared with the PN group, the AT group (ablation group) had shorter hospital stay (WMD − 2.37 day, 95% CI -3.05, -1.69; p < 0.00001) (Fig. 2-A), shorter operation time (WMD − 57.06 min, 95% CI -88.92, -25.19; p = 0.0004) (Fig. 2-B). Four studies provided changes in postoperative creatinine, and the AT group had less postoperative creatinine increase (WMD − 0.17 mg/dL, 95% CI -0.29, -0.05; p = 0.006) (Fig. 2-C). Pooled analysis of 5 studies showed that the AT group had less postoperative glomerular filtration rate decrease (WMD − 9.84 mL/min/1.73 m2, 95% CI -14.25, -5.44; p < 0.0001) (Fig. 2-D) and less postoperative new chronic kidney disease (OR 0.33, 95% CI 0.16, 0.71; p = 0.005) (Fig. 2-E). intraoperative blood loss was less (WMD − 285.92 ml, 95% CI -428.44, -143.40; p < 0.0001) (Fig. 3-A). Pooled analysis of six studies showed that the AT was associated with a lower transfusion rate relative to the PN (OR 0.17, 95% CI 0.06, 0.51; p = 0.001) (Fig. 3-B). However, there was no statistical difference in the postoperative dialysis rate between the two surgical methods (OR 0.45, 95% CI 0.16, 1.24; p = 0.12) (Fig. 3-C).

Meta-analysis of Complications

Five studies provided data on intraoperative complications, which were summarized and showed that the AT group had fewer intraoperative complications (OR 0.23, 95% CI 0.08–0.62; p = 0.004) (Fig. 4-A) and fewer major complications (OR 0.51, 95% CI 0.27–0.95; p = 0.03) (Fig. 4-B) than the PN group. Eight studies were pooled, and it showed that postoperative complications were less frequent in the AT group (OR 0.21, 95% CI 0.11–0.38; p < 0.00001) (Fig. 4-C).

Meta-analysis of Functional outcomes

Data analysis of 11 studies showed a higher risk of local recurrence in the AT group compared to the PN group (OR 2.96, 95% CI 1.27–6.89; p = 0.01) (Fig. 5-A). Additionally, analysis of 9 studies revealed a higher risk of distant metastasis in the AT group (OR 2.81, 95% CI 1.28–6.18; p = 0.01) (Fig. 5-B). However, there was no significant difference in overall survival or cancer-specific survival between the two surgical modalities (Fig. 6).

sensibility analysis

In this meta-analysis, some results showed significant heterogeneity (I2 = 49% for hospital stay, I² = 93% for operation time, I² = 37% for postoperative creatinine increase, I² = 70% for blood loss, I² = 52% for local recurrence rate, and I² = 41% for postoperative complications). The heterogeneity of operation time and blood loss was high, and hospital stay, postoperative creatinine increase, local recurrence rate, and postoperative complications had some heterogeneity. The other results showed no significant heterogeneity.We performed sensitivity analyses on target parameters to obtain stable, convincing conclusions. We excluded studies using a leave-one-out approach from the pooled effect and found that heterogeneity decreased from I² = 49–38% after removing data provided by Turn 2009b. This may be because patients provided by Turn 2009b often received sedative analgesia in outpatients and percutaneous fine-needle ablation under CT guidance, which greatly reduced length of stay. This may also explain the reduction in heterogeneity from the original I² = 41% to I² = 16% after removing the two sets of data provided by Turn 2000 for postoperative complications. Because more minimally invasive procedures seem to be associated with fewer complications.After removing Turn 2009 data using a leave-one-out approach for length of hospital stay and postoperative complications, the results still suggest a potential advantage for AT over PN in terms of operative time and intraoperative complications. The remaining results were found to be stable after exclusion using the leave-one-out method (Fig. 7).

Perioperative outcomes

The perioperative parameters that varied most significantly between the AT and PN groups were length of hospital stay, operation time, postoperative creatinine change, postoperative glomerular filtration rate change, estimated blood loss, postoperative new chronic kidney disease rate, blood transfusion, and postoperative dialysis rate. However, except for postoperative dialysis rate, the remaining perioperative parameters suggested that AT had an advantage over PN.Compared to partial nephrectomy, percutaneous ablation is more commonly used in the ablation group. In the Panumatrassame study, patients were assigned to receive percutaneous or laparoscopic ablation based on tumor location and technical ability at that time. Percutaneous ablation resulted in a significant reduction in operative time, and even partial ablation procedures could be performed as outpatients²⁷. As percutaneous ablation is more minimally invasive than partial nephrectomy, the advantages in terms of blood loss and transfusion rate are predictable.

