Locally advanced differentiated thyroid cancer (DTC) refers primarily to:
Gross macroscopic extension beyond the thyroid gland into adjacent cervical structures, including the:
Strap muscles, recurrent laryngeal nerve (RLN), larynx, trachea, pharynx or esophagus, subcutaneous soft tissues, prevertebral fascia, or major cervical and mediastinal vessels
Among these structures, the strap muscles and RLN are most frequently involved, followed by the trachea, laryngotracheal junction, pharyngoesophageal tract, and major vessels
The clinical significance of ETE, however, is heterogeneous and is strongly influenced by the:
Extent of invasion
The specific structure involved
The presence of regional or distant metastatic disease
Tumor biology
The ability to achieve complete gross resection (Figure)
The National Comprehensive Cancer Network (NCCN) recommends:
That every patient with suspected oropharyngeal squamous cell carcinoma (OPSCC) undergo a structured workup anchored by:
Mandatory tumor HPV testing by p16 immunohistochemistry (IHC), tissue confirmation, cross-sectional imaging, and clinical staging by AJCC 8th edition:
With p16 status determining which staging table and treatment algorithm applies
Required workup elements (base of tongue / tonsil / posterior pharyngeal wall / soft palate):
Tumor HPV testing by p16 IHC is required:
The 70% cutoff with nuclear and cytoplasmic expression of at least moderate-to-strong intensity is used:
Direct HPV confirmatory testing (PCR or RNA ISH) is recommended, especially for clinical trials and when p16 is used as a surrogate
History and physical including a complete head and neck exam, with mirror and fiberoptic examination as clinically indicated:
H&P should document / quantify tobacco (pack-years) and alcohol use with counseling, and screen for distress
Biopsy of the primary site or FNA of the neck:
Image-guided (US or CT) needle biopsy of cystic neck nodes offers better yield than palpation-guided FNA:
A core biopsy is preferred when biomarker testing is planned for unresectable / metastatic disease
CT with contrast and / or MRI with and without contrast of the primary and neck
Additional studies as clinically indicated EUA with endoscopy:
Prior to treatment, EUA with biopsy confirmation of the oropharyngeal primary is recommended for patients presenting with a p16+ cervical node
FDG-PET/CT; chest CT (with or without contrast)
Dental evaluation:
Including Panorex
Nutrition, speech, and swallowing evaluation / therapy, and audiogram
Smoking cessation counseling
Fertility / reproductive counseling
Hepatitis B screening
PD-L1 testing by IHC (CPS)
Multidisciplinary consultation.
Imaging principles:
Assess the primary with CT (with contrast) or MRI (with and without contrast) of the neck:
Imaging from skull base to thoracic inlet:
CT is complementary for cortical bone erosion
MRI is preferred for bone marrow invasion, skull base / intracranial / orbital invasion, and perineural spread, and in patients with extensive dental amalgam
Evaluate nodal disease with the same modality
Consider FDG-PET / CT for its higher sensitivity:
Particularly for midline tumors approaching the contralateral neck or when definitive RT is planned
For locoregionally advanced disease (T3 to T4 or ≥ N1), FDG-PET/CT is preferred to evaluate for distant / thoracic metastases:
If PET / CT is not done, obtain chest CT
FDG-PET/CT cannot exclude brain metastasis
If imaging does not reveal an obvious primary:
PET / CT should be obtained before EUA, biopsies, and tonsillectomy to identify potential primary sites before intervention
Search for the occult primary (neck mass presentation):
Because the first sign of OPSCC is often a neck mass with a small, asymptomatic, radiographically occult primary:
The NCCN emphasizes diligent identification and pathologic confirmation of the primary:
Usually in the base of tongue or tonsil
Cross-sectional imaging:
Should precede direct examination and confirmatory biopsy
EUA may entail unilateral or bilateral biopsies of suspicious oropharyngeal areas:
Palatine tonsillectomy may reveal a small primary, and lingual tonsillectomy may be considered if palatine tonsils and biopsies are negative:
Bilateral palatine and lingual tonsillectomies are ill-advised due to swallowing morbidity
FNA of the neck mass (often US-guided) usually establishes metastatic carcinoma:
p16 immunostaining supports HPV-associated OPSCC when an oropharyngeal primary is present
In occult-primary cases with p16-positive nodal metastasis, confirmation with HPV ISH / PCR is recommended:
Open excisional node biopsy is rarely needed:
If performed, the surgeon should be prepared for neck dissection if frozen section confirms SCC
The occult-primary pathway similarly directs HPV / EBV testing on nodal SCC:
If HPV-positive with a T0 primary, the patient is treated as oropharyngeal cancer (ORPH-1)
Clinical staging (AJCC 8th edition):
p16 status splits OPSCC into two separate staging systems:
p16-negative OPSCC is staged with the oropharynx (p16-) / hypopharynx TNM (ST-6):
Which incorporates extranodal extension (ENE) into N categories
p16-positive (HPV-mediated) OPSCC uses a distinct TNM (ST-7):
With different clinical N categories:
N1: ipsilateral nodes ≤ 6 cm
N2: contralateral / bilateral ≤ 6 cm
N3: > 6 cm
A separate pathologic N classification:
pN1 ≤ 4 nodes
pN2 > 4 nodes
Stage groups that markedly downstage nodal disease relative to p16-negative cancer
There is no Tis or T4b category, and no histologic grading system, for HPV-mediated tumors
The following NCCN algorithm summarizes the oropharynx workup and the p16-based staging / treatment branch point
HPV / p16 testing nuances that affect prognosis and staging:
While p16 IHC is the preferred surrogate for AJCC 8th edition staging:
Roughly 9% to 20% of p16-positive OPSCC lack detectable HPV DNA / mRNA, and these p16+ / HPV− (and p16−/HPV+) discordant tumors:
Carry a worse prognosis than double-positive tumors
The 2025 College of American Pathologists update supports p16 IHC alone in high-prevalence regions (US, Canada, Northern Europe) when clinicopathologic surrogates of HPV disease are present:
But recommends adding HPV-specific testing (RNA-ISH or DNA PCR) when p16 is equivocal, when morphology and p16 are discordant, for large multisite tumors, for nontonsillar / non–base-of-tongue oropharyngeal sites, in low-prevalence regions, and for clinical trials
Examination under anesthesia and tonsillectomy for the occult primary :
The AAO-HNS neck mass guideline advises that when a persistent neck mass evades diagnosis after FNA, imaging, and exam, endoscopy under anesthesia with directed biopsies should precede open neck biopsy to avoid tumor seeding and its associated complications:
A meta-analysis found palatine tonsillectomy has ~ 10-fold higher diagnostic yield than blind tonsil biopsy for detecting occult primaries:
Because tonsillar tumors often lie deep within crypts or submucosa
Dedicated brain imaging is reserved for neurologic symptoms
The ACR Appropriateness Criteria list CT neck with contrast, MRI without / with contrast, and FDG-PET / CT as the recommended studies for initial staging of oral cavity / oropharyngeal cancer, with FDG-PET / CT complementary for mapping systemic disease and detecting synchronous second primaries
Special populations:
A diagnosis of HNSCC in an adolescent or young adult without risk factors warrants evaluation for Fanconi anemia
Why Not All Thyroid Cancers Need Aggressive Treatment
Not all thyroid cancers behave the same. Modern care is personalized—the goal is to treat what matters while avoiding unnecessary treatment.
🧠 The key concept: Risk-adapted management
Many thyroid cancers—especially low-risk papillary thyroid cancers—are:
Slow-growing Unlikely to spread Associated with excellent long-term survival
Because of this, more treatment is not always better.
⚖️ Treatment options today
Depending on risk, options may include:
Active surveillance (careful ultrasound follow-up, no immediate surgery) Thyroid lobectomy instead of total thyroidectomy Selective use of radioactive iodine (not routine for everyone)
➡️ These approaches are evidence-based and safe for appropriately selected patients.
