T1a Tumors Research Articles

Partial Nephrectomy in pT3a Tumors Less Than 7 cm in Diameter Has a Superior Overall Survival Compared to Radical Nephrectomy.

ObjectivesWe conducted this study to analyze the survival rates of patients with advanced renal tumors <7 cm in diameter treated surgically by partial nephrectomy (PN) compared to those who received radical nephrectomy (RN).Material and methodsWe retrospectively analyzed clinical data from 55 consecutive patients from our institutional database with T3a renal cell carcinoma of <7 cm treated surgically either by PN (n = 38) or RN (n = 17) in the Department of Urology of Ludwig Maximilians University from January 2006 to August 2014. The overall survival (OS) rates were calculated according to Kaplan-Meier estimation.ResultsThe median age of the population was 67.9 years (range: 39.4 to 87.9 years). The median blood loss was 164.1 ml (range: 0 to 1200 ml), and the median clamping time was 8.85 minutes (range: 0 to 38 minutes). On average, the surgery lasted for 118 minutes (range: 40 to 210 minutes). The median serum creatinine level measured was 1.2 mg/dl (range: 0.7 to 2.3 mg/dl) preoperatively, and 1.4 mg/dl (range: 0.7 to 4.3 mg/dl) postoperatively. The median creatinine serum level measured during follow up was 1.4 ng/ml in individuals with a PN (range: 0.7 to 3.2 ng/ml), and 1.5 ng/ml in those with an RN (range: 0.9 to 4.3 ng/ml). Patients with an RN had a median OS of 38.6 months (range: 0 to 63.3 months). The median OS for patients with a PN was not reached after a follow-up of 80 months. The difference in OS in patients with PN and RN was statistically significant (P < 0.005).ConclusionPerforming a PN in T3a tumors leads to better survival rates compared to an RN. In tumors <7cm, cT3a does not seem to be a contraindication for a PN. Further data should be analyzed to prove this survival benefit in a larger, multi-institutional cohort.

Influencing Factors on Radiotherapy Outcome in Stage I-II Glottic Larynx Cancer-A Multicenter Study.

Background and Purpose: Larynx cancer represents one of the most frequently diagnosed head and neck malignancies, which is most often confined to the glottic area. The aim of this study was to report the oncological outcome and identify prognostic factors in early-stage glottic squamous cell carcinoma treated with radiotherapy.Material and Methods: Patients (n = 761) diagnosed and treated in 10 centers between 1990 and 2015 were retrospectively analyzed. Probabilities of loco-regional control (LRC) and overall survival (OS) were calculated and possible prognostic factors were analyzed using Cox proportional hazards models.Results: The median follow-up was 63 months (range: 2–243). Three hundred and sixty-four, 148 and 249 patients had cT1a, cT1b, and cT2 stage I-II disease, respectively. Five and 10-years LRC/OS rates in the whole cohort were 83/82% and 80/68%, respectively. Three patients developed distant recurrences. In univariate analysis, male sex (HR: 3.49; 95% CI: 1.47–11.37; p < 0.01), T2 vs. T1a (HR: 1.62; 95% CI: 1.08–2.43; p = 0.02) and anterior commissure involvement (ACI) (HR: 1.66; 95% CI: 1.38–2.45; p < 0.01) were associated with impaired LRC. In multivariate analysis, male sex (HR: 3.42; 95% CI: 1.44–11.17; p < 0.01) and ACI (HR: 1.51; 95% CI: 1.01–2.28; p = 0.047) remained poor prognostic factors. No relation of treatment technique and biologically equivalent dose (BED) to oncological outcome was identified except for higher BED10(L = 25; T = 1) yielding better LRC in T1a tumors (p = 0.04) in univariate analyses.Conclusion: Our results highlight the negative impact of ACI on tumor control. A less-expected finding was the impact of sex on tumor control. Further research is needed to validate its prognostic value and investigate any related biologic or behavioral factors, which may be modified to improve oncologic outcome.

Is multidetector CT-scan able to detect T3a renal tumor before surgery?

