International Recommendations on Postoperative Management for Potentially Resectable Locally Recurrent Nasopharyngeal Carcinoma

Locally recurrent nasopharyngeal carcinoma (NPC) presents substantial challenges in clinical management. Although postoperative re-irradiation (re-RT) has been acknowledged as a potential treatment option, standardized guidelines and consensus regarding the use of re-RT in this context are lacking. This article provides a comprehensive review and summary of international recommendations on postoperative management for potentially resectable locally recurrent NPC, with a special focus on postoperative re-RT. A thorough search was conducted to identify relevant studies on postoperative re-RT for locally recurrent NPC. Controversial issues, including resectability criteria, margin assessment, indications for postoperative re-RT, and the optimal dose and method of re-RT, were addressed through a Delphi consensus process. The consensus recommendations emphasize the need for a clearer and broader definition of resectability, highlighting the importance of achieving clear surgical margins, preferably through an en bloc approach with frozen section margin assessment. Furthermore, these guidelines suggest considering re-RT for patients with positive or close margins. Optimal postoperative re-RT doses typically range around 60 Gy, and hyperfractionation has shown promise in reducing toxicity. These guidelines aim to assist clinicians in making evidence-based decisions and improving patient outcomes in the management of potentially resectable locally recurrent NPC. By addressing key areas of controversy and providing recommendations on resectability, margin assessment, and re-RT parameters, these guidelines serve as a valuable resource for clinical experts involved in the treatment of locally recurrent NPC. Locally recurrent nasopharyngeal carcinoma (NPC) presents substantial challenges in clinical management. Although postoperative re-irradiation (re-RT) has been acknowledged as a potential treatment option, standardized guidelines and consensus regarding the use of re-RT in this context are lacking. This article provides a comprehensive review and summary of international recommendations on postoperative management for potentially resectable locally recurrent NPC, with a special focus on postoperative re-RT. A thorough search was conducted to identify relevant studies on postoperative re-RT for locally recurrent NPC. Controversial issues, including resectability criteria, margin assessment, indications for postoperative re-RT, and the optimal dose and method of re-RT, were addressed through a Delphi consensus process. The consensus recommendations emphasize the need for a clearer and broader definition of resectability, highlighting the importance of achieving clear surgical margins, preferably through an en bloc approach with frozen section margin assessment. Furthermore, these guidelines suggest considering re-RT for patients with positive or close margins. Optimal postoperative re-RT doses typically range around 60 Gy, and hyperfractionation has shown promise in reducing toxicity. These guidelines aim to assist clinicians in making evidence-based decisions and improving patient outcomes in the management of potentially resectable locally recurrent NPC. By addressing key areas of controversy and providing recommendations on resectability, margin assessment, and re-RT parameters, these guidelines serve as a valuable resource for clinical experts involved in the treatment of locally recurrent NPC. Locally recurrent nasopharyngeal carcinoma (NPC) poses substantial challenges in terms of both treatment and management. The disease exhibits high curability in the primary setting, and advancements in intensity modulated radiation therapy (IMRT) have resulted in relatively low rates of local recurrence.1Tian Y Huang WZ Zeng L Bai L Han F Lan Y. The failure patterns of nasopharygeal carcinoma after intensity-modulated radiotherapy and implications for surveillance.Cancer Manag Res. 2022; 14: 2813-2823Crossref PubMed Scopus (3) Google Scholar,2Chen S Yang D Liao X et al.Failure patterns of recurrence and metastasis after intensity-modulated radiotherapy in patients with nasopharyngeal carcinoma: Results of a multicentric clinical study.Front Oncol. 