📉 Why avoid overtreatment?
Unnecessary aggressive treatment can:
Increase risk of hypocalcemia and voice changes Require lifelong thyroid hormone replacement Affect quality of life without improving outcomes
🦋 What matters most
Treatment decisions should be guided by:
✔️ Tumor size and ultrasound features
✔️ Pathology and risk of recurrence
✔️ Patient age, preferences, and values
✔️ Expertise of a multidisciplinary thyroid team
👨⚕️ Dr. Rodrigo Arrangoiz, MD
Surgical Oncologist – Thyroid, Head & Neck, Breast
Mount Sinai Medical Center
📌 Take-home message:
The best thyroid cancer treatment is the right treatment for the right patient—not the most aggressive one.
📚 References
Haugen BR et al. ATA Guidelines for Differentiated Thyroid Cancer. Thyroid Tuttle RM et al. Active surveillance for low-risk papillary thyroid cancer. JAMA Brito JP et al. Overdiagnosis and overtreatment of thyroid cancer. BMJ
Lobectomy may be considered in select patients with sporadic medullary thyroid cancer (MTC), though total thyroidectomy with central neck dissection remains the standard of care. The evidence base is evolving, with growing data supporting comparable oncologic outcomes for carefully selected patients.
Guideline Recommendations
The NCCN Thyroid Carcinoma Guidelines (v2.2026) recommend total thyroidectomy with central neck dissection (level VI) as the standard primary treatment for MTC. However, the guidelines now explicitly state that “lobectomy can be considered in select cases without RET pathogenic variant if no concerns for contralateral nodules.” This represents a notable shift toward acknowledging lobectomy as an option.
For MTC diagnosed after initial thyroid surgery (e.g., lobectomy), the NCCN notes that completion thyroidectomy may not be necessary unless there is a positive germline RET pathogenic variant or radiographic evidence of disease (biopsy-proven residual neck disease).
The ATA Guidelines similarly state that completion thyroidectomy following hemithyroidectomy is not indicated unless the patient has a RET germline mutation, significant postoperative calcitonin elevation, or imaging showing residual MTC. In a prospective study of 15 patients with sporadic MTC treated by hemithyroidectomy, 80% achieved biochemical cure.
Hereditary MTC (MEN2A/MEN2B) remains a strict indication for total thyroidectomy, as the likelihood of bilateral disease approaches 100%.
Key Evidence Supporting Lobectomy in Sporadic MTC
A 2026 systematic review and meta-analysis in JAMA Otolaryngology (9 studies, 1,371 patients) found that lobectomy was associated with comparable oncologic outcomes to total thyroidectomy in selected patients with sporadic MTC:
– Mortality: No difference at 5 years (RR 0.30; 95% CI 0.07–1.35) or beyond (RR 1.00; 95% CI 0.40–2.47)
– Overall survival at 5 years: Similar (RR 1.02; 95% CI 0.94–1.11)
– Biochemical cure: No difference at 5 or beyond 5 years
– Structural recurrence at 5 years: No difference (OR 0.45; 95% CI 0.14–1.49), though total thyroidectomy was associated with lower recurrence beyond 5 years (OR 7.26; 95% CI 1.07–49.21) — a finding with very wide confidence intervals
– Postoperative complications: More common with total thyroidectomy
Multiple SEER-based analyses corroborate these findings:
– A propensity-matched study (122 pairs, median follow-up 99 months) showed no significant difference in 10-year overall survival (85.2% vs. 83.1%) or disease-specific survival between total thyroidectomy and lobectomy for localized MTC.
– Another SEER analysis of T1N0/1M0 MTC (398 patients, median follow-up 8.75 years) found no survival difference between approaches (cancer-specific mortality HR 0.44, p = 0.23).
