Nomogram to Predict Distant Metastasis Probability for Pathological Complete Response Rectal Cancer Patients After Neoadjuvant Chemoradiotherapy

Background: After achieving a clinical complete response through neoadjuvant chemoradiotherapy, a nonoperative management approach for rectal cancer patients known as Wait and Watch (W&W) has gained increasing attention. However, the W&W strategy has been related to higher local recurrence and ambiguous long-term survival. This meta-analysis compared key prognosis indicators between W&W and surgical treatment in an effort to clarify some long-standing points of confusion. Methods: Pubmed, Web of Science, EMbase, Cochrane Library were searched for relevant researches comparing W&W with surgery treatment, with a time criteria set from 1 January 2002 to 4 July 2019. Endpoints were 2-year local regrowth/recurrence, 2-year distant metastasis (plus local regrowth/recurrence), 3- and 5-year disease-free survival (DFS), and overall survival (OS). Results: In total, nine studies with 801 patients were enrolled, of which 348 were managed by W&W and 453 by surgery. Surgery patients were further divided into a pathological complete response (pCR) group (all included patients achieved pCR) and a surgery group (consisting of both pCR and non-pCR patients without deliberate screening). Compared with the surgery group, W&W patients have higher 3- and 5-year OS, and are not inferior on 2-year local regrowth (LR), 2-year distant metastasis (DM)/DM+LR, and 3- and 5-year DFS. On the other hand, compared with the pCR group, the W&W group is inferior on 2-year LR, 3- and 5-year DFS, and 5-year OS, and not inferior on 2-year DM/DM+LR and 3-year OS. Conclusions: In contrast with patients undergoing surgical treatment, the W&W group has higher 3- and 5-year OS, and is not inferior on other major prognostic indicators, which, however, is based on the fact that the tumor stage in the W&W group is generally earlier. Versus surgically treated patients who acquired pCR, W&W group is inferior on all major prognostic indicators except 2-year DM/DM+LR and 3-year OS. Additionally, by comparison of cCR definitions across different studies, we conclude that implementation of the strictest cCR criteria is critical for W&W patients to acquire maximum prognostic benefit.

Download Full-text

Is Adjuvant Chemotherapy Necessary for Locally Advanced Rectal Cancer Patients with Pathological Complete Response after Neoadjuvant Chemoradiotherapy and Radical Surgery?

European Journal of Surgical Oncology ◽

10.1016/j.ejso.2019.11.196 ◽

2020 ◽

Vol 46 (2) ◽

pp. e84

Author(s):

K.G. Dharma Kumar ◽

Sanjeev Kumar ◽

Sajit Sasi ◽

Avanish Saklani ◽

Vikas Ostwal ◽

...

Keyword(s):

Rectal Cancer ◽

Adjuvant Chemotherapy ◽

Cancer Patients ◽

Pathological Complete Response ◽

Radical Surgery ◽

Locally Advanced ◽

Neoadjuvant Chemoradiotherapy ◽

Complete Response ◽

Advanced Rectal Cancer ◽

Locally Advanced Rectal Cancer

Download Full-text

A panel of tumor biomarkers to predict complete pathological response to neo-adjuvant treatment in Locally Advanced Rectal Cancer

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504021x16232280278813 ◽

2021 ◽

Author(s):

Chiara Dalle Fratte ◽

Silvia Mezzalira ◽

Jerry Polesel ◽

Elena De Mattia ◽

Antonio Palumbo ◽

...

