Study reference

Study characteristics

Patient characteristics ²

Intervention (I)

Comparison / control (C) ³

Follow-up

Outcome measures and effect size ⁴

Comments

Active surveillance, deferred therapy

Alam,

2019

Type of study:

analysis of registry data

Setting and country: DISSRM Registry (multi-institutional), USA

Funding:

NIH and National Center for Advancing Translational Sciences

CoI: none.

Inclusion criteria:

≥ 18 years

renal mass ≤ 4 cm

Exclusion criteria:

N total at baseline:

Intervention:

PN 231

RN 41

ablation 27

Control:

AS 339

Important prognostic factors²:

not reported

Groups comparable at baseline? No

Describe intervention (treatment/procedure/test):

partial nephrectomy (PN)

radical nephrectomy (RN)

ablation

Describe control (treatment/procedure/test):

active surveillance (AS)

Length of follow-up:

median (IQR) follow-up time 3.0 (1.6-5.0) years

Loss-to-follow-up:

not reported

Incomplete outcome data:

Intervention:

N (%)

Reasons (describe)

Control:

N (%)

Reasons (describe)

Outcome measures and effect size (include 95%CI and p-value if available):

Cancer-specific survival after 7 years:

PN 98.8%

RN 100%

ablation 100%

AS 100%

log-rank p=0.5

Overall survival at 7 years
PN 87.9%

RN 90.2%

ablation 83.5%

AS 66.1%

log-rank p=0.005

HR (95% CI) for AS compared to any intervention adjusted for age, sex and Charlson Comorbidity Index:

1.66 (0.72 – 3.81)

SF-12 AS compared to PN adjusted for time, age, gender, CCI and BMI: -3.23 (95% CI -5.99 to -0.47), p=0.02

Adjustment for confounding only for OS, comparison with any intervention, not with PN

Xing,

2018

Type of study:

retrospective propensity score-matched study

Setting and country: SEER database, USA

Funding: not reported conflicts of interest: none

Inclusion criteria:

T1a RCC

>65 years

Exclusion criteria:

autopsy or death certificate diagnoses;

no Medicare enrolment;

pre-existing end-stage renal disease

N total at baseline: 10.218

AS: 1978

TA: 898

PN: 2820

(RN: 4522)

Groups comparable at baseline? Yes, after matching

Describe intervention (treatment/procedure/test):

Active Surveillance (AS)

Describe control (treatment/procedure/test):

Partial Nephrectomy (PN)

Thermal Ablation (TA)

Length of follow-up:

at least 1 year

Loss-to-follow-up:

not reported

Incomplete outcome data:

not reported

Outcome measures and effect size (include 95%CI and p-value if available):

Cancer-specific mortality

PN versus TA: AHR (95% CI) 0.38 (0.17 to 1.15)

AS versus TA: AHR (95% CI) 1.45 (1.13 to 2.59)

AS versus PN: AHR (95% CI) 2.02 (1.35 to 3.09)

propensity scores calculated on the basis of 17 predefined covariates: age, sex, race, Charlson comorbidity index, cardiovascular disease, hypertension, diabetes,

moderate or severe renal disease, socioeconomic status, marital status, region, urban or rural location, tumor size, histologic characteristics, Fuhrman grade, year of diagnosis, and length of follow-up

Uhlig,

2018

Type of study:

retrospective registry study

Setting and country: SEER database, USA

Funding: not reported conflicts of interest: none

Inclusion criteria:

unilateral T1a renal clear cell carcinoma

thermal ablation, cryosurgery or deferred therapy

Exclusion criteria:

primary nephrectomy or radiation therapy

survival status unknown

definitive therapy not documented

metastases or positive nodes or M, N status not documented

N total at baseline: 733

Cryosurgery: 315

Thermal ablation: 155

Deferred therapy: 263

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test):

cryosurgery (CS) or thermal ablation (TA)

Describe control (treatment/procedure/test):

deferred therapy (DT) (not receiving surgical or ablative therapy during the first course of treatment within 4 months after initial

cancer diagnosis)

Length of follow-up: median (range) 34 (1-114) months

Loss-to-follow-up:

not reported

Incomplete outcome data:

not reported

Outcome measures and effect size (include 95%CI and p-value if available):

Cancer-specific survival:

CS versus DT:

HR (95% CI) 0.25 (0.14 to 0.45)

TA versus DT:

HR (95%CI) 0.27 (0.13 to 0.55)

adjustment for age at diagnosis, tumor grade, tumor size

RAPN

Ramirez 2016

Type of study:

data extracted from hospital dataset

Setting and country: high-volume academic centre, USA

Funding and conflicts of interest:

No financial support,

one of the authors serves a consultant for

Endocare, Inc.