Objective: To evaluate the diagnostic accuracy of multidetector Computed Tomography (MDCT) in predicting T3a renal cell carcinoma (RCC).Materials and methods: Preoperative MDCT of 96 patients with 100 pathologically proven RCC were assessed by two radiologists focusing on the presence of peritumoral fat, sinus fat or venous invasion for cT3a staging. Nature of tumor margins and the presence of peritumoral neovessels were also evaluated, as the influence of perinephric soft-tissue stranding in the interpretation of peritumoral fat.Results: Sensitivity for the identification of peritumoral fat, sinus fat or renal vein invasion was 77%, 86% and 86%, and specificity was 72%, 88% and 97%, respectively. Sensitivity and specificity in the prediction of T3a tumors were 72% and 70% respectively (κ score = 0.38 (0.29–0.47)). Among the 38 pT3 tumors, 6 (16%) were under-staged, and the neovessels and irregular tumor edge as secondary CT signs did not significantly increase the accuracy of the prediction of local invasion. Among the 62 confined tumors, 17 (27%) were over-staged as cT3 and among these 17 false positives cases, perinephric soft-tissue stranding was present in 14 cases.Conclusion: MDCT provides good results in detecting sinus fat, venous invasion and kidney-confined tumors, but evaluation of perinephric fat remains a difficult task, leading to reduced accuracy in T3a staging.

Human Papilloma Virus DNA in Tumor Tissue and Urine in Different Stage of Bladder Cancer.

There are some previous reports on the relationship between pathological grades and HPV detection. To determine the Human Papilloma Virus(HPV) DNA in Tumor Tissue and Urine in Different Stage of Bladder Cancer conducted this study.MaterialsandMethods: Polymerase chain reaction (PCR) was used to detect general HPV and HPV16 and 18 subtypes in 110 bladder tumor tissue and urine specimens of patients with TCC of bladder between January 2014 to May 2016 that underwent transurethral resection of bladder tumor. Exclusion criteria were genital wart and cases with immunosupression. Mean age of 110 patients was 61.6±10 years and fourteen (12.7%) of patients were female. PCR for general HPV primer in bladder tumor tissue was positive in 3 (9.4%), 22 (38.6%) and 15 (71.4%) of Ta, T1 and T2 bladder tumors, respectively (p<0.001). PCR for HPV16 in bladder tumor tissue was positive in 2(6.3%), 10 (17.5%) and 13 (61.9%) and PCR for HPV18 in bladder tumor tissue was positive in 1 (3.1%), 14 (24.6%) and 12 (57.1%) of Ta, T1 and T2 bladder tumors, respectively (p<0.001, p<0.001). Thirty seven (33.6%) of urine specimens were positive for general HPV using PCR and HPV16 and 18 subtypes were positive in 17 (15.5%) and 14 (12.7%) of urine specimens, respectively. HPV infection may be associated with higher stages and grades of bladder carcinomas. Urine sampling for HPV detection is is as reliable as tumor tissue sample which could be considered for prognostic and follow up implications.

CD8+ Cytotoxic Immune Infiltrate in Non-Muscle Invasive Bladder Cancer: A Standardized Methodology to Study Association with Clinico-Pathological Features and Prognosis.

Background:Major interest lies in the evaluation of immune infiltrate in bladder cancer. CD8+ cytotoxic lymphocytes are key effectors of adaptive immune response.Objectives:The aims of the study were to set up a standardized methodology for CD8+ lymphocytes estimation in NMIBC and investigate how intra-tumoral heterogeneity influences CD8+ immune infiltrate.Methods:We considered 995 NMIBC included in the Spanish Bladder Cancer (SBC)/EPICURO Study. Duplicate 0.6mm TMA spots and paired full sections (FS) for 50 selected cases were double stained with anti-pan cytokeratin antibody and anti-CD8 antibody. Slides were digitalized and CD8+ cells were automatically counted after tissue recognition (tumor vs stroma). Spatial heterogeneity was assessed and a resampling strategy was applied to estimate the proper number of 0.6mm TMA spots providing an adequate CD8+ cell estimate. Association between CD8+ count and expression of urothelial differentiation markers was estimated. Cox regression models were performed to assess association between CD8+ cell count and risk of recurrence and progression.Results:Microscopic examination of full sections showed spatial heterogeneity for CD8+ infiltrates. Simulation analyses demonstrated that 5 TMA regions provided a correct sampling of tumor and stromal compartments in Ta while 2 and 6 TMA regions were necessary in T1, respectively. CD8+ cells infiltration was associated with stage, regardless of the histological compartment analyzed (median CD8+ /mm2 were 25/mm2 and 129/mm2 in tumor and stroma respectively in Ta and 111/mm2 and 344/mm2 in T1; p-value = 0.006). CD8+ infiltration in tumor compartment was significantly associated with low FGFR3 expression. CD8+/mm2 count in the tumor compartment was not associated with prognosis.Conclusion:Differences identified between Ta and T1 tumours supported the hypothesis that rigorous efforts should be placed in proper study design. These results provide a new framework to investigate microenvironment complexity in bladder cancer.

