Abstract
Purpose
To examine the association between high-risk patient status (age >75 years or Charlson comorbidity [CCI] count >2) and post-operative complications in patients undergoing surgical management for clinically localized renal tumors.
Materials and Methods
Patients undergoing radical (RN) or PN (2005-2012) for localized RCC were analyzed. Multivariate logistic regressions were used to test the association between high-risk status and post-operative complications adjusting for patient, tumor, and operative characteristics.
Results
Of 1,092 patients undergoing PN (71.9%) or RN (28.1%) for clinically localized renal tumors, 255 (23.4%) were classified as high risk, and 175 patients (16%) suffered at least one complication (mean 1.6±1.0). 22.4% and 14.1% of high and low risk patients suffered a complication, respectively (p=0.002). Comparing high and low risk patients, significant differences in Clavien III (20.4 vs. 11.1%; p<0.001) and medical (16.1 vs. 8.1%, p<0.001) complications were observed, while no differences were seen in Clavien III-V or surgical complications. No differences in complications were observed comparing patients treated with RN and PN, albeit high-risk patients were more likely to undergo RN (35.3 vs. 25.9%, p=0.04). Following adjustment, the odds of incurring any complication were 1.9 times higher in high compared to low risk patients (OR 1.9 [CI 1.3-2.8]).
Conclusions
Regardless of surgical type, patients deemed high risk by age and comorbidity criteria were more likely to incur a post-operative complication following renal mass resection. Improved understanding of surgical risks in the elderly and infirmed will help better inform patients deciding between active surveillance and resection of renal tumors.
Keywords: Renal cell carcinoma, complications, surgery, robotics, partial nephrectomy, nephrectomy
Introduction
The increased utilization of cross-sectional imaging has resulted in a stage and size migration towards smaller, early stage renal tumors.1 Given the predominance of renal cell carcinoma (RCC) among those in the sixth and seventh decades of life coupled with increasing incidental renal tumor detection, rates of renal surgery in the elderly and infirmed are rising.2 Advances in nephron sparing surgery (NSS) have made partial nephrectomy (PN) the preferred treatment for small renal masses if technically feasible.3 While PN reduces the risk of chronic kidney disease4, and may lower risk of cardiovascular events5 compared with radical nephrectomy (RN), results from a controversial EORTC trial failed to demonstrate a survival benefit with PN in patients with renal tumors ≤ 5cm and a normal contralateral kidney.6
These data have raised concerns that the protective benefit of NSS may not be universal across patient groups, such as elderly or infirmed patients in whom the increased perioperative risks of PN are nontrivial and for whom long-term benefits of PN are uncertain.7 Further, as the evidence accumulates that an initial period of active surveillance is safe with intermediate term follow up,8 the selection of elderly patients or patients with significant competing risks for up front surgical intervention has been questioned.9 Hypothesizing that age and comorbidity status may contribute more to complication risk than type of procedure performed in patients with low stage disease, our aim was to examine the association between high-risk patient status (defined as age >75 years or Charlson comorbidity [CCI] count >2) and post-operative complications in patients undergoing surgical management for clinically localized renal tumors.
Material and Methods
After institutional review board approval, our prospectively maintained kidney tumor database was queried to identify all patients undergoing radical nephrectomy (RN) or PN for clinical stage I-II renal tumors from 2005-2012. Minimally invasive or open PN was preferentially performed in all patients with absolute indications (solitary kidney, bilateral masses and/or severe renal insufficiency) and offered to patients with relative or elective indications when considered technically feasible at the surgeon's discretion. Clinical variables evaluated included patient (age, gender, race, Eastern Cooperative Oncology Group [ECOG] performance status, BMI), tumor (NS, hilar designation, solitary kidney), and operative (year of surgery, surgical type [PN vs. RN], minimally invasive (MIS) vs. open, blood loss, operative time) characteristics. Co-morbidity status was determined using the Charlson comorbidity index (CCI). Tumor anatomic characteristics were assessed using the R.E.N.A.L.-Nephrometry scoring system,10 and patients were stratified into low (NS 4-6), intermediate (NS 7-9), and high (NS 10-12) anatomic complexity groups. Tumor staging was designated according to the TNM classification based on the 2010 American Joint Committee on Cancer/International Union Against Cancer classification system.
