Abstract
Background
Upper tract urothelial carcinoma (UTUC) is an aggressive disease with a high progression rate. The standardmanagement for this disease is nephroureterectomy. Nephron sparing nonradical surgery is an alternative therapeutic approach. In men with limited life expectancy, the potential harm of UTUC progression must be weighed against surgical morbidity and mortality, and thus, more conservative approaches may be selected. This study aims to investigate the comparative benefits of radical and conservative surgical management in patients older than 80 years with localized UTUC.
Materials and methods
A search was conducted in the Surveillance, Epidemiology, and End Results database for patients older than 80 years who were diagnosed with localized (T1–2N0M0) cancer in the renal pelvis or ureter as the only malignancy from 2004 to 2015. Patients were divided into 3 therapeutic groups: no surgery, local intervention (ie, local tumor excision or segmented ureterectomy), and radical surgery (nephroureterectomy). Demographic and cancer-related parameter data were collected. Logistic regression analysis was conducted to investigate predictors for surgical treatment. Kaplan-Meier curves and Cox regression were used to analyze survival outcomes.
Results
Data from 774 patients were analyzed, including 205 in the no-surgery group, 181 in the local intervention group, and 388 in the radical surgery group. Older, African American patients with T1 stage disease were less likely to receive surgical treatment. Among surgically treated patients, renal pelvic tumors, and high-grade and T2 stage disease were associated with radical resection. Surgically treated patients had a longer median overall survival (OS) than in those treated nonsurgically (13, 35, and 47 months in no-surgery, local intervention, and radical surgery groups, respectively; p < 0.001). Although surgically treated patients demonstrated higher 5-year OS (8.8% [no surgery], 23.2% [local intervention], and 23.5% [radical surgery], p < 0.001) and 5-year disease-specific survival (DSS) (41.0%[no surgery], 69.1%[local intervention], and 72.9%[radical surgery]; p < 0.001) than in those treated nonsurgically, no significant differences were found between the local intervention and radical surgery groups (p > 0.05). Based on multivariate Cox regression analysis, surgical treatments, including both nonradical and radical resection, were independently associated with improved OS and DSS after controlling for age, marital status, tumor grade, and radiation status.
Conclusions
Patients older than 80 years with localized UTUC who undergo surgery demonstrate longer survival. Radical and nonradical resections seemto have similar OS and DSS outcomes. Thus, when clinically indicated in this population, a more conservative surgical approach may be reasonable.
Keywords: Older adults; Surgery; Surveillance, Epidemiology, and End Results; Survival; Upper tract urothelial carcinoma
1. Introduction
Upper tract urothelial carcinoma (UTUC) accounts for only 5% of all urothelial cancers.[1] However, it is an aggressive disease with a poor prognosis, with 60% of patients presenting with advanced stage disease. Reported 5-year disease-specific survival (DSS) rates are less than 50% for invasive disease.[2–4] With diagnostic advances and improved survival among patients with bladder urothelial cancer, the incidence of UTUC has been rising, and the mean age at diagnosis has increased from 68 to 73 years over the last few decades.[5] However, survival rates have not improved despite improved treatment modalities.[6]
Currently, the standard treatment for clinically localized UTUC is radical nephroureterectomy (RNU) with bladder cuff resection combined with chemotherapy, if indicated.[7,8] Minimally invasive approaches such as laparoscopic and robotic assisted surgery have been shown to accelerate postoperative recovery. Nonetheless, radical resection still represents a major surgery and confers risk for severe adverse events and complications, especially in patients with advanced age and multiple comorbidities. A high rate of comorbidities was noted in a cohort study of 731 UTUC patients with a median age of 70 years; nearly 20% of patients had an Eastern Cooperative Oncology Group performance status ≥2 or a Charlson Comorbidity Index score >5, and half had chronic kidney disease ≥ stage 3.[9] In that cohort, 38% of patients experienced complications, 22% being higher than grade 2.