Renal volume matters: Assessing the association between excisional volume loss and renal function after partial nephrectomy

To investigate the oncological and functional outcomes after partial nephrectomy for clinical stage T1 (cT1) renal cell carcinoma (RCC), and assess the association between excisional volume loss (EVL) and postoperative renal function. We retrospectively reviewed 150 patients with cT1 RCC undergoing partial nephrectomy from 2002 to 2016. End-point evaluation was assessed by recurrence free survival (RFS), overall survival (OS), stage III and stage IV chronic kidney disease (CKD). Regression models were used to determine the risk factors of CKD after surgery. The relationship between EVL and renal function decline was evaluated using Spearman correlation method. Ninety patients with clinical stage T1a (cT1a) tumors and 60 patients with clinical stage T1b (cT1b) tumors were included. There were no differences in RFS, OS, and risk of stage III and stage IV CKD between the two groups. In Cox regression models, multivariate analysis showed that preoperative estimated glomerular filtration rate (eGFR) was an independent risk factor for developing stage III (hazard ratio 0.937, P<0.001) and stage IV CKD (hazard ratio 0.929, P=0.027). EVL was significantly associated with postoperative eGFR decrease. (Correlation Coefficient=0.325, P=0.003). Patients with cT1a and cT1b RCC have comparable oncological and functional outcome after partial nephrectomy, and preoperative eGFR is an independent factor to predict developing CKD. EVL has influence on the postoperative renal function decline.

Visceral pleural invasion in T1 tumors (≤3 cm), particularly T1a, in the eighth tumor-node-metastasis classification system for non-small cell lung cancer: a population-based study.

We aimed to validate the tumor (T) descriptors of visceral pleural invasion (VPI) for T1 tumors (<3 cm) in the 8th edition of the tumor-node-metastasis (TNM) classification system and the prognostic value of VPI for resected T1a tumors. The external cohort consisted of 23,501 patients with resected pN0 non-small cell lung cancer (NSCLC) selected from the Surveillance, Epidemiology, and End Results (SEER) database (2010 to 2013). The classification of T1 tumors with VPI was investigated using survival curves. The internal cohort consisted of patients diagnosed with pN0 NSCLC between 2011 and 2013 at Guangdong Lung Cancer Institute. The prognostic value of VPI for T1a tumors (<1 cm) was further assessed in these two cohorts. The overall survival (OS) and lung cancer-specific survival (LCSS) of the T1-VPI group and groups of each T stage (size only) were compared in the external (SEER) cohort. There were no significant survival differences between the T1-VPI and T2a groups (OS: P=0.706; LCSS: P=0.792) and T1-VPI and T2b groups, although the latter showed a trend toward lower P-values (OS: P=0.117; LCSS: P=0.094). In the internal cohort, a significant difference in OS was observed between patients with T1-VPI and those with T2b (P=0.049). Among patients with T1a tumors and VPI in the SEER database, the prognosis of the non-sub-lobectomy group was superior to that of the sub-lobectomy group, with intrathoracic recurrence as the predominant relapse pattern of T1 tumors with VPI (69.2%). T1 tumors (<3 cm) with VPI can be staged as T2a in the 8th TNM staging system and surgical resection of T1a tumors is a concern when VPI is present.