Inclusion criteria:

Patients who underwent either OPN or RAPN for unifocal, localized clinical T1a renal tumours between January 2011

and August 2015

Exclusion criteria:

clinical tumours >4 cm in size

ipsilateral, multifocal tumours

N total at baseline:

Intervention: 545

Control: 169

Important prognostic factors²:

median (IQR) age:

I: 59 (51-67)

C: 61 (53-69)

Sex:

I: 57.3 % M

C: 57.4 % M

Groups comparable at baseline? RENAL nephrometry score higher in I group (p<0.001)

Describe intervention (treatment/procedure/test):

Robot-Assisted Partial Nephrectomy (RAPN)

Describe control (treatment/procedure/test):

Open Partial Nephrectomy (OPN)

Length of follow-up: 30 days

Loss-to-follow-up:

not reported

Incomplete outcome data:

not reported

Outcome measures and effect size (include 95%CI and p-value if available):

Overall complication rate 18.2% (I) and (text) 25.4% (C)

RR (95% CI) 0.71 (0.52 to 0.98)

adjusted OR (95% CI) 0.63 (0.41 to 0.97) in favour of RAPN

Discrepancy in percentage of overall complications in OPN group between text (25.4%) and Table 4 (30.3%)

Maurice,

2017

Type of study:

retrospective analysis of clinical database

Setting and country: single center, USA

Funding: TUBITAK: Technology and Innovation

Support Programs, Directorate of the Scientific and Research

Council of Turkey

Conflicts of interest: consultancies for HealthTronics, Inc. and

Intuitive Surgical, Inc.

Inclusion criteria:

unifocal clinical T1 renal mass, suspicious for malignancy, with functioning

contralateral kidneys and 3–12-month postoperative GFR

follow-up

Exclusion criteria:

not reported

N total at baseline:

Intervention: 301

Control: 110

Important prognostic factors²:

For example

median (IQR) age:

I: 60 (52–68)

C: 63 (53–70)

Sex:

I: 58.1% M

C: 54.6% M

Groups comparable at baseline?

median R.E.N.A.L. score higher for RAPN

Describe intervention (treatment/procedure/test):

Robot-assisted partial nephrectomy (RAPN)

Describe control (treatment/procedure/test):

Open partial nephrectomy (OPN)

Length of follow-up:

median (IQR) 6 (6–12) months

Loss-to-follow-up:

not reported

Incomplete outcome data:

not reported

Outcome measures and effect size (include 95%CI and p-value if available):

Overall complications OR (95% CI) 0.46 (0.29; 0.75) p=0.0017

OPN increased rate of overall cardiovascular (1.3%

versus 6.4%; P = 0.01) and genitourinary (0.3% versus 3.6%;

P = 0.02) complications and surgical site infections (1.7% versus

8.2%; P < 0.01)

Separate results for T1a (reported here) and T1b

No adjustment for confounding

OR overall complications calculated based on numbers reported (RAPN 61/301; OPN 39/110)

Kim,

2015

Type of study:

retrospective analysis of clinical database

Setting and country: two university hospitals, South Korea

Funding: not reported

Conflicts of interest: none declared

Inclusion criteria:

single renal mass < 4 cm

without LN invasion or metastasis

CT or MRI confirmation of RCC

normal contralateral kidney

Exclusion criteria:

positive lymph nodes or metatstasis

serum Create > 1.4 ng/dl

solitary kidney,

eGFR< 60 ml/min/1.72 m²

N total at baseline:

Intervention: 41 (60 RFAs)

Control: 203 (206 RALPNs)

propensity matched:

I: 27, C: 27

Groups comparable at baseline? Yes, in propensity matched group

Describe intervention (treatment/procedure/test):

radiofrequency ablation (RFA)

Describe control (treatment/procedure/test):

robot-assisted laparoscopic partial nephrectomy (RALPN)

Length of follow-up:

median 14.6 months

Loss-to-follow-up:

not reported

Incomplete outcome data:

not reported

Outcome measures and effect size (include 95%CI and p-value if available):

mortality:

I: 7.4%; C: 7.4%; p=0.764

complications:

I: 14.8%; C: 11.1%; p=0.434

Not clear what variables were used to calculate propensity score

27 paired cases based on propensity score

Guillotreau,

2012

Type of study:

retrospective analysis of clinical database

Setting and country:

single centre, urological and kidney institute, USA

Funding: none Conflicts of interest: consultancies: Intuitive Surgical, Endocare, Covidien, honoraria:Applied Medical