– A 2025 SEER analysis with Chinese cohort validation confirmed no survival difference and demonstrated significantly more adverse events with total thyroidectomy, including transient hypocalcemia (p < 0.001) and vocal cord paralysis (p < 0.025).
Occult Contralateral Disease
A key concern with lobectomy is missing contralateral foci. A multi-institutional JAMA Otolaryngology study found that the prevalence of sonographically occult contralateral disease in sporadic MTC was only 5.0%, with a 95.7% reduction in odds compared to germline disease (adjusted OR 0.034). Among patients who underwent lobectomy alone, 41.7% achieved undetectable calcitonin levels. A 2026 European study found zero cases of occult contralateral disease in 48 patients with sporadic MTC when high-quality preoperative ultrasound was available.
Patient Selection Criteria for Lobectomy
Based on the available evidence, lobectomy with ipsilateral central neck dissection may be appropriate when all of the following are met:
– Sporadic disease (no germline RET pathogenic variant)
– Unifocal tumor confined to one lobe with no contralateral nodules on ultrasound
– Clinically node-negative (cN0) with preoperative calcitonin ≤250 pg/mL
– No extrathyroidal extension
– Tumor size <2 cm (most studied population)
– Absence of desmoplastic stroma reaction on intraoperative frozen section (if available)
—Important Caveats
Important Caveats
All existing data are retrospective, with inherent selection bias — patients who underwent lobectomy likely had lower-risk disease. The meta-analysis signal of potentially higher structural recurrence beyond 5 years with lobectomy warrants attention, though confidence intervals were very wide. Calcitonin surveillance is more complex after lobectomy, as residual normal C cells may produce low-level calcitonin, complicating interpretation. Prospective randomized trials are needed to definitively establish the safety of lobectomy in this setting.
Key References
– Lincango EP et al. Total Thyroidectomy vs Lobectomy for Sporadic Medullary Thyroid Cancer: A Systematic Review and Meta-Analysis. JAMA Otolaryngol Head Neck Surg. 2026.
– Mao YV et al. Extent of Surgery for Medullary Thyroid Cancer and Prevalence of Occult Contralateral Foci. JAMA Otolaryngol Head Neck Surg. 2024.
– Wells SA et al. Revised American Thyroid Association Guidelines for the Management of Medullary Thyroid Carcinoma. Thyroid. 2015.
– Liang W et al. Total Thyroidectomy vs Thyroid Lobectomy for Localized Medullary Thyroid Cancer in Adults: A Propensity-Matched Survival Analysis. Surgery. 2022.
– Yang J et al. Comparison of Lobectomy vs Total Thyroidectomy for Medullary Thyroid Carcinoma: A SEER Analysis With Chinese Cohort Validation. Oncologist. 2025.
– Spörlein A et al. Is Hemithyroidectomy Enough? Low Risk of Occult Contralateral Disease in Sporadic Medullary Thyroid Cancer. Eur Arch Otorhinolaryngol. 2026.
– Park H et al. Preoperative Identification of Low-Risk Medullary Thyroid Carcinoma: Potential Application to Reduce Total Thyroidectomy. Sci Rep. 2023.