In recent years, advances in endourology have enabled many small and early tumors in the upper urinary tract to be managed safely without removing the kidney and the entire ureter, known as nephron-sparing surgery (NSS).[10] For men with limited life expectancy, the potential harm of UTUC progression must be weighed against surgical morbidity and mortality, and thus, more conservative approaches may be selected. However, the impact of different approaches to surgical management of UTUC among octogenarians has been inadequately discussed. In this study, the Surveillance, Epidemiology, and End Results (SEER) database was used to investigate the comparative benefits of conservative and radical surgery among patients older than 80 years with localized UTUC.
2. Materials and methods
2.1. Data source
The SEER-18 database was accessed for data collection. This open-access database established by the National Institute of Cancer collects cancer-related patient information including demographics, cancer characteristics, treatments, and outcomes from population based cancer registries, representing approximately 34.6% of the US population. All data had previously been deidentified. This study was deemed exempt by the University of Maryland School of Medicine Institutional Review Board.
2.2. Patient population
Patients diagnosed with UTUC between 2004 and 2015 were identified, coded in SEER as a malignancy in the renal pelvis (C65.9) or ureter (C66.9) as the only primary cancer. Eligible patients were those 80 years or older at the time of diagnosis with localized nonmetastatic T1–2N0M0 disease (American Joint Committee on Cancer, sixth and seventh edition manual). All eligible patients were divided into 3 groups according to surgical management using site-specific surgery codes: Group 1, no surgery (NS; code 0); Group 2, local intervention (LI), including segmented ureterectomy (SU) and endoscopic local tumor resection (codes 10–15, 20–27, and 30); and Group 3, radical surgery (RS), including the entire removal of kidney and ureter (codes 40, 50, and 70).
2.3. Variables
Patient demographic information (age, sex, race), socioeconomic information (marital status, insurance), tumor characteristics (TNM stage, location, grade, histology), treatment details (year of diagnosis, surgical treatment, radiation, chemotherapy), and outcomes (survival status, survival time, cause of death) were extracted fromthe database for analysis.
2.4. Outcomes and statistical analysis
Categorical and continuous variables were compared using χ2 test and t test, respectively. Logistic regression was used to investigate factors predicting the likelihood of receiving surgical treatment and radical resection. Kaplan-Meier curves and Cox regression were established for survival outcome analysis. Any variables found to have a p value <0.2 on univariate analysis were included in the multivariate analysis. Data analysis was conducted using R software 4.0.0 (Foundation for Statistical Computing, Vienna, Austria). A p value <0.05 was considered statistically significant.
3. Results
In all, data from 774 patients were included, with 205 in the NS group, 181 in the LI group, and 388 in RS group. Patient characteristics are summarized in Table 1. Of note, patients in the nonsurgical treatment group were older (87.0, 84.6, and 84.8 yr in the NS, LI, and RS groups, respectively; p < 0.001), with a higher proportion of African Americans (6.8%, 0.6%, and 3.6%; p < 0.001), single marital status (62.9%, 48.6%, and 48.2%; p < 0.001), T1 stage tumors (89.3%, 68.0%, and 61.3%; p < 0.001), and radiation therapy (12.7%, 5.0%, and 1.0%; p < 0.001). More patients in the LI surgical treatment group had tumors in the ureter (36.6%, 71.3%, and 35.3%; p < 0.001) and received chemotherapy (2.9%, 9.9%, and 2.6%; p < 0.001). Those who underwent RS had the highest proportion of high-grade tumors (24.4%, 53.6%, and 71.1%; p < 0.001).
Table 1.