2021; 11693199Google Scholar When local recurrences do occur, they frequently manifest within the previously irradiated high-dose zone.3Kong F Ying H Du C et al.Patterns of local-regional failure after primary intensity modulated radiotherapy for nasopharyngeal carcinoma.Radiat Oncol. 2014; 9: 60Crossref PubMed Scopus (49) Google Scholar,4Liu X Wu B Huang J et al.Tumor factors associated with in-field failure for nasopharyngeal carcinoma after intensity-modulated radiotherapy.Head Neck. 2022; 44: 876-888Crossref Scopus (8) Google Scholar Notably, the incidences of marginal failure and geographical miss are ≤2% and 0% to 1%, respectively, suggesting that these local relapses are predominantly associated with radiation resistance.5Ng WT Lee MCH Hung WM et al.Clinical outcomes and patterns of failure after intensity-modulated radiotherapy for nasopharyngeal carcinoma.Int J Radiat Oncol Biol Phys. 2011; 79: 420-428Abstract Full Text Full Text PDF PubMed Scopus (228) Google Scholar With improvements in imaging and blood-based surveillance methods, many of these local recurrences are potentially detectable at an earlier stage, possibly making them salvageable through surgical means. Endoscopic nasopharyngectomy is recently regarded as the preferred option for resectable locally recurrent NPC.6Lee AWM Ng WT Chan JYW et al.Management of locally recurrent nasopharyngeal carcinoma.Cancer Treat Rev. 2019; 79101890Abstract Full Text Full Text PDF PubMed Scopus (207) Google Scholar,7Li G Wang J Tang H et al.Comparing endoscopic surgeries with open surgeries in terms of effectiveness and safety in salvaging residual or recurrent nasopharyngeal cancer: systematic review and meta-analysis.Head Neck. 2020; 42: 3415-3426Crossref Scopus (12) Google Scholar Small recurrent tumors confined to the nasopharyngeal cavity, the postnaris or nasal septum, the superficial parapharyngeal space, or the sphenoid sinus floor are usually readily resectable. However, the resectability criteria vary considerably for more advanced lesions, especially if the tumor is close to the carotid vessel or involves other parts of the skull base beyond the sphenoid sinus floor. Accurate histopathological margin assessment is also challenging as it is more difficult to carry out en bloc resection with more extensive skull base involvement. To eradicate residual disease and enhance local control, postoperative re-irradiation (re-RT) may be necessary for patients with positive or close resection margins. However, late complications related to re-RT are not uncommon, and high-quality data supporting its efficacy are lacking. There is currently no consensus on which patients would benefit from postoperative re-RT. In this study, we aimed to establish a consensus guideline on resectability criteria, margin assessment, indications for postoperative re-RT, and the dose and method of re-RT. A systematic literature review was first conducted to formulate pertinent questions, and a modified Delphi process was then used to build consensus among internationally regarded clinical opinion leaders from major centers worldwide. The goal of this process was to enhance treatment outcomes, minimize complications, and guide clinicians in making informed decisions regarding the management of locally recurrent NPC. This study was composed of 3 parts. First, a comprehensive literature search was conducted using EMBASE, Cochrane CENTRAL, CINAHL Plus, and PubMed databases to investigate the clinical outcomes of recurrent NPC treated with salvage operations, with or without re-RT. The search covered publications from the inception of the databases up to December 10, 2022. The search terms used were "recurrent nasopharyngeal carcinoma" OR "rnpc" OR "nasopharyngeal cancer" AND "recurrence" (Table E1). Additionally, the CNKI and Weipu (VIP) databases were searched for studies published in Chinese. Both prospective and retrospective studies published between January 2000 and December 2022 were reviewed, and data on the operation, failure pattern, survival, and/or toxicity outcomes were tabulated. Publications in languages other than Chinese and English were excluded. Furthermore, the references of included research articles were examined for potentially