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Partial nephrectomy vs. radical nephrectomy for stage I renal cell carcinoma in the presence of predisposing systemic diseases for chronic kidney disease
+
MODEL
Kaohsiung Journal of Medical Sciences (2017) xx, 1e5
Available online at www.sciencedirect.com
ScienceDirect journal homepage: http://www.kjms-online.com
Original Article
Partial nephrectomy vs. radical nephrectomy for stage I renal cell carcinoma in the presence of predisposing systemic diseases for chronic kidney disease ¨ mer Demir*, Ozan Bozkurt, Serdar C ¨ven Aslan, O ¸elik, Kaan C ¸¨ omez, Gu _ Ugur Mungan, Ilhan C ¸elebi, Adil Esen Department of Urology, Dokuz Eylul University School of Medicine, Izmir, Turkey Received 22 February 2017; accepted 27 April 2017
KEYWORDS Partial nephrectomy; Kidney tumors; eGFR; Renal functions; Chronic kidney disease
Abstract Aim of this study is to compare the effects of partial nephrectomy (PN) and radical nephrectomy (RN) for stage I renal cell carcinoma (RCC) on renal functions in patients with diabetes mellitus (DM) and/or hypertension (HT). Charts of patients who underwent surgery for stage I RCC in our department were retrospectively reviewed and patients with DM and/or HT were enrolled. Preoperative and postoperative estimated glomerular filtration rates (eGFR) were calculated according to the Modification of Diet in Renal Disease (MDRD) formulation for both RN and PN groups. Groups were compared for patient demographics, preoperative eGFR, postoperative eGFR and DeGFR [(preoperative eGFR) e (postoperative eGFR)] which reflects the renal functional loss. There were 85 patients in the RN and 33 patients in the PN groups. Demographic data were similar but the patients in the PN group had smaller tumor size compared to RN group (32.2 11.8 mm vs 47.1 15.2 mm, p < 0.001). Preoperative eGFR did not differ between groups (75 28.4 mL/min/1.73 m2 vs 75.5 23.8 mL/min/1.73 m2 in RN and PN groups, p Z 0.929). However, there were significant differences between groups in terms of postoperative eGFR (57.5 21.7 mL/min/1.73 m2 vs 74 27.5 mL/min/1.73 m2 in RN and PN groups, p < 0.001) and DeGFR (17.5 4.2 mL/min/1.73 m2 vs 1.5 0.4 mL/min/ 1.73 m2 in RN and PN groups, p < 0.001). Our findings favor the use of PN over RN for stage I RCC whenever feasible in patients with predisposing systemic diseases for chronic kidney disease for better preservation of renal functions. Copyright ª 2017, Kaohsiung Medical University. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/ by-nc-nd/4.0/).
Conflicts of interest: All authors declare no conflicts of interest. * Corresponding author. Dokuz Eylul University School of Medicine, Department of Urology, Izmir, 35340, Turkey. ¨ . Demir). E-mail address: [email protected] (O http://dx.doi.org/10.1016/j.kjms.2017.05.007 1607-551X/Copyright ª 2017, Kaohsiung Medical University. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). ¨ , et al., Partial nephrectomy vs. radical nephrectomy for stage I renal cell carcinoma in the Please cite this article in press as: Demir O presence of predisposing systemic diseases for chronic kidney disease, Kaohsiung Journal of Medical Sciences (2017), http://dx.doi.org/ 10.1016/j.kjms.2017.05.007
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¨ . Demir et al. O
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Introduction Partial nephrectomy (PN) has been the preferred surgical approach over radical nephrectomy (RN) for stage I renal cell carcinoma (RCC) for the last decade when tumor and patient characteristics are suitable. Several retrospective studies demonstrated similar oncological outcomes for both approaches, whereas most of them reported better preservation of renal functions, lower rates of new-onset chronic kidney disease (CKD) and as a result higher overall survival (OS) rates in favor of PN [1e7]. The sole randomised prospective study on this topic did not find any significant difference between the two surgical approaches in terms of both survival and the development of end stage renal disease (ESRD) [8,9]. Nevertheless, that study also reported reduced incidence of moderate renal dysfunction in the PN arm. More recent studies elaborating on this topic suggested that preexisting medical risk factors for the development of CKD rather than surgical approach could be mainly responsible for new onset CKD and ESRD [10,11]. Another study proposed that non-neoplastic parenchymal changes, mainly glomerulosclerosis, might have an impact on the postoperative renal functional recovery after PN [12]. Diabetes mellitus (DM) and hypertension (HT) are the two main predisposing systemic diseases for the development of CKD [13]. However, PN is probably underutilized in these specific patient groups as shown by Abouassaly et al. that just 17.3% of patients with HT and 18.6% of patients with DM underwent partial nephrectomy in a large patient cohort consisting of 4292 patients [14]. Data comparing the renal functional impairment after PN or RN for stage I RCC solely in patients with DM and/or HT is scarce in the existing literature. This study aimed to report our surgical experience in stage I RCC with predisposing systemic diseases for CKD as stated above and compare the two surgical approaches, PN and RN, in terms of postoperative renal functions.
