Trends in the Characteristics, Treatment, and Outcomes of Rectal Adenocarcinoma in the US From 2004 to 2019

Abstract

ImportanceRectal cancer management has significantly evolved over the last 2 decades.ObjectiveThis study aimed to evaluate trends in the characteristics, treatment, and outcomes of rectal adenocarcinoma across 16 years.Design, Setting, and ParticipantsThis retrospective, observational case series study used data from the National Cancer Database (NCDB) to evaluate patients diagnosed with rectal adenocarcinoma from 2004 through 2019. Data analysis was performed from March to May 2022.ExposuresTrends in the treatment and outcomes of rectal adenocarcinoma in the US between 2004 and 2019 were explored. This period was subdivided into 4 equal periods: 2004-2007, 2008-2011, 2012-2015, and 2016-2019.Main Outcomes and MeasuresPatient and tumor characteristics, treatments, short-term outcomes, and overall survival.ResultsA total of 318 548 patients diagnosed with rectal adenocarcinoma were included in the analysis, 191 369 (60.1%) of whom were males and 127 179 (39.9%%) were females. The mean (SD) age of the patients was 63.5 (13.4) years, and 46 824 patients (14.8%) were younger than 50 years. Among the patients, 10 859 (3.4%) were of Asian race and ethnicity, 28 464 (8.9%) were Black, and 271 236 (85.1%) were White. The percentage of patients younger than 50 years who were diagnosed with rectal cancer increased by 1.5%, from 13.9% in period 1 to 15.4% in period 4. Patients in the last period (2016-2019) presented more often with stages III (36.2% vs 30.2% vs 25.0% vs 23.4%; P < .001) and IV (21.5% vs 19.3% vs 18.1% vs 18.6%; P < .001) disease compared with those in the remaining 3 periods. The use of chemotherapy (36.8% vs 48.1% vs 49.1% vs 47.0%; P < .001) and immunotherapy (0.4% vs 0.2% vs 3.5% vs 6.5%; P < .001) significantly increased across the 4 periods. Although neoadjuvant radiotherapy was used more often across the periods studied (28.6% in period 1 to 34.3% in period 4), the use of adjuvant radiotherapy was reduced by half (12.9% to 6.0%). The median (IQR) time from diagnosis to definitive surgery increased from 95 (15-126) days in period 1 to 128 (47-158) days in period 4. The rate of use of open surgery decreased by half (60.1% in period 2 to 30.1% in period 4), and the use of robotic surgery significantly increased (5.2% in period 2 to 28.4% in period 4). The conversion rate was significantly reduced (11.2% in period 2 to 7.3% in period 4) and the median (IQR) hospital stay decreased by 2 days, from 6 (3-9) days to 4 (2-7) days. The median (IQR) overall survival significantly increased across the periods (from 83.1 months [95% CI, 81.8-84.6 months] in period 1 to 92.1 months [95% CI, 90.2-93.6 months] in period 3; P < .001).Conclusion and RelevanceThe findings of this case series study suggest a treatment trend of increased use of chemotherapy, immunotherapy, sphincter-saving surgery, and minimally invasive surgery. In addition, the time between diagnosis and definitive surgery increased by a median of 33 days. This treatment trend was associated with a significant improvement in the overall survival, reduction in the conversion rate by 3.9%, and a 2-day shorter hospital stay. These findings have major clinical relevance to the management of rectal cancer. The improvements seen in short-term outcomes and survival of patients diagnosed with rectal cancer can probably be attributed to the treatment trends observed. Continued improvement in outcomes warrant further updates in treatments.

Reporting of Immunotherapy and Biologic Therapy in the National Cancer Database—Reply

“…In Reply We thank Dr Iorgulescu for his insightful comments on our case series study on the treatment and outcome trends of rectal cancer in the US over 16 years . After carefully reading the comments, we agree with Dr Iorgulescu that there is some uncertainty in the term used for describing immunotherapy in the National Cancer Database.…”

“…Dr Iorgulescu proposed that the increase in patients who received immunotherapy was due to the recategorization of patients who received monoclonal antibodies into the immunotherapy column instead of the chemotherapy column as was done before January 2013. While his thoughtful observation may elucidate the spiking increase in the use of immunotherapy in 2013 as depicted in Figure 1, it would not explain the continued trend of increased use of immunotherapy beyond 2013. As Figure 1 shows, the use of immunotherapy continued to increase from 2013 and onward, reaching 7.1% in 2019 compared with 3.4% in 2013, although the recategorization of patients who had monoclonal antibodies was consistent from 2013 to 2019.…”

Reporting of Immunotherapy and Biologic Therapy in the National Cancer Database

“…To the Editor I read with great interest the case series study by Emile et al, in which the authors use the American College of Surgeons’ National Cancer Database (NCDB) to examine the practice patterns for patients with rectal adenocarcinoma in the US. The NCDB and related national cancer registry programs (eg, the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program [SEER]) have become invaluable resources for investigating cancer care delivery and outcomes; however, the unique design of their variables requires close consideration.…”

“…In Figure 1, the authors report a rise in “immunotherapy” use among patients with rectal adenocarcinoma from less than 1% in 2004 to 2012 to 3% to 4% in 2013 to 2014 and up to 7% in 2019—described as “an increase of almost 20-fold in the use of immunotherapy.” To help interpret the authors’ findings, there are several important nuances to the “immunotherapy” variable’s design to consider, which pertain to both the NCDB and other US cancer registry programs. As described in the NCDB’s Participant User File Data Dictionary, the NCDB uses the SEER*Rx instructions for coding immunotherapeutic, chemotherapeutic, and hormonal agents.…”

“…Taken together, the authors’ Figure 1 findings likely reflect the changes in how the NCDB was categorizing and reporting first-line bevacizumab and cetuximab biologic therapies for patients with rectal adenocarcinoma, as opposed to an increase in the use of immunotherapy such as immune checkpoint inhibitors—which were not approved by the US Food and Drug Administration for the treatment of patients with microsatellite instability–high/mismatch repair deficient colorectal cancer until 2017 for second-line and 2020 for first-line settings.…”