Patients were classified as low (CCI ≤2 or age ≤75 years) or high (CCI >2 or age > 75 years) risk status to define our exposure of interest. These criteria were chosen largely based on recent population based data suggesting an attenuation of survival benefit from PN in patients aged >75 years11,12 and a strong association demonstrated using institutional data between perioperative morbidity and Charlson score >2.13
All complications within 90 days of surgery were classified according to the Clavien–Dindo classification system (CCS).14 Complications were grouped into major organ systems (cardiac, pulmonary, vascular, gastrointestinal, infectious, hematologic, dermatologic, genitourinary, infectious, musculoskeletal, and miscellaneous). CCS scores were further categorized as minor (grades I, II) or major (grades III, IV, V), as well as medical versus surgical complications. Multiple complications occurring in the same patient were independently rated and the highest grade was used for statistical analysis.
Statistical Analysis
Patient and tumor characteristics were compared between high and low risk status groups using analysis of variance and Pearson chi-square analyses. The association between high-risk status and any postoperative complication was assessed using multinomial logistic regression models. Covariates meeting a P < 0.10 level of significance were included for model development, and our final model was adjusted for year of surgery, gender, race, ECOG performance status, surgical type, surgical approach, clinical stage, NS complexity group, hilar designation, presence of solitary kidney, operative time, and blood loss. Sensitivity analyses were performed using different comorbidity and age cut-offs and excluding patients with missing clinical stage and NS data. A sub-cohort analysis was performed to compare complication rates in patients with cT1b-II tumors treated with PN and RN. All analyses were performed using Stata, version 10 (StataCorp, College Station, TX), all hypothesis tests were 2-sided, and the criterion for statistical significance was P <.05.
Results
A total of 1,092 patients (mean age 59.2 ± 11.9 years, 64.2% male, 86.0% Caucasian, and mean CCI count 1.2 ± 1.6) with clinical stage I (88.6%) or II (11.5%) renal tumors (mean tumor size 4.2 ± 2.9 cm, mean NS sum 7.8 ± 2.0) met study inclusion criteria (Table 1). 255 (23.4%) patients were classified as high risk due to age (n=78 [30.6%]) and co-morbidity (n=177 [69.4%]) criteria. PN and RN were performed in 785 (71.9%) and 307 (28.1%) patients respectively (62.2% were performed in a minimally invasive fashion). There were 186 (17.0%) patients with an absolute indication for NSS, including 60 (5.5%) patients who had a solitary kidney and 126 (11.5%) patients with bilateral tumors. As objectified by NS, tumors were categorized as low (20.9%), intermediate (40.8%) and high (18.8%) complexity lesions.
Table 1.
Pretreatment patient characteristics stratified by risk status