Methods Patients who were operated for stage I RCC confirmed by pathological examination between 2004 and 2013 in our department were enrolled and patient charts were retrospectively reviewed. Patients were excluded if they do not have at least one month follow-up with a serum creatinine measurement or have an imperative indication for PN such as a solitary kidney or poorly functioning contralateral kidney. Patient demographics including age, sex, smoking status, presence of DM and/or HT, tumor size which is defined as the maximum diameter on imaging studies, surgical approach, duration of hospitalization, duration of follow-up, preoperative and postoperative serum creatinine levels were recorded. The presence of DM and/or HT depended on the patient history as taking any medication for these diseases. Estimated glomerular filtration rate (eGFR) was used for the evaluation of renal functions and calculated according to the Modification of Diet in Renal Disease (MDRD) formula; eGFR Z 175 [(Serum Creatinine/88.4) e 1.1540] (age e 0.203) (0.742 if female); using preoperative and postoperative (last visit of the patient) serum creatinine measurements. DeGFR which reflects the renal functional loss in an individual patient was
defined as the equation, DeGFR Z [(preoperative eGFR) e (postoperative eGFR)]. All procedures were in accordance with the Helsinki Declaration of 1975, as revised in 2008.
Statistical analysis Comparison of the two surgical approaches in terms of postoperative renal functions were performed in three different subgroups. First, all patients with or without DM and/or HT were compared for PN and RN. Then, analysis of the patients with DM and/or HT were performed. And lastly, patients with diminished renal functions (eGFR < 60 mL/ min/1.73 m2) were taken into consideration for the comparison of two surgical approaches. Student’s t test (two-tailed), ManneWhitney U test for numerical variables and chi-square test for categorical variables were used to compare patient demographics and renal functions. Results were expressed as mean values and standard deviations. SPSS version 20 (IBM Corp., Somers, NY, USA) was used for all statistical evaluation. p < 0.05 was deemed statistically significant.
Results Totally 214 patients underwent renal surgery for stage I RCC in the study period, 158 were RN and 56 were PN. 35 and 12 of the surgeries were performed laparoscopically in the RN and PN groups, respectively. Average ischemia time was 10.4 11.1 (0e35) minutes in the PN group. Regarding the first analysis including the whole patients; patient demographics including age, duration of follow-up, presence of DM and/or HT, smoking status and preoperative eGFR were similar between PN and RN groups. Tumor size was lower in PN group compared to RN group. Mean postoperative eGFR measured on the last visit was significantly higher and mean DeGFR was significantly lower in patients who underwent PN compared to RN (Table 1). Second analysis included patients with DM and/or HT and 118 out of 214 patients had DM and/or HT. There were 85 and 33 patients in RN and PN groups, respectively. Average ischemia time was 9.6 11.4 (0e30) minutes in the PN group. Tumor size was again lower in PN group whereas other demographic data were similar for RN and PN groups. In terms of preventing renal functional loss, PN overweighted RN in this specific patient group who are under risk for reduced eGFR (Table 2). Considering the patients with diminished renal functions in the third analysis, there were 30 patients in RN and 8 patients in PN groups. Demographic characteristics were not significantly different between two surgical approaches but the tumor size was lower in PN group. However, apart from the previous analyses there were not any statistical significant differences found for the postoperative eGFR and DeGFR in PN and RN groups in this subgroup of patients (Table 3).
Discussion In the present study, only patients with pathologically confirmed stage I RCC were included for the analysis in
¨ , et al., Partial nephrectomy vs. radical nephrectomy for stage I renal cell carcinoma in the Please cite this article in press as: Demir O presence of predisposing systemic diseases for chronic kidney disease, Kaohsiung Journal of Medical Sciences (2017), http://dx.doi.org/ 10.1016/j.kjms.2017.05.007
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Partial nephrectomy in the presence of DM and/or HT
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Table 1 Comparison of demographic characteristics and renal functions of patients who underwent surgery, RN or PN, for stage I renal cell carcinoma.
Age (years) Follow-up (months) Hospitalization (days) DM (%) HT (%) Current smokers (%) Tumor size (mm) Preoperative e eGFR (mL/min/1.73 m2) Postoperative e eGFR (mL/min/1.73 m2) DeGFR (mL/min/1.73 m2) (%)
RN (n Z 158)
PN (n Z 56)
p*
59.6 11.6 38.5 42.7 7 4.5 18.4 48.1 34.2 48.5 14.1 79.7 25.8 62.4 22.7 17.2 4.3 (21.5)
56.2 12.3 36 35.3 7.5 6.3 25 53.6 26.8 33.4 12.4 85.1 26.8 83.3 27.7 1.8 1.1 (2.1)
0.076 0.678 0.826 0.332 0.535 0.406 <0.001 0.196 <0.001 <0.001
RN Z radical nephrectomy; PN Z partial nephrectomy; DM Z Diabetes Mellitus; HT Z Hypertension; eGFR Z Estimated glomerular filtration rate. *p < 0.05 was deemed statistically significant.