Inclusion criteria:

small renal mass ≤ 4 cm

Exclusion criteria:

not reported

N total at baseline: 436 (446 tumors)

Intervention: 226

Control: 210

Important prognostic factors²:

For example

age ± SD:

I: 67.4 (11.3) yrs

C: 57.8 (11.8) yrs

Sex:

I: 71% M

C: 58% M

Groups comparable at baseline? No; I: older, higher ASA, higher preop Create and lower eGFR, smaller tumors

Describe intervention (treatment/procedure/test):

laparoscopic cryoablation (LCA)

Describe control (treatment/procedure/test):

robotic partial nephrectomy (RPN)

Length of follow-up:

median (IQR)

I: 44.5 months (8.7-66.8)

C: 4.8 months (1-7.9)

Loss-to-follow-up:

not reported

Incomplete outcome data:

not reported

Outcome measures and effect size (include 95%CI and p-value if available):

intraoperative complication rate: I: 0; C: 3.3%; p= 0.005

postoperative complication rate: I: 12%; C: 20%; p=0.015

minor complication rate:

I: 8%; C: 17%

major complication rate:

I: 3%; C: 3%

adjusted OR (95% CI) for complications (any grade):

0.55 ( 0.29; 1.11)

recurrence:

I: 11%; C: 0; p<0.0001

metastasis:

I: 5.6%; C: 0.5%; p=0.0021

“Variables entered into the model for the postoperative

complications were treatment modality, age, gender, BMI, ASA score,

preoperative eGFR, and EBL.”

About 25% of tumors benign or inconclusive

Results biased by differential follow-up

Thermo-ablation (RFA, MWA)

Chang,

2015

Type of study:

retrospective analysis of clinical database

Setting and country: university hospital, China

Funding: not reported Conflicts of interest: none

Inclusion criteria:

localized tumor measuring no more than 4.0 cm

(clinical T1a) in maximum diameter,

pathologically

confirmed RCC,

minimum postoperative follow-up

5 years

Exclusion criteria:

multiple

ipsilateral, metachronous, synchronous bilateral tumors or

distant metastatic diseases

or familial history of RCC or a

history of hereditary RCC syndromes

N total at baseline:

Intervention: 134

Control: 134

After propensity score matching:

I: 45; C:45

Groups comparable at baseline? Yes, after propensity score matching

Describe intervention (treatment/procedure/test):

radiofrequency ablation (RFA)

Describe control (treatment/procedure/test):

partial nephrectomy (PN)

Length of follow-up:

5 years

Loss-to-follow-up:

none in the included propensity matched population

Incomplete outcome data:

none in the included propensity matched population

Outcome measures and effect size (include 95% CI and p-value if available):

5-year OS (95% CI)

I: 90.2% (78.6–98.8); C: 93.2% (85.8–98.9)

5-year CSS (95% CI)

I: 95.6% (89.5–98.1); C: 97.7% (93.4–99.3)

5-year DFS (95% CI)

I: 86.7% (89.5–96.7); C: 88.5% (79.1–97.9)

OR (95% CI) for DFS in propensity score-matched groups, adjusted for age, sex, tumor size, nephrometry score: 0.766 (0.197; 2.984) , p=0.701

“The propensity

score was built by way of a multivariable logistic regression

model considering the following variables: Age, sex, ASA score, tumor size, tumor side, tumor histology, R.E.N.A.L. (radius; exophytic/endophytic; nearness; anterior/posterior;

location) nephrometry score, and preoperative GFR”

Results reported here for propensity matched population

Timing of DFS endpoint used in logistic regression not specified

Olweny,

2012

Type of study:

retrospective analysis of clinical database

Setting and country: single center university hospital, USA

Funding and conflicts of interest: none declared

Inclusion criteria:

histologic confirmation of RCC and minimum follow-up of 5 years

Exclusion criteria:

multiple, bilateral, metastatic disease, hereditary RCC syndromes, family history of RCC

N total at baseline:

Intervention: 37

Control: 37

Important prognostic factors²:

For example

median (IQR) age:

I:63.8 years (56.3-69.1)

C: 54.8 years (47.8-59.1)

Sex:

I: 65% M

C: 54% M

Groups comparable at baseline? No; I older, higher ASA

Describe intervention (treatment/procedure/test):

 radiofrequency ablation (RFA)

Describe control (treatment/procedure/test):

partial nephrectomy (PN)

Length of follow-up:

at least 5 years

median (IQR):