In the Mues study, 98 patients underwent ablation surgery, and intraoperative blood loss was significantly reduced compared with 100 patients who underwent partial nephrectomy. None of the ablation patients received blood transfusion, and the amount of intraoperative blood loss was partly related to the rate of blood transfusion, which was also confirmed by relevant reports³³. Additionally, patients in the included literature tended to have larger tumors in the partial nephrectomy group compared to the ablation group, which means more difficult procedures and bleeding.A pooled analysis of 14 studies presented in 13 articles showed that ablation had less effect on postoperative creatinine and postoperative glomerular filtration rate than partial nephrectomy. This may be explained by the greater surgical trauma of PN than RFA, which can aggravate the damage to the kidney. Partial nephrectomy often requires clipping of the renal artery, which will lead to warm ischemia in the patient's kidney, which is an important factor in postoperative renal function decreases²³. In addition, PN may remove more renal parenchyma, which will to some extent affect postoperative renal function more. For patients with solitary renal tumors, the quality of renal function is often very important because a lonely kidney is the most important risk factor for postoperative acute renal failure, and increased risk of worsening renal function is associated with cardiovascular morbidity and mortality³⁴.Preoperative conditions can affect creatinine and glomerular filtration rate increases after nephrectomy. Analysis of the baseline data of the included articles found that patients with solitary kidney tumors who chose radiofrequency ablation tended to have lower preoperative glomerular filtration rates. Although analysis of the included articles found no statistical difference in age between the two surgical modalities, in-depth analysis of the various studies found that the radiofrequency group tended to be older, with a mean age of 64 years in the ablation group and 60 years in the partial nephrectomy group, as shown in the Panuma 2013 study.Walach ³⁵et al. recently showed that factors such as poor preoperative patient condition, older age, and solitary kidney tumor were decisive factors in allowing clinicians to choose ablation over other procedures. In other words, because of factors such as poor preoperative physical condition or poor preoperative renal function, only more minimally invasive modalities and treatments that have less impact on renal function are selected for this patient. This inevitably leads to better perioperative outcomes.

Complications

A pooled analysis of the data from the included studies showed that ablation was superior to partial nephrectomy in terms of intraoperative, postoperative, and major complications. This is consistent with the conclusions of Larcher³³ and Pieroraziode³⁶. Compared with partial nephrectomy, ablation has the advantages of minimal invasiveness and faster postoperative recovery. In the Panuma 2013 study, ablation was performed in 43 patients, and postoperative complications occurred in only 3 patients compared to 13 patients in the PN group. However, with the development of surgical robots, robotic surgery has better vision, more flexible and precise operations, and robot-assisted laparoscopic partial nephrectomy can reduce the occurrence of complications to some extent compared with traditional laparoscopic and open surgery³⁷. As shown in the Pandolfo 2022 study, there was no significant difference in complications between the PAPN and AT groups.

Oncologic outcomes

A pooled analysis of the data included in the study showed that the risk of local recurrence and the risk of distant metastasis were higher in the ablation group compared with the partial nephrectomy group. The main goal of treating solitary renal tumors is not only to maintain better renal function but also to achieve better tumor control. However, this does not mean that the ablation procedure cannot be selected for patients. Unlike partial nephrectomy, ablation can be performed multiple times without increasing the corresponding difficulty of the procedure³⁸. In the Xiaobing study, 1 of 16 ablated patients showed recurrence after surgery, and the patient underwent ablation surgery again 8 months later, and no recurrence was found during long-term follow-up. A pooled analysis showed no statistical difference in overall survival and tumor-specific survival between the two treatment modalities. Bianchi ³⁹et al reported similar overall survival between the radiofrequency ablation and partial nephrectomy groups (91% vs 95.8%, P = 0.6). These results imply that although ablation is associated with a higher risk of local recurrence and distant metastasis than PN, no significant difference in overall survival is observed between the two treatment modalities. Unfortunately, most of the data we included in the study had only 5 years of follow-up. This conclusion needs to be confirmed by more prospective randomized trials with long-term rigorous follow-up.