Keyword(s):

Rectal Cancer ◽

Cancer Patients ◽

Pathological Complete Response ◽

Locally Advanced ◽

Neoadjuvant Chemoradiotherapy ◽

Complete Response ◽

Advanced Rectal Cancer ◽

Locally Advanced Rectal Cancer ◽

Classification And Regression Tree ◽

Pre Treatment

Pathological complete response after neoadjuvant chemoradiotherapy in locally advanced rectal cancer patients is related to a favorable prognosis. The identification of early biomarkers predictive of pathological complete response would help to optimize the multimodality management of the patients. A panel of 11 tumor-related proteins was investigated by immunohistochemistry in the pre-treatment biopsy of a group of locally advanced rectal cancer patients, to identify early biomarkers of pathological complete response to neoadjuvant chemoradiotherapy. A mono-institutional retrospective cohort of 95 stage II/III locally advanced rectal cancer patients treated with neoadjuvant chemoradiotherapy and surgery was selected based on clinical-pathological characteristics and the availability of a pre-treatment tumor biopsy. Eleven selected protein markers expression (MLH1, GLUT1, Ki67, CA-IX, CXCR4, COX2, CXCL12, HIF1, VEGF, CD44, and RAD51) was investigated. The optimal cut-off values were calculated by receiver operating characteristic curve analysis. Classification and regression tree analysis was performed to investigate the biomarkers interaction. Patients presenting either Ki67, HIF1 or RAD51 below the cut-off value, or CXCR4 or COX2 above the cut-off value, were more likely to get a pathological complete response. Classification and regression tree analysis identified three groups of patients resulting from the combination of Ki67 and CXCR4 expression. Patients with high expression of Ki67 had the lowest chance to get a pathological complete response (18%), as compared to patients with low expression of both Ki67 and CXCR4 (29%), and patients with low Ki67 and high CXCR4 expression (70%). Pre-treatment Ki67, CXCR4, COX2, HIF1, RAD51 in tumor biopsies are associated with pathological complete response after neoadjuvant chemoradiotherapy in locally advanced rectal cancer. A combined evaluation of Ki67 and CXCR4 would increase their predictive potential. If validated, their optimal cut-off could be used to select patients for a tailored multi-modality treatment.

Download Full-text

CEA, EpCAM, αvβ6 and uPAR Expression in Rectal Cancer Patients with a Pathological Complete Response after Neoadjuvant Therapy

Diagnostics ◽

10.3390/diagnostics11030516 ◽

2021 ◽

Vol 11 (3) ◽

pp. 516

Author(s):

Daan Linders ◽

Marion Deken ◽

Maxime van der Valk ◽

Willemieke Tummers ◽

Shadhvi Bhairosingh ◽

...

Keyword(s):

Rectal Cancer ◽

Neoadjuvant Therapy ◽

Cancer Patients ◽

Pathological Complete Response ◽

Neoadjuvant Treatment ◽

Complete Response ◽

Response Evaluation ◽

Tumor Bed ◽

Upar Expression ◽

Diagnostic Biopsy

Rectal cancer patients with a complete response after neoadjuvant therapy can be monitored with a watch-and-wait strategy. However, regrowth rates indicate that identification of patients with a pathological complete response (pCR) remains challenging. Targeted near-infrared fluorescence endoscopy is a potential tool to improve response evaluation. Promising tumor targets include carcinoembryonic antigen (CEA), epithelial cell adhesion molecule (EpCAM), integrin αvβ6, and urokinase-type plasminogen activator receptor (uPAR). To investigate the applicability of these targets, we analyzed protein expression by immunohistochemistry and quantified these by a total immunostaining score (TIS) in tissue of rectal cancer patients with a pCR. CEA, EpCAM, αvβ6, and uPAR expression in the diagnostic biopsy was high (TIS > 6) in, respectively, 100%, 100%, 33%, and 46% of cases. CEA and EpCAM expressions were significantly higher in the diagnostic biopsy compared with the corresponding tumor bed (p < 0.01). CEA, EpCAM, αvβ6, and uPAR expressions were low (TIS < 6) in the tumor bed in, respectively, 93%, 95%, 85%, and 62.5% of cases. Immunohistochemical evaluation shows that CEA and EpCAM could be suitable targets for response evaluation after neoadjuvant treatment, since expression of these targets in the primary tumor bed is low compared with the diagnostic biopsy and adjacent pre-existent rectal mucosa in more than 90% of patients with a pCR.

Download Full-text