A painless neck mass (metastatic cervical lymphadenopathy) and sore throat:
Are the two most common presenting features of oropharyngeal squamous cell carcinoma (OPSCC):
But the pattern differs strongly by HPV status:
HPV-associated tumors (tonsil, base of tongue) frequently present with an asymptomatic or occult primary and a cervical neck mass
HPV-negative tumors more often produce local symptoms from the primary site such as sore throat, dysphagia, and odynophagia:
Because these symptoms overlap with benign conditions (reflux, globus, branchial cleft cyst), any persistent neck mass or throat symptom in an adult should be considered malignant until proven otherwise
Most common presenting symptoms / signs:
Neck mass (cervical lymphadenopathy):
The single most frequent initial complaint (~ 44% to 52%):
Typically a new, painless, often cystic level II node:
Commonly the first and only sign of an HPV-associated primary
Sore throat:
Persistent, often unilateral (~ 33%)
Dysphagia:
Difficulty swallowing
Odynophagia:
Pain on swallowing
Otalgia:
Referred ear pain via the glossopharyngeal /vagal pathways:
Especially with tonsil and base-of-tongue lesions
Globus sensation:
Feeling of a mass or fullness in the throat
Visualized oropharyngeal mass or tonsillar asymmetry / ulceration
Less common / advanced-disease features:
Voice change / muffled (“hot potato”) voice
Hemoptysis or blood-tinged saliva
Unintentional weight loss
Trismus and impaired tongue mobility / dysarthria:
Reflecting deep muscular or hypoglossal nerve involvement (base of tongue), often signaling locally advanced disease
Otalgia with a normal otologic exam:
Should specifically prompt oropharyngeal evaluation
HPV-positive vs HPV-negative presentation:
This distinction is clinically important because it drives suspicion in patients lacking traditional tobacco / alcohol risk factors
Clinical caveats:
HPV-associated cystic nodal metastases are frequently mistaken for benign cysts:
The prevalence of malignancy in a cystic neck mass in patients > 40 years is approximately 80%:
So FNA (ideally image-guided) is warranted rather than observation
Anatomically hidden oropharyngeal primaries become symptomatic late, so absence of a visible lesion does not exclude malignancy:
Nasolaryngoscopy and cross-sectional imaging are indicated for persistent symptoms
OPSCC is a leading cause of carcinoma of unknown primary:
p16 / HPV testing of nodal tissue helps localize the oropharynx as the source
References:
Dunn LA, Ho AL, Pfister DG. Head and Neck Cancer. JAMA. 2025.
McIlwain WR, Sood AJ, Nguyen SA, Day TA. Initial Symptoms in Patients With HPV-Positive and HPV-Negative Oropharyngeal Cancer. JAMA Otolaryngol Head Neck Surg. 2014.
Johnson DE, Burtness B, Leemans CR, et al. Head and neck squamous cell carcinoma. Nat Rev Dis Primers. 2020.
Lechner M, Liu J, Masterson L, Fenton TR. HPV-associated oropharyngeal cancer: epidemiology, molecular biology and clinical management. Nat Rev Clin Oncol. 2022.
Wilbur J, Tran VL, Doobay MF. Evaluation of Neck Masses in Adults. Am Fam Physician. 2026. Dunn LA, Ho AL, Pfister DG. Head and Neck Cancer. JAMA. 2025.
Khalid MB, Ting P, Pai A, et al. Initial Presentation of Human Papillomavirus-Related Head and Neck Cancer: A Retrospective Review. Laryngoscope. 2019.
McIlwain WR, Sood AJ, Nguyen SA, Day TA. Initial Symptoms in Patients With HPV-Positive and HPV-Negative Oropharyngeal Cancer. JAMA Otolaryngol Head Neck Surg. 2014.
Lawless AK, Duruchukwu E, Bergamin S, et al. De-Escalation of Radiotherapy in the Treatment of Human Papillomavirus-Associated Oropharyngeal Cancer. Cochrane Database Syst Rev. 2025.
McIlwain WR, Sood AJ, Nguyen SA, Day TA. Initial Symptoms in Patients With HPV-Positive and HPV-Negative Oropharyngeal Cancer. JAMA Otolaryngol Head Neck Surg. 2014.
Johnson DE, Burtness B, Leemans CR, et al. Head and neck squamous cell carcinoma. Nat Rev Dis Primers. 2020.
Jerjes W, Upile T, Hamdoon Z, et al. Photodynamic therapy: The minimally invasive surgical intervention for advanced and/or recurrent tongue base carcinoma. Lasers Surg Med. 2011.
Wilbur J, Tran VL, Doobay MF. Evaluation of Neck Masses in Adults. Am Fam Physician. 2026.
Amin JD, Rodriggs T, Weir KA, Snider JW, Hatten KM. Prospective Evaluation of Swallowing Symptoms in Human Papillomavirus-Associated Oropharynx Cancer. Dysphagia. 2022.
