2022 NCCN Guidelines Update for Esophageal Cancer: Comprehensive revision of the preferred first-line treatment for patients without HER2 overexpression

The 2022 version of the NCCN Guidelines for Esophageal Cancer and Esophagogastric Junction (EGJ) Cancer has been updated to the V2 version.
Compared with the 2022.
V1 version, the V2 version only partially updated the discussion, and did not revise the treatment route and medication recommendations
.

Compared with the 2021.
V4 version, the 2022.
V1 version has major changes.
The editor of Yimaitong will organize the update points as follows and share them with readers
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ESOPH-1——Examination, staging and histological classification >>>>Inspection and revision Article 10, from "if metastatic disease occurs or is suspected to occur, use PCR method to detect MSI/IHC method to detect MMR and PD-L1 detection" Amended to "If metastatic disease occurs or is suspected, perform MSI and PD-L1 testing"; Amend Article 12 to "Consider next-generation sequencing (NGS) if sufficient tissue is available after completion of the above testing" As "Next-generation sequencing (NGS) may be considered"; add a new item, "If anemia is suspected, see NCCN Guidelines for Hematopoietic Growth Factors"
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ESOPH-3——Squamous cell carcinoma suitable for surgery >>>>pTis patients revised the order of endoscopic treatment, "ER, followed by ablation" moved from the last position to the second position
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"ESOPH-8 - Squamous cell carcinoma not suitable for surgery", "ESOPH-12 - Adenocarcinoma suitable for surgery" and "ESOPH-17 - Adenocarcinoma not suitable for surgery" were also updated with this revision
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ESOPH-10——Palliative treatment of squamous cell carcinoma >>>>KPS score ≥ 60% or ECOG score ≤ 2" If metastatic squamous cell carcinoma is suspected, use PCR method to detect MSI/IHC method to detect MMR and PD-L1 detection ( If not previously performed)" is revised to "If metastatic squamous cell carcinoma is suspected, perform MSI and PD-L1 testing (if not performed previously)"; "If sufficient tissue is available after the above tests are completed, NGS may be considered" revised to read "Consider NGS testing by effective testing methods"
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"ESOPH-19 - Palliative care for adenocarcinoma" was also updated with these two revisions
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 ESOPH-15——Postoperative management of adenocarcinoma patients without preoperative chemoradiotherapy or chemotherapy >>>>R0 resection For lymph node-negative pT3 and pT4a patients, a new postoperative treatment option "chemotherapy" was added; for lymph node-negative pT3 and pT4a patients For patients with positive (any T), a new postoperative treatment option "monitoring" was added
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 ESOPH-B 3/6 - Principles of Pathological Evaluation and Biomarker Detection >>>>Evaluation of HER2 Overexpression or Amplification in Esophageal and EGJ Cancers "It should be noted that NGS has certain inherent limitations, so Where possible, gold standard analysis (IHC/ISH) should be used first, and if sufficient tissue is available, additional NGS testing may be considered" revised to "IHC/ISH should be considered first, followed by NGS testing as appropriate
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For In patients with advanced/metastatic esophageal/EGJ adenocarcinoma, re-testing of biomarkers may be considered upon clinical or imaging progression
.
"
ESOPH-B 4/6 - Principles of Pathological Assessment and Biomarker Testing >>>> Microsatellite Instability (MSI) or Mismatch Repair (MMR) Testing "MMR or MSI testing may only be available in CLIA-approved assays laboratory” was revised to “Tests must only be performed in CLIA-approved laboratories”; Footnote 1, “Detect MSI by PCR” was revised to “Detect MSI by PCR/NGS”
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ESOPH-B 5/6 - Principles of Pathological Evaluation and Biomarker Detection >>>> Next Generation Sequencing (NGS) "Three targeted therapies" was revised to "Multiple targeted therapies", "Ramucirumab" was deleted, "HER2 positive" was revised to "HER2 overexpression", "PCR detection of MSI" was revised to "PCR/NGS detection of MSI", and "MMR mutation" was revised to "MMR deficiency"; "It should be noted that NGS has some Inherent limitations, therefore gold standard assays (IHC/FISH/targeted PCR) should be used first where possible and additional NGS testing may be considered if sufficient tissue is available" revised to "Should be considered first IHC/FISH/targeted PCR followed by NGS as appropriate”
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>>>>Liquid biopsy "Liquid biopsy is increasingly used in patients with advanced disease for whom clinical biopsy is not available for disease monitoring and management" revised to "Liquid biopsy is increasingly used in patients with advanced disease, especially those Patients who cannot undergo clinical biopsy for disease monitoring and management", "For patients with metastatic or advanced esophageal/EGJ cancer who cannot undergo conventional biopsy" is revised to "For patients with metastatic or advanced esophageal/EGJ cancer who cannot undergo conventional biopsy or monitoring of disease progression Patients with Advanced Esophageal/EGJ Cancer"
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ESOPH-D 1/2 - Principles of Genetic Risk Assessment >>>>
Further Risk Assessment Criteria for High-Risk Syndromes Added "The most effective strategy for identifying disease-causing genetic variants in a family is testing of close relatives with cancer .