Characteristics of patients treated with and without surgeries.
| Variable | All patients (n = 774) | NS (n = 205) | LI (n = 181) | RS (n = 388) | p |
|---|---|---|---|---|---|
| Age, yr, mean ± SD | 85.3 ± 4.0 | 87.0 ± 4.5 | 84.6 ± 3.9 | 84.8 ± 3.5 | |
| Sex, n (%) | 0.568 | ||||
| Male | 366 (47.3) | 103 (50.2) | 86 (47.5) | 177 (45.6) | |
| Female | 408 (52.7) | 102 (49.8) | 95 (52.5) | 211 (54.4) | |
| Race, n (%) | 0.005 | ||||
| White | 681 (88.0) | 179 (87.3) | 162 (89.5) | 340 (87.6) | |
| African American | 29 (3.7) | 14 (6.8) | 1 (0.6) | 14 (3.6) | |
| Other | 62 (8.0) | 12 (5.9) | 16 (8.8) | 34 (8.8) | |
| Unknown | 2 (0.3) | 0 | 2 (1.1) | 0 | |
| Insurance, n (%) | 0.402 | ||||
| Insured | 625 (80.7) | 172 (83.9) | 147 (81.2) | 306 (78.9) | |
| No | 6 (0.8) | 0 | 1 (0.6) | 5 (1.3) | |
| Unknown | 143 (18.5) | 33 (16.1) | 33 (18.2) | 77 (19.8) | |
| Marital status, n (%) | <0.001 | ||||
| Married | 333 (43.0) | 69 (33.7) | 86 (47.5) | 178 (45.9) | |
| Single | 404 (52.2) | 129 (62.9) | 88 (48.6) | 187 (48.2) | |
| Unknown | 103 (13.3) | 7 (3.4) | 73 (3.9) | 23 (5.9) | |
| Year of diagnosis, n (%) | 0.981 | ||||
| 2004–2007 | 204 (26.4) | 52 (25.4) | 47 (30.0) | 105 (27.1) | |
| 2008–2011 | 287 (37.1) | 75 (36.6) | 67 (37.0) | 145 (37.4) | |
| 2012–2015 | 283 (36.6) | 78 (38.0) | 67 (37.0) | 138 (35.6) | |
| Primary site, n (%) | <0.001 | ||||
| Pelvis | 433 (55.9) | 130 (63.4) | 52 (28.7) | 251 (64.7) | |
| Ureter | 341 (44.1) | 75 (36.6) | 129 (71.3) | 137 (35.3) | |
| Laterality, n (%) | 0.124 | ||||
| Unilateral | 772 (99.7) | 203 (99.0) | 181 (100) | 388 (100) | |
| Bilateral | 2 (0.3) | 2 (1) | 0 | 0 | |
| Histology, n (%) | <0.001 | ||||
| Transitional cell ca | 745 (96.3) | 189 (92.2) | 176 (97.2) | 380 (97.9) | |
| Nontransitional cell ca | 13 (1.7) | 3 (1.5) | 3 (1.7) | 7 (1.8) | |
| Not specified | 16 (2.1) | 13 (6.3) | 2 (1.1) | 1 (0.3) | |
| Stage (T), n (%) | <0.001 | ||||
| T1 | 544 (70.3) | 183 (89.3) | 123 (68) | 238 (61.3) | |
| T2 | 230 (29.7) | 22 (10.7) | 58 (32.0) | 150 (38.7) | |
| Grade, n (%) | <0.001 | ||||
| Low grade (I + II) | 174 (22.5) | 29 (14.1) | 59 (32.6) | 86 (22.2) | |
| High grade (III + IV) | 423 (54.7) | 50 (24.4) | 97 (53.6) | 276 (71.1) | |
| Unknown | 177 (22.9) | 126 (61.5) | 25 (13.8) | 26 (6.7) | |
| Chemotherapy, n (%) | <0.001 | ||||
| Yes | 34 (4.4) | 6 (2.9) | 18 (9.9) | 10 (2.6) | |
| No/unknown | 740 (95.6) | 199 (97.1) | 163 (90.1) | 378 (97.4) | |
| Radiation, n (%) | <0.001 | ||||
| Yes | 39 (5.0) | 26 (12.7) | 9 (5.0) | 4 (1.0) | |
| No/unknown | 735 (95.0) | 179 (87.3) | 172 (95.0) | 384 (99.0) |
ca = carcinoma; LI = local intervention; NS = no surgery; RS = radical surgery.
