[A Patient with Cancer of Unknown Primary Who Responded to Chemotherapy].

Cancer of unknown primary is a class of malignant tumors, histologically identified as metastatic lesions whose primary origin is unknown despite adequate investigations for the primary tumor. Although the prognosis of cancer of unknown primary is generally poor, here, we report our experience with a patient who responded to chemotherapy. The patient was a 78-year-old woman. She had a history of gastric cancer at the age of 76 years. In June of year X-1, she was diagnosed with gastric cancer(tub1>tub2, pT1bN0M0, pStage Ⅰa)and underwent distal gastrectomy. One year after surgery, computed tomography revealed right supraclavicular lymphadenopathy, for which cervical lymphadenectomy was performed. The pathological diagnosis was ductal carcinoma with comedo necrosis and poorly differentiated solid adenocarcinoma that were suggestive of metastases from breast cancer. However, a detailed examination of the mammary glands revealed no mass. Imaging studies led to a diagnosis of cancer of unknown primary. Therefore, chemotherapy, according to the treatment of pancreatic cancer, was planned based on immunostaining, tumor markers, etc. Chemotherapy response evaluation after completing 4 courses demonstrated a partial response; the patient responded to the chemotherapy. We considered that estimating primary lesions from histopathological images, tumor markers, etc., may help determine effective chemotherapy regimens.

Inguinal nodal metastatic squamous cell carcinoma of unknown primary (CUP) detected 7 years before the diagnosis of vulvar squamous cell carcinoma: A case report.

OBJECTIVE: Metastatic squamous cell carcinoma (SCC) of inguinal lymph node region with unknown origin is a rare condition. A patient was diagnosed to have vulvar SCC 7 years after the initial diagnosis of inguinal nodal metastatic SCC of unknown primary. CASE REPORT: A 59-year-old woman with metastatic SCC of unknown origin in the right inguinal lymph node underwent tumor resection and no evidence of residual disease or possible tumor origin was detected after the surgery and a comprehensive work-up. Seven years later, she was diagnosed to have invasive right vulvar SCC with right pelvic lymph node metastasis. We performed a series of tests to evaluate the relationship between these two events. CONCLUSION: According to our investigation, the possible relationship between the two events could not be ruled out. This case emphasizes the possibility of late recurrence and the importance of long-term follow up for patients with isolated nodal CUP.

Transoral robotic surgery in HPV+ oropharyngeal cancer of unknown primary.

PURPOSE: This study was designed to assess trends in and outcomes associated with TORS-treated HNCUP using a large national database. MATERIALS AND METHODS: HPV+ oropharyngeal HNCUPs were isolated from the 2004-2017 National Cancer Database. Overall survival (OS) was assessed, with patients stratified by 1) use of TORS and 2) whether the occult tumor was ultimately located. Demographic and oncologic predictors of survival were evaluated on regression. RESULTS: The cohort contained 284,734 cases, of which 8336 were HNCUPs. HNCUPs represented 2.49 % of all HNSCC in 2010 versus 3.13 % in 2017. 3897 (46.7 %) of these unknown primaries were ultimately identified. The proportion of cases treated with TORS increased from 6.9 % in 2010 to 18.1 % in 2017 (p < 0.001). Kaplan-Meier analysis of 2991 HPV+ oropharyngeal HNCUPs demonstrated higher 5-year overall survival (OS) for patients treated with robotic surgery versus no robotic surgery (95.4 % ± 1.7 % standard error [SE] versus 84.0 % ± 0.9 % SE; p < 0.001). Patients with primary tumors identified during treatment had improved OS compared to those whose tumors were not located (5-year OS was 90.5 % ± 0.9 % SE and 77.3 % ± 1.5 % SE, respectively; p < 0.001). For patients in which the primary tumor was found, those who received robotic surgery survived longer than those who did not (96.5 % ± 1.4 % SE versus 89.1 % ± 1.0 % SE 5-year OS; p < 0.001). The relationship between TORS and OS remained significant on Cox regression controlling for confounders. CONCLUSIONS: Use of TORS in the workup for HPV+ HNCUP is associated with higher rates of tumor identification and improved OS.