Table 2 Analysis of patients with predisposing systemic diseases as DM and/or HT for chronic kidney disease development who underwent RN or PN for stage I renal cell carcinoma.
Age (years) Tumor size (mm) Hospitalization (days) Follow-up (months) Preoperative e eGFR (mL/min/1.73 m2) Postoperative e eGFR (mL/min/1.73 m2) DeGFR (mL/min/1.73 m2) (%)
RN (n Z 85)
PN (n Z 33)
p*
62.4 10.4 47.1 15.2 6.5 3.4 32.4 35.4 75 28.4 57.5 21.7 17.5 4.2 (23.3)
62.4 8.2 32.2 11.8 7.6 5.8 35.4 29.1 75.5 23.8 74 27.5 1.5 0.4 (1.9)
0.973 <0.001 0.522 0.649 0.929 <0.001 <0.001
RN Z radical nephrectomy; PN Z partial nephrectomy; DM Z Diabetes Mellitus; HT Z Hypertension; eGFR Z Estimated glomerular filtration rate. *p < 0.05 was deemed statistically significant.
Table 3 Patients with already diminished renal functions (eGFR < 60 mL/min/1.73 m2) who underwent RN or PN for stage I renal cell carcinoma did not differ in terms of renal functions postoperatively.
Age (years) Follow-up (months) Tumor size (mm) Preoperative e eGFR (mL/min/1.73 m2) Postoperative e eGFR (mL/min/1.73 m2) DeGFR (mL/min/1.73 m2) (%)
RN (n Z 30)
PN (n Z 8)
p*
63.4 12.9 54.1 44.8 49.3 14.8 42.5 15 38.6 17.2 3.9 1.3 (9.1)
65.9 5.6 39.5 34.9 35.2 12.2 44.3 16.1 42.6 26.4 1.7 1.1 (3.8)
0.635 0.428 <0.001 0.562 0.661 0.211
RN Z radical nephrectomy; PN Z partial nephrectomy; eGFR Z Estimated glomerular filtration rate. *p < 0.05 was deemed statistically significant.
order to avoid possible confounding factors originating from the biological behaviour of the benign or higher stage tumors and to provide a homogeneous data for the compared surgical approaches. PN was superior to RN for the prevention of renal functional loss postoperatively in the whole study group. This finding is in concordance with previous retrospective studies demonstrating OS benefit for PN compared to RN in localised RCC which was attributed to the better preservation of renal functions and prevention of CKD development and related cardiovascular events associated with mortality [1e7]. On the contrary, the sole prospective study, EORTC 30904, reported no significant
difference for the ESRD risk and OS between treatment arms despite lower renal functional loss in PN arm [8,9]. A recent retrospective study supported the EORTC 30904 results in young patients whereas they reported better OS rates in the elderly and better prevention of renal functions for PN in all age groups [15]. This looks like a debate in terms of renal functions for the role of PN in small renal tumors if there is not a role for preventing ESRD or providing survival benefit. However, there is agreement among the above-mentioned studies on the fact that PN mostly prevents renal functional loss postoperatively despite different study protocols and heterogeneous
¨ , et al., Partial nephrectomy vs. radical nephrectomy for stage I renal cell carcinoma in the Please cite this article in press as: Demir O presence of predisposing systemic diseases for chronic kidney disease, Kaohsiung Journal of Medical Sciences (2017), http://dx.doi.org/ 10.1016/j.kjms.2017.05.007
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4 patient cohorts. The first adjusted analysis of solely T1 tumors came from a multi-institutional European study including 1331 patients with normal preoperative renal functions which demonstrated that PN significantly decreased the risk of cardiovascular events compared to RN in T1 tumors after accounting for confounding factors such as age, DM and HT with a median follow-up of 52 months [16]. In a further analysis of the same group, PN has been shown to protect patients against ESRD independently relative to RN [17]. Confounding factors such as age, smoking status and presence of DM and/or HT were also similar between PN and RN groups in our patient cohort providing to see the net effect of the surgical approaches on postoperative renal functions. Considering the patients with predisposing factors for CKD such as DM and/or HT, the present study is unique for the comparison of PN and RN in terms of long-term renal functions in this specific cohort. Suer et al. reported the association of HT with new-onset CKD in patients undergoing RN and suggested that risk factors for CKD development should be taken into account in decision-making [4]. A recent study by Satasivam et al. concluded that utility of RN and presence of DM were significantly associated with new-onset CKD. In addition, patients with medical risk factors for CKD development were likely to have worse renal functions after surgery even if they underwent PN [11]. However, both studies were performed with heterogeneous tumor stages and did not directly compare postoperative eGFR alterations for PN and RN in patients with DM and/or HT. Considering our results for the 1.9% mean eGFR loss in PN group compared to 23.3% in RN group with a mean follow-up of 3 years, PN almost preserves the preoperative renal functions even in patients with DM and/ or HT. Importance of this finding comes from the association of lower postoperative eGFR levels with higher mortality risk which was demonstrated by Streja et al. in a large patient cohort from Racial and Cardiovascular risk anomalies in CKD study [7]. Most of the patients had DM and/or HT in their study and eGFR decline was also greater in RN arm compared to PN. They additionally reported that after an initial postsurgical decline in eGFR, it remained almost stable for the following 6 months and at a median follow-up of 39 months. Low eGFR levels prior to surgery is an independent risk factor for new-onset CKD and mortality in both PN and RN as already demonstrated by several previous reports [5,7,11]. Patients with preexisting low eGFR (eGFR < 60 mL/min/1.73 m2) may experience stage progression even after PN [11]. For patients with already diminished renal functions prior to surgery (eGFR < 60 mL/ min/1.73 m2), there was not any significant difference found in postoperative renal functions and renal functional loss in PN and RN groups in the present study although PN did better. This may be due to the very low number of patients included in the analysis. Additionally; PN may not prevent the progressive renal functional loss associated with the results of the preexisting renal impairment due to DM and/or HT. However, lack of detailed analysis of postoperative eGFR for this patient group in the existing literature keep us from further comments and indicate the need for future prospective studies.
