REVIEW Partial Versus Radical Nephrectomy in Patients with Renal Cell Carcinoma: A Systematic Review and Meta-analysis Yong Yang* Purpose: Radical nephrectomy (RN) and partial nephrectomy (PN) are widely used for early-stage renal cell car- cinoma (RCC). However, the results were inconsistent while comparing the efficiency of RN and PN. This study aimed to assess the perioperative effectiveness of RN and PN for treating RCC. Material and Methods: PubMed, Embase, and the Cochrane Library electronic database were searched for stud- ies on adults with RCC comparing RN and PN published until September 2019. The perioperative efficacy and safety outcomes were calculated using odds ratio (OR) and standard mean difference (SMD) with 95% confidence intervals (CIs) for dichotomous and continuous data, respectively. Subgroup analysis were conducted based on tumor stage and surgery methods for evaluation of the treatment effect on specific subsets. Results: A total of 23 studies involving 30,018 patients with RCC were included in this meta-analysis. Notably, RCC treated with PN was associated with low incidences of hospital mortality (OR: 0.58; 95% CI: 0.38–0.89; P = 0.013) and reoperation rate (OR: 0.74; 95% CI: 0.58–0.95; P = 0.016) as compared to RN. However, PN was associated with an increased risk of overall postoperative complications (OR: 1.40; 95% CI: 1.17–1.68, P < 0.001), postoperative hemorrhagic complications (OR: 1.92; 95% CI: 1.28–2.87, P = 0.002), and urinary fistula (OR: 17.65; 95% CI: 5.35–58.30, P < 0.001) as compared to RN. Conclusion: These findings suggested that PN was associated with lower incidences of hospital mortality and reoperation rate, whereas RN was associated with fewer complications. Keywords: radical nephrectomy; partial nephrectomy; renal cell carcinoma; perioperative; meta-analysis INTRODUCTION Renal cell carcinoma (RCC) is the third most com-mon urological cancer, accounting for 2–3% of cancer-related deaths in adults(1,2). The incidence of RCC increases with age, maximal at 70 years of age, and 2-fold more prevalent in men than women(3,4). The predisposing factors of RCC include age, gender, smoke, excessive weight, long-term dialysis, hereditary factor, and exposure to hazardous materials (cadmium, benzene, trichloroethylene, and asbestos)(5-7). Surgical removal is regarded as the standard treat- ment for patients with RCC, as the tumor is resistant to chemotherapy and radiotherapy(8,9). Radical nephrecto- my (RN) removes the affected kidney within Gerota’s fascia, including the ipsilateral adrenal gland and re- gional lymph nodes, which is still the gold standard for treating RCC (10,11). However, whether nephron-sparing surgery, termed as partial nephrectomy (PN), is an ideal alternative to RN is yet a controversy. PN is a feasible organ-preserving approach that avoids unnecessary loss of a viable kidney, especially in the case of small renal tumors with diameter ≤ 4 cm (stage T1a) and normal contralateral kidney(12,13). RN and PN were both recom- mended according to the NCCN Guidelines for patients with RCC in the T1b stage(14). Therefore, selection of the surgical technique is yet controversial, especially in patients with RCC in the T1b stage(15,16). Although various treatment guidelines were avail- able on RCC, a majority were based on personal ex- Department of Urology, The Ninth Hospital of Xi'an, Xi'an, 710016, Shanxi, China *Correspondence: Department of Urology, The Ninth Hospital of Xi'an, Xi'an, 710054, China. Tel: +86-13571976611. Fax: +86-21-57643271. Email: yangyong_2016@sina.com. Received May 2019 & Accepted December 2019 perience(17,18). Previous meta-analyses analyzed the differences in clinical outcomes between RN and PN, including overall mortality, cancer-related mortality, and