| Patient Characteristics Stratified by Risk Status | ||||
|---|---|---|---|---|
| Characteristics | Overall (n=1092) | High-Risk Status (n=255) | Low-Risk Status (n=837) | P-value |
| PATIENT LEVEL | ||||
| Age (yrs) (mean ± SD; range) | 59.2 ± 11.9; 22-89 | 69 ± 10.0; 37-89 | 56.2 ± 10.7; 22-75 | <0.001 |
| Gender | 0.581 | |||
| Male | 701 (64.2) | 160 (62.8) | 541 (64.6) | |
| Race | 0.956 | |||
| White | 939 (86) | 219 (85.8) | 720 (86.0) | |
| Non-white | 153 (14) | 36 (14.1) | 117 (14) | |
| ECOG PS | <0.001 | |||
| 0 | 1056 (96.7) | 235 (92.2) | 821 (98.1) | |
| ≥ 1 | 36 (3.3) | 20 (7.8) | 16 (1.9) | |
| BMI (kg/m2) | 30.3 ± 7.2 | 30.0±6.2 | 30.4±7.5 | 0.516 |
| CCI (mean ± SD) | 1.2 ± 1.6 | 3.3±1.7 | 0.6±0.8 | <0.001 |
| Bilateral tumors | 126 (11.5) | |||
| Solitary Kidney | 60 (5.5) | 32 (12.6) | 28 (3.4) | <0.001 |
| High-risk Status | 255 (23.4) | 255 (23.4) | 837 (76.6) | - |
| TUMOR LEVEL | ||||
| Clinical stage | 0.789 | |||
| T1 | 967 (88.6) | 227 (89.0) | 740 (88.4) | |
| T2 | 125 (11.5) | 28 (11.0) | 97 (11.6) | |
| Maximal Tumor Size (cm) | 4.2±2.9 | 4.4±2.7 | 4.1±3.0 | 0.208 |
| Nephrometry Score | 7.8 ± 2.0 | 7.7±2.0 | 7.8±2.0 | 0.499 |
| Nephrometry Score | 0.921 | |||
| Complexity Group | ||||
| Low (NS 4-6) | 228 (20.9) | 54 (21.2) | 174 (20.8) | |
| Intermediate (NS 7-9) | 445 (40.8) | 103 (40.4) | 342 (40.9) | |
| High (NS 10-12) | 205 (18.8) | 45 (17.7) | 160 (19.1) | |
| Missing data | 214 (19.6) | 53 (20.8) | 161 (19.2) | |
| Hilar Tumor Designation | 149 (13.6) | 31 (12.2) | 118 (14.1) | 0.676 |
| OPERATIVE LEVEL | ||||
| Operative Time (min) | 189±62 | 187±61 | 189±62 | 0.660 |
| EBL (mL) | 179±257 | 175±245 | 180±261 | 0.769 |
| Surgery Type | 0.004 | |||
| Partial Nx | 785 (71.9) | 165 (64.7) | 620 (74.1) | |
| Radical Nx | 307 (28.1) | 90 (35.3) | 217 (25.9) | |
| MIS | 679 (62.2) | 147 (57.7) | 532 (63.6) | 0.088 |
BMI, body mass index; CCI, Charlson comorbidity index; EBL, estimated blood loss; ECOG, Eastern Cooperative Oncology Group; NS, tumor nephrometry score; SD, standard deviation. High-risk status was defined by CCI >2 or age >75 years. Data presented as n (%) excluding patients with missing data, unless otherwise noted.
175 patients (16%) suffered at least one complication (mean 1.6±1.0; 62.3% medical, 53.1% surgical). Minor complications occurred in 13.3% of patients (47.8% grade I, 52.2% grade II), and consisted mainly of genitourinary (17.4%), gastrointestinal (13.5%), and infectious (11.1%) complications. 5.7% of patients experienced a major complication, 23.6% of which required intervention (14.4% grade IIIa, 9.2% grade IIIb). The most common major complications included urine leak (7%), hemorrhage (2.4%), and perinephric abscess (1.7%). Life threatening complications requiring intensive care admission occurred in less than 1%, and there were 2 (0.18%) grade V complications leading to death (concomitant distal pancreatectomy complicated by pancreatic leak leading to sepsis and respiratory failure; pulmonary thromboembolism) (Table 2).
Table 2.
