Discordance in TME Specimen Grading in a Prospective Phase II Multicenter Rectal Cancer Trial

Marchegiani et al suggested that worse total mesorectal excision (TME) grade in the experimental arm in the RAPIDO trial may have been central to worse local recurrence rates (LRR). 1,2 However, we believe that TME grade may not be the sole justification here.First, grading of the mesorectum may exhibit significant discordance between examiners. 3 Also, the actual differences in the quality of the mesorectum between arms in RAPIDO were marginal, although statistically significant.Breaches in the mesorectum in the proximity of the primary tumor are believed to be associated with higher LRR due to direct spillage of cancer cells (R1 resections). Instead, breaches away from the primary tumor (R0) are considered to be less worrisome. The rates of R1 resections were not different between arms of the RAPIDO study, and LRR was still worse when the analysis was restricted to R0. 1 It has been suggested that the pattern of "fragmented" tumor response could have contributed to the increased LRR through spillage of tumor-scattered cells in the proximity of mesorectal breaches. 4 Still, pathologists would have been able to spot tumor scatter in the proximity of the resection margins and clearly indicated an R1 resection. 5 The absence of more R1 specimens and the significant differences sustained among R0 resections makes it difficult to understand that TME grading here was solely responsible for worse LRR.Although the exact reasons are controversial, the recipe of RAPIDO remains on hold for the purpose of optimal local disease control in rectal cancer.

mentioning

confidence: 94%

RAPIDO: Rest in Peace

Vailati,

Cerdán-Santacruz,

Julião

et al. 2023

Quality Still Counts

Keller,

Reif de Paula,

Marks

2023

total mesorectal excision (TME) is a dissection in the anatomic "holy plane, " where the rectal tumor is removed en bloc with the surrounding mesorectum containing the blood vessels, lymph nodes, and potential routes for cancer spread. Heald et al popularized TME as the optimal technique to ensure complete tumor resection while minimizing the risk of local recurrence and improving long-term outcomes. 1 Quirk et al then assigned a grading system to describe the completeness of the TME plane as a metric for the quality of the surgery performed. 2 At the time it was described, it was common to have a "V"-shaped specimen coned in on the rectal tube and local recurrence rates of 30% to 40%. There was widespread adoption of TME specimen completeness because innumerable studies with the highest level of evidence validated the independent predictive value of the TME grade for significantly reducing local recurrence. [3][4][5] Recently, the importance of the quality of TME excision on the patient's prognosis has been brought into question. Garoufalia et al 6 suggested that the grade of the TME may not be a critical factor impacting recurrence in rectal cancer surgery. This notion is simultaneously a potentially dangerous shift from the standard in rectal cancer care and a stimulating area for future research.Adjuvant chemotherapy cannot correct for an imprecise dissection. 7 The importance of the TME grade is further demonstrated as it serves as a key performance metric in the American College of Surgeons Commission on Cancer's National Accreditation Program for Rectal Cancer. Suggesting a shift away from this standard of care could potentially be dangerous.

Reply

Garoufalia,

Wexner

2023

Before reading this letter, 1 we had not considered our surgery as "bad, " but rather our pathology as "excellent. " We are fortunate that our lead pathologist, Dr Mariana Berho, is internationally recognized as a leader in colorectal pathology and was the reference pathologist for the creation of the total mesorectal excision (TME) standards for the National Accreditation Program for Rectal Cancer (NAPRC). 2-5 While many, if not most, studies in the literature cite rates of complete mesorectal excision close to 100%, 6-8 our rates may be lower because of the scrutiny through which our specimens are thankfully routinely subjected.Our findings are consistent with the transanal TME study in which 100 consecutive TME specimens were assessed on a local level and then by 1 of 2 expert pathologists. 9 The 90% rate of complete or near complete TME was almost identical to that of our "bad" surgery of 87.1%. The transanal TME study found that the site pathologist agreed with the first expert reviewer in only 54% of cases, with minor disagreement in 32% of cases and major disagreement in 14% of cases.During central expert pathologist review, downgrading occurred from complete to near complete or incomplete in 13.8% of specimens originally graded by the individual site pathologists as complete. Thus, either "bad" surgery is more prevalent than previously thought or excellent pathology is less prevalent than desirable; we are not alone in our findings. [10][11][12] We are optimistic that the NAPRC will result in more pathologists being more diligent in their TME specimen reviews. Early evidence from the NAPRC indicates that outcomes are already improving.