incidence of renal failure(19-24). Nevertheless, po- tential limitations are also presented. First, previous meta-analyses discussed several surgical methods or provided a qualitative comparison between RN and PN; however, the direct quantitative comparison of RN with PN was not included. Second, the impact of tumor stage on clinical outcomes was neglected. Third, previous studies primarily focused on mortality, while the peri- operative side-effects were not summarized. Thus, the present study aimed to provide comprehensive results for the treatment strategies of RN and PN in patients with RCC. MATERIALS AND METHODS Search strategy and selection criteria This review was conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Statement issued in 2009(25) (Check- list S1). PubMed, Embase, and Cochrane Library elec- tronic database were systematically searched for stud- ies published until September 2019. “Nephrectomy,” “kidney neoplasms,” “renal cell carcinoma*,” “renal mass*,” “renal tumor*,” and “renal cancer*” were used as core search terms. The reference lists of all relevant original and review articles were searched manually to identify additional eligible studies. Urology Journal/Vol 17 No. 2/ March-April 2020/ pp. 109-117. [DOI: 10.22037/uj.v0i0.5358] Table 1. Characteristics of included studies. Author Design Region Study No. of Mean age Male (%) Criteria for TNM Compared Operation Perioperative JADAD or NOS (year) period patients (years) kidney lesions surgical arms outcomes Butler (1995) [36] Retrospective USA 1975–1992 88 62 61 Solitary (<4 cm) T1a Open PN Open LOS, IT, OC, PO severe unilateral RCCs (n = 46) hemorrhage, incidence of 5 vs. open RN urinary fistula, spleen (n = 42) damage, reoperation, ARF, sCr levels Indudhara (1997) [37] Retrospective UK 1989–1995 106 45 65 Solitary (<5 cm) T1 Open PN Open Blood loss, LOS, mean 6 RCCs (n = 35) PO sCr levels, incidence of vs. open RN urinary fistula, PO (n = 71) severe hemorrhage, CC, ARF Uzzo (1999) [38] Retrospective USA 1991–1995 80 Median: 65 Solitary (<4 cm) T1a Open PN Open OC, LOS 6 67.1 (RN) unilateral RCCs (n = 52) vs. vs. 61.5 (NSS) open RN (n = 28) Corman (2000) [39] Prospective USA 1991–1998 1885 62 98 Heterogeneous NA Open PN Open 30-day mortality, 8 RCCs (n = 512) vs. OC, ARF, PO open RN (n = 1373) severe hemorrhage, LOS, mean PO sCr levels Shekarrizet al. (2002) Retrospective USA 1991–1997 120 64 NA Solitary (<7 cm) T1 Open PN Open LOS, OC, incidence 7 [40] unilateral RCCs (n = 60) of urinary fistula, vs. open RN (n = 60) IT, blood loss Kim (2003) [41] Retrospective USA 1998–2002 114 58 65 Solitary (<4.5 cm) T1 LPN (n = 79) ) MIPN IT, ARF, spleen damage, 6 unilateral RCCs vs. LRN (n = 35 OC, LOS, mean PO sCr levels Stephenson (2004) Retrospective USA 1995–2002 1049 62 NA Renal cortical NA Open PN Open OC, 30-day mortality, 7 [42] neoplasm (n = 361) incidence of urinary fistula, vs. open RN (n = 688) ARF, PO severe hemorrhage, LOS, reoperation, mean PO sCr levels, CC Van Poppel (2007) RCT Multicenter 1992–2003 541 NA 67 Solitary T1 Open PN Open PO severe hemorrhage, 3^ [43] (<5 cm) (n = 268) incidence of urinary fistula, T1–T2N0M0 RCCs vs. open RN (n = 273) pleural damage, spleen damage, reoperation Miller (2008) [44] Retrospective USA 1991–2002 10123 75 62 RCCs NA Open PN Open CC 7 (n = 763) vs. open RN (n = 10123) Gratzke (2009) [45] Prospective Switzerland January– 81 61 64 T1–T2 RCCs NA Open PN Open LOS, 30-day mortality, 7 December 2005 (n = 44) vs. ARF, IT, PO severe open RN (n = 37) hemorrhage, reoperation Simmons (2009) Retrospective USA 2001–2005 110 63 59 T1b–T3N0M0 NA LRN (n = 75) MIPN OC, PO mean sCr levels 5 [46] RCCs vs LPN (n = 35) Roos (2010) [47] Retrospective Germany 1981–2007 166 Range: 57 > 4 cm RCCs T1a Open PN Open