Main limitations of the present study are the relatively small patient cohort and retrospective design. However, analysis for a homogeneous patient cohort and relatively long follow-up compared to most of the previous reports provide a net look for the comparison of surgical approaches. Another limitation is the lack of the follow-up of cardiovascular events in both groups. However, the association of reduced eGFR with future cardiovascular events is well-documented in previous studies and the present study may provide valuable information in this regard [18,19]. Tumor size is an important factor for the selection of the surgical approach. However, patients who underwent PN had smaller size tumors compared to the patients who underwent RN in the present study which may also cause a selection bias. In conclusion, PN overweights RN for the preservation of postoperative renal functions even in the presence of predisposing systemic diseases for CKD such as DM and/or HT. However, PN is not superior to RN if the patient has already diminished renal functions. If surgical resection is going to be performed, we recommend PN for clinical stage I tumors whenever feasible especially in patients with predisposing factors for CKD. Further studies including larger patient cohorts with longer follow-up will better clarify the course of renal functions for this specific patient group.
References [1] Thompson RH, Boorjian SA, Lohse CM, Leibovich BC, Kwon ED, Cheville JC, et al. Radical nephrectomy for pT1a renal masses may be associated with decreased overall survival compared with partial nephrectomy. J Urol 2008;179:468e71. [2] Huang WC, Elkin EB, Levey AS, Jang TL, Russo P. Partial nephrectomy versus radical nephrectomy in patients with small renal tumors e is there a difference in mortality and cardiovascular outcomes? J Urol 2009;181:55e61. [3] Zini L, Perrotte P, Capitanio U, Jeldres C, Shariat SF, Antebi E, et al. Radical versus partial nephrectomy: effect on overall and noncancer mortality. Cancer 2009;115:1465e71. [4] Su ¨kce M_I, Tu ¨lmez K, Bedu ¨er E, Burgu B, Go ¨rko ¨k Y, Baltaci S. Comparison of radical and partial nephrectomy in terms of renal function: a retrospective cohort study. Scand J Urol Nephrol 2011;45:24e9. [5] Choi YS, Park YH, Kim YJ, Kang SH, Byun SS, Hong SH. Predictive factors for the development of chronic renal insufficiency after renal surgery: a multicenter study. Int Urol Nephrol 2014;46:681e6. http://dx.doi.org/10.1007/s11255013-0534-8. [6] Forbes CM, Rendon RA, Finelli A, Kapoor A, Moore RB, Breau RH, et al. Disease progression and kidney function after partial vs. radical nephrectomy for T1 renal cancer. Urol Oncol 2016;34: 486. http://dx.doi.org/10.1016/j.urolonc.2016.05.034. e17486.e23. [7] Streja E, Kalantar-Zadeh K, Molnar MZ, Landman J, Arah OA, Kovesdy CP. Radical versus partial nephrectomy, chronic kidney disease progression and mortality in US veterans. Nephrol Dial Transpl 2016;0:1e7. http://dx.doi.org/10.1093/ndt/gfw358. [8] Van Poppel H, Da Pozzo L, Albrecht W, Matveev V, Bono A, Borkowski A, et al. A prospective, randomised EORTC intergroup phase 3 study comparing the oncologic outcome of elective nephron-sparing surgery and radical nephrectomy for low-stage renal cell carcinoma. Eur Urol 2011;59:543e52. [9] Scosyrev E, Messing EM, Sylvester R, Campbell S, Van Poppel H. Renal function after nephron-sparing surgery versus
¨ , et al., Partial nephrectomy vs. radical nephrectomy for stage I renal cell carcinoma in the Please cite this article in press as: Demir O presence of predisposing systemic diseases for chronic kidney disease, Kaohsiung Journal of Medical Sciences (2017), http://dx.doi.org/ 10.1016/j.kjms.2017.05.007
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Partial nephrectomy in the presence of DM and/or HT
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[14]
radical nephrectomy: results from EORTC randomized trial 30904. Eur Urol 2014;65:372e7. Lane BR, Campbell SC, Demirjian S, Fergany AF. Surgically induced chronic kidney disease may be associated with a lower risk of progression and mortality than medical chronic kidney disease. J Urol 2013;189:1649e55. http: //dx.doi.org/10.1016/j.juro.2012.11.121. Satasivam P, Reeves F, Rao K, Ivey Z, Basto M, Yip M, et al. Patients with medical risk factors for chronic kidney disease are at increased risk of renal impairment despite the use of nephron-sparing surgery. BJU Int 2015;116:590e5. http: //dx.doi.org/10.1111/bju.13075. Bazzi WM, Chen LY, Cordon BH, Mashni J, Sjoberg DD, Bernstein M, et al. Non-neoplastic parenchymal changes in kidney cancer and post-partial nephrectomy recovery of renal function. Int Urol Nephrol 2015;47:1499e502. http: //dx.doi.org/10.1007/s11255-015-1066-1. Webster AC, Nagler EV, Morton RL, Masson P. Chronic kidney disease. Lancet 2016. http://dx.doi.org/10.1016/S01406736(16)32064-5. pii: S0140e6736(16)32064-5. Abouassaly R, Finelli A, Tomlinson GA, Urbach DR, Alibhai SM. How often are patients with diabetes or hypertension being treated with partial nephrectomy for renal cell carcinoma? A population-based analysis. BJU Int 2011;108(11):1806e12. http://dx.doi.org/10.1111/j.1464-410X.2011.10254.x.