Limitations

This study has several limitations that need to be considered. First, no further subgroup analysis was performed because fewer articles were included for radiofrequency ablation and cryoablation. Second, analysis of the baseline data included in the study showed that patients in the AT group tended to be older, have smaller tumors, and have worse preoperative renal function, which may overestimate the advantages of AT in terms of complications, perioperative outcomes, etc. Finally, the study included is based on cohort studies, and further larger randomized trials are needed to provide more reliable evidence for the results of the pooled analysis.

Both partial nephrectomy and ablation are safe and effective treatments for small solitary kidney tumors. Ablative therapy is associated with shorter procedure times, fewer complications, and less renal impairment than partial nephrectomy. Although ablation is relative to a greater risk of local recurrence and metastasis compared to partial nephrectomy, there is no apparent difference in overall and cancer-specific survival. Ablation is a better option for patients with poor physical condition or preoperative renal function.

Author Contributions

Substantial contributions to the concept or design of the work: Yang xue-song. Data extraction and literature review: W-L and H-J. Drafting the work or revising it critically for important intellectual content: Chen Cai-xia and Huang Jing. All authors contributed to the article and approved the submitted version.

Data Availability Statement

The original contributions presented in the study are included in the article material, further inquiries can be directed to the corresponding author/s.

Funding ：None

Acknowledgments: None

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no conflict of interest.

