Lack of Pathological Response of Rectal Cancer to Neoadjuvant Chemoradiotherapy is Associated with Poorer Long-Term Oncological Outcomes

Abstract

Keywords:Tumor regression score neoadjuvant response rectal cancer A B S T R A C TPurpose: Tumor regression scores are used to evaluate local response to preoperative treatment. Complete pathological response (tumor regression score=0) is associated with excellent prognosis. In this study we evaluated the prevalence and impact of poor-to-no pathological response to neoadjuvant treatment (tumor regression score=3), based on a recently revised grading system on long term oncologic outcomes among rectal cancer patients. Methods: This retrospective study included rectal cancer patients who received . neoadjuvant chemoradiotherapy and surgical resection at our medical center. Pathological specimens were ren evaluated and graded (grades 0-3) based on the revised tumor regression scores. Disease free survival and cancer specific survival rates were documented and matched with the patients' tumor regression scores. Results: Initially 78 patients were included. 6 patients were later excluded from the long-term follow up since they developed disease progression during neoadjuvant treatment. Among the other 72 patients, 38 (52.8%) were classified as tumor regression score=3 (no response) and 34 (47.2%) tumor regression score=0-2 (any level of response). Conversion from laparoscopy to open surgery was higher in the tumor regression score=3 group (21% vs. 2.9%, p=0.02). Follow-up ranged from 5 months to 12 years. Nine (12.5%) patients experienced disease recurrence, 8 with tumor regression score=3. Most recurrences were metastases to liver and lungs. Disease free survival was lower in tumor regression score=3 patients as compared to tumor regression score=0-2.Conclusions: Non-responders to neoadjuvant therapy are at higher risk for disease recurrence, conversion to open surgery and disease-related mortality. Systemic recurrence of tumor regression score=3 tumors suggests an aggressive biology of these tumors. Further studies are needed to characterize tumors that are less likely to respond to radiotherapy and to personalize preoperative treatment decisions .

Not All Patients With Locally Advanced Rectal Cancer Benefit From Neoadjuvant Therapy

“…2,[4][5][6][7][8][9] Conversely, non-responders experience higher rates of recurrence and diseaserelated mortality. 10 It is unclear why certain patients experience non-response, as this subset of patients is less frequently studied. Furthermore, the possibility of harm derived from tumor growth or spread during NA-CMT has not been fully explored.…”

“…10 Previous studies focused on the prognostic value of tumor regression grade (TRG) in predicting disease-free survival (DFS), long term outcomes and overall survival (OS), but no studies to date have focused on identifying patient characteristics of progressors. 10 Moreover, the majority of studies compare pathologic complete response (pCR) with non-pCR, grouping partial response and no response together. 7 A recent meta-analysis focusing on each response group sought to determine the correlation of different levels of tumor response with long-term survival outcomes, and similar to our findings, they found a negative association between non-responders and OS.…”

“…In this study, 52 patients (33.3%) were categorized as non-responders, which is consistent with current literature. 10 Previous studies focused on the prognostic value of tumor regression grade (TRG) in predicting disease-free survival (DFS), long term outcomes and overall survival (OS), but no studies to date have focused on identifying patient characteristics of progressors. 10 Moreover, the majority of studies compare pathologic complete response (pCR) with non-pCR, grouping partial response and no response together.…”

“…In this study, 52 patients (33.3%) were categorized as non-responders, which is consistent with current literature. 10…”