5 [15] Takagi T, Kondo T, Iizuka J, Omae K, Kobayashi H, Yoshida K, et al. Comparison of survival rates in stage 1 renal cell carcinoma between partial nephrectomy and radical nephrectomy patients according to age distribution: a propensity score matching study. BJU Int 2016;117:E52e9. http: //dx.doi.org/10.1111/bju.13200. [16] Capitanio U, Terrone C, Antonelli A, Minervini A, Volpe A, Furlan M, et al. Nephron-sparing techniques independently decrease the risk of cardiovascular events relative to radical nephrectomy in patients with a T1aeT1b renal mass and normal preoperative renal function. Eur Urol 2015;67:683e9. http://dx.doi.org/10.1016/j.eururo.2014.09.027. [17] Capitanio U, Larcher A, Terrone C, Antonelli A, Volpe A, Fiori C, et al. End-stage renal disease after renal surgery in patients with normal preoperative kidney function: balancing surgical strategy and individual disorders at baseline. Eur Urol 2016;70:558e61. [18] Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 2004;351:1296e305. [19] Takeshita H, Yokoyama M, Fujii Y, Chiba K, Ishioka J, Noro A, et al. Impact of renal function on cardiovascular events in patients undergoing radical nephrectomy for renal cancer. Int J Urol 2012;19:722e8.
¨ , et al., Partial nephrectomy vs. radical nephrectomy for stage I renal cell carcinoma in the Please cite this article in press as: Demir O presence of predisposing systemic diseases for chronic kidney disease, Kaohsiung Journal of Medical Sciences (2017), http://dx.doi.org/ 10.1016/j.kjms.2017.05.007
MODEL
Kaohsiung Journal of Medical Sciences (2017) xx, 1e5
Available online at www.sciencedirect.com
ScienceDirect journal homepage: http://www.kjms-online.com
Original Article
Partial nephrectomy vs. radical nephrectomy for stage I renal cell carcinoma in the presence of predisposing systemic diseases for chronic kidney disease ¨ mer Demir*, Ozan Bozkurt, Serdar C ¨ven Aslan, O ¸elik, Kaan C ¸¨ omez, Gu _ Ugur Mungan, Ilhan C ¸elebi, Adil Esen Department of Urology, Dokuz Eylul University School of Medicine, Izmir, Turkey Received 22 February 2017; accepted 27 April 2017
KEYWORDS Partial nephrectomy; Kidney tumors; eGFR; Renal functions; Chronic kidney disease
Abstract Aim of this study is to compare the effects of partial nephrectomy (PN) and radical nephrectomy (RN) for stage I renal cell carcinoma (RCC) on renal functions in patients with diabetes mellitus (DM) and/or hypertension (HT). Charts of patients who underwent surgery for stage I RCC in our department were retrospectively reviewed and patients with DM and/or HT were enrolled. Preoperative and postoperative estimated glomerular filtration rates (eGFR) were calculated according to the Modification of Diet in Renal Disease (MDRD) formulation for both RN and PN groups. Groups were compared for patient demographics, preoperative eGFR, postoperative eGFR and DeGFR [(preoperative eGFR) e (postoperative eGFR)] which reflects the renal functional loss. There were 85 patients in the RN and 33 patients in the PN groups. Demographic data were similar but the patients in the PN group had smaller tumor size compared to RN group (32.2 11.8 mm vs 47.1 15.2 mm, p < 0.001). Preoperative eGFR did not differ between groups (75 28.4 mL/min/1.73 m2 vs 75.5 23.8 mL/min/1.73 m2 in RN and PN groups, p Z 0.929). However, there were significant differences between groups in terms of postoperative eGFR (57.5 21.7 mL/min/1.73 m2 vs 74 27.5 mL/min/1.73 m2 in RN and PN groups, p < 0.001) and DeGFR (17.5 4.2 mL/min/1.73 m2 vs 1.5 0.4 mL/min/ 1.73 m2 in RN and PN groups, p < 0.001). Our findings favor the use of PN over RN for stage I RCC whenever feasible in patients with predisposing systemic diseases for chronic kidney disease for better preservation of renal functions. Copyright ª 2017, Kaohsiung Medical University. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/ by-nc-nd/4.0/).
