Clinical outcomes following definitive treatment of young-onset, locally advanced rectal cancer: A single institution experience.
Authors: Taku Nicolette , You Y. Nancy , Ludmir Ethan B. , Smith Grace L. , Rodriguez-Bigas Miguel A. , Chang George J. , Skibber John Michael , Koong Albert C. , Minsky Bruce D. , Holliday Emma Brey , Koay Eugene Jon , Dasari Arvind , Taniguchi Cullen M. , Bednarski Brian K. , Morris Van K. , Overman Michael J. , Kopetz Scott , Raghav Kanwal Pratap Singh , Das Prajnan 
Published: June 2021

e15601

Background: We evaluated demographic, treatment, and survival outcomes of adults age 18 to 49 years treated at our institution with long course chemoradiotherapy (CRT) followed by total mesorectal excision (TME) for locally advanced rectal cancer. Additionally, we compared outcomes between those age < 45 vs. > 45 years. Methods: The records of 219 patients diagnosed with non-metastatic, clinical T3, T4, or node positive rectal adenocarcinoma and treated between April 2000 and November 2017 were reviewed for age, sex, and presenting symptoms; clinical stage and microsatellite stable (MSS)/DNA mismatch repair (MMR) proficiency status; treatments delivered and sequence; pathologic response to pre-operative therapies; and the development of locoregional recurrence (LRR), distant metastasis (DM), and secondary pelvic malignancy. The Kaplan-Meier method and Log-Rank test were used to calculate and compare disease-free survival (DFS) and overall survival (OS) rates from the date of TME. Results: The median age at diagnosis was 44 years (range 19-49) and there was no sex predominance. Rectal bleeding was the most common presenting symptom (91%), with a median time to diagnosis of 5 months. Clinical tumor/nodal categories were T1-2 in 4%, T3 in 87%, T4 in 7%, N0 in 17%, and N1–2 in 80% of patients. MSS/MMR proficient disease was identified in 95% of tumors with status reported (n = 170). CRT followed by TME and post-operative chemotherapy was the most frequent treatment sequence (n = 196), with capecitabine (n = 176) and FOLFOX (n = 115) as the predominant concurrent and post-operative chemotherapies, respectively. Pathologic complete response at both primary and nodal sites occurred in 15% of all cases and 16% of MSS/MMR proficient cases. There was no difference in sex, tumor category, nodal category, MSS/MMR proficiency status, or pathologic complete response, by age ( < 45 years [n = 111] vs. > 45 years [n = 108]). At a median DFS follow-up time of 5.0 years, there were 11 LRR, 40 DM (including 11 DM detected prior to/at time of TME), and 1 synchronous presentation of LRR and DM. The 5-year rate of DFS was 70.4% for age < 45 years and 85.3% for age > 45 years ( P = 0.02). At an OS median follow-up time of 7.5 years, there were 38 deaths. The 5-year rate of OS was 87.7% for age < 45 years and 94.4% for age > 45 years ( P = 0.126). Two patients developed non-rectal pelvic malignancies. Conclusions: The outcomes reported here from one of the largest single-institution series for young-onset, locally advanced rectal cancer could serve as a benchmark to evaluate newer treatment approaches. Rectal bleeding was the leading presenting symptom, with approximately half-year delay from development of symptoms to diagnosis. Most tumors were MSS/MMR proficient. At 5 years’ follow-up time, the DFS rate was lower for patients age < 45 years when compared to those > 45 years. Secondary pelvic malignancies were a rare occurrence.