OC, CC, incidence 6 23-84 (n = 69) of urinary fistula, vs. open RN IT, spleen damage (n = 97) Lowrance (2010) Retrospective USA 2000–2008 1712 NA 62 <7 cm RCCs T1 Mixed PN Mix OC, in-hospital mortality 6 [48] (n = 1061) vs. mixed RN (n = 651) Sun (2012) [49] Retrospective Canada 1988–2005 1680 72 59 T1aN0M0 RCCs T1a Open PN Open ARF 8 matched (n = 840) vs. open RN (n = 840) Becker (2014)*[50] Retrospective Canada 1992–2005 1223 >66 53 T1N0M0 RCCs T1 LRN MIPN PO severe hemorrhage, 7 (n = 1066) ARF, CC, 30-day mortality vs. LPN Liu (2014) [51] Retrospective USA 2005–2011 8361 61 NA RCCs NA (n = 157) Mix IT, ARF, CC, 30-day 7 MIRN (n = 3014) mortality, reoperation vs. MIPN (n = 1439); Open RN (n = 2445) vs. open PN (n = 1463) Hadjipavlou (2015) Prospective UK January– 1768 62 61 T1 RCCs T1 Mixed RN Mix OC, IT 8 [52] December 2012 (n = 1082) vs. mixed PN (n = 686) Cai (2018) [53] Retrospective China 2005-2012 199 54 64 solitary tumor T1b LRN (n = 160) MIPN Overall survival 6 with a maximum vs. LPN (n = 39) diameter of 4.0 to 7.0 cm Rinott Mizrahi (2018) Retrospective Israel 2012-2017 29 65 83 T2 RCC T2 LRN (n = 16) MIPN OC 5 [54] vs. LPN (n = 13) Reix (2018) [55] Retrospective France 2000-2014 267 60 67 localized RCC T2a Mixed RN Mix Overall survival 6 stage cT2a (7.1—10 cm) (n = 176) vs. mixed PN (n = 91) Janssen (2018) [56] Retrospective Germany 1980-2010 123 61 65 Large (>7cm) T1b-T3 Open RN Open Overall survival 6 clear cell RCC (n = 105) vs. open PN (n = 18) de Saint Aubert Retrospective France 2000-2013 130 58 63 Large (>7cm) T2 Mixed RN Mix OC, hemorrhage, 7 (2018) [57] RCC (n = 81) hospital stay, ARF vs. mixed PN (n = 49) Yang (2018) [58] Retrospective China 2014-2017 63 58 54 Clinical T1 T1 LRN (n = 38) MIPN OC 5 Renal Hilar Tumor vs. LPN (n = 25) Abbreviations: ARF, acute renal failure; CC, cardiovascular complications; IT, intraoperative transfusion; LOS, length of stay; MIPN, minimally invasive PN; NSS, nephron-sparing surgery; OC, overall complications; PN, partial nephrectomy; PO, postoperative; RCC, renal cell carcinoma; RN, radical nephrectomy; sCr, serum creatinine *Data on open PN vs laparoscopic RN were discarded ^using JADAD scale Partial vs. radical nephrectomy for RCC-Yang et al. Review 110 Vol 17 No 02 March-April 2020 111 The literature search was undertaken by two reviewers independently, and any inconsistencies were settled by the primary author (Yong Yang) until a consensus was reached. The study was eligible for inclusion if the fol- lowing criteria were fulfilled: (1) study with retrospec- tive/prospective cohort or randomized/non-randomized controlled design; (2) study investigating RN versus PN in patients with RCC; (3) outcomes including one of the following: hospital mortality, overall postoperative complications, postoperative hemorrhagic complica- tions, cardiovascular complications, acute renal failure (ARF), spleen damage, reoperation, urinary fistula, in- traoperative blood transfusion, hospital stay, and mean postoperative sCr. All studies describing patients with other diseases or lacking the direct comparison of RN and PN were excluded. Data collection and quality assessment Two reviewers independently extracted all data; the discrepancies were resolved after consulting with the primary author (Yong Yang). The following items were extracted from the included studies: first author’s name, design, region, study period, number of patients, mean age, the percentage of males, criteria for kidney lesions, TNM stages, compared surgical arms, opera- tion types, and perioperative outcomes. The following outcomes were evaluated: hospital mortality, overall Table 2. Subgroup analyses according to tumor stage and surgery methods Outcome Subgroup No. of studies OR or SMD and 95% CI P value Heterogeneity (%) P for heterogeneity Hospital mortality T1 6 1.11 (0.52-2.33) 0.792 0.0 0.558 Other 5 0.46 (0.29-0.73) 0.001 28.3 0.223 Open 6 0.45 (0.26-0.78) 0.005 24.7 0.249 MIPN 3 0.91 (0.37-2.24) 0.844 37.3 0.203 Mixed 3 0.69 (0.30-1.59) 0.378 3.8 0.354 Overall postoperative T1 9 1.46 (1.19-1.79) < 0.001 25.6 0.200 complications Other 5 1.38 (0.95-2.00) 0.094 50.7 0.088 Open 6 1.20 (0.99-1.47) 0.066 0.0 0.706 MIPN 5 1.17 (0.72-1.89) 0.536 53.2 0.058 Mixed 3 1.73 (1.29-2.33) < 0.001 48.6 0.143 Postoperative T1 4 2.25 (1.44-3.50) < 0.001 0.0 0.555 hemorrhagic complications Other 4 1.73 (0.65-4.60) 0.275 27.0 0.250 Open 6 1.71 (1.00-2.90) 0.048 14.1 0.324 MIPN 1 2.20 (1.15-4.20) 0.017 - - Mixed 1 12.27 (0.62-242.79) 0.100 - - Cardiovascular T1 3 0.48 (0.07-3.20) 0.450 76.2 0.015 complications Other 3 1.02 (0.92-1.12) 0.766 0.0 0.773 Open 5 1.00 (0.82-1.22) 0.968 46.2 0.098 MIPN 2 0.89 (0.43-1.84) 0.746 8.7 0.295 Mixed 0 - - - - Acute renal failure T1 5 1.25 (0.55-2.86) 0.596 49.8 0.093 Other 5 0.78 (0.36-1.66) 0.518 58.2 0.035 Open 7 0.87 (0.58-1.32) 0.510 34.4 0.165 MIPN 3 0.72 (0.10-4.96) 0.737 80.9 0.005 Mixed 1 0.51 (0.05-5.16) 0.568 - - Spleen damage T1 4 0.41 (0.10-1.72) 0.224 0.0 0.769 Other 0 - - - - Open 3 0.31 (0.06-1.52) 0.148 0.0 0.783 MIPN 1 1.36 (0.05-35.53) 0.853 - - Mixed 0 - - - - Reoperation T1 2 1.50 (0.59-3.85) 0.396 0.0 0.320 Other 3 0.71 (0.55-0.91) 0.006 0.0 0.657 Open 5 0.85 (0.49-1.47) 0.568 18.6 0.296 MIPN 1 0.74 (0.49-1.13) 0.162 - - Mixed 0 - - - - Urinary fistula T1 5 12.55 (3.35-47.00) < 0.001 0.0 0.981 Other 1 82.66 (4.98-1371.41) 0.002 - - Open 6 17.65 (5.35-58.30) <0.001 0.0 0.871 MIPN 0 - - - - Mixed 0 - - - - Hospital stay T1 2 0.06 (-0.21 to 0.33) 0.671 0.0 0.620 Other 3 0.04 (-0.05 to 0.13) 0.411 0.0 0.805 Open 4 0.05 (-0.04 to 0.14) 0.316 0.0 0.923 MIPN 0 - - - - Mixed 1 -0.04 (-0.39 to 0.31) 0.825 - - Intraoperative T1 4 1.05 (0.60-1.82) 0.866 31.1 0.214 blood transfusion Other 3 0.75 (0.46-1.25) 0.272 86.8 < 0.001 Open 5 1.04 (0.55-1.99) 0.895 84.0 < 0.001 MIPN 2 0.70 (0.53-0.94) 0.017 0.0 0.801 Mixed 1 0.81 (0.45-1.44) 0.475 - - Mean T1 2 -0.41 (-2.00 to 1.18) 0.613 96.4 < 0.001 postoperative sCr Other 2 -0.01 (-0.11 to 0.09) 0.849 0.0 0.962 Open 2 0.14 (-0.25 to 0.53) 0.476 70.5 0.066 MIPN 2 -0.61 (-1.80 to 0.59) 0.319 94.0 < 0.001 Mixed 0 - - - - Partial vs. radical nephrectomy for RCC-Yang et al. postoperative complications, postoperative hemorrhag- ic complications, cardiovascular complications, ARF, spleen damage, reoperation, urinary fistula, intraopera- tive blood transfusion, hospital stay, and mean postop- erative sCr. The quality of randomized controlled trial was assessed using JADAD scale, which was based on randomization, blinding, allocation concealment, withdrawals and dropouts, and use of intention-to-treat analysis(26). Then, the quality of prospective or retro- spective observational studies was evaluated using the Newcastle–Ottawa Scale (NOS), which was based on the following three subscales: selection (4 items), com- parability (1 item), and outcome (3 items)(27). Statistical analysis An inverse variance method was used to pool the con- tinuous data, and the results were presented as standard mean difference (SMD) with 95% confidence inter- vals (CIs). The results were presented as the odds ratio (OR) with 95% CIs for dichotomous data as most of the included studies consisted of retrospective cohorts. Given the lower prevalence of investigated outcomes, the relative risk could be considered as equivalent to OR. The pooled results were further evaluated using the random-effects model(28,29). The statistical heteroge- neity was assessed with the I2 test, and I2 > 50% was considered as significant heterogeneity(30). A sensitivi- ty analysis assessed the influence of a single