Complications stratified by Clavien–Dindo classification system (CCS) type categorized by organ system and surgery type
| Complication Type | All (CCS I-V) | Minor (CCS I-II) | Major (CCS III-V) | PN | RN |
|---|---|---|---|---|---|
| Genitourinary | 83 (28.8) | 50 (17.4) | 33 (11.5) | 67 (32) | 16 (20.5) |
| Urinary leak | 43 (14.9) | 23 (8.0) | 20 (6.9) | 43 (20.5) | - |
| Embolization Pseudoaneurysm | 4 (1.4) | - | 4 (1.4) | 4 (1.9) | - |
| Dialysis | 3 (1.0) | - | 3 (1.0) | - | 3 (3.8) |
| Obstructing hydronephrosis | 1 (0.35) | - | 1 (0.35) | 1 (0.5) | - |
| Urinary retention | 8 (2.8) | 8 (2.8) | - | 4 (1.9) | 4 (5.1) |
| Gross hematuria | 1 (0.35) | - | 1 (0.35) | 1 (0.5) | - |
| Ureteral stricture | 2 (0.69) | - | 2 (0.69) | 2 (1.0) | - |
| Acute kidney injury* | 10 (3.5) | 10 (3.5) | - | 4 (1.9) | 6 (7.7) |
| Perinephric hematoma | 5 (1.7) | 5 (1.7) | - | 5 (2.4) | - |
| Chylous ascites | 5 (1.7) | 3 (1.0) | 2 (0.69) | 2 (1.0) | 3 (3.8) |
| Renal vein thrombus | 1 (0.35) | 1 (0.35) | - | 1 (0.5) | - |
| Infectious | 44 (15.3) | 32 (11.1) | 12 (4.2) | 30 (14.3) | 14 (18) |
| Urinary tract infection | 10 (3.5) | 10 (3.5) | - | 6 (4.3) | 4 (5.1) |
| Pyelonephritis | 4 (1.4) | 4 (1.4) | - | 4 (1.9) | - |
| Perinephric abscess | 6 (2.1) | 1 (0.35) | 5 (1.7) | 6 (4.3) | - |
| Lymphocele | 2 (0.69) | 1 (0.35) | 1 (0.35) | 1 (0.5) | 1 (1.3) |
| Lymphocele requiring drainage | 1 (0.35) | - | 1 (0.35) | 1 (1.3) | |
| Wound infection | 4 (1.4) | 4 (1.4) | - | 2 (1.0) | 2 (2.6) |
| Cellulitis | 4 (1.4) | 4 (1.4) | - | 3 (1.4) | 1 (1.3) |
| Pneumonia | 8 (2.8) | 6 (2.1) | 2 (0.69) | 6 (4.3) | 2 (2.6) |
| Sepsis | 1 (0.35) | 1 (0.35) | - | 1 (0.5) | - |
| Necrotizing fasciitis | 1 (0.35) | - | 1 (0.35) | - | 1 (1.3) |
| Perirectal abscess | 1 (0.35) | - | 1 (0.35) | - | 1 (1.3) |
| Peritonitis | 2 (0.69) | 1 (0.35) | 1 (0.35) | 1 (0.5) | 1 (1.3) |
| Gastrointestinal | 48 (16.7) | 39 (13.5) | 9 (3.1) | 30 (14.3) | 18 (23.1) |
| Ileus | 29 (10.0) | 28 (9.7) | 1 (0.35) | 19 (9.0) | 10 (12.8) |
| Clostridium difficile infection | 3 (1.0) | 3 (1.0) | - | 1 (0.5) | 2 (2.6) |
| Pancreatitis | 1 (0.35) | 1 (0.35) | - | - | 1 (1.3) |
| Pancreatic leak | 1 (0.35) | - | 1 (0.35) | 1 (0.5) | - |
| Small bowel obstruction | 4 (1.4) | - | 4 (1.4) | 1 (0.5) | 3 (3.8) |
| Emesis | 1 (0.35) | 1 (0.35) | - | 1 (0.5) | - |
| Constipation | 1 (0.35) | 1 (0.35) | - | 1 (0.5) | - |
| Diarrhea | 2 (0.69) | 2 (0.69) | - | 1 (0.5) | 1 (1.3) |
| Abdominal pain | 3 (1.0) | 3 (1.0) | - | 3 (1.4) | - |
| Abdominal compartment syndrome | 1 (0.35) | - | 1 (0.35) | 1 (0.5) | - |
| Upper GI bleed | 2 (0.69) | - | 2 (0.69) | 1 (0.5) | 1 (1.3) |
| Hematologic | 32 (11.1) | 23 (8.0) | 9 (33.1) | 27 (12.9) | 5 (6.4) |
| Arteriovenous fistula | 2 (0.69) | - | 2 (0.69) | 2 (1.0) | - |
| Transfusion | 15 (5.2) | 15 (5.2) | - | 12 (5.7) | 3 (3.8) |