Multivariate logistic analysis revealed that older patients (odds ratio [OR], 0.57 and 0.21 for age groups 85–89 and ≥90 yr, respectively; p < 0.05) and African American patients (OR, 0.27; p = 0.018) were less likely to be treated surgically, after controlling for marital status, tumor location, histology, and grade (Table 2). Among patients who received surgical treatment, those with stage T2 disease and higher tumor grade were more likely to receive RS (Table 3).
Table 2.
Univariate and multivariate logistic regression analyses describing predictors of surgical treatment.
| Variable | Univariate | Multivariate | ||
|---|---|---|---|---|
| OR (95% CI) | p | OR (95% CI) | p | |
| Age, yr | ||||
| 80–84 | 1 | 1 | ||
| 85–89 | 0.567 (0.392–0.822) | 0.003 | 0.532 (0.337–0.840) | 0.007 |
| ≥90 | 0.206 (0.131–0.324) | <0.001 | 0.238 (0.134–0.425) | <0.001 |
| Sex | ||||
| Male | 1 | |||
| Female | 1.175 (0.854–1.617) | 0.323 | ||
| Race | ||||
| White | 1 | 1 | ||
| African American | 0.382 (0.181–0.807) | 0.012 | 0.273 (0.093–0.800) | 0.018 |
| Others | 1.486 (0.773–2.854) | 0.235 | 0.919 (0.425–1.989) | 0.830 |
| Insurance | ||||
| Insured | 1 | |||
| No | - | - | ||
| Marital status | ||||
| Married | 1 | 1 | ||
| Single | 0.557 (0.398–0.781) | 0.001 | 0.701 (0.455–1.077) | 0.105 |
| Year of diagnosis | ||||
| 2004–2007 | 1 | |||
| 2008–2011 | 0.967 (0.641–1.458) | 0.873 | ||
| 2012–2015 | 0.899 (0.597–1.353) | 0.610 | ||
| Primary site | ||||
| Pelvis | 1 | 1 | ||
| Ureter | 1.522 (1.096–2.113) | 0.012 | 0.938 (0.614–1.433) | 0.768 |
| Laterality | ||||
| Unilateral | 1 | |||
| Bilateral | - | - | ||
| Histology | ||||
| Transitional cell ca | 1 | 1 | ||
| Nontransitional cell ca | 1.133 (0.309–4.161) | 0.851 | 2.149 (0.356–12.98) | 0.404 |
| Not specified | 0.078 (0.022–0.278) | <0.001 | 0.233 (0.048–1.118) | 0.069 |
| Stage (T) | ||||
| T1 | 1 | 1 | ||
| T2 | 4.793 (2.983–7.699) | <0.001 | 4.817 (2.699–8.598) | <0.001 |
| Grade | ||||
| Low grade (I + II) | 1 | 1 | ||
| High grade (III + IV) | 1.492 (0.909–2.450) | 0.114 | 1.377 (0.811–2.339) | 0.236 |
ca = carcinoma; CI = confidence interval; OR = odds ratio.
Table 3.
Univariate and multivariate logistic regression analyses describing predictors of radical surgical treatment.