study on overall ORs and SMDs(31). The subgroup analysis for the investigated outcomes was performed according to the tumor TNM stage (T1 stage or other) and surgical procedures (open, minimally invasive PN procedure, or mixed). Funnel plots were used for assessing the publi- cation bias; the Begg–Mazumdar(32) and Egger tests (33,34) evaluated the publication bias quantitatively. The trim- and-fill method was used to correct the publication bias if necessary(35). All tests were two-tailed, and a P-value < 0.05 was considered as statistically significant. STA- TA software (Version 12.0; StataCorp, TX, USA) was used to analyze the data. RESULTS This meta-analysis yielded 1,561 studies after remov- ing duplications, of which, 23 assessing 30,018 patients were included in the systematic review (Figure 1)(36-58). 1/23 was a randomized controlled trial (RCT) design (43), 3/23 had a prospective study design(39,45,52), and the remaining had a retrospective design. The RCT was a multicenter clinical study; however, blinding was not employed to conceal the intervener and/or the asses- sor(43) (Table 1). Moreover, the quality of remaining observational studies were assessed using the NOS; 3 studies had 8 stars, 7 had 7 stars, 8 had 6 stars, and the remaining 4 had 5 stars. The summary results of the treatment effects between RN and PN are presented in Figures 2–5. The me- ta-analysis revealed that PN had a significantly lower hospital mortality (OR: 0.58; 95% CI: 0.38–0.89; P = 0.013; unimportant heterogeneity) and reoperation rate (OR: 0.74; 95% CI: 0.58–0.95; P = 0.016; no evidence of heterogeneity) as compared to RN after pooling the results. However, patients treated with PN were asso- ciated with a greater risk of overall postoperative com- plications (OR: 1.40; 95% CI: 1.17–1.68, P < 0.001; moderate heterogeneity), postoperative hemorrhag- ic complications (OR: 1.92; 95% CI: 1.28–2.87, P = 0.002; unimportant heterogeneity), and urinary fistula (OR: 17.65; 95% CI: 5.35–58.30, P < 0.001; no evi- dence of heterogeneity) as compared to RN. Finally, no significant differences were detected between PN and RN with respect to the outcomes of cardiovascu- lar complications (OR: 0.99; 95% CI: 0.83–1.19, P = 0.932; moderate heterogeneity), ARF (OR: 0.91; 95% CI: 0.57–1.43, P = 0.675; significant heterogenei- ty), spleen damage (OR: 0.41; 95% CI: 0.10–1.72, P = 0.224; no evidence of heterogeneity), intraoperative blood transfusion (OR: 0.87; 95% CI: 0.59–1.28, P = 0.475; significant heterogeneity), hospital stay (SMD: 0.04; 95% CI: -0.05 to 0.13; P = 0.360; no evidence of heterogeneity), and mean postoperative sCr (SMD: Figure 1. Schematic representation. Preferred Reporting Items for Systematic Reviews and meta-Analysis flow diagram. Figure 2. A:PN vs. RN on the risk of in-hospital mortality; B: PN vs. RN on the risk of overall postoperative complications; C: PN vs. RN on the risk of postoperative hemorrhagic complications Partial vs. radical nephrectomy for RCC-Yang et al. Review 112 Vol 17 No 02 March-April 2020 113 -0.20; 95% CI: -0.72 to 0.33, P = 0.462; significant het- erogeneity). The results of sensitivity analysis indicated that the overall pooled ORs and SMDs were not affect- ed by sequential exclusion of individual study except hospital mortality and reoperation rate (Supplemental Figure 1). The summary results for subgroup analyses are shown in Table 2. First, we noted that PN was associated with a reduced risk of hospital mortality if the included pa- tients exhibited other stage of tumor and underwent an open procedure. Second, the risk of overall postoper- ative complications was significantly increased in T1 stage tumor patients or received mixed PN. Third, PN was associated with an increased risk of postoperative hemorrhagic