Dunn LA, Ho AL, Pfister DG. Head and Neck Cancer. JAMA. 2025.
A totally implantable venous access port (TIVAP / port-a-cath) provides reliable long-term central venous access for chemotherapy, parenteral nutrition, blood products, and antibiotics. Overall reported complication rates range from about 2% to 14.4%, and are broadly lower with ultrasound-guided internal jugular vein (IJV) access and standardized protocols (Tabatabaie et al., American Journal of Clinical Oncology, 2017; Camargo et al., Scientific Reports, 2026). Complications are grouped by timing (intraoperative/immediate, early ≤30 days, late >30 days) and by anatomic origin (incision/pocket, catheter, reservoir/port).
Complication Categories and Reported Incidence
Complication Timing Reported incidence Key management Pneumothorax Intraoperative ~0.5–6% (higher with subclavian/landmark technique; ~0 with US + IJV) Observation vs. chest tube depending on size; US guidance largely eliminates risk Hemothorax Intraoperative Rare Drainage/chest tube; vascular repair if arterial laceration Arterial puncture (carotid ~3%, subclavian rarer) Intraoperative ~3% carotid Manual compression; vascular surgery if large-vessel injury Air embolism Intraoperative Rare Trendelenburg/left lateral position, 100% O2, aspiration Cardiac arrhythmia (guidewire/tip) Intraoperative Up to ~9% with tip migration Withdraw guidewire/reposition tip to cavoatrial junction Catheter malposition Early ~0.3% Fluoroscopic/endovascular repositioning (pigtail, gooseneck snare) Hematoma / pocket bleeding Early Low (minor) Compression; evacuation if expanding Wound dehiscence / skin erosion / port extrusion Early–late ~0.6% extrusion Wound care; often requires revision/explantation Infection (pocket, tunnel, exit site, CRBSI) Early–late (most common) ~1.5–5% pocket/site; CRBSI ~0.05–0.9/1000 catheter-days Systemic antibiotics ± antibiotic lock; removal for complicated infection Catheter-related thrombosis / venous stenosis Late Thrombosis ~0.3–28% (series-dependent); venous stenosis ~7% Anticoagulation; thrombolysis or removal in severe cases Catheter occlusion / fibrin sheath Late Variable Thrombolytic instillation (e.g., alteplase); fibrin sheath stripping Catheter fracture / disconnection / embolization Late Rare Endovascular retrieval; surgical revision Port flip / rotation Late Rare (single cases) Manual or surgical repositioning Extravasation Late Rare Stop infusion, aspirate, antidote per agent, surgical consult
Timing Patterns from Recent Cohorts
Standardized US-guided IJV series (n=175): 100% procedural success, no early complications, 8.0% late complications (all skin ulceration around port/catheter). Concurrent diabetes + hypertension was the only independent risk factor (HR 12.2) (Ma et al., The American Surgeon, 2026).
>1000 TIVAP series: No intraoperative/perioperative complications; 12% total complications (26.7% early, 73.3% late). Most common were infection (4.7%) and thrombosis (3.6%). Infectious complications carried the highest explantation rates; thrombotic complications were usually managed conservatively (Thiel et al., Langenbeck’s Archives of Surgery, 2022).
Large oncology cohort (n=1180): 100% technical success; early events mostly minor (pain 24.7%, bruising 9.2%). Late: site cellulitis 3.8%, CRBSI 0.25%, thrombosis 0.25%, port extrusion 0.6% (Tashi et al., Annals of the Academy of Medicine, Singapore, 2024).
Vascular surgeon image-guided series (n=443): No intraoperative/early complications; 2.0% late (infection, thrombosis, erosion, malfunction) (Kim, Journal of Surgical Research, 2025).
Infection is both the most frequent and earliest category, with a steep early rise; catheter- and port-related events accrue more gradually (Tsuruta et al., Supportive Care in Cancer, 2020).