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2018;68(6):394–424. https://doi.org/10.3322/caac.21492.
Escudier B, Porta C, Schmidinger M, Rioux-Leclercq N, Bex A, Khoo V, Gruenvald V, Horwich A, ESMO Guidelines Committee. Renal Cell Carcinoma: ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-Up. Ann Oncol Off J Eur Soc Med Oncol. 2016;27(suppl 5):v58–v68. https://doi.org/10.1093/annonc/mdw328.
Psutka SP, Gulati R, Jewett MAS, Fadaak K, Finelli A, Legere L, Morgan TM, Pierorazio PM, Allaf ME, Herrin J, Lohse CM, Houston Thompson R, Boorjian SA, Atwell TD, Schmit GD, Costello BA, Shah ND, Leibovich BC. A Clinical Decision Aid to Support Personalized Treatment Selection for Patients with Clinical T1 Renal Masses: Results from a Multi-Institutional Competing-Risks Analysis. Eur Urol. 2022;81(6):576–85. https://doi.org/10.1016/j.eururo.2021.11.002.
Thompson RH, Boorjian SA, Lohse CM, Leibovich BC, Kwon ED, Cheville JC, Blute ML. Radical Nephrectomy for PT1a Renal Masses May Be Associated with Decreased Overall Survival Compared with Partial Nephrectomy. J. Urol. 2008, 179 (2), 468–471; discussion 472–473. https://doi.org/10.1016/j.juro.2007.09.077.
Reifsnyder JE, Ramasamy R, Ng CK, Dipietro J, Shin B, Shariat SF, Del Pizzo JJ, Scherr DS. Laparoscopic and Open Partial Nephrectomy: Complication Comparison Using the Clavien System. JSLS 2012, 16 (1), 38–44. https://doi.org/10.4293/108680812X13291597716942.
Mershon JP, Tuong MN, Schenkman NS. Thermal Ablation of the Small Renal Mass: A Critical Analysis of Current Literature. Minerva Urol E Nefrol Ital J Urol Nephrol. 2020;72(2):123–34. https://doi.org/10.23736/S0393-2249.19.03572-0.
Woldu SL, Thoreson GR, Okhunov Z, Ghandour R, Rothberg MB, RoyChoudhury A, Kim HHR, Bozoghlanian M, Newhouse JH, Helmy MA, Badani KK, Landman J, Cadeddu JA, McKiernan JM. Comparison of Renal Parenchymal Volume Preservation Between Partial Nephrectomy, Cryoablation, and Radiofrequency Ablation Using 3D Volume Measurements. J Endourol. 2015;29(8):948–55. https://doi.org/10.1089/end.2014.0866.
Higgins LJ, Hong K. Renal Ablation Techniques: State of the Art. AJR Am J Roentgenol. 2015;205(4):735–41. https://doi.org/10.2214/AJR.15.14752.
Shingleton WB, Sewell PE. Cryoablation of Renal Tumours in Patients with Solitary Kidneys. BJU Int. 2003;92(3):237–9. https://doi.org/10.1046/j.1464-410x.2003.04322.x.
Ghavamian R, Cheville JC, Lohse CM, Weaver AL, Zincke H, Blute ML. Renal Cell Carcinoma in the Solitary Kidney: An Analysis of Complications and Outcome after Nephron Sparing Surgery. J Urol. 2002;168(2):454–9. https://doi.org/10.1016/s0022-5347(05)64657-5.
Levinson AW, Su L-M, Agarwal D, Sroka M, Jarrett TW, Kavoussi LR, Solomon SB. Long-Term Oncological and Overall Outcomes of Percutaneous Radio Frequency Ablation in High Risk Surgical Patients with a Solitary Small Renal Mass. J. Urol. 2008, 180 (2), 499–504; discussion 504. https://doi.org/10.1016/j.juro.2008.04.031.
McDougal WS, Gervais DA, McGovern FJ, Mueller PR. Long-Term Followup of Patients with Renal Cell Carcinoma Treated with Radio Frequency Ablation with Curative Intent. J Urol. 2005;174(1):61–3. https://doi.org/10.1097/01.ju.0000162046.45024.2b.
Stern JM, Svatek R, Park S, Hermann M, Lotan Y, Sagalowsky AI, Cadeddu JA. Intermediate Comparison of Partial Nephrectomy and Radiofrequency Ablation for Clinical T1a Renal Tumours. BJU Int. 2007;100(2):287–90. https://doi.org/10.1111/j.1464-410X.2007.06937.x.
Kunkle DA, Kutikov A, Uzzo RG. Management of Small Renal Masses. Semin Ultrasound CT MR. 2009;30(4):352–8. https://doi.org/10.1053/j.sult.2009.03.002.
Mues AC, Landman J. Results of Kidney Tumor Cryoablation: Renal Function Preservation and Oncologic Efficacy. World J Urol. 2010;28(5):565–70. https://doi.org/10.1007/s00345-010-0552-4.