Conflicts of interest: All authors declare no conflicts of interest. * Corresponding author. Dokuz Eylul University School of Medicine, Department of Urology, Izmir, 35340, Turkey. ¨ . Demir). E-mail address: [email protected] (O http://dx.doi.org/10.1016/j.kjms.2017.05.007 1607-551X/Copyright ª 2017, Kaohsiung Medical University. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). ¨ , et al., Partial nephrectomy vs. radical nephrectomy for stage I renal cell carcinoma in the Please cite this article in press as: Demir O presence of predisposing systemic diseases for chronic kidney disease, Kaohsiung Journal of Medical Sciences (2017), http://dx.doi.org/ 10.1016/j.kjms.2017.05.007
+
MODEL
¨ . Demir et al. O
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Introduction Partial nephrectomy (PN) has been the preferred surgical approach over radical nephrectomy (RN) for stage I renal cell carcinoma (RCC) for the last decade when tumor and patient characteristics are suitable. Several retrospective studies demonstrated similar oncological outcomes for both approaches, whereas most of them reported better preservation of renal functions, lower rates of new-onset chronic kidney disease (CKD) and as a result higher overall survival (OS) rates in favor of PN [1e7]. The sole randomised prospective study on this topic did not find any significant difference between the two surgical approaches in terms of both survival and the development of end stage renal disease (ESRD) [8,9]. Nevertheless, that study also reported reduced incidence of moderate renal dysfunction in the PN arm. More recent studies elaborating on this topic suggested that preexisting medical risk factors for the development of CKD rather than surgical approach could be mainly responsible for new onset CKD and ESRD [10,11]. Another study proposed that non-neoplastic parenchymal changes, mainly glomerulosclerosis, might have an impact on the postoperative renal functional recovery after PN [12]. Diabetes mellitus (DM) and hypertension (HT) are the two main predisposing systemic diseases for the development of CKD [13]. However, PN is probably underutilized in these specific patient groups as shown by Abouassaly et al. that just 17.3% of patients with HT and 18.6% of patients with DM underwent partial nephrectomy in a large patient cohort consisting of 4292 patients [14]. Data comparing the renal functional impairment after PN or RN for stage I RCC solely in patients with DM and/or HT is scarce in the existing literature. This study aimed to report our surgical experience in stage I RCC with predisposing systemic diseases for CKD as stated above and compare the two surgical approaches, PN and RN, in terms of postoperative renal functions.
Methods Patients who were operated for stage I RCC confirmed by pathological examination between 2004 and 2013 in our department were enrolled and patient charts were retrospectively reviewed. Patients were excluded if they do not have at least one month follow-up with a serum creatinine measurement or have an imperative indication for PN such as a solitary kidney or poorly functioning contralateral kidney. Patient demographics including age, sex, smoking status, presence of DM and/or HT, tumor size which is defined as the maximum diameter on imaging studies, surgical approach, duration of hospitalization, duration of follow-up, preoperative and postoperative serum creatinine levels were recorded. The presence of DM and/or HT depended on the patient history as taking any medication for these diseases. Estimated glomerular filtration rate (eGFR) was used for the evaluation of renal functions and calculated according to the Modification of Diet in Renal Disease (MDRD) formula; eGFR Z 175 [(Serum Creatinine/88.4) e 1.1540] (age e 0.203) (0.742 if female); using preoperative and postoperative (last visit of the patient) serum creatinine measurements. DeGFR which reflects the renal functional loss in an individual patient was
defined as the equation, DeGFR Z [(preoperative eGFR) e (postoperative eGFR)]. All procedures were in accordance with the Helsinki Declaration of 1975, as revised in 2008.
Statistical analysis Comparison of the two surgical approaches in terms of postoperative renal functions were performed in three different subgroups. First, all patients with or without DM and/or HT were compared for PN and RN. Then, analysis of the patients with DM and/or HT were performed. And lastly, patients with diminished renal functions (eGFR < 60 mL/ min/1.73 m2) were taken into consideration for the comparison of two surgical approaches. Student’s t test (two-tailed), ManneWhitney U test for numerical variables and chi-square test for categorical variables were used to compare patient demographics and renal functions. Results were expressed as mean values and standard deviations. SPSS version 20 (IBM Corp., Somers, NY, USA) was used for all statistical evaluation. p < 0.05 was deemed statistically significant.