eligible studies. The literature review followed the PRISMA workflow,8Page MJ McKenzie JE Bossuyt PM et al.The PRISMA 2020 statement: An updated guideline for reporting systematic reviews.Int J Surg. 2021; 88105906Crossref PubMed Scopus (4431) Google Scholar as depicted in Figure 1. The extracted information included characteristics of patients, follow-up period, details of postoperative treatments, recurrence rate, as well as survival data. Tables E2 and E3 provide further details on the research articles included in the first part of the study. Second, an initial list of questions related to resectability criteria, margin assessment, indications for postoperative re-RT, and dose and method of re-RT was compiled based on the findings from the literature review. This list of questions was then distributed to a panel of international experts, including surgeons and oncologists specializing in recurrent NPC from Asia, Europe, and North America. The experts participated in an initial voting process and exchanged comments using a modified Delphi process. The decision-making process of the panelists was facilitated by considering 2 criteria from the evidence-to-decision framework: benefits and feasibility.9Alonso-Coello P Schünemann HJ Moberg J et al.GRADE Evidence to Decision (EtD) frameworks: A systematic and transparent approach to making well informed healthcare choices. 1: Introduction.BMJ. 2016; 353: i2016Crossref PubMed Scopus (525) Google Scholar The experts were then asked to give a final rating on each research question using a 4-point Likert scale, ranging from "Fully agree," "Agree," "Not agree," to "Strongly disagree." They were also invited to provide qualitative comments explaining their rating. Lastly, after repeated iterations and summarizing the feedback received, a follow-up list of questions addressing specific aspects of controversial issues was recirculated for a second round of voting if initial agreement on the subject was below the cut-off of 75%. Considering the limited availability of high-quality published data on this specific clinical problem,10Milholland AV Wheeler SG Heieck JJ. Medical assessment by a Delphi group opinion technic.N Engl J Med. 1973; 288: 1272-1275Crossref PubMed Scopus (199) Google Scholar,11Boulkedid R Abdoul H Loustau M Sibony O. Alberti C. Using and reporting the Delphi method for selecting healthcare quality indicators: A systematic review.PLOS ONE. 2011; 6: e20476Crossref PubMed Scopus (1253) Google Scholar this consensus-building process served as the fundamental basis for the group's final recommendations. The systematic literature search identified a total of 47 studies that met the inclusion criteria and were included in the review. The included studies consisted of 46 retrospective cohort or case series studies and 1 prospective trial. The number of patients included in the studies ranged from 2 to 312. The studies reported on surgical methods, the rate of positive margins, postoperative modalities, local control rates, overall survival (OS), disease-free survival, and treatment-related toxicity. The pooled analysis showed that the 5-year OS rates were respectively 48% (95% CI, 39%-57%; I² = 79%; P < .01) for the era of open surgery and 59% (95% CI, 45%-72%; I² = 90%; P < .01) for endoscopic nasopharyngectomy (Fig. 2A, B). However, there was significant heterogeneity in both meta-analyses. During the literature search, a single open-label phase III trial was identified,16Liu YP Wen YH Tang J et al.Endoscopic surgery compared with intensity-modulated radiotherapy in resectable locally recurrent nasopharyngeal carcinoma: A multicentre, open-label, randomised, controlled, phase 3 trial.Lancet Oncol. 