Rouprêt M, Babjuk M, Burger M, Capoun O, Cohen D, Compérat EM, Cowan NC, Dominguez-Escrig JL, Gontero P, Hugh Mostafid A, Palou J, Peyronnet B, Seisen T, Soukup V, Sylvester RJ, Rhijn BWG. European Association of Urology Guidelines on Upper Urinary Tract Urothelial Carcinoma: 2020 Update. Eur Urol. 2021;79(1):62–79. https://doi.org/10.1016/j.eururo.2020.05.042. ZigeunerR.Shariat, S. F..
Beksac AT, Corrigan D, Abou Zeinab M, Ferguson E, Kaviani A, Schwen ZR, Kaouk JH. Long-Term Comparative Outcomes of Partial Nephrectomy and Cryoablation in Patients with Solitary Kidneys: A Single-Center Analysis. Minerva Urol Nephrol. 2023;74(6). https://doi.org/10.23736/S2724-6051.22.04840-6.
Bhindi B, Mason RJ, Haddad MM, Boorjian SA, Leibovich BC, Atwell TD, Weisbrod AJ, Schmit GD, Thompson RH. Outcomes After Cryoablation Versus Partial Nephrectomy for Sporadic Renal Tumors in a Solitary Kidney: A Propensity Score Analysis. Eur Urol. 2018;73(2):254–9. https://doi.org/10.1016/j.eururo.2017.09.009.
Goyal J, Sidana A, Georgiades CS, Rodriguez R. Renal Function and Oncologic Outcomes after Cryoablation or Partial Nephrectomy for Tumors in Solitary Kidneys. Korean J Urol. 2011;52(6):384. https://doi.org/10.4111/kju.2011.52.6.384.
Haber G-P, Lee MC, Crouzet S, Kamoi K, Gill IS. Tumour in Solitary Kidney: Laparoscopic Partial Nephrectomy vs Laparoscopic Cryoablation: LAPAROSCOPIC NEPHRON-SPARING SURGERY IN SOLITARY KIDNEY. BJU Int. 2012;109(1):118–24. https://doi.org/10.1111/j.1464-410X.2011.10287.x.
Mitchell CR, Atwell TD, Weisbrod AJ, Lohse CM, Boorjian SA, Leibovich BC, Thompson RH. Renal Function Outcomes in Patients Treated With Partial Nephrectomy Versus Percutaneous Ablation for Renal Tumors in a Solitary Kidney. J Urol. 2011;186(5):1786–90. https://doi.org/10.1016/j.juro.2011.07.036.
Mues AC, Korets R, Graversen JA, Badani KK, Bird VG, Best SL, Cadeddu JA, Clayman RV, McDougall E, Barwari K, Laguna P, de la Rosette J, Kavoussi L, Okhunov Z, Munver R, Patel SR, Nakada S, Tsivian M, Polascik TJ, Shalhav A, Shingleton WB, Johnson EK, Wolf JS, Landman J. Clinical, Pathologic, and Functional Outcomes After Nephron-Sparing Surgery in Patients with a Solitary Kidney: A Multicenter Experience. J Endourol. 2012;26(10):1361–6. https://doi.org/10.1089/end.2012.0114.
Olweny EO, Park SK, Tan YK, Best SL, Trimmer C, Cadeddu JA. Radiofrequency Ablation Versus Partial Nephrectomy in Patients with Solitary Clinical T1a Renal Cell Carcinoma: Comparable Oncologic Outcomes at a Minimum of 5 Years of Follow-Up. Eur Urol. 2012;61(6):1156–61. https://doi.org/10.1016/j.eururo.2012.01.001.
Pandolfo SD, Loizzo D, Beksac AT, Derweesh I, Celia A, Bianchi L, Elbich J, Costa G, Carbonara U, Lucarelli G, Cerrato C, Meagher M, Ditonno P, Hampton LJ, Basile G, Kim FJ, Schiavina R, Capitanio U, Kaouk J, Autorino R. Percutaneous Thermal Ablation for CT1 Renal Mass in Solitary Kidney: A Multicenter Trifecta Comparative Analysis versus Robot-Assisted Partial Nephrectomy. Eur J Surg Oncol. 2023;49(2):486–90. https://doi.org/10.1016/j.ejso.2022.09.022.
Panumatrassamee K, Kaouk JH, Autorino R, Lenis AT, Laydner H, Isac W, Long J-A, Eyraud R, Kassab A, Khalifeh A, Hillyer S, Rizkala E, Haber G-P, Stein RJ. Cryoablation Versus Minimally Invasive Partial Nephrectomy for Small Renal Masses in the Solitary Kidney: Impact of Approach on Functional Outcomes. J Urol. 2013;189(3):818–22. https://doi.org/10.1016/j.juro.2012.09.075.
Raman JD, Raj GV, Lucas SM, Williams SK, Lauer EM, Ahrar K, Matin SF, Leveillee RJ, Cadeddu JA. Renal Functional Outcomes for Tumours in a Solitary Kidney Managed by Ablative or Extirpative Techniques. BJU Int. 2010;105(4):496–500. https://doi.org/10.1111/j.1464-410X.2009.08776.x.
Turna B, Kaouk JH, Frota R, Stein RJ, Kamoi K, Gill IS, Novick AC. Minimally Invasive Nephron Sparing Management for Renal Tumors in Solitary Kidneys. J Urol. 2009;182(5):2150–7. https://doi.org/10.1016/j.juro.2009.07.066.
Xiaobing W, Wentao G, Guangxiang L, Fan Z, Weidong G, Hongqian G, Gutian Z. Comparison of Radiofrequency Ablation and Partial Nephrectomy for Tumor in a Solitary Kidney. BMC Urol. 2017;17(1):79. https://doi.org/10.1186/s12894-017-0269-4.