complications than RN when patients with T1 stage tumor used open or minimally invasive PN procedure. Fourth, stratified results for cardiovascular complications, ARF, spleen damage, urinary fistula, hospital stay, and mean postoperative sCr were consist- ent with the overall analyses. Fifth, the rate of reopera- tion in PN was significantly lower than RN in patients with the other tumor stage. Finally, the incidence of intraoperative blood transfusion in the PN group was lower than that in the RN group when minimally inva- sive PN procedure was carried out. The putative publication bias was examined in various results and was found only in the results of urinary fis- tula (Begg test, P = 0.060; Egger test, P = 0.034; Sup- plemental Figure 2). These results remained unaltered after trim-and-fill correction (OR: 2.87; 95% CI: 1.68– 4.07; P < 0.001). DISCUSSION RN and PN used for treating RCC were analyzed in this study; 23 articles that fulfilled the inclusion criteria, comprising of 30,018 patients, were included. The pres- ent findings of this study demonstrated relatively fewer overall and hemorrhagic complications in RN, while PN had a lower hospital mortality, and reoperation. In a previous meta-analysis, Manikandan et al. first Figure 3. A: PN vs. RN on the risk of cardiovascular complica- tions; B: PN vs. RN on the risk of acute renal failure Figure 4. PN vs. RN on the risk of spleen damage, reoperation, and urinary fistula Figure 5. A: PN vs. RN on the incidence of intraoperative blood transfusion; B:. PN vs. RN on hospital stay and mean postoperative sCr Partial vs. radical nephrectomy for RCC-Yang et al. compared the PN and RN in patients with RCC with clinical outcomes including survival rate, recurrence, and metastasis. The disease-specific survival rate (P = 0.001) and incidence of metastasis (P < 0.050) were found to be significantly enhanced in the PN group; however, no significant difference was found regard- ing recurrence (P = 0.220). They also demonstrated that the efficacy of PN was similar to that of RN in patients with renal cell tumors up to 4 cm in diameter. However, this study did not discuss the perioperative complica- tions and analyze the differences among variances of patients in the TNM stage(24). A meta-analysis conduct- ed by Deng et al. contained 13 retrospective studies encompassing 2,906 patients with large (> 7 cm) renal tumors. The study speculated that PN was associated with improved OS and preserved renal function, and was also accompanied by high risk of surgical compli- cations than RN(59). MacLennan et al. comprehensive- ly analyzed the laparoscopic approach, open surgery, robot-assisted surgery, and radiofrequency surgery for RCC treatment. The study considered that PN either showed an equivalent or better survival of RCC patients with tumors < 4 cm in diameter, while open surgery and laparoscopic approach achieved an equivalent survival for either RN or PN. Therefore, localized PN would be ideally managed in patients with RCC in the T1a stage, which was better in the preservation of renal function and quality of life (QOL) as compared to RN. However, these studies primarily focused on the qualitative com- parison of RN and PN, while the quantitative results were not illustrated. Furthermore, the summary results of perioperative complications were less described in this study (20,21) Kim et al. compared RN and PN with re- spect to the overall and cancer-related mortality as pri- mary outcomes, and severe renal failure as a secondary outcome. Their study indicated that PN was associated with a 19% reduced risk in all-cause mortality (HR: 0.81; P < 0.001), a 29% reduced risk in cancer-specific mortality (HR: 0.71, P < 0.001), and a 61% reduced risk in severe chronic kidney