Management Principles
Infection
Systemic antimicrobial therapy is the treatment of choice; device removal is required for complicated infection (tunnel/pocket infection, severe sepsis/septic shock, endocarditis, septic thrombophlebitis, osteomyelitis, hematogenous seeding).
Infections due to S. aureus or Candida spp. generally warrant removal. Uncomplicated CRBSI not caused by these organisms may be treated conservatively with systemic antibiotics + antibiotic lock therapy.
Remove if blood cultures remain positive 72 h after starting antibiotics (Lebeaux et al., The Lancet Infectious Diseases, 2014).
Most guidelines cite ~0.3 infections/1000 catheter-days as an acceptable upper threshold (Walser, Cardiovascular and Interventional Radiology, 2012).
Thrombosis / occlusion
Mechanical occlusions need cause-specific treatment; thrombotic occlusions usually resolve with thrombolytic instillation (e.g., alteplase).
Catheter-related thrombosis: anticoagulation for ~6 weeks to a year depending on extent and persistence of risk factors; balance against bleeding/coagulopathy risk. Anticoagulation prophylaxis is not routinely recommended (Baskin et al., Lancet, 2009).
Preventive measures: correct tip positioning at the cavoatrial junction and infection prevention.
Mechanical (fracture, migration, port flip)
Endovascular retrieval/repositioning (pigtail catheter, gooseneck snare) under fluoroscopy; surgical revision or replacement for breakage or port separation (Wang et al., Current Medical Research and Opinion, 2025).
Local skin/pocket problems
Port repositioning to a new pocket may salvage the device in selected local infections, avoiding full re-implantation (Sun et al., European Journal of Medical Research, 2025).
Prevention
Ultrasound-guided venous puncture and fluoroscopic tip confirmation reduce pneumothorax, arterial injury, and malposition.
Right IJV access is associated with lower rates of malposition, thrombosis, and pneumothorax than subclavian access.
Operator experience matters: complication likelihood is roughly halved for operators with ≥50 insertions.
Strict sterile access technique and standardized maintenance/locking protocols reduce CLABSI and occlusion.
In this comprehensive review, Fernando Cordera and I examine the evolving management of oral cavity squamous cell carcinoma (OCSCC), a disease in which surgery remains the cornerstone of treatment, but where optimal outcomes increasingly depend on precise risk stratification and coordinated multidisciplinary care.
Several important concepts emerge from the contemporary evidence:
🔹 Depth of invasion (DOI) matters. DOI has become a critical prognostic variable in oral cavity SCC, influencing T classification, the risk of occult cervical nodal metastasis, and decisions regarding management of the clinically N0 neck.
🔹 The neck must be addressed appropriately. Elective neck treatment remains a fundamental component of management for patients at meaningful risk of occult nodal disease. Sentinel lymph node biopsy is also emerging as an effective alternative to elective neck dissection in appropriately selected early-stage patients and experienced centers.
🔹 Pathology drives postoperative treatment. Margin status, nodal burden, extranodal extension, perineural invasion, lymphovascular invasion, and DOI are central to postoperative risk stratification and decisions regarding adjuvant radiation or chemoradiation.
🔹 Surgery is evolving toward oncologic control with functional preservation. Achieving adequate oncologic resection remains paramount, but contemporary treatment must simultaneously consider speech, swallowing, reconstruction, appearance, and long-term quality of life.
🔹 Immunotherapy is changing the treatment landscape. The KEYNOTE-689 trial represents an important shift in the management of selected patients with locally advanced, resectable head and neck squamous cell carcinoma, demonstrating improved event-free survival with the integration of perioperative pembrolizumab into standard treatment.
Perhaps the most important message is that oral cavity cancer can no longer be approached as surgery alone. Optimal care requires integration of head and neck surgical oncology, reconstructive surgery, radiation oncology, medical oncology, pathology, radiology, dentistry, speech and swallowing rehabilitation, nutrition, psychosocial support, and survivorship care.