Step Serial Sectioning in Head and Neck Squamous Cell Carcinoma of Unknown Primary.

Importance: Patients with suspected head and neck squamous cell carcinoma of unknown primary (HNSCCUP) may undergo tonsillectomy and tongue base mucosectomy (TBM) to help identify clinicoradiologically occult primary disease. It is hypothesized that when these diagnostic specimens are analyzed, conventional histopathological (CH) techniques risk missing small primary tumors that may be hidden in the tissue blocks. Objective: To establish the outcomes of a step serial sectioning (SSS) histopathological technique vs CH when analyzing diagnostic tissue specimens from TBM and tonsillectomy performed for HNSCCUP. Design, Setting, and Participants: The MOSES prospective multicenter noninterventional cohort study was conducted over a 25-month period from November 2019 at secondary and tertiary care ear, nose, and throat departments in the United Kingdom and included adults with clinicoradiologically occult HNSCCUP who were undergoing TBM. Intervention: Conventional histopathological techniques performed on TBM and tonsillectomy specimens at participating centers, followed by SSS performed at the central laboratory. Main Outcome: Identification of cancer on central histopathological review of TBM and tonsillectomy specimens. Results: Tissue from 58 eligible patients was analyzed (median [range] age, 58 [47-82] years; 10 women [17%]), with 20 480 sections cut in the laboratory and 4096 sections directly examined by a pathologist (median [range], 64 [28-135] per patient). The overall identification rate for TBM following SSS according to study protocol was 50.0% (95% CI, 37.5%-62.5%) and by subgroups was 42.9% (95% CI, 21.4%-67.4%) when performed following a negative bilateral tonsillectomy, 46.7% (95% CI, 24.8%-69.9%) at the same time as bilateral tonsillectomy, and 57.1% (95% CI, 36.5%-75.5%) following historic tonsillectomy. Conventional histopathological techniques at central review identified 2 undiagnosed primary tumors and revised the diagnosis of 2 other cases (1 nonmalignant and another down staged). Step serial sectioning identified a single additional tumor: an ipsilateral synchronous tongue base tumor for which a contralateral tumor had been identified on CH. Multifocal disease was seen in 5 (8.6%); all were human papillomavirus-related and in the tongue base. Conclusions and Relevance: In this multicenter cohort study of patients undergoing TBM for HNSCCUP, SSS was associated with added considerable histopathological workload with minimal additional diagnostic benefit. A second opinion for conventional histological techniques may be more beneficial. Synchronous primary disease should be considered when planning diagnostic oropharyngeal surgery for these patients.

A Look at the Other Side: High-Risk Lesions and Occult Contralateral Malignancy in Symmetry Procedures for Patients Undergoing Oncoplastic Breast-Conserving Surgery.

BACKGROUND: The incidence of occult breast cancer among patients undergoing reduction mammoplasty or risk-reducing mastectomies ranges from 1% to approximately 10%, respectively. Identification of incidental cancer often mandates subsequent mastectomy due to ambiguous margins. This study aimed to determine the incidence of contralateral malignancy among patients undergoing oncoplastic breast-conserving surgery (OBCS) with concurrent symmetry procedures. METHODS: The authors reviewed their prospectively maintained institutional database of patients with unilateral breast cancer who underwent OBCS. Patients who underwent excisional biopsy on the contralateral breast were analyzed separately. Patient demographics, pathologic features, and subsequent disease management were evaluated. RESULTS: Between March 2018 and July 2022, 289 patients underwent OBCS with a symmetry procedure, and 100 patients yielded contralateral breast tissue specimens. For 14 patients, a planned excisional biopsy was performed with their symmetry procedure, and five lesions (36%) were found to be malignant. Of the remaining 86 patients, 92% underwent preoperative breast magnetic resonance imaging (MRI). Four patients (4.7%) had occult malignancies identified on the contralateral breast pathology; three patients with ductal carcinoma in situ and one patient with invasive lobular carcinoma. Three patients had undergone preoperative MRI without suspicious findings. No patients required mastectomy for treatment of the contralateral breast cancer. CONCLUSION: The incidence of occult malignancy among OBCS symmetry procedures approaches 5%. The final pathology of excisional biopsies had a higher upgrade rate than previously reported. All identified malignancies were early-stage disease. The higher incidence of occult breast cancer in this population warrants the routine orientation of all specimens, which allows patients with incidental early-stage cancer the option of breast preservation.