Abstract LB-051: Integrative, targeted deep sequencing of bladder tumors reveals novel associations between cancer gene mutations and mutational signatures with major risk factors

Abstract Exome and whole-genome sequencing of muscle-invasive (MI) bladder cancer has revealed important insights into the molecular landscape; however, there are few studies of non-muscle invasive (NMI) bladder cancer with detailed information on bladder cancer risk factors. We used deep, targeted amplicon sequencing of the coding regions of 44 genes frequently mutated in bladder cancer (average 630x coverage for tumor and 350x for germline DNA) to characterize somatic mutations and the mutational spectrum in 307 formalin fixed paraffin embedded bladder tumors (n=260 NMI and n=47 MI) from a population-based case-control study with detailed information on smoking and other risk factors. Variants identified by mutation calling pipelines were validated by manual review of aligned sequences. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate somatic mutations and risk factors. We used SignatureEstimation to extract the four known single base substitution mutational signatures (COSMIC: Sig1, Sig2, Sig13, ERCC2-Signature) and Poisson regression to calculate risk ratios (RRs) and 95%CIs to evaluate signatures and risk factors. The most frequently mutated gene in NMI tumors was FGFR3 (52% mutated) and in MI tumors was TP53 (51% mutated). FGFR3 (89%), STAG2 (81%), and PIK3CA (78%) mutations were significantly higher in Ta tumors compared to T1 or MI tumors. Mutations in histone/chromatin regulating genes (KDM6A, KMT2D, KMT2C, CREBBP, ARID1A, and EP300) were present at a high frequency in low grade Ta tumors. Non-silent KDM6Amutations were significantly more common in females compared to males (OR=1.79,95%CI:1.03-3.11); in females these mutations largely occurred in Ta tumors (86%). There was striking heterogeneity in the relationship between smoking status (current, former, never) and the established signatures: only current smoking was associated with greater ERCC2-Signature variants compared to both former smoking (p-value=0.015) and never smoking (p-value=0.023); only former smoking was associated with APOBEC-Sig13 variants (RR=1.83,95%CI: 1.10-3.04,p-value=0.019); and only never smoking was associated with the APOBEC-Sig2 variants (RR=1.52,95%CI: 1.15-2.01,p-value=0.003). Further, there was significant evidence that smoking duration, the component of smoking most strongly associated with bladder cancer risk, was associated with ERCC2-Signature variants and APOBEC-Sig13 variants among current (p-trend=0.013) and former smokers (p=0.002), respectively. Exploration of insertion/deletions revealed that both status and duration of smoking was significantly associated with presence of any 1bp deletions (p-trend=0.007); these were enriched for deletions in KDM6A (p=0.0003). In conclusion, these data quantify the contribution of bladder cancer risk factors to mutational burden in a population-based series of tumors and reveal distinct signature contributions among never, former and current smokers. Citation Format: Stella Koutros, Nina Rao, Lee E. Moore, Michael L. Nickerson, Donghyuk Lee, Bin Zhu, Larissa Pardo, Dalsu Baris, Molly Schwenn, Alison Johnson, Kristine Jones, Montserrat Garcia-Closas, Ludmila Prokunina-Olsson, Debra T. Silverman, Nathaniel Rothman, Michael Dean. Integrative, targeted deep sequencing of bladder tumors reveals novel associations between cancer gene mutations and mutational signatures with major risk factors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-051.

Tumor Depth of Invasion (Tumor > 4cm/Depth > 10mm and Depth > 20mm) and Through Cortex/Skin Invasion are Both Valid Criteria for Classifying Tumors as pT4a in AJCC 2018 Oral Cavity Cancer Staging System.