2021; 22: 381-390Abstract Full Text Full Text PDF PubMed Scopus (99) Google Scholar which randomly assigned 200 patients with recurrent NPC to undergo endoscopic nasopharyngectomy or re-RT with IMRT. This trial included patients with tumors limited to the nasopharyngeal cavity, postnaris or nasal septum, superficial parapharyngeal space, or the floor of the sphenoid sinus. The findings showed that the majority of patients who underwent surgery (94%) did not require additional adjuvant radiation therapy or chemotherapy. Similarly, most patients who received IMRT completed the full course of treatment, with the majority (71%) receiving cisplatin as concurrent chemotherapy. Patients undergoing endoscopic nasopharyngectomy had a 3-year OS rate of 86%, compared to 68% for those receiving IMRT (hazard ratio, 0.47; 95% CI, 0.29-0.76). However, the survival benefit was observed only in patients with T1 and T2 tumors, and not in those with T3 tumors. Furthermore, endoscopic nasopharyngectomy was associated with lower rates of grade ≥3 overall adverse events and late adverse events when compared to IMRT (13% versus 37% for both outcomes). Based on the results of this randomized trial, endoscopic nasopharyngectomy could be used for readily resectable disease, such as rT1 disease, rT2 disease with limited parapharyngeal space involvement, and rT3 disease confined to the floor of the sphenoid sinus. However, resectability criteria for advanced diseases involving the internal carotid artery (ICA), skull base other than the floor of the sphenoid sinus, and rT4 were not well-defined. There was a lack of standardization in the assessment of surgical margins, resulting in variable rates of reporting close and positive margins. Furthermore, indications for postoperative radiation therapy and the dose and methods of re-RT were also poorly described. The lack of uniformity in re-RT approaches highlighted the necessity for proposing guidelines to bridge these gaps and optimize treatment outcomes. Hence, voting questions were focused on the following 5 areas (Table 1): definition of resectability, assessment of surgical margins, definition of the surgical margin, indications for postoperative re-RT, and method and dose for postoperative re-RT. Instead of restricting the voting on surgical questions to surgeons and radiation therapy questions to radiation oncologists (except for specific questions on carotid artery protection, radiation dose, and re-RT method), our study involved the participation of both professions in rating each research question, similar to a multidisciplinary tumor board. This approach ensures that expertise from both specialties is comprehensively considered when formulating the treatment plan for postoperative management of locally recurrent NPC.Table 1Results of the 2-round Delphi survey on formulating the recommendations on postoperative management for locally recurrent NPCCategoryRecommendation with positive consensusRecommendation without consensus1. Definition of resectabilityPotentially resectable disease includes:a. rT3 with posterior maxillary sinus and pterygoid process invasion(surgeons' agreement: 89% [8 of 9 voters]; oncologists' agreement: 86% [18 of 21 voters]; reached consensus in round 1)b. rT3 cases involve the "outer table" of the clivus but do not invade the marrow (where the outer table refers to the bony surface facing the nasopharynx) (surgeons' agreement: 100% [9 of 9 voters]; oncologists' agreement: 75% [15 of 20 voters]; reached consensus in round 2)c. rT2 with an extension close to the ICA(surgeons' agreement: 100% [9 of 9 voters]; oncologists' agreement: 85% [17 of 20 voters]; reached consensus in round 2)Potentially resectable disease includes:a. rT2 with an extension involving the ICA(surgeons' agreement: 56% [5 of 9 voters]; oncologists' agreement: 5% [1 of 21 voters]; did not reach consensus after 2 rounds)Unresectable diseases are as follows:a. rT3 with tumor invading both cortices of the clivus (surgeons' agreement: 100% [9 of 9 voters]; oncologists' agreement: 76% [16 of 21 voters]; reached consensus in round 1)b. rT3 with significant involvement of the lateral wall of the sphenoid sinus (surgeons' agreement: 100% [9 of 9 voters]; oncologists' agreement: 76% [16 of 21 voters]; reached consensus in round 1)c. rT4 with frank cavernous sinus or intracranial invasion(surgeons' agreement: 100% [9 of 9 voters]; oncologists' agreement: 81% [17 of 21 voters]; reached consensus in round 1)d. rT3 with multiple areas of skull base involvement (surgeons' agreement: 89% [8 of 9 voters]; oncologists' agreement: 85% [17 of 20 voters]; reached consensus in round 2)Unresectable diseases are as follows:a. rT3 with foramen lacerum and petrous apex involvement(surgeons' agreement: 67% [6 of 9 voters]; oncologists' agreement: 95% [19 of 20 voters]; reached consensus