Portsite metastasis of adenocarcinoma after laparoscopic cholecystectomy with an unknown primary tumor: a case report.

Port site metastasis of adenocarcinoma after laparoscopic cholecystectomy with an unknown primary tumor is rare. To the best of our knowledge, there are only four such cases reported worldwide. We report a woman in her 70s with cholecystitis who underwent laparoscopic cholecystectomy. Intraoperative laparoscopic exploration did not reveal an abdominal tumor, and postoperative gallbladder pathology did not suggest malignancy. However, 11 months later, she developed an incisional mass in the epigastric port site. In another 6 months, magnetic resonance imaging revealed an abdominal wall tumor. Therefore, she underwent radical resection of the subcutaneous tumor, and postoperative pathology revealed adenocarcinoma. However, no primary tumor was found after systemic imaging examination.

Surgical debulking is associated with improved survival for patients with neuroendocrine liver metastases of unknown primary.

BACKGROUND: Resection of neuroendocrine tumors (NET) with surgical debulking of liver metastasis (NETLM) is associated with improved survival. In patients with an unknown primary (UP-NETLM), the effects of debulking remains unclear. METHODS: The National Cancer Database (2004-2016) was queried for patients with small intestine (SI) and pancreas (P) NETLMs. If the liver was listed as the primary site, the patient's disease was classified as UP-NETLM. RESULTS: Patients with UP-NETLM, SI-NETLM, and P-NETLM who were managed non-operatively demonstrated a significant difference in 5-year overall survival (OS) (21.5% vs. 39.2% vs. 17.1%; p < 0.0001). OS in patients who underwent debulking was higher (63.7% vs. 73.2% vs. 54.2%). Patients with UP-NETLMs who underwent debulking had similar OS to patient with SI-NETLM (p = 0.051), but significantly higher OS, depending on tumor differentiation, compared to patients with P-NETLMs. If well-differentiated, surgery for UP-NETLMs was associated with a higher rate of OS (p = 0.009), while no difference was observed if moderately (p = 0.209) or poorly/undifferentiated (p = 0.633). P-NETLMs were associated with worse OS (p < 0.001) on multivariate analysis. DISCUSSION: Debulking in patients with UP-NETLMs was associated with similar OS compared to patients with SI-NETLMs and better or similar OS compared to patient with P-NETLMs.

Clinical characteristics and outcomes of cervical lymph node metastasis from unknown primary sites: a single institution's 14-year experience.