If relatives are unwilling or unable to be tested, consider testing of unaffected relatives A detailed discussion
of
genetic counseling and testing can be found in the NCCN Guidelines for the Assessment of Genetic/Familial High Risk: Colorectal and the NCCN Guidelines for the Assessment of Genetic/Familial High Risk: Breast, Ovarian, and Pancreas
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ESOPH-F 1/17 - Article 4 of the Principles of Systemic Therapy, delete "the three-cytotoxic drug regimen should be reserved for healthy patients with good PS and opportunities for frequent toxicity assessment", and add "the use of the three-cytotoxic drug regimen should be reserved" to healthy patients with good PS and easy access to frequent toxicity assessments"
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ESOPH-F 3/17——First-line treatment of unresectable locally advanced, recurrent or metastatic disease >>>>First-line treatment-preferred regimen-non-HER2 overexpression The original regimen was revised to 5 regimens, namely "only Adenocarcinoma, fluoropyrimidines (5-FU or capecitabine), oxaliplatin and nivolumab (PD-L1 CPS ≥ 5 for category 1 evidence; PD-L1 CPS <5 for category 2B evidence) ” regimen, “fluoropyrimidines (5-FU or capecitabine), oxaliplatin combined with pembrolizumab (PD-L1 CPS ≥ 10 is category 2A evidence; PD-L1 CPS < 10 is category 2B evidence )" regimen, "fluoropyrimidines (5-FU or capecitabine), cisplatin combined with pembrolizumab (PD-L1 CPS ≥ 10 is type 1 evidence; PD-L1 CPS <10 is type 2B evidence) ", "Fluoropyrimidine (5-FU or capecitabine) combined with oxaliplatin" and "fluoropyrimidine (5-FU or capecitabine) combined with cisplatin"
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 ESOPH-F 4/17 - Second-line treatment of unresectable locally advanced, recurrent or metastatic disease >>>> Second-line or follow-up treatment - useful in some cases Added "Dostarlimab-gxly for MSI-H or dMMR Oncology”; new footnote k: “For patients with disease progression during or after prior therapy (excluding checkpoint inhibitors, such as PD-1 inhibitors, PD-L1 inhibitors, or CTLA4 inhibitors) and no satisfactory alternative treatment options Patients
.