I: 6.5 yr (5.8-7.1)

C: 6.1 yr (5.4-7.3)

Loss-to-follow-up:

not reported

Incomplete outcome data:

not reported

Outcome measures and effect size (include 95%CI and p-value if available):

5 years overall survival (95% CI):

I: 97.2% (81.9; 99.6); C: 100%; log rank test p=0.31

5 yr cancer-specific survival (95% CI):

I: 97.2% (81.9; 99.6); C: 100%; log rank test p=0.31

5 yr disease free survival (95% CI):

I: 89.2% (73.7; 95.8); C: 89.2% (73.7; 95.8); log rank test p=0.78

OR (95% CI) (adjusted for age, tumor size, years of follow-up, histology?) 0.31 (0.05; 1.93); p=0.21

Multivariable regression analysis evaluating risk factors for disease-free survival: not clear what determinants included in the model (probably age, tumor size, years of follow-up, histology)

Stern,

2007

Type of study:

retrospective analysis of clinical database

Setting and country: single center, university hospital, USA

Funding: not reported

Conflicts of interest: none declared

Inclusion criteria:

clinical T1a renal tumor, complete 2 year follow-up

Exclusion criteria:

bilateral synchronous or metachronous tumours, metastatic disease at presentation, or hereditary renal cancer syndromes

N total at baseline:

Intervention: 40

Control: 37

Important prognostic factors²:

For example

age ± SD:

I: 60.5 (13.5)

C: 56.4 (12.5)

Groups comparable at baseline? No; I older, shorter follow-up

Describe intervention (treatment/procedure/test):

percutaneous or laparoscopic radiofrequency ablation (RFA)

Describe control (treatment/procedure/test):

open or laparoscopic partial nephrectomy (PN)

Length of follow-up:

at least 2 years

mean (range)

I: 30 months (18-42)

C: 47 months (24-93)

Loss-to-follow-up:

Intervention:

1 ( 2%)

Reason: patient had a PUJ obstruction and underwent nephrectomy after 18 months

Control:

N (%)

Reasons (describe)

Incomplete outcome data:

Intervention:

N (%)

Reasons (describe)

Control:

N (%)

Reasons (describe)

Outcome measures and effect size (include 95%CI and p-value if available):

Complications:

minor:

I: 2/40 (5%); C: 2/37 (5%)

major:

I: 3/40 (7%); C: 1/37 (2%)

Recurrence:

I: 2/40 (5%); C: 2/37 (5%)

3 years recurrence free survival rate:

I: 93.4%; C: 95.8%; log rank test p=0.67

subgroup with pathologically confirmed RCC:

I: 91.4%; C: 95.2%; log rank test p=0.58

No adjustment for confounding

Takaki,

2010

Type of study:

retrospective analysis of clinical database

Setting and country: single center, university hospital, Japan

Funding and conflicts of interest: not reported

Inclusion criteria:

single RCC ≤ 4 cm

Exclusion criteria:

RCC with vascular invasion or extrarenal spread

follow-up < 6 months

N total at baseline:

Intervention: 51

Control: 10

Important prognostic factors²:

For example

mean age (SD):

I: 69.4 (9.6)

C: 64.0 (9.6)

Sex:

I: 71% M

C: 80% M

Comorbid disease:

I: 90%

C: 80%

mean (SD) tumor diameter:

I: 2.4 (0.7) cm

C: 1.9 (0.7) cm

Groups comparable at baseline? No; I older, more comorbidity, larger tumors, longer follow-up

Describe intervention (treatment/procedure/test):

radiofrequency ablation (RFA)

Describe control (treatment/procedure/test):

partial nephrectomy (PN) (radical nephrectomy (RN))

Length of follow-up:

mean (SD):

I: 34 (23.2) months

C: 26 (16.9) months

Loss-to-follow-up:

not reported

Incomplete outcome data:

not reported

Outcome measures and effect size (include 95%CI and p-value if available):

5-yr overall survival rate ( 95% CI):

I: 75% (58.1; 85.9); C: 100%

5-yr DFS log rank test p=0.13

major complications: I: 0, C: 0

minor complications:

I: 3 after 60 RF sessions;

C: 10%; p=0.47

Only results reported here for RFA and PN

15/51 patients (29%) underwent selective arterial embolization before RFA

No adjustment for confounding

Park,

2018

Type of study:

retrospective cohort

Setting and country: single center, university hospital Republic of Korea

Funding: not reported; conflicts of interest: none reported

Inclusion criteria:

histologically confirmed renal

cell carcinoma, small (< 4 cm) solitary tumor,

followed up for at least 2 years after surgery

Exclusion criteria:

bilateral renal

tumors,

metastasis at presentation, hereditary renal

tumor

N total at baseline:

Intervention: 62

Control: 53

Important prognostic factors²:

For example

mean age (range):

I: 58 (32-84)

C: 53 (17-77)

Sex:

I: 72.5% M

C: 75.5% M

Groups comparable at baseline? No, I group older, more diabetes, more hypertension, higher BMI, smaller tumors

Describe intervention (treatment/procedure/test):

laparoscopic radiofrequency ablation

Describe control (treatment/procedure/test):

open partial nephrectomy

Length of follow-up: at least 2 years after surgery

Loss-to-follow-up:

not reported

Incomplete outcome data:

not reported

Outcome measures and effect size (include 95%CI and p-value if available):

5 year recurrence free survival 100% in both groups

No adjustment for confounding

Ji,

2016

Type of study:

retrospective analysis of clinical database

Setting and country:

single center, university hospital China

Funding and conflicts of interest: none reported

Inclusion criteria:

single cT1a tumor, > 5 years follow-up

Exclusion criteria:

prior

renal surgery, history of RCC or hereditary RCC syndromes

N total at baseline: 179

Intervention: 105

Control: 74

Important prognostic factors²:

For example

mean age:

I: 64.2 yrs

C: 57.3 yrs

Sex:

I: 63% M

C: 55% M

Groups comparable at baseline? No; I older, higher ASA, smaller tumors

Describe intervention (treatment/procedure/test):

laparoscopic radiofrequency ablation (LRFA)

Describe control (treatment/procedure/test):

laparoscopic partial nephrectomy (LPN)

Length of follow-up:

at least 5 years

median (range):

I: 78 months (60-106)

C: 82 months (63-104)

Loss-to-follow-up:

not reported

Incomplete outcome data:

not reported

Outcome measures and effect size (include 95%CI and p-value if available):

Overall survival (5 years)(95% CI):

I: 93.3% (88.6; 98.0)

C: 94.6% (89.5; 99.7)

Cancer-specific survival (5 years)(95% CI):

I: 98.0% (95.3; 100)

C: 98.5% (95.6; 100)

Disease free survival (5 years)(95% CI):

I: 97.1% (93.9; 100)

C: 97.3% (93.6; 100)

OR (95% CI) (adjusted for age, tumor size, histology and years of follow-up?):

1.04 (0.06; 18.55); p=0.27

Multivariable regression analysis evaluating risk factors for disease-free survival: not clear what determinants included in the model (probably age, tumor size, histology and years of follow-up)

Bensalah,

2007

Type of study:

retrospective analysis of clinical database

Setting and country: several hospitals (not clear how many) of one institution, USA

Funding not reported Conflicts of interest: none declared

Inclusion criteria:

small renal masses

treated with LPN or LRFA

Exclusion criteria:

multiple unilateral tumors, LRFA and LPN in the same operation

other surgical procedure in the same operation

N total at baseline:

Intervention: 38

Control: 50

Important prognostic factors²:

For example

mean age (SD):

I: 62 (17.5) yrs

C: 56.5 (11.7) yrs

Sex:

I: 58% M

C: 62% M

Groups comparable at baseline? No; I older, worse ASA score

Describe intervention (treatment/procedure/test):

laparoscopic radiofrequency ablation (LRFA)

Describe control (treatment/procedure/test):

laparoscopic partial nephrectomy (LPN)

Length of follow-up:

I: mean 25 months

C: mean 15 months

Loss-to-follow-up:

strict clinical programme for follow-up of RFA, whereas LPN patients return to their primary urologist if they are doing well

Incomplete outcome data:

not reported

Outcome measures and effect size (include 95%CI and p-value if available):

Complications:

I: 3/38; C: 5/50

Recurrences:

I: 1/38; C: 0

Mortality:

I: 6/38; C: 1/50

Differential outcome verification, no adjustment for confounding

Guan,

2012

Type of study:

RCT

Setting and country:

single center, China

Funding and conflicts of interest: not reported

Inclusion criteria:

solitary, unilateral solid renal mass ≤ 4 cm

Exclusion criteria:

bilateral tumors

metastatic disease

hereditary renal cancer syndrome

N total at baseline: 102

Intervention: 48

Control: 54

Important prognostic factors²:

For example

age ± SD:

I: 45.5 (14.4) yrs

C: 46.4 (13.2) yrs

Sex:

I: 40% M

C: 52% M

Groups comparable at baseline? Randomised; however, I lower preop Creat

Describe intervention (treatment/procedure/test):

microwave ablation (open or laparoscopic)