BACKGROUND: Cervical lymph node metastasis from unknown primary sites is a challenging clinical issue with a changing therapy model and unpredictable outcomes, which leads to the difficulty in selecting optimal treatments. Thus, it is valuable to analyze the clinical characteristics and outcomes of the patients who receive different management styles. METHODS: All patients with cervical lymph node metastasis from unknown primary sites were reviewed and no primary lesions were found. In addition, this work was funded by the Clinical Trial Fund Project of Tianjin Medical University Cancer Institute and Hospital (No. C1716). Specifically, we used univariate, multiple regression analysis to evaluate the factors associated with prognosis. RESULTS: 365 patients met the inclusion criteria, and the 2- and 5-year survival rates were 77.0% and 33.4%, respectively, with a median survival of 45 months. Gender, age, pathological type, nodal status, and necessary cervical lymph node dissection affected locoregional control. Distant metastasis was common in individuals with a pathological type of adenocarcinoma, poor differentiation, and advanced nodal status. Furthermore, patients who received induction chemotherapy had a better prognosis than those treated with postoperative chemotherapy. Multiple regression analysis showed that pathological grade, treatment models, and distant metastasis were associated with overall survival (OS) and progression-free survival (PFS). In addition, local recurrence exerted a significant influence on OS. Induction chemotherapy and postsurgical radiotherapy seemed to improve the prognosis of patients at the advanced stage compared with simple surgery and postsurgical chemotherapy. CONCLUSIONS: Pathological grade, treatment models, and distant metastasis were independent risk factors for prognosis. Induction chemotherapy or postoperative radiotherapy benefited patients at the advanced stage, and patients with adenocarcinoma, poor differentiation, and advanced nodal status should undergo induction chemotherapy in light of the increased risk of distant metastasis.

Survival after lymphadenectomy of nodal metastases from melanoma of unknown primary site.

Although the vast majority of melanomas have a primary site, 3%-4% of all melanomas in distant sites display no known primary site (MUP). This phenomenon is not fully understood and various hypotheses have been introduced. The prognostic significance of MUP has been unclear, with some studies showing no survival benefit while others find improved survival compared to stage-matched patients with melanoma of known primary site (MKP). Between 1997 and 2014, 864 patients underwent an en bloc resection of clinical nodal metastases at a referral centre for metastatic melanoma in Norway. The MUP (n = 113) and MKP (n = 751) patients were graded with stage III or IV. The overall survival (OS) was calculated with the Kaplan-Meier method, and multivariate analysis identified factors of significance for the two groups. A significant five-year OS emerged for stage III, MUP = 58% and 42% for MKP, but not for stage IV. The five-year relapse-free survival (RFS) was 41% and 31% for MUP and MKP respectively (p = 0.049). The statistically significant inter-group differences (MUP/MKP) were observed in the univariate and multivariate analyses of age, gender, number of affected nodes, tumour size and perinodal growth within stage III and tumour size within stage IV. After regional lymphadenectomy, MUP patients with clinical nodal metastases had a better outcome than MKP patients. This finding supports the theory that an endogenously mediated immune response may promote the regression of a cutaneous melanoma.

Laser tongue base mucosectomy is a useful diagnostic tool in the management of unknown primary cancers of the head and neck region.

OBJECTIVE: Tongue base mucosectomy identified cancer in 78 per cent of cancers of unknown primary in a recent meta-analysis. The carbon dioxide laser is an alternative technique if there is no access to a robot. This study aimed to describe the steps for undertaking tongue base mucosectomy using the carbon dioxide laser and its diagnostic utility in cancers of unknown primary. METHOD: This was a prospective feasibility study utilising carbon dioxide laser for tongue base mucosectomy in cancers of unknown primary. Data collected included demographic data and p16 status. RESULTS: There were 14 cancers of unknown primary with 86 per cent p16 positivity on immunohistochemistry. Laser tongue base mucosectomy alone identified the cancer primary in 7 of 12 (58 per cent) cancers of unknown primary among p16 positive tumours and 0 of 2 (0 per cent) among p16 negative tumours. Combining bilateral tonsillectomy with laser tongue base mucosectomy resulted in identification of the primary cancer in 8 of 12 (67 per cent) p16 positive tumours. CONCLUSION: In centres without a robot, tongue base mucosectomy using the carbon dioxide laser is a viable alternative, especially in combination with bilateral tonsillectomy in p16 positive cases.

Transoral endoscopic ultrasonic surgery (TOUSS) in head & neck unknown primary carcinoma investigation.