Dostardolimab-gxly will not be suitable for patients who have previously used tumor immunotherapy
.
”
 ESOPH-F 5/17 - Principles of Systemic Treatment - Preoperative Radiotherapy and Chemotherapy >>>> Preoperative Radiotherapy and Chemotherapy - Other Recommended Programs The dosing cycle of the "irinotecan + cisplatin" regimen was changed to every 35 days as a cycle
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"ESOPH-F 7/17 - Principles of Systemic Therapy - Regimen and Dosing Schedules" was also updated with this revision
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 ESOPH-F 6/17 - Principles of Systemic Therapy - Perioperative Chemotherapy >>>> Perioperative Chemotherapy (for thymic adenocarcinoma or EGJ) - Administration of the preferred regimen "fluoropyrimidine + oxaliplatin" The protocol was changed from "3 cycles before surgery and 3 cycles after surgery" to "4 cycles before surgery and 4 cycles after surgery"
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 ESOPH-F 8/17 - Principles of Systemic Therapy - Postoperative Radiotherapy and Chemotherapy >>>> Postoperative Radiotherapy and Chemotherapy (for EGJ adenocarcinoma only) New in the dosing strategy of "5-FU" and "capecitabine" regimens Add the following statement: "For dosing cycles after chemoradiation, chemotherapy begins 1 month after chemoradiation
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"
 ESOPH-F 12/17—Principles of Systemic Therapy—First-Line Therapy >>>>First-Line Therapy—Other recommended regimens The dose of “paclitaxel with or without cisplatin or carboplatin” was revised to “paclitaxel 135–200 mg/m² IV, Day 1; Cisplatin 75 mg/m² IV on Day 21; every 21 days as a cycle" and "Paclitaxel 80 mg/m² IV on Day 1; once a week; every 28 days as a cycle"
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 ESOPH-F 14/17 - Principles of Systemic Therapy - Second-Line and Subsequent Treatments >>>> Second-Line and Subsequent Treatments - For Certain Conditions New regimen "Dostarlimab-gxly (MSI-H/dMMR tumors)" at a dose of " Dostarlimab-gxly 500 mg IV every 3 weeks for 4 times, followed by 1,000 mg IV every 6 weeks
.
”
 ESOPH-F 15-17 - Principles of Systemic Therapy - References Updated bibliography; added bibliography for Dostarlimab-gxly: Berton D, Banerjee SN, Curigliano G, et al.
Antitumor activity of dostarlimab in patients with mismatch repair deficient/ microsatellite instability–high tumors: A combined analysis of two cohorts in the GARNET study.
J Clin Oncol 2021;39(15_suppl):Abstract 2564.
ESOPH-G 1/5 - Principles of Radiation Therapy >>>> Simulation and Treatment Planning Section 1 revision to read: "CT simulation and conformal treatment planning should be used in conjunction with 3D conformal radiotherapy or intensity-modulated radiotherapy (IMRT)
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Proton beam therapy is appropriate when dose reduction to organs at risk (eg, heart, lungs) is required but 3D technology cannot The implemented clinical setting, ideally in a clinical trial or registry study
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" ESOPH-G 3/5 - Radiation Therapy Dose Limits >>>> Normal Tissue Tolerable Dose Limits This section has been extensively revised
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 ESOPH-G 4/5 - Recommended dose of radiation therapy >>>> RT ​​dose Preoperative RT was revised to: "41.
4-50.
4 Gy (1.
8-2.
0 Gy/day) (23-28 times in total)"; Postoperative RT was revised As: "45-50.
4 Gy (1.
8-2.
0 Gy/day) (25-28 total)"; Radical RT revised to: "50-50.
4 Gy (1.
8-2.
0 Gy/day) (25-28 total) "; delete "Higher doses may be appropriate for cervical esophageal tumors, especially when surgery is not planned"; delete footnote: "Published studies have reported radiation doses of 60-66 Gy (1.
8-2.
However, there is no randomized evidence to support any benefit or harm over the dose range of 50-50.
4 Gy (1.
8-2.
0 Gy/day)
.

References 1.
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines).
Esophageal and Esophagogastric Junction Cancers.
Version 4.
20212.
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines).
Esophageal and Esophagogastric Junction Cancers.
Version 1.
20223.
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines).
Esophageal and Esophagogastric Junction Cancers.
Version 2.
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