Trends in Treatment of T1N0 Esophageal Cancer

Tara R. Semenkovich, MD, MPHS; Jessica L. Hudson, MD, MPHS; Melanie Subramanian, MD; Daniel K. Mullady, MD; Bryan F. Meyers, MD, MPH; Varun Puri, MD, MSCI; Benjamin D. Kozower, MD, MPHY

Disclosures

Annals of Surgery. 2019;270(3):434-443. 

In This Article

Results

Overall T1N0 Cohort Treatment Trends

From 2004 to 2014, 12,383 patients with clinical T1N0M0 esophageal cancer met criteria for analysis: 2957 (23.9%) received endoscopic therapy; 3850 (31.1%) underwent esophagectomy; 3103 (25.1%) received chemotherapy, radiation, or both; and 2473 (20.0%) received no treatment (Figure 1). During the 11-year period, utilization of endoscopic therapy rapidly increased from 12.7% to 33.6% (P < 0.001), whereas the proportions receiving chemoradiation and esophagectomy decreased (Figure 2, Supplementary Table 1, http://links.lww.com/SLA/B697). Of the patients receiving endoscopic therapy, the percentage of patients receiving local tumor excision increased from 61.3% to 94.0% and the percentage receiving local tumor destruction decreased from 38.7% to 6.0% during the years of the study (P < 0.001, Supplementary Figure 1, http://links.lww.com/SLA/B697). Chemoradiation usage decreased from 39.8% to 20.6% (P < 0.001) and esophagectomy remained stable between 32% and 34% throughout most of the time period before decreasing to 25.1% in the last several years of the study (P < 0.001). The percentage of patients receiving no treatment remained stable at approximately 20% throughout the entire period of the study (P = 0.7). For the 2473 patients receiving no treatment, surgery, chemotherapy, and radiation were specifically documented as not recommended in 84% (n = 2083), 81% (n = 1993), and 83% (n = 2060), respectively. Surgery, chemotherapy, and radiation were recommended in 12% (n = 290), 17% (n = 419), and 12% (n = 298), respectively, and it was unknown whether or not treatments were recommended for the remainder of the patients. For those who did not receive recommended treatment, patient or family refusal was documented as the reason for 42% (123/290) for surgery, 55% (231/419) for chemotherapy, and 67% (199/298) for radiation. These results remained consistent when only the subset of patient with a Charlson Deyo Score of 0 who received no treatment was examined.

Figure 1.

Patient selection diagram.

Figure 2.

Trends in treatment modality usage for clinical T1N0 esophageal cancer.

Of the patients undergoing esophagectomy with pathologic staging data available, clinical staging was accurate 70% of the time. Interestingly, staging accuracy did not improve over the years of the study (P = 0.11). Of the entire esophagectomy cohort, 15.1% had a higher pathologic T stage documented, 13.5% had nodal metastases, and 0.5% had metastases on pathologic examination. Looking specifically at the subgroup from 2010 to 2014 wherein detailed clinical stage information was available, 65% of the T1aN0 patients and 58% of the T1bN0 patients were staged accurately. Of the T1a patients, 20.2% had a higher pathologic T stage and 8.7% had nodal metastases. Of the T1b patients, 12.2% had a higher pathologic T stage and 14.0% had nodal metastases (Supplementary Table 2, http://links.lww.com/SLA/B697).

Patient Characteristics and Treatment Modalities

There were numerous differences in baseline characteristics for patients who received the 4 different treatment modalities (Table 1). Esophagectomy patients were younger (mean 64.0 years); more likely to be male, white, and have private insurance; and less likely to have a low income, low education status, and be from highly populated urban areas (all P < 0.001). Patients treated with either esophagectomy or endoscopy were more likely to have adenocarcinoma histology (esophagectomy: 83.5%, endoscopic treatment: 84.4%, P < 0.001). Patients treated endoscopically shared many of the same demographic features as esophagectomy patients, but were also much more likely to be treated at an academic center (70.1%, P < 0.001). On multivariable analysis, factors independently associated with receipt of endoscopic treatment versus esophagectomy included: older age, treatment at an academic center, increased comorbidity (Charlson Deyo Score of ≥2), later year of diagnosis, smaller tumor size, and grade 1 or X disease (all P < 0.001, Table 2).