| Variable | Univariate | Multivariate | ||
|---|---|---|---|---|
| OR (95% CI) | p | OR (95% CI) | p | |
| Age, yr | ||||
| 80–84 | 1 | |||
| 85–89 | 0.928 (0.636–1.355) | 0.699 | ||
| ≥90 | 0.872 (0.476–1.595) | 0.656 | ||
| Sex | ||||
| Male | 1 | |||
| Female | 1.079 (0.758–1.537) | 0.673 | ||
| Race | ||||
| White | 1 | 1 | ||
| African American | 6.671 (0.870–51.17) | 0.068 | 4.668 (0.581–37.52) | 0.147 |
| Others | 1/012 (0.543–1.888) | 0.969 | 1.079 (0.546–2.136) | 0.826 |
| Insurance | ||||
| Insured | 1 | |||
| No | 2.402 (0.278–20.75) | 0.426 | ||
| Marital status | ||||
| Married | 1 | |||
| Single | 1.027 (0.715–1.473) | 0.886 | ||
| Year of diagnosis | ||||
| 2004–2007 | 1 | |||
| 2008–2011 | 0.969 (0.618–1.519) | 0.890 | ||
| 2012–2015 | 0.922 (0.587–1.448) | 0.724 | ||
| Primary site | ||||
| Pelvis | 1 | 1 | ||
| Ureter | 0.220 (0.150–0.323) | <0.001 | 0.183 (0.121–0.277) | <0.001 |
| Laterality | ||||
| Unilateral | 1 | |||
| Bilateral | - | - | ||
| Histology | ||||
| Transitional cell ca | 1 | |||
| Nontransitional cell ca | 1.081 (0.276–4.229) | 0.911 | ||
| Not specified | 0.232 (0.021–2.571) | 0.234 | ||
| Stage (T) | ||||
| T1 | 1 | 1 | ||
| T2 | 1.337 (0.920–1.941) | 0.128 | 1.725 (1.123–2.650) | 0.013 |
| Grade | ||||
| Low grade (I + II) | 1 | 1 | ||
| High grade (III + IV) | 1.952 (1.303–2.924) | 0.001 | 1.675 (1.070–2.622) | 0.024 |
ca = carcinoma; CI = confidence interval; OR = odds ratio.
During a median follow-up time of 76.0 months, 541 deaths (69.9%) were noted, with 177 (86.3%) in the NS group, 115 (63.5%) in the LI group, and 249 (64.2%) in the RS group (p < 0.001). Of those deaths, 247 (45.7%) were caused by non-UTUC reasons, with 30.5%, 47.8%, and 55.4% in the NS, LI, and RS groups, respectively (p < 0.001). There was no difference between the LI group and the RS group (p = 0.18). Cardio-cerebrovascular disease was the most common cause of death reported (24.0%; Fig. 1).
Figure 1.
Distribution of causes of death among all patients and OS in different treatment groups. OS = overall survival.
Surgically treated patients had a longer median overall survival (OS; 13, 35, and 47 months for NS, LI, and RS; p < 0.001; Fig. 2). Patients treated surgically also had higher 5-year OS (8.8%, 23.2%, and 23.5% for NS, LI and RS; p < 0.001) and 5-year DSS (41.0%, 69.1%, and 72.9%, for NS, LI, and RS; p < 0.001) than those treated without surgery. However, no significant differences were found between LI and RS patients for 5-year OS and DSS (p > 0.05). Univariate analysis found that surgical treatment and radiation were associated with improved OS and DSS (Tables 4 and 5). Multivariate Cox regression analysis revealed that surgical treatment, including both LI and radical resections, was independently associated with improved OS and DSS while controlling for age, marital status, tumor grade, and radiation therapy (Tables 4 and 5).
Figure 2.
Kaplan-Meier curves demonstrating DSS (A) and OS (B) stratified by surgical treatments. DSS = disease-specific survival; LI = local intervention; NS = no surgery; OS = overall survival; RS = radical surgery.
Table 4.
Univariate and multivariate Cox regression analyses describing predictors of overall mortality.