Results Totally 214 patients underwent renal surgery for stage I RCC in the study period, 158 were RN and 56 were PN. 35 and 12 of the surgeries were performed laparoscopically in the RN and PN groups, respectively. Average ischemia time was 10.4 11.1 (0e35) minutes in the PN group. Regarding the first analysis including the whole patients; patient demographics including age, duration of follow-up, presence of DM and/or HT, smoking status and preoperative eGFR were similar between PN and RN groups. Tumor size was lower in PN group compared to RN group. Mean postoperative eGFR measured on the last visit was significantly higher and mean DeGFR was significantly lower in patients who underwent PN compared to RN (Table 1). Second analysis included patients with DM and/or HT and 118 out of 214 patients had DM and/or HT. There were 85 and 33 patients in RN and PN groups, respectively. Average ischemia time was 9.6 11.4 (0e30) minutes in the PN group. Tumor size was again lower in PN group whereas other demographic data were similar for RN and PN groups. In terms of preventing renal functional loss, PN overweighted RN in this specific patient group who are under risk for reduced eGFR (Table 2). Considering the patients with diminished renal functions in the third analysis, there were 30 patients in RN and 8 patients in PN groups. Demographic characteristics were not significantly different between two surgical approaches but the tumor size was lower in PN group. However, apart from the previous analyses there were not any statistical significant differences found for the postoperative eGFR and DeGFR in PN and RN groups in this subgroup of patients (Table 3).
Discussion In the present study, only patients with pathologically confirmed stage I RCC were included for the analysis in
¨ , et al., Partial nephrectomy vs. radical nephrectomy for stage I renal cell carcinoma in the Please cite this article in press as: Demir O presence of predisposing systemic diseases for chronic kidney disease, Kaohsiung Journal of Medical Sciences (2017), http://dx.doi.org/ 10.1016/j.kjms.2017.05.007
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Table 1 Comparison of demographic characteristics and renal functions of patients who underwent surgery, RN or PN, for stage I renal cell carcinoma.
Age (years) Follow-up (months) Hospitalization (days) DM (%) HT (%) Current smokers (%) Tumor size (mm) Preoperative e eGFR (mL/min/1.73 m2) Postoperative e eGFR (mL/min/1.73 m2) DeGFR (mL/min/1.73 m2) (%)
RN (n Z 158)
PN (n Z 56)
p*
59.6 11.6 38.5 42.7 7 4.5 18.4 48.1 34.2 48.5 14.1 79.7 25.8 62.4 22.7 17.2 4.3 (21.5)
56.2 12.3 36 35.3 7.5 6.3 25 53.6 26.8 33.4 12.4 85.1 26.8 83.3 27.7 1.8 1.1 (2.1)
0.076 0.678 0.826 0.332 0.535 0.406 <0.001 0.196 <0.001 <0.001
RN Z radical nephrectomy; PN Z partial nephrectomy; DM Z Diabetes Mellitus; HT Z Hypertension; eGFR Z Estimated glomerular filtration rate. *p < 0.05 was deemed statistically significant.
Table 2 Analysis of patients with predisposing systemic diseases as DM and/or HT for chronic kidney disease development who underwent RN or PN for stage I renal cell carcinoma.
Age (years) Tumor size (mm) Hospitalization (days) Follow-up (months) Preoperative e eGFR (mL/min/1.73 m2) Postoperative e eGFR (mL/min/1.73 m2) DeGFR (mL/min/1.73 m2) (%)
RN (n Z 85)
PN (n Z 33)
p*
62.4 10.4 47.1 15.2 6.5 3.4 32.4 35.4 75 28.4 57.5 21.7 17.5 4.2 (23.3)
62.4 8.2 32.2 11.8 7.6 5.8 35.4 29.1 75.5 23.8 74 27.5 1.5 0.4 (1.9)
0.973 <0.001 0.522 0.649 0.929 <0.001 <0.001
RN Z radical nephrectomy; PN Z partial nephrectomy; DM Z Diabetes Mellitus; HT Z Hypertension; eGFR Z Estimated glomerular filtration rate. *p < 0.05 was deemed statistically significant.
Table 3 Patients with already diminished renal functions (eGFR < 60 mL/min/1.73 m2) who underwent RN or PN for stage I renal cell carcinoma did not differ in terms of renal functions postoperatively.
Age (years) Follow-up (months) Tumor size (mm) Preoperative e eGFR (mL/min/1.73 m2) Postoperative e eGFR (mL/min/1.73 m2) DeGFR (mL/min/1.73 m2) (%)
RN (n Z 30)
PN (n Z 8)
p*
63.4 12.9 54.1 44.8 49.3 14.8 42.5 15 38.6 17.2 3.9 1.3 (9.1)
65.9 5.6 39.5 34.9 35.2 12.2 44.3 16.1 42.6 26.4 1.7 1.1 (3.8)
0.635 0.428 <0.001 0.562 0.661 0.211
RN Z radical nephrectomy; PN Z partial nephrectomy; eGFR Z Estimated glomerular filtration rate. *p < 0.05 was deemed statistically significant.