Describe control (treatment/procedure/test):

partial nephrectomy (open or laparoscopic)

Length of follow-up:

at least 2 years;

median (range):

I: 32 (24-54);

C: 36 (25-66)

Loss-to-follow-up:

not reported

Incomplete outcome data:

not reported

Outcome measures and effect size (include 95%CI and p-value if available):

3 years recurrence-free survival rate (95% CI):

I: 91.3% (74.7; 97.2)

C: 96% (83.8; 99.1);

log rank test p=0.5414

subgroup pathologically confirmed RCC:

I: 90.4% (65.3; 97.6)

C: 96.6% (78.0; 99.6); log rank test p=0.4650

postoperative complications (Clavien I to III):

I: 12.5%; C: 33.3%; p=0.0187

Almost 30% in both groups had a benign condition or no biopsy was available

Poorly reported RCT

Cryo-ablation

Atwell,

2013

Type of study: retrospective analysis of clinic database

Setting and country: single center, USA

Funding: not reported Conflicts of interest: received research grants from Siemens Healthcare and Endocare

Inclusion criteria:

patients

who underwent percutaneous ablation of a

renal mass 3.0 cm or smaller with curative intent

Exclusion criteria:

N total at baseline: n=385; 445 tumors

Intervention: n= 163; 189 tumors

Control: n= 222; 256 tumors

Important prognostic factors²:

mean age ± SD:

I: 68.2 (11.3) yrs

C: 68.8 (11.6) yrs

Sex:

I: 66% M

C: 64% M

Groups comparable at baseline? No; tumors larger, and more history of renal cancer in cryoablation group

Describe intervention (treatment/procedure/test):

cryoablation

Describe control (treatment/procedure/test):

radiofrequency ablation (RFA)

Length of follow-up: 3 months

Loss-to-follow-up:

Intervention:

44 (23%)

Reasons not reported

Control:

38 (15%)

Reasons not reported

Incomplete outcome data:

In Figure 1 (local recurrence-free survival) the Kaplan Meier plot starts with I: n= 145, C: n=218

Reasons not reported

Outcome measures and effect size (include 95%CI and p-value if available):

Major complications

I: 9/176 (5.1%)

C: 10/232 (4.3%)

Very limited information about persons, merely about tumors

Data are difficult to understand

“Tumors treated with cryoablation were significantly

less likely to be followed for at

least 3 months compared with tumors treated

with RFA (145/189 (77%) versus 218/256 (85%);

p = 0.023).”

Thompson,

2015

Type of study:

retrospective analysis of clinical database

Setting and country: single setting, university hospital, USA

Funding and conflicts of interest: none declared

Inclusion criteria:

localized cT1 solid renal mass

Exclusion criteria:

history of prior renal cell carcinoma, genetic syndromes

N total at baseline:

RFA: 180

CA: 187

PN: 1057

Important prognostic factors²:

median (IQR) age:

RFA: 72 (64-78)

CA: 72 (65-79)

PN: 62 (52-69)

median (IQR) Charlson score:

RFA: 1 (0-3)

CA: 2 (0-3)

PN: 1 (0-2)

median (IQR) tumor size (cm):

RFA: 1.9 (1.5-2.5)

CA: 2.8 (2.4-3.4)

PN: 2.4 (1.8-3.1)

Histologic type benign or unknown:

RFA: 59%

CA: 42%

PN: 21%

Groups comparable at baseline? No

Describe intervention (treatment/procedure/test):

percutaneous radiofrequency ablation (RFA), cryoablation (CA)

Describe control (treatment/procedure/test):

partial nephrectomy (PN)

Length of follow-up:

median (IQR):

RFA: 2.9 yrs (1.4-4.9)

CA: 1.4 yrs (0.6-3.1)

PN: 5 yrs (3.1-7.7)

Loss-to-follow-up:

RFA: 14 ( 7.8%)

CA: 13 ( 7.0%)

Reasons (describe): no oncologic follow-up

PN:

0

Incomplete outcome data:

not reported

Outcome measures and effect size (include 95%CI and p-value if available):

3 yr local recurrence-free survival rate (95% CI):

RFA: 98% (96; 100)

CA: 98% (95; 100)

PN: 98% (97; 99)

p=0.49

biopsy-proven RCC: p=0.49

Overall mortality

HR (95%CI) adjusted for age and Charlson score:

RFA versus PN: 1.43 (0.96; 2.13); p=0.080

CA versus PN: 1.72 (1.09; 2.71); p=0.019

T1a and T1b reported separately, here only T1a reported

Klatte,

2011

Type of study:

retrospective

analysis of clinical database

Setting and country:

single center university hospital, Austria

Funding: not reported

Conflicts of interest: none declared

Inclusion criteria:

incidental, solitary, solid, clinical T1aN0M0 renal mass

Exclusion criteria:

not reported

N total at baseline:

Intervention: 41

Control: 253

Propensity matched:

I: 41; C: 82

Groups comparable at baseline? Yes, in propensity matched group

Describe intervention (treatment/procedure/test):

laparoscopic cryoablation

Describe control (treatment/procedure/test):

partial nephrectomy

Length of follow-up:

median (range) 33.6 months (3-52)

Loss-to-follow-up:

not reported

Incomplete outcome data:

not reported

Outcome measures and effect size (include 95%CI and p-value if available):

complications of operation:

I: 20%: C: 17%; p=0.739

3 years recurrence-free survival:

I: 83%; C: 100%;

log rank test p=0.015

matched for age-adjusted Charlson comorbidity index (ACCI), PADUA score (anatomic classification of renal tumors), preoperative

eGFR, and sex

Desai,

2005

Type of study:

retrospective analysis of clinical database

Setting and country:

singels center urological institute, USA

Funding and conflicts of interest:

not reported

Inclusion criteria:

suspicious peripheral nonhilar renal tumor ≤3cm

Exclusion criteria:

not reported

N total at baseline:

Intervention: 78 (89 tumors)

Control: 153 (153 tumors)

Important prognostic factors²:

For example

age ± SD:

I: 65.6 (12.7)yrs

C: 60.6 (13.2)

Sex:

I: 69% M

C: 58% M

ASA class 3 or 4:

I: 75%

C: 46%

Groups comparable at baseline? No; I older, worse ASA, smaller tumor, higher serum Creat

Describe intervention (treatment/procedure/test):

laparoscopic renal cryoablation

Describe control (treatment/procedure/test):

laparoscopic partial nephrectomy

Length of follow-up:

I: mean (range): 24.6 (1-60) months

C: mean 5.8 (1-36) months

Loss-to-follow-up:

not reported

Incomplete outcome data:

not reported

Outcome measures and effect size (include 95%CI and p-value if available):

recurrences:

I: 2/78 (3%); C: 1/153 (0.6%); p=0.08

deaths:

I: 3 (4%); C: 0; p=0.09

differential follow-up; no adjustment for confounding

ablation

Talenfeld,

2018

Type of study:

retrospective registry study

Setting and country: SEER database, USA

Funding: Association of University Radiologists GE Radiology Research Academic Fellowship, Society of Interventional Radiology Foundation, NIH; Conflicts of interest: no commercial CoI reported

Inclusion criteria:

>65 years

treated for T1a RCC between 1-1-2006 and 31-12-2011

Exclusion criteria:

metastatic disease, month of diagnosis missing, cancer not diagnosed until death, chemotherapy or radiation within 12 months of diagnosis, incomplete data

N total at baseline:

Intervention: 456

Control: 1748

Important prognostic factors²:

For example

age ± SD:

I:

C:

Sex:

I: % M

C: % M

Groups comparable at baseline?

Describe intervention (treatment/procedure/test):

Percutaneous Ablation (PA)

Describe control (treatment/procedure/test):

Partial Nephrectomy (PN)

Length of follow-up:

at least one year

Loss-to-follow-up:

not reported

Incomplete outcome data:

not reported

Outcome measures and effect size (include 95%CI and p-value if available):

Overall mortality:

AHR (95% CI) 1.93 (1.50 to 2.49)

RCC-specific mortality:

AHR (95% CI) 1.99 (0.96 to 4.14)

Inverse probability of treatment-weighted Cox regression

Information about a third group undergoing RN is not reported here

Larcher,

2017

Type of study:

retrospective analysis of data from Surveillance, Epidemiology,

and End Results (SEER)-Medicare dataset

Setting and country: USA

Funding none

Conflicts of interest none reported

Inclusion criteria:

T1a, organ

confined, unilateral, renal cell carcinoma (RCC)

Exclusion criteria:

not reported

N total at baseline:

Intervention: 510

Control: 1961 (after propensity score matching 510)

Groups comparable at baseline? Yes, after propensity score matching

Describe intervention (treatment/procedure/test):

Local tumor ablation (LTA)

Describe control (treatment/procedure/test):

Partial nephrectomy (PN)