Our goal with this review was to bring together the contemporary evidence—from epidemiology, anatomy and staging to surgical management, neck dissection, reconstruction, adjuvant therapy, immunotherapy, surveillance, recurrence, and survivorship—into a practical framework for clinicians treating patients with oral cavity cancer.
Reference: Arrangoiz R, Cordera F. Oral Cavity Squamous Cell Carcinoma: Contemporary Evidence-Based Management and Multidisciplinary Care. JSM Head Neck Cancer Cases Rev. 2026;6(1):1013.
An important new analysis from the NRG Oncology/NSABP B-35 randomized clinical trial, published in JAMA Surgery, challenges how rigidly we should apply margin-width thresholds in selected patients with ductal carcinoma in situ (DCIS).
Wapnir and colleagues evaluated the association between lumpectomy margin width and ipsilateral breast tumor recurrence (IBTR) among 3,104 postmenopausal women with hormone receptor–positive DCIS enrolled in NSABP B-35. All patients underwent breast-conserving surgery followed by whole-breast irradiation (WBI) and received 5 years of endocrine therapy with either tamoxifen or anastrozole. (JAMA Network)
🔹 What did the study find?
Using a 1-mm threshold, the 10-year cumulative incidence of IBTR was:
Although these differences were statistically significant or borderline significant on unadjusted analysis, the absolute differences were small—approximately 1.5–1.6% at 10 years. (JAMA Network)
More importantly, after adjustment for patient and tumor characteristics, margin width was no longer a significant independent predictor of ipsilateral recurrence. For the 2-mm threshold, the adjusted HR was 1.33 (95% CI, 0.86–2.06). (JAMA Network)
🔹 Why is this important?
Current SSO-ASTRO-ASCO consensus guidance has established 2 mm as the standard adequate margin for DCIS treated with breast-conserving surgery and WBI. However, the guideline already emphasizes that a negative margin <2 mm does not automatically mandate additional surgery and that clinical judgment should guide re-excision decisions. (ASCO Publications)
The B-35 data strengthen that concept.
For an appropriately selected postmenopausal patient with HR-positive DCIS, a negative but close margin should not necessarily trigger an automatic return to the operating room when the patient will receive whole-breast radiation and endocrine therapy.
The decision should incorporate the entire clinical picture: extent of DCIS near the margin, residual calcifications, which margin is close, patient age and comorbidities, anticipated radiation and endocrine therapy, and the potential cosmetic and morbidity consequences of another operation. (ASCO Publications)
My takeaway: The goal of DCIS surgery should remain oncologically sound excision, but margin width should be interpreted as part of the overall treatment strategy rather than as an isolated number.
A 2-mm margin remains an important benchmark, but these prospective trial data support a more individualized approach to re-excision—particularly when the margin is negative and effective adjuvant therapy is planned.
Importantly, these findings should not be generalized to all patients with DCIS. The B-35 population consisted specifically of postmenopausal women with HR-positive DCIS receiving both WBI and endocrine therapy. (JAMA Network)
References
Wapnir IL, Cecchini RS, Dignam JJ, et al. Lumpectomy Margins and Local Recurrence in DCIS: Results From the NRG Oncology/NSABP B-35 Randomized Clinical Trial. JAMA Surg. 2026;161(9):861-869. doi:10.1001/jamasurg.2026.2340. (JAMA Network)
Morrow M, Van Zee KJ, Solin LJ, et al. Society of Surgical Oncology–American Society for Radiation Oncology–American Society of Clinical Oncology Consensus Guideline on Margins for Breast-Conserving Surgery With Whole-Breast Irradiation in Ductal Carcinoma In Situ. J Clin Oncol. 2016;34(33):4040-4046. (ASCO Publications)
Morrow M, Abrahamse P, Hofer TP, et al. Lumpectomy Margins for Invasive Breast Cancer and Ductal Carcinoma in Situ: Current Guideline Recommendations, Their Implications, and Impact. J Clin Oncol. 2020. (ASCO Publications)