Metastatic carcinoma of unknown primary (CUP) to cervical lymph nodes represents less than 5% of all head and neck malignancies. Recent publications support the use of transoral surgery during the diagnosis work-up, and transoral endoscopic ultrasonic surgery represent a recently described alternative technique in transoral surgery. A pilot study to assess the feasibility of trans-oral ultrasonic base of tongue (BOT) mucosectomy and bilateral tonsillectomy approach in CUP diagnosis work-up was conducted. Ten patients were included consecutively. In 2 cases (20%) the primary was found, in one case in the right tonsil, and another one in the left BOT. According to our results, the use of trans-oral ultrasonic surgery to perform the base of tongue mucosectomy and bilateral tonsillectomy in CUP patient's during the diagnosis work-up represents an effective option in patients with good anatomical exposure.

Prophylactic mastectomy and occult malignancy: Surgical and imaging considerations.

BACKGROUND: Sentinel node biopsy (SLNB) is not routinely recommended for patients undergoing prophylactic mastectomy (PM), yet omission remains a subject of debate among surgeons. A modern patient cohort was examined to determine occult malignancy (OM) incidence within PM specimens to reinforce current recommendations. METHODS: All PM performed over a 5-year period were retrospectively identified, including women with unilateral breast cancer who underwent synchronous or delayed contralateral PM or women with elevated cancer risk who underwent bilateral PM. RESULTS: The study population included 772 patients (598 CPM, 174 BPM) with a total of 39 OM identified: 17 invasive cancers (14 CPM, 3 BPM) and 22 DCIS (19 CPM, 3 BPM). Of the 86 patients for whom SLNB was selectively performed, 1 micrometastasis was identified. In the CPM cohort, risk of OM increased with age, presence of LCIS of either breast, or presence of a non-BRCA high-penetrance gene mutation, while preoperative magnetic resonance imaging was associated with lower likelihood of OM. CONCLUSIONS: Given the low incidence of invasive OM in this updated series, routine SLNB is of low value for patients undergoing PM. For patients with indeterminate radiographic findings, discordant preoperative biopsies, LCIS, or non-BRCA high-penetrance gene mutations, selective SLNB implementation could be considered.

Microsatellite Instability-high-positive Cancer of Unknown Primary Origin with a Long-term Survival after Surgery Alone.

An 80-year-old woman was referred to our hospital for a thorough examination of enlarged lymph nodes on the lesser curvature of the stomach. Upon suspicion of malignant lymphoma, the patient underwent open lymphadenectomy and was diagnosed with lymph node metastasis of poorly differentiated adenocarcinoma. The patient was subsequently diagnosed with microsatellite instability-high cancer of unknown primary origin. Surgical removal of the affected lymph nodes achieved full remission. Chemotherapy was considered in case of recurrence or identification of the primary site. Recurrence has not occurred in three years since the surgery. However, a long-term survival without chemotherapy is rare.

Intraoperative delineation of p16+ oropharyngeal carcinoma of unknown primary origin with fluorescence lifetime imaging: Preliminary report.

BACKGROUND: This study evaluated whether fluorescence lifetime imaging (FLIm), coupled with standard diagnostic workups, could enhance primary lesion detection in patients with p16+ head and neck squamous cell carcinoma of the unknown primary (HNSCCUP). METHODS: FLIm was integrated into transoral robotic surgery to acquire optical data on six HNSCCUP patients' oropharyngeal tissues. An additional 55-patient FLIm dataset, comprising conventional primary tumors, trained a machine learning classifier; the output predicted the presence and location of HNSCCUP for the six patients. Validation was performed using histopathology. RESULTS: Among the six HNSCCUP patients, p16+ occult primary was surgically identified in three patients, whereas three patients ultimately had no identifiable primary site in the oropharynx. FLIm correctly detected HNSCCUP in all three patients (ROC-AUC: 0.90 ± 0.06), and correctly predicted benign oropharyngeal tissue for the remaining three patients. The mean sensitivity was 95% ± 3.5%, and specificity 89% ± 12.7%. CONCLUSIONS: FLIm may be a useful diagnostic adjunct for detecting HNSCCUP.

An abdominal wall neuroendocrine tumor of unknown primary origin: A case report and review of the literature.