| Variable | Univariate | Multivariate | ||
|---|---|---|---|---|
| HR (95% CI) | p | HR (95% CI) | p | |
| Treatment | ||||
| NS | 1 | 1 | ||
| LI | 0.448 (0.353–0.567) | <0.001 | 0.546 (0.414–0.720) | <0.001 |
| RS | 0.412 (0.339–0.500) | <0.001 | 0.489 (0.379–0.631) | <0.001 |
| Age, yr | ||||
| 80–84 | 1 | 1 | ||
| 85–89 | 1.720 (1.427–2.073) | <0.001 | 1.691 (1.400–2.041) | <0.001 |
| ≥90 | 2.552 (1.994–3.265) | <0.001 | 2.148 (1.662–2.777) | <0.001 |
| Sex | ||||
| Male | 1 | |||
| Female | 1.114 (0.940–1.319) | 0.213 | ||
| Race | ||||
| White | 1 | |||
| African American | 2.103 (0.296–14.96) | 0.458 | ||
| Others | 2.187 (0.293–16.29) | 0.445 | ||
| Insurance | ||||
| Insured | 1 | |||
| No | 1.074 (0.871–1.324) | 0.506 | ||
| Marital status | ||||
| Married | 1 | 1 | ||
| Single | 1.142 (0.959–1.360) | 0.136 | 0.984 (0.823–1.178) | 0.864 |
| Year of diagnosis | ||||
| 2004–2007 | 1 | |||
| 2008–2011 | 1.140 (0.931–1.395) | 0.205 | ||
| 2012–2015 | 0.994 (0.781–1.264) | 0.959 | ||
| Primary site | ||||
| Pelvis | 1 | |||
| Ureter | 0.967 (0.816–1.146) | 0.698 | ||
| Laterality | ||||
| Unilateral | 1 | |||
| Bilateral | 1.140 (0.284–4.571) | 0.854 | ||
| Histology | ||||
| Transitional cell ca | 1 | |||
| Nontransitional cell ca | 0.834 (0.470–1.480) | 0.535 | ||
| Not specified | 0.562 (0.230–1.376) | 0.207 | ||
| Stage (T) | ||||
| T1 | 1 | |||
| T2 | 0.928 (0.770–1.119) | 0.433 | ||
| Grade | ||||
| Low grade (I + II) | 1 | 1 | ||
| High grade (III + IV) | 1.234 (0.988–1.542) | 0.063 | 1.289 (1.028–1.617) | 0.028 |
| Chemotherapy | ||||
| Yes | 1 | |||
| No/unknown | 1.169 (0.756–1.809) | 0.483 | ||
| Radiation | ||||
| Yes | 1 | 1 | ||
| No/unknown | 0.495 (0.351–0.700) | <0.001 | 0.717 (0.500–1.030) | 0.072 |
ca = carcinoma; CI = confidence interval; HR = hazard ratio; LI = local intervention; NS = no surgery; RS = radical surgery.
Table 5.
Univariate and multivariate Cox regression analyses describing predictors of disease-specific mortality.
| Variable | Univariate | Multivariate | ||
|---|---|---|---|---|
| HR (95% CI) | p | HR (95% CI) | p | |
| Treatment | ||||
| NS | 1 | 1 | ||
| LI | 0.361 (0.264–0.492) | <0.001 | 0.446 (0.312–0.637) | <0.001 |
| RS | 0.285 (0.220–0.369) | <0.001 | 0.333 (0.238–0.464) | <0.001 |
| Age, yr | ||||
| 80–84 | 1 | 1 | ||
| 85–89 | 1.804 (1.394–2.335) | <0.001 | 1.694 (1.306–2.198) | <0.001 |
| ≥90 | 2.833 (2.059–3.898) | <0.001 | 2.117 (1.523–2.943) | <0.001 |
| Sex | ||||
| Male | 1 | |||
| Female | 1.014 (0.806–1.275) | 0.909 | ||
| Race | ||||
| White | 1 | |||
| African American | 0.812 (0.418–1.579) | 0.539 | ||
| Others | 1.050 (0.706–1.561) | 0.810 | ||
| Insurance | ||||
| Insured | 1 | |||
| No | 1.159 (0.288–4.665) | 0.836 | ||
| Marital status | ||||
| Married | 1 | |||
| Single | 1.135 (0.896–1.438) | 0.294 | ||
| Year of diagnosis | ||||
| 2004–2007 | 1 | |||
| 2008–2011 | 0.924 (0.673–1.267) | 0.621 | ||
| 2012–2015 | 1.195 (0.904–1.580) | 0.210 | ||
| Primary site | ||||
| Pelvis | 1 | |||
| Ureter | 0.925 (0.734–1.166) | 0.511 | ||
| Laterality | ||||
| Unilateral | 1 | |||
| Bilateral | 0.962 (0.135–6.858) | 0.970 | ||
| Histology | ||||
| Transitional cell ca | 1 | |||
| Nontransitional cell ca | 0.828 (0.342–2.005) | 0.675 | ||
| Not specified | 1.382 (0.652–2.926) | 0.399 | ||
| Stage (T) | ||||
| T1 | 1 | |||
| T2 | 0.994 (0.774–1.275) | 0.959 | ||
| Grade | ||||
| Low grade (I + II) | 1 | 1 | ||
| High grade (III + IV) | 1.440 (1.040–1.994) | 0.028 | 1.604 (1.151–2.233) | 0.005 |
| Chemotherapy | ||||
| Yes | 1 | |||
| No/unknown | 1.015 (0.582–1.771) | 0.957 | ||
| Radiation | ||||
| Yes | 1 | 1 | ||
| No/unknown | 0.467 (0.304–0.716) | <0.001 | 0.789 (0.512–1.243) | 0.319 |
ca = carcinoma; CI = confidence interval; HR = hazard ratio; LI = local intervention; NS = no surgery; RS = radical surgery.