Survival Analysis

Kaplan Meier analysis (Figure 3A, entire cohort) showed unadjusted median survival was significantly longer for patients undergoing resection: esophagectomy, 98.6 months [95% confidence interval (CI), 93.5–106.8], local endoscopic therapy, 77.7 months (95% CI, 71.8–87.2), chemoradiation, 17.3 months (95% CI, 16.2–18.3), no treatment, 8.2 months (95% CI, 7.4–9.3); P < 0.001. Esophagectomy conferred a slightly increased upfront mortality risk compared to endoscopic treatment, but had better long-term outcome in the overall cohort with separation of the survival curves after 5 years. Perioperative mortality within 30 days was 3.2% for the esophagectomy cohort, and did not change significantly over time (P = 0.9). Cox proportional hazards modeling of long-term survival showed that esophagectomy had a 15% decreased risk of mortality [hazard ratio (HR) 0.85; 95% CI, 0.75–0.96) compared to endoscopic therapy, whereas chemoradiation had an 80% increased risk of mortality (HR: 1.79; 95% CI, 1.56–2.04), adjusting for age, race, insurance status, income, treatment center type, Charlson Deyo score, tumor size, histology, and grade (Table 3).

Figure 3.

Overall survival of clinical T1N0 esophageal cancer patients by treatment group. (A) Entire cohort, (B) T1a subgroup, (C) T1b subgroup.

T1a and T1b Treatment Trends and Characteristics

From 2010 to 2014, 3595 patients had detailed data on tumor stage: 2449 (68.1%) were T1a and 1146 (31.9%) were T1b. Over 5 years, the use of endoscopic treatment for T1a disease rose significantly from 42.7% to 50.6% (P = 0.002), whereas esophagectomies decreased from 21.7% to 12.8%, (P < 0.001). No significant changes occurred in the use of chemoradiation or no treatment (both P = 0.6). For T1b disease, the rise in endoscopic treatment from 16.9% to 25.1% (P = 0.03) was accompanied by nonstatistically significant decreases in no treatment (12.3%–9.2%, P= 0.3) and chemoradiation (19.2%–15.9%, P = 0.3), whereas the rate of esophagectomies remained around 50% (P = 0.7, Table 4).

In the T1a subgroup, 1123 (45.9%) patients received endoscopic treatment, 428 (17.5%) underwent esophagectomy, 365 (14.9%) received chemoradiation, and 533 (21.8%) had no treatment. Variables independently associated with T1a patients receiving endoscopic treatment versus esophagectomy included: increasing age, Charlson Deyo Score ≥2, later year of diagnosis, smaller tumor size, and grade (all P < 0.001, Supplementary Table 3, http://links.lww.com/SLA/B697). In the T1b subgroup, 259 (22.6%) patients received endoscopic treatment, 588 (51.3%) underwent esophagectomy, 193 (16.8%) received chemoradiation, and 106 (9.3%) received no treatment. Variables independently associated with T1b patients receiving endoscopic treatment versus esophagectomy included: increasing age, smaller tumor size, and grade (all P < 0.001, Supplementary Table 3, http://links.lww.com/SLA/B697).

For T1a patients, Kaplan-Meier analysis showed no significant difference in survival between patients receiving endoscopic treatment versus esophagectomy (P = 0.8, Figure 3B, T1a Subgroup), whereas both endoscopic treatment and esophagectomy conferred significantly better survival than both chemoradiation and no treatment (P < 0.001). Cox proportional hazards modeling showed that esophagectomy had a comparable mortality risk to endoscopic therapy (HR: 0.95; 95% CI, 0.66–1.39), adjusting for age, Charlson Deyo Score, tumor size, and grade. Chemoradiation (HR: 2.60; 95% CI, 1.81–3.75) and no treatment (HR: 5.63; 95% CI, 4.02–7.88) conferred a substantially higher risk of mortality than endoscopic therapy (Supplementary Table 4, http://links.lww.com/SLA/B697).

For T1b patients, Kaplan-Meier analysis showed there was a trend toward better survival for patients receiving esophagectomy that did not reach statistical significance (P = 0.07, Figure 3C, T1b Subgroup), whereas both endoscopic treatment and esophagectomy again conferred significantly better survival than both chemoradiation and no treatment (P < 0.001). For T1b disease, esophagectomy patients had a more favorable mortality risk (HR: 0.76; 95% CI, 0.52–1.11) compared to those receiving endoscopic therapy, and no treatment (HR: 3.27; 95% CI, 1.94–5.50) patients fared worse, adjusting for age, insurance status, tumor size, and grade (Supplementary Table 4, http://links.lww.com/SLA/B697).

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