among oncologists only, but not surgeons after 2 rounds)a. Carotid artery protection/embolization should be considered in recurrent lesion abutting/involving the ICA(surgeons' agreement: 89% [8 of 9 voters]; reached consensus in round 1)b. Some form of carotid artery protection should be considered in recurrent lesions located less than 5 mm from ICA(surgeons' agreement: 89% [8 of 9 voters]; reached consensus in round 2)Not applicable2. Assessment of surgical marginsa. Routine frozen section examination of the soft tissue resection margins should be performed (surgeons' agreement: 89% (8 of 9 voters); oncologists' agreement: 100% (21 of 21 voters); reached consensus in round 1)b. En bloc resection is the preferred approach whenever possible, but piece-meal removal may be necessary, especially for infiltrative recurrence (surgeons' agreement: 89% [8 of 9 voters]; oncologists' agreement: 85% [17 of 20 voters]; reached consensus in round 2)Not applicable3. Definition of the surgical margina. Close margin should be defined as >1 and <3 mm (surgeons' agreement: 100% [9 of 9 voters]; oncologists' agreement: 90% [19 of 21 voters]; reached consensus in round 1)a. A margin that is ≤1 mm but doesn't actually reach the margin should be classified as a "close" margin rather than a "positive" margin(surgeons' agreement: 89% [8 of 9 voters]; oncologists' agreement: 65% [13 of 20 voters]; reached consensus among surgeons only, but not oncologists after 2 rounds)4. Indications for postoperative re-RTa. Postoperative re-RT should be offered for tumor cells seen on the surgical margin(Surgeons' agreement: 78% [7 of 9 voters]; oncologists' agreement: 95% [20 of 21 voters]; reached consensus in round 1)b. Postoperative re-RT should be considered for margins less than 1 mm after a thorough evaluation of the prior RT plan and dosimetric feasibility(surgeons' agreement: 100% [9 of 9 voters]; oncologists' agreement: 95% (19 of 20 voters); reached consensus in round 2)a. Postoperative re-RT is not recommended if the margin is >1 mm but less than <3 mm.(surgeons' agreement: 67% [6 of 9 voters]; oncologists' agreement: 85% [17 of 20 voters]; reached consensus among oncologists only, but not surgeons after 2 rounds)5. Method and dose for postoperative re-RTa. CTV should include the postoperative tumor bed with a 5 mm margin (to account for microscopic disease extension) while respecting the adjacent critical organs at risk(oncologists' agreement: 100% [21 of 21 voters]; reached consensus in round 1)b. A dose of ≥60 Gy (in EQD2) should be given, but should not exceed 66 Gy (EQD2) (oncologists' agreement: 81% [17 of 21 voters]; reached consensus in round 1)c. Conventional fractionation is an acceptable treatment technique in the postoperative setting(oncologists' agreement: 76% [16 of 21 voters]; reached consensus in round 1)d. Doses>2 Gy per fraction should be avoided(oncologists' consensus: 76% [16 of 21 voters]; reached consensus in round 1)a. Hyperfractionated IMRT should be the preferred treatment technique if resources allow(oncologists' agreement: 70% [14 of 20 voters]; did not reach consensus after 2 rounds)Abbreviations: CTV = clinical target volume; EQD2 = equivalent dose in 2 Gy fractions; ICA = internal carotid artery; IMRT = intensity modulated radiation therapy; NPC = nasopharyngeal carcinoma; re-RT = re-irradiation. Open table in a new tab Abbreviations: CTV = clinical target volume; EQD2 = equivalent dose in 2 Gy fractions; ICA = internal carotid artery; IMRT = intensity modulated radiation therapy; NPC = nasopharyngeal carcinoma; re-RT = re-irradiation. During round 1, a total of 12 questions and their subquestions achieved positive consensus, with an agreement level of more than 75%.17Diamond IR Grant RC Feldman BM et al.Defining consensus: A systematic review recommends methodologic criteria for reporting of Delphi studies.J Clin Epidemiol. 2014; 67: 401-409Abstract Full Text Full Text PDF PubMed Scopus (1747) Google Scholar However, the remaining 11 questions required additional discussion and iteration. The subsequent agreement percentage in round 2 represented the final voting results for those specific questions after further deliberation and consideration by the expert panel (Table E4). Building upon the commonly accepted resectability criteria as stated in the randomized study by Liu et al,16Liu YP Wen YH Tang J et al.Endoscopic surgery compared with intensity-modulated radiotherapy in resectable locally recurrent nasopharyngeal carcinoma: A multicentre, open-label, randomised, controlled, phase 3 trial.Lancet Oncol. 