BACKGROUND: Neuroendocrine tumors (NETs) are neoplasms that arise from cells of the endocrine and nervous system. NETs, often found in the gastrointestinal tract, can be found anywhere in the body, and have metastatic potential. NETs occasionally present with metastatic disease without an identifiable primary tumor. CASE: A 79-year-old female patient presented with an abdominal wall mass. Percutaneous biopsy was consistent with a NET. Preoperative endoscopy and PillCam were unremarkable. PET Dotatate demonstrated uptake in the abdominal wall as well as vague uptake in the pelvis. Intraoperatively, we identified a suspicious nodule on the sigmoid colon, which was consistent with a drop metastasis on final pathology. CONCLUSION: In this case report we present a patient with a NET metastasis to the abdominal wall without a known primary site. This case highlights the limitations of endoscopy and imaging in the workup of metastatic NETs. Additionally, this is a novel case report of a metastatic NET to the abdominal wall without an identifiable primary site.

Relevance of the time interval between surgery and adjuvant radio (chemo) therapy in HPV-negative and advanced head and neck carcinoma of unknown primary (CUP).

INTRODUCTION: In contrast to head and neck squamous cell carcinoma (HNSCC), the effect of treatment duration in HNSCC-CUP has not been thoroughly investigated. Thus, this study aimed to assess the impact of the time interval between surgery and adjuvant therapy on the oncologic outcome, in particular the 5-year overall survival rate (OS), in advanced stage, HPV-negative CUPs at a tertiary referral hospital. 5-year disease specific survival rate (DSS) and progression free survival rate (PFS) are defined as secondary objectives. MATERIAL AND METHODS: Between January 1st, 2007, and March 31st, 2020 a total of 131 patients with CUP were treated. Out of these, 59 patients with a confirmed negative p16 analysis were referred to a so-called CUP-panendoscopy with simultaneous unilateral neck dissection followed by adjuvant therapy. The cut-off between tumor removal and delivery of adjuvant therapy was set at the median, i.e. patients receiving adjuvant therapy below or above the median time interval. RESULTS: Depending on the median time interval of 55 days (d) (95% CI 51.42-84.52), 30 patients received adjuvant therapy within 55 d (mean 41.69 d, SD = 9.03) after surgery in contrast to 29 patients at least after 55 d (mean 73.21 d, SD = 19.16). All patients involved in the study were diagnosed in advanced tumor stages UICC III (n = 4; 6.8%), IVA (n = 27; 45.8%) and IVB (n = 28; 47.5%). Every patient was treated with curative neck dissection. Adjuvant chemo (immune) radiation was performed in 55 patients (93.2%), 4 patients (6.8%) underwent adjuvant radiation only. The mean follow-up time was 43.6 months (SD = 36.7 months). The 5-year OS rate for all patients involved was 71% (95% CI 0.55-0.86). For those patients receiving adjuvant therapy within 55 d (77, 95% CI 0.48-1.06) the OS rate was higher, yet not significantly different from those with delayed treatment (64, 95% CI 0.42-0.80; X2(1) = 1.16, p = 0.281). Regarding all patients, the 5-year DSS rate was 86% (95% CI 0.75-0.96). Patients submitted to adjuvant treatment in less than 55 d the DSS rate was 95% (95% CI 0.89-1.01) compared to patients submitted to adjuvant treatment equal or later than 55 d (76% (95% CI 0.57-0.95; X2(1) = 2.32, p = 0.128). The 5-year PFS rate of the entire cohort was 72% (95% CI 0.59-0.85). In the group < 55 d the PFS rate was 78% (95% CI 0.63-0.94) and thus not significantly different from 65% (95% CI 0.45-0.85) of the group ≥55 d; (X2(1) = 0.29, p = 0.589). CONCLUSIONS: The results presented suggest that the oncologic outcome of patients with advanced, HPV-negative CUP of the head and neck was not significantly affected by a prolonged period between surgery and adjuvant therapy. Nevertheless, oncologic outcome tends to be superior for early adjuvant therapy.