Yasuda Y, Zhang JjH, Attawettayanon W, Rathi N, Wilkins L, Roversi G, Zhang A, Accioly JPE, Shah S, Munoz-Lopez C, Palacios DA, Hofmann M, Campbell RA, Kaouk J, Haber G-P, Eltemamy M, Krishnamurthi V, Abouassaly R, Martin C, Li J, Weight C, Campbell SC. Comprehensive Management of Renal Masses in Solitary Kidneys. Eur Urol Oncol. 2023;6(1):84–94. https://doi.org/10.1016/j.euo.2022.11.004.
The PRISMA 2020 statement: an updated guideline for reporting systematic reviews - PubMed. https://pubmed.ncbi.nlm.nih.gov/33782057/ (accessed 2023-03-19).
McGrath S, Zhao X, Steele R, Thombs BD, Benedetti A, DEPRESsion. Screening Data (DEPRESSD) Collaboration. Estimating the Sample Mean and Standard Deviation from Commonly Reported Quantiles in Meta-Analysis. Stat Methods Med Res. 2020;29(9):2520–37. https://doi.org/10.1177/0962280219889080.
Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, Schünemann HJ, GRADE, Working Group. GRADE: An Emerging Consensus on Rating Quality of Evidence and Strength of Recommendations. BMJ. 2008;336(7650):924–6. https://doi.org/10.1136/bmj.39489.470347.AD.
Larcher A, Fossati N, Tian Z, Boehm K, Meskawi M, Valdivieso R, Trudeau V, DellOglio P, Buffi N, Montorsi F, Guazzoni G, Sun M, Karakiewicz PI. Prediction of Complications Following Partial Nephrectomy: Implications for Ablative Techniques Candidates. Eur Urol. 2016;69(4):676–82. https://doi.org/10.1016/j.eururo.2015.07.003.
Go AS, Chertow GM, Fan D, McCulloch CE, Hsu C. Chronic Kidney Disease and the Risks of Death, Cardiovascular Events, and Hospitalization. N Engl J Med. 2004;351(13):1296–305. https://doi.org/10.1056/NEJMoa041031.
Walach MT, Wunderle MF, Haertel N, Mühlbauer JK, Kowalewski KF, Wagener N, Rathmann N, Kriegmair MC. Frailty Predicts Outcome of Partial Nephrectomy and Guides Treatment Decision towards Active Surveillance and Tumor Ablation. World J Urol. 2021;39(8):2843–51. https://doi.org/10.1007/s00345-020-03556-7.
Pierorazio PM, Johnson MH, Patel HD, Sozio SM, Sharma R, Iyoha E, Bass EB, Allaf ME. Management of Renal Masses and Localized Renal Cancer: Systematic Review and Meta-Analysis. J Urol. 2016;196(4):989–99. https://doi.org/10.1016/j.juro.2016.04.081.
Feußner H, Wilhelm D. [Minimally invasive surgery and robotic surgery: surgery 4.0?]. Chir Z Alle Geb Oper Medizen. 2016;87(3):189–94. https://doi.org/10.1007/s00104-015-0145-2.
Matsumoto ED, Johnson DB, Ogan K, Trimmer C, Sagalowsky A, Margulis V, Cadeddu JA. Short-Term Efficacy of Temperature-Based Radiofrequency Ablation of Small Renal Tumors. Urology. 2005;65(5):877–81. https://doi.org/10.1016/j.urology.2004.12.011.
Bianchi L, Chessa F, Piazza P, Ercolino A, Mottaran A, Recenti D, Serra C, Gaudiano C, Cappelli A, Modestino F, Golfieri R, Bertaccini A, Marcelli E, Porreca A, Celia A, Schiavina R. Percutaneous Ablation or Minimally Invasive Partial Nephrectomy for CT1a Renal Masses? A Propensity Score-Matched Analysis. Int J Urol Off J Jpn Urol Assoc. 2022;29(3):222–8. https://doi.org/10.1111/iju.14758.

No competing interests reported.

Download PDF

Version 1

posted

You are reading this latest preprint version

Perioperative, functional, and oncologic outcomes after ablation or partial nephrectomy for solitary renal tumors: a systematic review and meta-analysis of comparative trials

Status:

Version 1

Abstract

Objectives

Methods

Results

Conclusions

Figures

Introduction

Literature search

Selection criteria

Study screening and selection

Statistical analysis

Bias risk assessment

Sensitivity Analysis

Publication Bias

Result

Baseline characteristics

Assessment of quality

Meta-analysis of Perioperative outcomes

Meta-analysis of Complications

Meta-analysis of Functional outcomes

sensibility analysis

Discussion

Perioperative outcomes

Complications

Oncologic outcomes

Limitations

Conclusion

Declarations

References

Additional Declarations

Status:

Version 1