4. Discussion
Upper tract urothelial carcinoma is morphologically similar to bladder cancer but differs in terms of various phenotypical and genotypical features.[11] Although tremendous advances have been made in clinical imaging and early diagnosis, survival outcomes after surgical treatment are still poor, with 5-year OS in patients, with localized disease and regional lymph node metastasis being only 35%–50%.[12–14] A retrospective study at MD Anderson found no significant improvement in DSS of UTUC from 1986 to 2004, underscoring the need for a change in treatment paradigm.[15]
At present, the TNM system is still the predominant evaluation system for UTUC.[4] However, it is difficult to obtain accurate tumor staging among patients with UTUC during preoperative evaluation. Because of potential risks related to imprecise staging, RNU plus bladder cuff resection has long been considered the criterion standard surgical treatment. However, RNU potentially makes patients more susceptible to chronic kidney disease and end-stage renal failure, with the associated financial burden of hemodialysis.[16]
Patients diagnosed with UTUC are usually those with advanced age and more likely to have comorbidities. Data from US Medicare beneficiaries indicates that 40% of cancer patients have at least 1 other chronic condition, and 15% have 2 or more.[17] Although not usually life-threatening in the short term, many chronic diseases increase mortality risk when patients undergo acute stress such as major surgery. In fact, postoperative complications and advanced age may be more likely to result in death than cancer itself. A study from Canada reported that 38% of patients experienced complications within 30 days after RNU, and 12% of these were major complications. An Eastern Cooperative Oncology Group performance status ≥2 (OR, 3.9; p < 0.001) was an independent predictor for postoperative complications.[18] Another multicenter study reported a complication rate of 26% (46 of 177) after RNU, of which one-quarter were grade 3 or 4.[19] Therefore, the patient's age and preoperative performance status should be carefully considered when making decisions regarding cancer management and estimating survival benefit of treatment options.
Unfortunately, data are relatively scarce on the optimal management of localized UTUC in older patients who are candidates for RS. In our study, 541 (69.9%) patients died during follow-up, of which 45.7% were due to non-UTUC causes, with cardiocerebrovascular disease being the most common (24.0%). This finding is consistent with those of a study of 830 patients with UTUC from Canada, in whom the mean age at diagnosis was 70 years, 5-year OS was 57.2%, and 41% died of noncancer causes.[20] Likewise, another study of UTUC patients reported a 46% rate of noncancer causes of death.[21]
Nephron-sparing surgery facilitates preservation of the ipsilateral kidney without compromising oncologic outcomes. Numerous studies have demonstrated a similar survival rates for NSS and RNU in low-risk diseases.[22] Despite strong recommendations by current guidelines that NSS should be considered for low-risk disease in select patients,[7,8] few studies have previously evaluated the surgical treatment of older patients with high-grade and T2 disease. In our study, after controlling for age and tumor grade, both nonradical and radical resection demonstrated similar DSS and OS outcomes. Accordingly, such evidence could inform current management algorithms to include NSS options for older patents with localized high-grade UTUC.