2021; 22: 381-390Abstract Full Text Full Text PDF PubMed Scopus (99) Google Scholar we suggested further expanding the resectability criteria for rT3 NPC to include the posterior maxillary sinus, pterygoid process, and outer table of the clivus as resectable regions. Regarding the relationship between the recurrent lesion and the ICA, surgeons commonly considered lesions that were at least 5 mm away from the ICA as resectable, while "close to" referred to locations less than 5 mm from the ICA, which was also one of the exclusion criteria in the randomized trial.16Liu YP Wen YH Tang J et al.Endoscopic surgery compared with intensity-modulated radiotherapy in resectable locally recurrent nasopharyngeal carcinoma: A multicentre, open-label, randomised, controlled, phase 3 trial.Lancet Oncol. 2021; 22: 381-390Abstract Full Text Full Text PDF PubMed Scopus (99) Google Scholar There was a high consensus among surgeons that rT2 lesions close to the ICA were resectable. For cases of more advanced rT2 disease in close proximity to the ICA, a balloon occlusion test was proposed to assess the collateral blood flow in the brain during temporary occlusion of the ICA.18Liu J Yu H Sun X et al.Salvage endoscopic nasopharyngectomy for local recurrent or residual nasopharyngeal carcinoma: A 10-year experience.Int J Clin Oncol. 2017; 22: 834-842Crossref PubMed Scopus (65) Google Scholar By evaluating cerebral blood flow and collateral circulation, the surgeon could make informed decisions regarding the risks of ICA manipulation during the resection. The assessment of resectability in cases involving the ICA varied among surgeons and oncologists, highlighting the importance of a multidisciplinary approach to decision-making.19Lee VH Au JSK Mu JW et al.Real-world perspectives from surgeons and oncologists on resectability definition and multidisciplinary team discussion of stage III NSCLC in People's Republic of China, Hong Kong, and Macau: A physician survey.JTO Clin Res Rep. 2022; 3100308Google Scholar Although the majority of oncologists considered tumors involving the ICA as unresectable, more than half of the surgeons still viewed them as potentially resectable. Managing the ICA presented the greatest challenge in salvage operations, and specialized cancer centers have reported several case series exploring this issue.18Liu J Yu H Sun X et al.Salvage endoscopic nasopharyngectomy for local recurrent or residual nasopharyngeal carcinoma: A 10-year experience.Int J Clin Oncol. 2017; 22: 834-842Crossref PubMed Scopus (65) Google Scholar The surgical technique used in these cases was extracranial-intracranial vascular bypass, which involved bypassing the affected section of the ICA by means of a vascular graft connecting the carotid vessel in the neck to the middle cerebral artery intracranially.20Chan JYW Wong STS Chan RCL Wei WI. Extracranial/intracranial vascular bypass and craniofacial resection: New hope for patients with locally advanced recurrent nasopharyngeal carcinoma.Head Neck. 2016; 38: E1404-E1412Crossref PubMed Scopus (27) Google Scholar This bypass procedure established a new route of anterior cerebral circulation and hence enabled safe resection of the tumor with the old route, that is, the affected ICA. However, it is noteworthy that the surgeon's expertise and performance were key determinants of surgical success. Hence, the generalizability of this highly sophisticated surgical technique in different health care settings would be limited. The role of endoscopic nasopharyngectomy has been generally limited in cases of more advanced rT3 (such as multiple areas of skull base involvement) and rT4 disease. Specifically, lesions involving the foramen lacerum, petrous apex, or the lateral wall of the sphenoid sinus might pose challenges because of their proximity to critical structures such as the cavernous sinus, which comprises multiple cranial nerves and the ICA. It was more difficult to perform resection in these cases. Additionally, repairing the dura in a watertight manner could be challenging if it was inadvertently damaged during the resection of tumors invading both cortices of the clivus. Surgeons might consider performing such surgery given their strong expertise in neurosurgery and skull base surgery, coupled with access to vascular surgical support.18Liu J Yu H Sun X et al.Salvage endoscopic nasopharyngectomy for local recurrent or residual nasopharyngeal carcinoma: A 10-year experience.Int J Clin Oncol. 