Occult invasive disease was present in approximately 25% of patients with oral cavity carcinoma in situ, according to results of a retrospective study of data from nearly 2000 individuals.
Although de-escalated treatment strategies are appealing, the risk for occult invasive disease in an oral cavity lesion in patients with biopsy-confirmed oral cavity carcinoma in situ remains unknown, said Dylan Cooper, BA, a fourth-year medical student at the Zucker School of Medicine at Hofstra/Northwell Health, New York City.
“Knowing whether occult invasive disease is present — and its impact on survival outcomes — will lead to more informed management decisions and enable providers to have more effective communication and discussions with patients while managing this relatively common condition,” Cooper told Medscape Medical News.
In the study, which was presented at the annual meeting of the American Academy of Otolaryngology-Head and Neck Surgery, the researchers characterized the rate of occult invasive disease in patients with biopsies indicative of oral cavity carcinoma in situ.
“We also compared clinical outcomes in patients who proceeded with observation vs surgical excision,” Cooper explained.
Cooper and colleagues reviewed 1876 patients from the National Cancer Database with biopsy-proven cTis of the oral cavity from 2004 through 2020. Of these, 1733 proceeded to surgical resection and 143 remained under observation.
After resection, 449 of the 1733 patients (25.9%) had invasive occult disease, defined by the American Joint Committee on Cancer (AJCC) as a pathologic T stage of pT1 or above.
The majority of the patients with invasive disease (83.3%) were at the pT1 stage.
Rates of invasion varied with anatomic location. In a multivariable analysis, the alveolar ridge/retromolar site was associated with a significantly higher rate of occult invasive disease at resection (40%) than the oral tongue, which had the lowest rate (24.1%, P < .001). Over a mean follow-up period of 68 months, surgical resection was associated with an almost 30% increase in 5-year overall survival compared with patients who did not undergo resection (84.8% vs. 55.2%).
The increased risk of invasive disease associated with lesions of the alveolar ridge/retromolar trigone may be attributable to larger lesion size at detection or difficulty fully visualizing lesions in this area, as this site remained a significant predictor of invasive disease in a multivariate analysis.
The findings were limited by several factors, including the retrospective design and incomplete data on local control and disease-specific survival, as well as selection bias and variability in biopsy sampling, Cooper noted.
However, the study is the first known to characterize the risk of occult invasion in oral cavity carcinoma in situ, and the findings make a case for definitive resection after biopsies demonstrating invasive disease in these patients, he said.
Foundation for Future Research
“The discrepancy in 5-year overall survival between patients who were observed vs resected was starker than we had anticipated,” Cooper told Medscape Medical News.
“We also discovered certain factors that led to greater odds of occult invasive disease at resection, including female sex, Black race, and alveolar ridge, vestibule, and retromolar subsite, so it’s important to keep an eye out for these higher-risk patients,” he said.
For clinical practice, the take-home message is simple: “Given the high risk of occult invasive disease, definitive surgical resection of biopsy-proven carcinoma in situ is the optimal management strategy for this challenging clinical scenario,” said Cooper.
Looking ahead, “increased attention is being paid toward identifying early driver mutations in oral cancer and mapping the temporal order of these lesions throughout the steps of cancer progression,” he added. “A better understanding of the mutational signature patterns of these lesions may lead to a more accurate prediction of the cancer progression trajectory.”
“Further research is needed to triangulate molecular profiling of biopsied tumors with clinical knowledge of areas with increased risk for occult invasion to improve patient outcomes in the future,” Cooper explained.
“We hope this study will provide guidance to patients and physicians confronted with this challenging clinical scenario,” said senior author Wesley Talcott, MD, MBA, also from the Zucker School of Medicine at Hofstra/Northwell Health.
Correct Identification Promotes Informed Care
Studying the management of oral cavity carcinoma in situ “helps guide our discussions with patients on the recommendation for removal rather than observation,” said Rod Rezaee, MD, of Case Western Reserve University, Cleveland, Ohio, in an interview.
With a diagnosis of carcinoma in situ, clinicians can tell patients that, while they do not have cancer, there is a 25% chance of cancer somewhere in the area of the lesion that was not biopsied, said Rezaee, who served as a moderator for the session in which the study was presented. This information will help patients make informed decisions about treatment, he said.
The findings of the current study were not surprising, “as it can be challenging to determine early invasion with visual and physical exam alone in some cases,” Rezaee told Medscape Medical News. The findings support the concept that biopsy and pathological analysis are critical in helping to correctly identify the lesion.
“While the study is limited by its retrospective and database nature, it nonetheless tells us that in 25% of patients something that was thought to be precancerous actually had a component of cancer present near the initial biopsy site,” he said.
In practice, the data can help guide discussions with patients to support the recommendation of removal and the technique of removal, said Rezaee. The data support “actual surgical removal with specimen analysis to check the entire lesion, rather than techniques that do not allow for this analysis,” such as the laser ablation offered to patients for oral cavity lesions in some settings, he explained.
Looking ahead, “there are many limitations to database and retrospective studies, so these results need to be interpreted with caution,” said Rezaee. A prospective, randomized trial is needed to confirm the findings from a statistical and study design standpoint, he noted.
The study received no outside funding. The researchers and Rezaee reported no relevant financial relationships.
AAO/HNSF 2023: Occult Invasive Disease in Oral Cavity Carcinoma In Situ. Presented October 1, 2023, Best of the Scientific Orals 2.
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