| Hemorrhage | 5 (1.7) | 2 (0.69) | 3 (1.0) | 3 (1.4) | 2 (2.6) |
| Hemorrhage requiring embolization | 4 (1.4) | - | 4 (1.4) | 4 (1.9) | - |
| Heparin induced thrombocytopenia | 1 (0.35) | 1 (0.35) | - | 1 (0.5) | - |
| Perirenal hematoma | 5 (1.7) | 5 (1.7) | - | 5 (2.4) | - |
| Pulmonary | 26 (9.0) | 13 (4.5) | 13 (4.5) | 20 (9.5) | 6 (7.7) |
| Respiratory failure/intubation | 2 (0.69) | - | 2 (0.69) | 1 (0.5) | 1 (1.3) |
| Atelectasis | 1 (0.35) | 1 (0.35) | - | 1 (0.5) | - |
| Pneumonitis | 1 (0.35) | 1 (0.35) | - | 1 (0.5) | - |
| Pneumothorax | 5 (1.7) | 4 (1.4) | 1 (0.35) | 4 (1.9) | 1 (1.3) |
| Pleural effusion | 14 (4.9) | 4 (1.4) | 10 (3.5) | 11 (5.2) | 3 (5.8) |
| Hypoxia | 3 (1.0) | 3 (1.0) | - | 2 (1.0) | 1 (1.3) |
| Cardiovascular | 23 (8.0) | 19 (6.6) | 4 (1.4) | 16 (7.6) | 7 (9.0) |
| Elevated troponin | 2 (1.0) | 2 (0.69) | - | 2 (1.0) | - |
| Hypotension | 2 (0.69) | 2 (0.69) | - | 2 (1.0) | - |
| Atrial fibrillation | 8 (2.8) | 7 (2.4) | 1 (0.35) | 4 (1.9) | 4 (5.1) |
| Congestive heart failure | 5 (1.7) | 5 (1.7) | - | 4 (1.9) | 1 (1.3) |
| Angina | 1 (0.35) | 1 (0.35) | - | 1 (0.5) | - |
| Pericardial effusion | 1 (0.35) | 1 (0.35) | - | 1 (0.5) | - |
| Dysrhythmia requiring pacemaker | 1 (0.35) | - | 1 (0.35) | 1 (0.5) | - |
| Myocardial infarction | 1 (0.35) | - | 1 (0.35) | - | 1 (1.3) |
| Death | 2 (0.70) | - | 2 (0.70) | 1 (0.5) | 1 (1.3) |
| Thromboembolic | 12 (4.2) | 8 (2.8) | 4 (1.4) | 8 (3.8) | 4 (5.1) |
| Deep Vein Thrombosis/Pulmonary embolism | 11 (4.2) | 8 (2.8) | 4 (1.4) | 8 (3.8) | 4 (5.1) |
| Arterial thrombosis (death) | 1 (0.35) | - | 1 (0.35) | 1 (0.5) | - |
| Dermatologic | 7 (2.4) | 7 (2.4) | - | 5 (2.4) | 2 (2.6) |
| Dermatitis | 1 (0.35) | 1 (0.35) | - | 1 (0.5) | - |
| Papular rash | 2 (0.69) | 2 (0.69) | - | 2 (1.0) | - |
| Drug reaction | 1 (0.35) | 1 (0.35) | - | - | 1 (1.3) |
| Superficial separation of incision | 3 (1.0) | 3 (1.0) | - | 2 (1.0) | 1 (1.3) |
| Musculoskeletal | 4 (1.4) | 3 (1.0) | 1 (0.35) | 2 (0.95) | 2 (2.6) |
| Rhabdomyolysis | 1 (0.35) | 1 (0.35) | - | - | 1 (1.3) |
| Weakness | 2 (0.69) | 2 (0.69) | - | 2 (1.0) | - |
| Gouty flare | 1 (0.35) | - | 1 (0.35) | - | 1 (1.3) |
| Misc/Electrolyte/Metabolic | 9 (3.1) | 8 (2.8) | 1 (0.35) | 6 (2.9) | 3 (3.8) |
| Failure to thrive | 2 (0.69) | 2 (0.69) | - | - | 2 (2.6) |
| Dehydration | 1 (0.35) | 1 (0.35) | - | 1 (0.5) | - |
| Headache | 1 (0.35) | 1 (0.35) | - | 1 (0.5) | |
| Pain | 2 (0.69) | 2 (0.69) | - | 2 (1.0) | - |
| Gouty flare | 1 (0.35) | - | 1 (0.35) | - | 1 (1.3) |
| Diplopia | 1 (0.35) | 1 (0.35) | - | 1 (0.5) | - |
| Fever of unknown origin | 1 (0.35) | 1 (0.35) | - | 1 (0.5) | - |
CCS, Clavien-Dindo classification system; PN, partial nephrectomy; RN, radical nephrectomy; other abbreviations as in Table 1. Data presented at tumor level as proportions, excluding patients with missing data.