Does knowledge of the primary tumour affect survival after surgery for spinal metastatic disease? A retrospective longitudinal cohort study.

OBJECTIVES: To compare survival after surgery for patients with spinal metastatic disease with known primary tumour (KPT) versus patients with unknown primary tumour (UPT). PARTICIPANTS: 393 patients 18 years or older (270 men and 123 women, mean age 67.3 years) undergoing surgery at Uppsala University Hospital in Swedenbetween 2006 and 2016due to spinal metastatic disease . 271 patients (69%) had a KPT at the time of surgery and 122 (31%) had an UPT. INTERVENTIONS: Decompressive and/or stabilising spine surgery due to spinal metastatic disease. PRIMARY OUTCOME: Survival (median and mean) after surgery. RESULTS: The estimated median survival time after surgery for patients with KPT was 7.4 months (95% CI 6.0 to 8.7) and mean survival time was 21.6 months (95% CI 17.2 to 26.0). For patients with UPT, the median estimated survival time after surgery was 15.6 months (95% CI 7.5 to 23.7) and the mean survival time was 48.1 months (95% CI 37.3 to 59.0) (Breslow, p=0.001). Unknown primary cancer was a positive predictor of survival after surgery (Cox regression, HR=0.58, 95% CI 0.46 to 0.73). CONCLUSION: In this study, patients with spinal metastasis and UPT had a longer expected survival after surgery compared with patients with KPT. This suggests that patients with UPT and spinal metastasis should not be withheld from surgery only based on the fact that the primary tumour is unknown.

TORS elective lingual tonsillectomy has less acute morbidity than therapeutic base of tongue TORS.

OBJECTIVE: To determine the impact of diagnostic TORS lingual tonsillectomy (DTLT) on objective swallowing measures for carcinoma of unknown primary (CUP). METHODS: Between 10/2016-1/2020, 27 patients with p16+ squamous cell carcinoma (SCC) level 2a nodal disease underwent DTLT and ipsilateral neck dissection for CUP. No patient had a history of cutaneous SCC. Patients participated in Modified Barium Swallow (MBS) three weeks post-TORS, which were then compared to those from a contemporaneous cohort of 40 patients with clinically-identified p16+ base of tongue (BOT) primary tumors. DIGEST scores were retrospectively calculated. Univariate and multivariate analysis performed, stratified by BOT glossectomy (n = 40) versus lingual tonsillectomy for CUP (n = 27). Radiation to the resected primary or potential primary sources was omitted if margins were ≥3 mm or if no primary identified. RESULTS: Twenty-seven consecutive patients with clinical stage cT0N1 HPV-associated OPSCC had a BOT primary pathologically identified in 18/27 (67%). Univariate analysis of functional swallow assessment on MBSImP correlated with improved post-TORS DIGEST scores for CUP. On multivariate analysis (MVA) DIGEST safety scores were improved for CUP than cT1 BOT glossectomy [Odds Ratio (OR) 0.28, p = 0.038]. MVA on matched pT1 CUP (n = 27) vs. pT1 BOT (n = 19), OR of moderate/severe dysphagia for CUP was 0.54 [0.12-2.38, p = 0.417] for DIGEST safety scores and 0.27 [0.06-1.18, p = 0.082] for DIGEST efficiency scores. Moderate/severe dysphagia as determined by DIGEST overall scores for CUP compared to cT1 and pT1 yielded an OR of 0.39 (p = 0.081) and 0.42 (p = 0.195), respectively. Twenty-six total patients received adjuvant RT, and 18 (11 with ≥3 mm margins, 9 with negative specimens) were spared intentional RT to the oropharynx. Median follow-up was 22.6 months with 100% PFS. CONCLUSIONS: Patients undergoing DTLT for CUP demonstrated acute swallow defecits in the post-operative setting. A comparison of long-term functional results between DTLT and elective irradiation of the primary site should be studied. LEVEL OF EVIDENCE: Level III.