2017; 22: 834-842Crossref PubMed Scopus (65) Google Scholar,21Wong EHC Liew YT Abu Bakar MZ Lim EYL Prepageran N A preliminary report on the role of endoscopic endonasal nasopharyngectomy in recurrent rT3 and rT4 nasopharyngeal carcinoma.Eur Arch Otorhinolaryngol. 2017; 274: 275-281Crossref Scopus (39) Google Scholar,22Wong EHC Liew YT Loong SP Prepageran N. Five-year survival data on the role of endoscopic endonasal nasopharyngectomy in advanced recurrent rT3 and rT4 nasopharyngeal carcinoma.Ann Otol Rhinol Laryngol. 2020; 129: 287-293Crossref Scopus (20) Google Scholar However, such high-level expertise was lacking globally and only a few successful cases have been reported. For instance, a reported series of endoscopic endonasal nasopharyngectomy for 15 patients with rT3 to rT4 disease was conducted at the University Malaya Medical Centre. This procedure was performed without encountering severe operative complications. The 2-year OS and disease-free survival rates were found to be 66.7% and 40%, respectively. Among the cohort, 53.8% of the rT4 patients achieved negative margins. Additionally, the reported 5-year OS and Progression Free Survival (PFS) rates for 12 patients within the same period were 50% and 20%, respectively.21Wong EHC Liew YT Abu Bakar MZ Lim EYL Prepageran N A preliminary report on the role of endoscopic endonasal nasopharyngectomy in recurrent rT3 and rT4 nasopharyngeal carcinoma.Eur Arch Otorhinolaryngol. 2017; 274: 275-281Crossref Scopus (39) Google Scholar Notably, a meta-analysis conducted on patients with recurrent rT3 to rT4 NPC indicated that endoscopic surgery might improve survival outcomes compared to IMRT in cases of recurrent NPC with rT3 to rT4 disease. The 5-year OS rates were 52% for patients receiving endoscopic surgery and 31% for IMRT. However, specific details regarding postoperative re-RT in the context of rT3 to rT4 disease following the surgical procedure were not reported in the study.23Peng Z Wang Y Wang Y et al.Comparing the effectiveness of endoscopic surgeries with intensity-modulated radiotherapy for recurrent rT3 and rT4 nasopharyngeal carcinoma: A meta-analysis.Front Oncol. 2021; 11703954Google Scholar Carotid artery protection techniques have been recommended to safeguard the integrity of the ICA during endoscopic resection of recurrent NPC. These techniques involved measures to prevent injury to the ICA and minimize the risk of carotid blowout syndrome, a potentially life-threatening complication. For instance, the use of a vascularized flap to cover the exposed ICA posttumor extirpation was found to minimize the risk of ICA blowout bleeding.24Song B Kim HY Jung YG Baek C-H Chung MK Hong SD. Endoscopic debridement of post-radiation nasopharyngeal necrosis: The effects of resurfacing with a vascularized flap.Clin Exp Otorhinolaryngol. 2022; 15: 354-363Crossref Scopus (1) Google Scholar, 25Hadad G Bassagasteguy L Carrau RL et al.A novel reconstructive technique after endoscopic expanded endonasal approaches: Vascular pedicle nasoseptal flap.Laryngoscope. 2006; 116: 1882-1886Crossref PubMed Scopus (1544) Google Scholar, 26Gan JY, Yeo MSW, Fu EWZ, Tan NC, Lim M. Surgery N. Reconstruction of nasopharynx defect using a free flap after endoscopic nasopharyngectomy—Feasibility and technical considerations. 2021;147:104-106.Google Scholar Pretreatment ICA embolization was another strategy that can be employed in managing recurrent NPC with ICA involvement. This technique selectively blocked the tumor's blood supply by injecting embolic agents into the ICA before surgery. Embolization reduced tumor vascularity, making subsequent tumor resection safer and more effective. By decreasing blood flow to the tumor, embolization could facilitate complete tumor excision, achieve negative margins