order to avoid possible confounding factors originating from the biological behaviour of the benign or higher stage tumors and to provide a homogeneous data for the compared surgical approaches. PN was superior to RN for the prevention of renal functional loss postoperatively in the whole study group. This finding is in concordance with previous retrospective studies demonstrating OS benefit for PN compared to RN in localised RCC which was attributed to the better preservation of renal functions and prevention of CKD development and related cardiovascular events associated with mortality [1e7]. On the contrary, the sole prospective study, EORTC 30904, reported no significant
difference for the ESRD risk and OS between treatment arms despite lower renal functional loss in PN arm [8,9]. A recent retrospective study supported the EORTC 30904 results in young patients whereas they reported better OS rates in the elderly and better prevention of renal functions for PN in all age groups [15]. This looks like a debate in terms of renal functions for the role of PN in small renal tumors if there is not a role for preventing ESRD or providing survival benefit. However, there is agreement among the above-mentioned studies on the fact that PN mostly prevents renal functional loss postoperatively despite different study protocols and heterogeneous
¨ , et al., Partial nephrectomy vs. radical nephrectomy for stage I renal cell carcinoma in the Please cite this article in press as: Demir O presence of predisposing systemic diseases for chronic kidney disease, Kaohsiung Journal of Medical Sciences (2017), http://dx.doi.org/ 10.1016/j.kjms.2017.05.007
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¨ . Demir et al. O
4 patient cohorts. The first adjusted analysis of solely T1 tumors came from a multi-institutional European study including 1331 patients with normal preoperative renal functions which demonstrated that PN significantly decreased the risk of cardiovascular events compared to RN in T1 tumors after accounting for confounding factors such as age, DM and HT with a median follow-up of 52 months [16]. In a further analysis of the same group, PN has been shown to protect patients against ESRD independently relative to RN [17]. Confounding factors such as age, smoking status and presence of DM and/or HT were also similar between PN and RN groups in our patient cohort providing to see the net effect of the surgical approaches on postoperative renal functions. Considering the patients with predisposing factors for CKD such as DM and/or HT, the present study is unique for the comparison of PN and RN in terms of long-term renal functions in this specific cohort. Suer et al. reported the association of HT with new-onset CKD in patients undergoing RN and suggested that risk factors for CKD development should be taken into account in decision-making [4]. A recent study by Satasivam et al. concluded that utility of RN and presence of DM were significantly associated with new-onset CKD. In addition, patients with medical risk factors for CKD development were likely to have worse renal functions after surgery even if they underwent PN [11]. However, both studies were performed with heterogeneous tumor stages and did not directly compare postoperative eGFR alterations for PN and RN in patients with DM and/or HT. Considering our results for the 1.9% mean eGFR loss in PN group compared to 23.3% in RN group with a mean follow-up of 3 years, PN almost preserves the preoperative renal functions even in patients with DM and/ or HT. Importance of this finding comes from the association of lower postoperative eGFR levels with higher mortality risk which was demonstrated by Streja et al. in a large patient cohort from Racial and Cardiovascular risk anomalies in CKD study [7]. Most of the patients had DM and/or HT in their study and eGFR decline was also greater in RN arm compared to PN. They additionally reported that after an initial postsurgical decline in eGFR, it remained almost stable for the following 6 months and at a median follow-up of 39 months. Low eGFR levels prior to surgery is an independent risk factor for new-onset CKD and mortality in both PN and RN as already demonstrated by several previous reports [5,7,11]. Patients with preexisting low eGFR (eGFR < 60 mL/min/1.73 m2) may experience stage progression even after PN [11]. For patients with already diminished renal functions prior to surgery (eGFR < 60 mL/ min/1.73 m2), there was not any significant difference found in postoperative renal functions and renal functional loss in PN and RN groups in the present study although PN did better. This may be due to the very low number of patients included in the analysis. Additionally; PN may not prevent the progressive renal functional loss associated with the results of the preexisting renal impairment due to DM and/or HT. However, lack of detailed analysis of postoperative eGFR for this patient group in the existing literature keep us from further comments and indicate the need for future prospective studies.
Main limitations of the present study are the relatively small patient cohort and retrospective design. However, analysis for a homogeneous patient cohort and relatively long follow-up compared to most of the previous reports provide a net look for the comparison of surgical approaches. Another limitation is the lack of the follow-up of cardiovascular events in both groups. However, the association of reduced eGFR with future cardiovascular events is well-documented in previous studies and the present study may provide valuable information in this regard [18,19]. Tumor size is an important factor for the selection of the surgical approach. However, patients who underwent PN had smaller size tumors compared to the patients who underwent RN in the present study which may also cause a selection bias. In conclusion, PN overweights RN for the preservation of postoperative renal functions even in the presence of predisposing systemic diseases for CKD such as DM and/or HT. However, PN is not superior to RN if the patient has already diminished renal functions. If surgical resection is going to be performed, we recommend PN for clinical stage I tumors whenever feasible especially in patients with predisposing factors for CKD. Further studies including larger patient cohorts with longer follow-up will better clarify the course of renal functions for this specific patient group.
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¨ , et al., Partial nephrectomy vs. radical nephrectomy for stage I renal cell carcinoma in the Please cite this article in press as: Demir O presence of predisposing systemic diseases for chronic kidney disease, Kaohsiung Journal of Medical Sciences (2017), http://dx.doi.org/ 10.1016/j.kjms.2017.05.007