disease (HR: 0.39, P < 0.001). However, the estimation of cancer-specific mortality was limited by the lack of robust significant heteroge- neity across studies (19). Tobert et al. analyzed the over- all mortality as the primary outcome measure between RN and PN in 2014 (22); the study confirmed that PN had a 19% reduction in the all-cause mortality (P < 0.001) and 29% reduction in cancer-specific mortality (P < 0.001). Although the study did not discuss the postop- erative renal function, perioperative complications, and QOL, the current study arrived at a similar conclusion on overall mortality. Intriguingly, PN had an advantage regarding reoperation, while RN had an advantage in terms of overall and hemorrhagic complications. A multicenter prospective RCT included patients in the T1-2N0M0 stage and found that the rate of periopera- tive blood loss was slightly high after RN and the rate of severe hemorrhage was slightly high after PN (43). This RCT further demonstrated that 4.4% patients developed urinary fistulas after PN; the incidences of pleural dam- age and spleen damage were similar in both groups. Therefore, not only mortality but improved QOL and reduced perioperative complications were evaluated in surgery modalities. (43) The present study also demon- strated a relatively low mortality in PN and fewer com- plications in RN. The detection rate of a tumor ≤ 4 cm in diameter would promote advanced iconography, and PN would be the ideal method for this kind of disease. The protection of normal renal function would be fur- ther strengthened with developed anatomical structure and function of kidneys as well as improved PN tech- nology. Thus, implementation of PN would be more advantageous, avoiding inconsequential trauma in pa- tients with RCC in the T1a stage. However, the conclu- sions might be variable because as a small number of studies were included in such subsets. Hence, a relative result and a synthetic and comprehensive review have been conferred. The subgroup analysis suggested that RN had a low incidence of overall complications, hemorrhagic com- plications, and incidence of urinary fistula in patients in the T1 stage (maximum tumor diameter ≤ 7 cm). Nevertheless, in the patients in T1a stage (tumor ≤ 4 cm), the number of included studies was not sufficient to yield robust results. In the surgical subgroup analy- sis, the mortality reduced by PN was primarily based on open surgery, and minimally invasive surgery did not show any difference between RN and PN. Presently, the minimally invasive surgery is less utilized as compared to open surgery for patients with RCC. However, min- imally invasive surgery, such as laparoscopy, exhibited advantages of fewer traumas, less bleeding, reduced in- fection probability, and reduced perioperative compli- cations post-surgery (60). The perioperative complica- tions may be reduced with an increase in the application of minimally invasive surgery in the future, suggesting the applicability of PN in patients with RCC (61-63). Nonetheless, the present study had some limitations as follows: (1) specific individual data were unavail- able for all trials, thereby restricting the analysis; (2) although the subgroup analysis was conducted, the heterogeneity continued to exist; (3) selection bias in- cluding tumor stages, complexity, and other potential confounders affected the resulting assessment due to the retrospective design of the study. In conclusions, RN had relatively fewer overall compli- cations, hemorrhagic complications, and incidence of urinary fistula, while PN had lower hospital mortality and incidence of reoperation. Thus, PN was associated with lower mortality and RN was associated with fewer complications. 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