Length of follow-up: 12 months from surgery

Loss-to-follow-up:

not reported

Incomplete outcome data:

not reported

Outcome measures and effect size (include 95%CI and p-value if available):

30-day mortality

adjusted OR (95% CI) 2.27 (0.7; 7.34); p=0.2

overall complications 30 days

adjusted OR (95% CI) 0.38 (0.28; 0.5); p<0.001

adjustment using a 1:1

nearest-neighbour propensity score matching ratio; independent variables: age at diagnosis, gender, race, marital status, socioeconomic status, residency status, baseline CCI, renal medical history, general medical history, tumour size, side and histology

Zhou, 2018

Type of study:

registry study, matched pairs

Setting and country: SEER database, collected from 20 registries covering about 28% of the American population, USA

Funding: not reported Conflicts of interest: none

Inclusion criteria:

stage 1a RCC

undergoing PN, CA or TA

Exclusion criteria:

N total at baseline:

Intervention: 611

Control: 611

Important prognostic factors²:

For example

mean age:

I: 64.5

C: 64.2

Sex:

I: 58.4 % M

C: 56.6 % M

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test):

Ablation: Cryo-ablation (CA) or thermo-ablation (TA)

Describe control (treatment/procedure/test):

partial nephrectomy (PN)

Length of follow-up: 10 years

Loss-to-follow-up:

not reported

Incomplete outcome data:

not reported

Outcome measures and effect size (include 95%CI and p-value if available):

Overall survival (OS) HR (95% CI) 1.442 (1.005 to 2.068); p=0.0457 in favour of PN

Renal Carcinoma Specific Survival HR (95% CI) 1.466 (0.599 to 3.59); p=0.4023 in favour of PN

propensity score matching based on variables:

age,

sex,

race,

tumor grade

tumor size

No parameters of dispersion reported (e.g. for age)

Also comparison between CA and TA, but not adjusted for confounding

Study reference

(first author, publication year)

Describe method of randomisation¹

Bias due to inadequate concealment of allocation?²

(unlikely/likely/unclear)

Bias due to inadequate blinding of participants to treatment allocation?³

(unlikely/likely/unclear)

Bias due to inadequate blinding of care providers to treatment allocation?³

(unlikely/likely/unclear)

Bias due to inadequate blinding of outcome assessors to treatment allocation?³

(unlikely/likely/unclear)

Bias due to selective outcome reporting on basis of the results?⁴

(unlikely/likely/unclear)

Bias due to loss to follow-up?⁵

(unlikely/likely/unclear)

Bias due to violation of

intention to treat analysis?⁶

(unlikely/likely/unclear)

Guan, 2012

prospectively randomised by a computer-generated program

unclear

unlikely

unlikely

unlikely

unclear

unlikely

unlikely

Study reference

(first author, year of publication)

Bias due to a non-representative or ill-defined sample of patients?¹

(unlikely/likely/unclear)

Bias due to insufficiently long, or incomplete follow-up, or differences in follow-up between treatment groups?²

(unlikely/likely/unclear)

Bias due to ill-defined or inadequately measured outcome ?³

(unlikely/likely/unclear)

Bias due to inadequate adjustment for all important prognostic factors?⁴

(unlikely/likely/unclear)

Alam, 2019

unlikely

unlikely

unlikely

likely

Xing, 2018

unlikely

unlikely

unlikely

unlikely

Uhlig, 2018

unlikely

unlikely

unlikely

unlikely

Ramirez 2016

unlikely

unlikely

unclear

likely

Maurice, 2017

unlikely

unlikely

unlikely

likely

Kim, 2015

unlikely

unclear

unlikely

unlikely

Guillotreau, 2012

unclear

likely

unlikely

unlikely

Chang, 2015

unlikely

unlikely

unlikely

unclear

Olweny, 2012

unlikely

unlikely

unlikely

likely

Stern, 2007

unlikely

likely

unlikely

likely

Takaki, 2010

unlikely

likely

unlikely

likely

Park, 2018

unlikely

unlikely

unlikely

likely

Ji, 2016

unlikely

unlikely

unlikely

unclear

Bensalah 2007

unclear

likely

likely

likely

Atwell, 2013

unclear

likely

unclear

likely

Thompson, 2015

unlikely

likely

unlikely

unlikely

Klatte, 2011

unlikely

unlikely

unlikely

unlikely

Desai, 2005

unclear

likely

unlikely

likely

Talenfeld, 2018

unlikely

unlikely

unlikely

unlikely

Larcher, 2017

unlikely

unlikely

unlikely

unlikely

Zhou, 2018

unlikely

unlikely

unlikely

unlikely