Conservative surgery for older patients could potentially reduce postoperative complications and the risk of renal insufficiency. However, such advantages would be achieved at the expense of an invasive and stricter monitoring plan. In addition to routine urinary cytology and CT scans, patients undergoing frequently NSS require additional ureteroscopy because of the high risk of recurrence in the ipsilateral upper urinary tract and bladder.[23] In a recent study using SEER data, Wu et al.[24] found that despite the similar OS and DSS after RNU and SU, patients with high-grade disease undergoing SU were more likely to have a shorter time to bladder cancer recurrence. Even after radical resection, the recurrence rate can be high. Yamashita et al.[25] reported a bladder cancer recurrence rate of 36% during a median follow-up period of 60 months, and Shigeta et al.[26] reported a bladder recurrence rate of 48.4% in a Ta–3N0M0 UTUC cohort after RNU. Therefore, nonradical surgery should considered after careful discussion between physicians and patients regarding risk of recurrence, frequent endoscopic surgery, quality of life, and survival benefit. Close follow-up and patient adherence are key factors related to better prognosis. To avoid treatment failure, conservative surgery should not be recommended for patients who refuse or are unable to adhere to such a stringent follow-up plan.[23]
At present, potentially curative treatment of UTUC can only achieved by surgical removal. This study's findings confirmed that without surgical management, both OS and DSS were extremely poor, consistent with another SEER-based study of nondefinitive treatments for UTUC.[27] Watchful waiting should not be recommended unless absolute surgical contraindications exist. Chemotherapy, immunotherapy, radiation therapy, and embolization may be considered as supplemental to watchful waiting or for palliative purposes.[28,29] In 2020, the US Food and Drug Administration approved Jelmyto (mitomycin gel) as an alternative nonsurgical treatment for low-grade UTUC.
Another noteworthy result from this study was that African American patients were less likely to receive surgery. The reasons for such healthcare system racial disparities, despite their longstanding existence, are not fully understood. A review by Haider et al.[30] described 3 domains contributing to racial disparities: systemic (low-volume hospitals, access to care), patient (socioeconomic status, disease burden/comorbidities, willingness for surgery), and provider (fewer specialist referrals, low volume surgeons).
Limitations
Several limitations of this study deserved further mention. First, data related to patient performance status such as comorbidities and postoperative complications were not recorded as such within the SEER database. Second,TNMstaging was largely recorded based on postoperative specimen histology. For nonsurgically treated patients, therefore, the lack of such grading and staging information could reduce the certainty of our findings. Third, further identification of patients with recurrence in the bladder and ipsilateral upper urinary tract was not feasible because of limited data available in the SEER database. Nevertheless, our study provided evidence for selection of treatment approaches based a population-based cohort of older adult patients with UTUC. Future prospective studies are needed among this subgroup of patients.
5. Conclusions
Patients older than 80 years with localized UTUC seem to benefit from surgical treatment in terms of prolonged survival. Radical resection and nonradical resection seem to confer similar OS and DSS outcomes. Thus, when clinically indicated in this population, a more conservative approach may be reasonable.
Acknowledgments
None.
Statement of ethics
Data within the SEER database have previously been deidentified. This study was deemed exempt by the local institutional review board. Informed consent was not applicable. All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Funding source
No funding to declare.
Author contributions
SW: Data acquisition, quality control of data and algorithms, study design, data analysis and interpretation, statistical analysis, manuscript preparation;
MP: Study design, manuscript review and editing;
MMS: Project supervision, study concept and design, manuscript review and editing.
Data availability
The datasets generated during and/or analyzed during the current study are not publicly available, but are available from the corresponding author on reasonable request.
Footnotes
How to cite this article: Wang S, Phelan M, Siddiqui MM. Impact of surgical management of upper tract urothelial cancer in octogenarians: A population-based study. Curr Urol 2024;18(3):225–231. doi: 10.1097/CU9.0000000000000164
Contributor Information
Shu Wang, Email: sh.wang@som.umaryland.edu.
Michael Phelan, Email: mphelan@som.umaryland.edu.
Conflicts of interest statement
No conflict of interest has been declared by the authors.
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