Defined according to the Acute Dialysis Quality Initiative definition reported originally in 2004 as a serum creatinine increase to 1.5-fold or glomerular filtration decrease >25% from baseline on discharge from hospital.
22.4% of high-risk patients suffered a complication compared to 14.1% of low risk patients (p=0.002). Comparing high and low risk patients, significant differences in Clavien I-II (20.4 vs. 11.1%; p<0.001) and medical (16.1 vs. 8.1%, p<0.001) complications were observed, while no differences were seen in Clavien III-V (6.7 vs. 5.4%; p=0.44) or surgical complications (9.8 vs. 8.1%; p=0.40). Among the entire cohort, no differences in complications were observed comparing patients treated with PN and RN (17.0 vs. 13.6%; p=0.327), albeit high-risk patients were more likely to undergo RN (35.3 vs. 25.9%; p=0.04). Among patients with pT1a tumors, there was no difference in complications for patients treated with PN and RN (14.1 vs. 9.2%; p=0.123). In a subset analysis of patients with cT1b-T2 tumors (n=341), more complications occurred in patients undergoing PN (25.1 vs. 14.9%; p=0.02), but there was no difference in Clavien III-V complications (8.6 vs. 5.8%; p=0.62) (Table 3). Due to the small number of outcomes in this restricted cohort, modeling was not performed. A sensitivity analysis assessing for interaction between age and CCI was performed which revealed that age >75 years was the strongest driver of complications (OR 2.4 [CI 1.2-4.6] age >75 yrs; OR 1.4 [OR 0.9-2.2] CCI >2; OR 6.1 [CI 2.5-14.8] age >75 yrs and CCI >2), however these results should be interpreted with caution given the small cohort size. While the combined estimated effect for the high-risk group is strong, the OR for the interaction term itself did not reach statistical significance (p=0.296).
Table 3.
Subset analysis of complications for patients with T1b-T2 tumors categorized by surgery type
| Complication Type | RN (n=154) | PN (n=187) | p-value |
|---|---|---|---|
|
Proportion of Patient with any complication
| |||
| All Complications | 23 (14.9) | 47 (25.1) | 0.02 |
|
Number of Complications by Type | |||
| Minor (CCS I-II) | 24 (15.6) | 36 (19.3) | 0.059 |
| Major (CCS III-V) | 9 (5.8) | 16 (8.6) | 0.618 |
| Medical | 22 (14.3) | 30 (16.0) | 0.370 |
| Surgical | 11 (7.1) | 22 (11.8) | 0.253 |
| Genitourinary | 7 (4.5) | 24 (12.8) | 0.088 |
| Urinary leak | - | 17 (9.1) | |
| Embolization | - | 1 (0.53) | |
| pseudoaneurysm | 1 (0.65) | 1 (0.53) | |
| Dialysis | 1 (0.65) | - | |
| Urinary retention | - | 1 (0.53) | |
| Ureteral stricture | 5 (3.2) | 3 (1.6) | |
| Acute kidney injury* | 1 (0.53) | ||
| Perinephric hematoma | |||
CCS, Clavien-Dindo classification system; PN, partial nephrectomy; RN, radical nephrectomy; other abbreviations as in Table 1. Data presented at tumor level as proportions, excluding patients with missing data.
Defined according to the Acute Dialysis Quality Initiative definition reported originally in 2004 as a serum creatinine increase to 1.5-fold or glomerular filtration decrease >25% from baseline on discharge from hospital.
Following adjustment, patients classified as high risk were 1.9 times more likely (OR 1.9 [CI 1.3-2.8]) to experience a post operative complication within 90 days of surgery. Other factors associated with postoperative complications included year of surgery (OR 1.3 [CI 1.1-1.4]), EBL >250mL (OR 1.8 [CI 1.1-2.7]), and operative time >3 hrs (OR 1.6 [CI 1.1-2.4]) (Table 4), while patients undergoing minimally invasive surgery (OR 0.6 [CI 0.4-0.9] were less likely to incur a post operative complication. Sensitivity analyses restricting the cohort to tumors with available NS (n = 878) or tumor size <10cm (n = 1045) did not change the main study findings (data not reported). A multivariable logistic regression analysis restricted to patients with T1a disease did not appreciably change our main study findings.
