Dilemmas in the Clinical Management of pT1 Colorectal Cancer

Round 1

Reviewer 1 Report

Population screening for early cancer detection has become increasingly common and has led to many more cancer diagnoses. But while this increase in early diagnosis may create the impression that more people are developing cancer, in fact most are simply being diagnosed at an earlier stage:  many early cancers never advance to become more malignant and therefore would never have come to clinicians’ attention. But modern medicine demands that any cancerous anomaly be treated, often with a very aggressive intervention. Yet some consider this practice of identifying and aggressively treating early cancers to be “overtreatment,” an idea that may be deeply contested by some.

In recent years, clinicians and researchers are increasingly concerned about the consequences of over-treatment and this article is an excellent example. It offers a comprehensive review of some of the challenges in the clinical management of pT1 colorectal cancer (CRC). CRC is the third most common cancer in Western countries; pT1 describes CRC at its earliest stage.

The authors seek to show that population screening for pT1 colorectal cancer has produced a much higher incidence of cancer diagnoses and with these diagnoses increasing use of aggressive treatment (surgery). This has been the case even for low-risk people, although more conservative localized methods (endoscopy) are often highly effective. Surprising data are offered to show that given current diagnostic criteria, most colorectal patients are classified as high risk and subjected to surgical intervention when a more conservative approach may produce a very favorable outcome. Moreover, not only does surgery have a much higher risk of adverse events (AEs), including permanent disability and mortality, it may also be significantly more expensive than localized treatment, without certain benefit.

The article includes a valuable discussion as to why there is lack of consensus about clinical guidelines for pT1 surgery vs. endoscopic treatment. These include the fact that some criteria that lead a patient to be considered “high risk” may not necessarily affect that individual’s actual prognosis.

The authors also describe two new conservative localized approaches for treating early CRC: endoscopic inter-muscular dissection and endoscopic full-thickness resection, although they note that comparative studies between these new approaches and conventional endoscopic and surgical techniques regarding safety and effectiveness remain to be done.  

The writing is very clear, and the arguments coherent and persuasive.  The studies on which analyses are based are presented in a very comprehensible manner.

 

The authors are based in Spain and a sentence as to whether the Spanish standard of aggressive surgical intervention is like the standard in other Western countries would be helpful.

Author Response

Thank you very much for the summary and comment on our article. We have added a sentence about the estimated percentage of surgery for CRC pT1 in Europe and the tendency to increase surgery even in benign polyps

Reviewer 2 Report

In this paper the Authors analayzed the current histological risk criteria for pT1 CRC. In fact, they are suboptimal, as there is no consensus among clinical guidelines. It is a debated topic a new analysis are advocated. A comprehensive and extensive literature review of the NCBI database PubMed was also carried out. The article was well conducted and it is interesting in its fields. It is a well-structured paper, written in good English and the References are up dated. 

Minor issues:

There are several minimal invasive method for low grade CRC. Please consider the paper:

Del Genio G, Lucido FS, Gambardella C. TECHNICAL ASPECTS OF ENDOSCOPIC SUBMUCOSAL DISSECTION (ESD). FROM LATERAL TO LONGITUDINAL DISSECTION: A NEW APPROACH TO TREAT COLONIC TUMORS. Arq Gastroenterol. 2021 Oct-Dec;58(4):566-568. doi: 10.1590/S0004-2803.202100000-99. PMID: 34909866.

Author Response

Thank you for highlighting this point: we added information on this topic in the updated version

Reviewer 3 Report

In my opinion, the analyzed topic is interesting enough to attract the readers’ attention. This article analyzed the limitations of histological evaluation, the prognostic implications of histological risk status and treatment performed, the adverse effects associated with both endoscopic and surgical treatments and new advances in endoscopic treatment in pT1 colorectal cancer. I think that the abstract of this article is well organized and clear.
In my opinion, the discussion could be studied in depth and extended. Maybe, it could be useful the evaluation of the preoperative frailty and possible complications in these particular patients. In particular I suggest this article as an example:" The role of preoperative frailty assessment in patients affected by gynecological cancer: a narrative review Ottavia D’Oria, Tullio Golia D’Auge, Ermelinda Baiocco, Cristina Vincenzoni, Emanuela Mancini, Valentina Bruno, Benito Chiofalo, Rosanna Mancari, Riccardo Vizza, Giuseppe Cutillo, Andrea Giannini Vol. 34 (No. 2) 2022 June, 76-83 doi: 10.36129/jog.2022.34." Because of these reasons, the article should be revised and completed. Considered all these points, I think it could be of interest for the readers and, in my opinion, it deserves the priority to be published after revisions.

A moderate correction of English grammar should be performed

Author Response

Thank you for your comment which greatly enhances the value of our article. Multidisciplinary decision-making and individualized perioperative risk assessment are crucial for the clinical management of CRC pT1

Currie et al (Gastrointestinal Endosc 2016) evaluates the impact regarding quality-of-life benefits and risks of endoscopic resection compared with results after colectomy. They show that in elderly comorbid patients, endoscopic treatment for both low and high-risk T1 CRCs  is related with a better  quality of life than surgery.

Regarding specifically the preoperative risk for surgery of CRC pT1, Veermer et al 2019 (BJS Open 2019), study referenced in the review, evaluated risk factors for postoperative severe complications in patients undergoing surgery. The study identified several independent risk factors, including male sex, cardiac comorbidity, ASA grade III-IV, previous abdominal surgery, open approach, and subtotal colectomy, which were associated with an increased risk of severe complications. These findings were used to establish a risk stratification where men with ASA grade III-IV undergoing right or left colectomy faced the highest risk of severe complications.

We have included a sentence in our review highlighting these risk factors to enhance the preoperative evaluation process

In addition, and updated version of the manuscript has been reviewed by an English editor (see letter enclosed).

Round 2

Reviewer 3 Report

I appreciate the authors' comments but I suggest to try to evaluate the frailty of these patients in a more evident way in order to enhance the aim of the work and to highlight all the importan decisions that the surgical equipe has to make. ( The role of preoperative frailty assessment in patients affected by gynecological cancer: a narrative review Ottavia D’Oria, Tullio Golia D’Auge, Ermelinda Baiocco, Cristina Vincenzoni, Emanuela Mancini, Valentina Bruno, Benito Chiofalo, Rosanna Mancari, Riccardo Vizza, Giuseppe Cutillo, Andrea Giannini Vol. 34 (No. 2) 2022 June, 76-83 doi: 10.36129/jog.2022.34).

Author Response

Thank you once again for your contribution. Undoubtedly, preoperative risk assessment is one of the greatest challenges in the clinical management of pT1.

In our latest revision, we have expanded information upon the topic of preoperative risk assessment, highlighting the potential value of the score mentioned in the article you provided. Notably, this score has undergone validation in the context of colorectal surgery as well, further supporting its applicability.

Author Response File: Author Response.docx