Table 4.
Multivariable logistic regression analysis adjusting for demographic characteristics, clinical severity, risk group status, anatomic complexity, operative factors, and year of surgery.
| Characteristic | All Complications | |
|---|---|---|
| OR (95% CI) | P Value | |
| Year of surgery | 1.3 (1.1-1.4) | <0.001 |
| Risk Status | ||
| Low | 1.0 | |
| High | 1.9 (1.3-2.8) | 0.001 |
| Gender | ||
| Male | 1.0 | |
| Female | 1.1 (0.8-1.6) | 0.603 |
| Race | ||
| Caucasian | 1.0 | |
| Non-Caucasian | 1.2 (0.7-1.9) | 0.485 |
| ECOG status | ||
| 0 | 1.0 | |
| ≥1 | 1.6 (0.7-3.4) | 0.252 |
| Surgical type | ||
| Radical nephrectomy | 1.0 | |
| Partial nephrectomy | 1.0 (0.6-1.6) | 0.914 |
| Surgical approach | ||
| Open | 1.0 | |
| Minimally Invasive | 0.6 (0.4-0.9) | 0.013 |
| Clinical stage | ||
| cT1 | 1.0 | |
| cT2 | 1.4 (0.8-2.3) | 0.276 |
| NS complexity group | ||
| Low | 1.0 | |
| Intermediate | 1.4 (0.9-2.3) | 0.180 |
| High | 1.4 (0.8-2.7) | 0.244 |
| Hilar designation | 1.1 (0.7-1.8) | 0.642 |
| Solitary kidney | 1.1 (0.5-2.1) | 0.881 |
| Operative time | ||
| <3 hrs | 1.0 | |
| >3 hrs | 1.6 (1.1-2.4) | 0.014 |
| Estimate blood loss | ||
| <250mL | 1.0 | |
| >250mL | 1.8 (1.1-2.7) | 0.011 |
CI, confidence interval; OR, odds ratio; other abbreviations as in Table 1.
Discussion
Prognostic importance of overall co-morbidity for patients with a cancer diagnosis considering definitive surgical resection is relative to the malignant potential of the index cancer.15 Using quantification of competing risks as selection criteria for definitive intervention becomes most important in situations where the prognostic impact of the tumor is small. With the increasing incidence of RCC in an elderly population, co-morbidity and advanced age are important factors that compete with RCC as the primary cause of death.7 Although over-treatment of indolent disease is an increasingly recognized phenomenon16 and enthusiasm for active surveillance in patients with early stage kidney cancer is growing8, surgical intervention is still considered the gold standard for the stage I renal mass.3
Moreover, debate often hinges on what type of procedure (PN versus RN) should be performed,17 rather than considering the risk of any intervention (including ablation) versus expectant management. Our retrospective examination of a large tertiary center experience revealed several notable findings. First, while renal surgery is generally considered safe and low risk, the overall burden of 90 day complications in the elderly and infirmed is not trivial (>22%) when rigorously measured using the Clavien classification system. Further, when adjusting for tumor complexity, risk status and not surgical type appears to be a major driver of complication rates for patients with early stage disease, which has important implications for the role of active surveillance strategies in at risk patients. Given that complications can often have long-term ramifications, appropriate pre-operative risk stratification becomes paramount.
Objective treatment counseling in the preoperative setting should balance oncologic and competing-risks in pursuit of individualized patient centered care. Nearly one-third of elderly patients will die from unrelated disease within 5 years of curative kidney cancer surgery18, so it is conceivable that age-related competing-cause mortality might dampen the benefits of surgery for some older patients with small renal masses regardless of the type of surgery performed. Furthermore, as the 90-day mortality rate for surgical resection of localized disease is very low (<1% in our series)19, peri-operative complication rates may be a more appropriate outcome measure for patient counseling purposes when discussing early impact on quality of life following treatment.
In our large single-institution cohort, elderly and co-morbid patients with RCC were nearly twice as likely to experience a complication regardless of treatment type. Minor and medical complications occurred more frequently in high-risk patients, but no differences were seen in major and surgical complications when compared to low-risk patients. Further, no difference was seen in overall complication rates between surgical types, with the important caveat that more high-risk patients were selected for RN compared to low risk patients (36 vs. 25%, p=0.04). While early results from EORTC 30904 reported higher complication and reoperation rates in patients with small tumors randomized to PN vs. RN,20 this may be due to differences in complication reporting methodology in which the study investigators focused primarily on surgically related adverse events such as hemorrhage, urinary fistulae, and damage to surrounding structures. Using the Clavien Dindo standardized post-operative complications grading system, our results are consistent with prior institutional series reporting equivalent complication rates between PN and RN,21-24 and represents the first analysis to date adjusting for anatomic tumor complexity in a cohort in which the majority of patients were treated in a minimally invasive fashion (62%), which may more accurately reflect contemporary practice patterns.
As metrics for measuring anatomic complexity have been adopted to accurately adjust for case mix between providers,10 it has become increasingly apparent that comparison of likewise tumors is necessary to meaningfully compare outcomes between partial and radical nephrectomy. Demonstrated in our study and others,25,26 partial nephrectomy for small, anatomically simple, renal tumors has a complication profile that is very similar to radical nephrectomy performed in either a minimally invasive or open fashion and minimally impacts post operative convalescence. As such, in elderly co-morbid patients with low risk tumors and a normal contralateral kidney, the decision to perform any intervention versus active surveillance may be more important than debate regarding surgical type.27 Further, at our institution, tumor ablation is rarely used as primary therapy, and instead is predominantly reserved for patients who progress to definitive therapy following a period of active surveillance who are not operative candidates.
In contrast, it is clear that further research is necessary to determine an optimal treatment strategy in patients with large (cT1b-2), anatomically complex tumors that are not candidates for active surveillance. In a subset analysis of 341 patients with cT1b-T2 tumors, more complications occurred in patients undergoing PN compared to RN (25.1% vs. 14.9%, p=0.02). Although the ability for adjustment was limited by the small number of outcomes, the differences in adverse events observed between treatment groups was predominantly due to differences in surgically related complications including urinary leak and hemorrhage requiring transfusion, which is expected with a more technically demanding procedure. While a surgical trial randomizing patients with cT1b-2 tumors to PN or RN is currently under consideration to further define oncologic and peri-operative outcomes28, significant accrual challenges are anticipated. Until such data is available, as the risks of active surveillance are largely unproven for larger complex lesions, the decision to proceed with complex PN in an elderly or infirmed patient with a normal contralateral kidney should be made cautiously.17
The principle limitations to our study include a retrospective methodology and inherent selection biases based on surgeon and patient preferences, and clearly our findings represent a contemporary tertiary care surgical experience that should not be considered generalizable to community practice. Also, in designing our multivariable model, it is possible that tumor or patient characteristics that were not included or measured may have biased our findings. Moreover, despite robust prospective data collection, the challenge of capturing non-index hospitalization outcomes data may contribute to observed differences in complication rates when compared to secondary data outcomes reliant on claims based coding.29 Most notably, the absence of defined criteria to determine an “at risk” population leaves our chosen thresholds for age and co-morbidity status open to criticism, but regardless of which cut points are chosen, our study findings support the notion that any surgical treatment of early stage kidney cancer is not without risk in the elderly and infirmed.
Conclusions
With increased utilization of cross-sectional imaging and prolonged life expectancy, the incidence of incidentally diagnosed renal tumors in the elderly will continue to rise. Our findings support the notion that patient risk status, and not surgical type, is associated with post-operative complications following surgical resection of localized RCC. As a result, the burden of complications in the elderly and infirmed should be strongly considered in the decision to pursue any surgical intervention compared to an initial period of active surveillance in elderly patients or those with substantial competing risks. Clarification of existing small renal mass management algorithms is necessary to inform patient decisions and optimally select elderly and co-morbid patients for primary surgery versus an initial period of expectant management.
Footnotes
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