According to the AJCC third to seventh edition staging manuals (1988-2010), the presence of through cortex and/or skin invasion in oral cavity squamous cell carcinoma (OCSCC) identifies T4a tumors. The AJCC eighth edition (2018) introduced a depth of invasion (DOI) > 20mm as a criterion for pT4a. Subsequently, a revision maintained that tumors > 4cm with a DOI > 10mm should be classified as pT4a. We sought to analyze the prognostic impact of the three distinct criteria identifying pT4a disease. We examined 667 consecutive patients with pT3-4 buccal/gum/hard palate/retromolar SCC who underwent surgery between 1996 and 2016. pT1/pT2 (n = 108/359) disease were included for comparison purposes. The 5-year outcomes of patients with pT1/pT2/without (n = 406)/with tumor > 4cm/DOI > 10mm (n = 261), pT1/pT2/DOI ≤ 20mm (n = 510)/> 20mm (n = 157), and pT1/pT2/without (n = 305)/with through cortex/skin invasion (n = 362) were as follows: disease-specific survival (DSS), 98%/89%/79%/65%, p < 0.001, 98%/89%/78%/59%, p < 0.001, and 98%/89%79%/69%, p < 0.001; overall survival (OS), 90%/79%/63%/51%, p < 0.001, 90%/79%/63%/42%, p < 0.001, and 90%/79%/65%/52%, p < 0.001. In pT3-4 disease, a tumor > 4cm/DOI > 10mm was an independent adverse prognosticator for 5-year DSS rate, DOI > 20mm was an independent adverse prognosticator for 5-year DSS and OS rates, whereas through cortex/skin invasion independently predicted 5-year OS rates. All of the three criteria (tumor > 4cm/DOI > 10mm, DOI > 20mm, and through cortex/skin invasion) identify high-risk patients, which should be reflected in further revisions of pT4a classification in OCSCC.

Recurrent Ta Low-grade Non-muscle-invasive Bladder Cancer: What Are the Options?

Recurrent low-grade Ta tumours, classified as intermediate-risk non-muscle-invasive bladder cancer (NMIBC), have a high risk of recurrence but a low risk of progression. This case presents a 60-yr-old female with intermediate-risk NMIBC who has been treated with sequential courses of mitomycin C followed by bacillus Calmette-Guérin (BCG). She continued to develop multiple episodes of recurrence. The discussion addresses whether the best course is repeat transurethral resection of the bladder with continued monitoring, more of the same intravesical treatments, new methods of applying these treatments, or novel treatments that might involve enrolling the patient in a clinical trial. The biggest unmet need in the field comes from the lack of a molecular marker that could help select patients for aggressive strategies. Patient summaryFollowing treatment of intermediate-risk non-muscle-invasive bladder cancer with a fairly standard course of intravesical drug therapy, the patient, a relatively young woman, continued to develop recurrences of the bladder cancer. The authors discuss whether the best next course is “more of the same”, device-assisted application of these treatments, or perhaps one of the new, still investigatory treatment approaches. Radical surgery (removal of the bladder) should not be necessary unless the recurrences show signs of disease progression.

Failure patterns after adjuvant chemoradiotherapy following endoscopic resection for superficial esophageal squamous cell carcinoma.

BackgroundThis study evaluated the locations of lymph node recurrence and their association with irradiation fields used for radiotherapy after adjuvant chemoradiotherapy following endoscopic resection for superficial esophageal squamous cell carcinoma.MethodsMedical records of 96 consecutive patients with superficial esophageal squamous cell carcinoma who underwent adjuvant chemoradiotherapy following endoscopic resection were reviewed. Computed tomography was used to identify whether nodal recurrences were within the elective nodal irradiation field. The cumulative incidence of recurrence was calculated, accounting for death as a competing risk. Univariate and multivariate analyses identified factors predicting nodal recurrence.ResultsThe median follow‐up period was 61 months (range: 6‐137 months). Seven patients (7.3%) developed lymph node recurrence only; two patients (2.1%) developed nodal plus local recurrence. Six of the seven cases without local recurrence involved the elective nodal irradiation field, with five cases involving the recurrent nerve lymph nodes. The 5‐year cumulative incidence of lymph node recurrence was higher for T1b tumors with lymphovascular invasion than for T1a tumors with lymphovascular invasion (17.6% vs 6.2%, P = 0.086; HR: 3.74, 95% CI: 0.80‐17.52, P = 0.094) and T1b tumors without lymphovascular invasion (17.6% vs 3.3%, P = 0.031; HR: 6.78, 95% CI: 0.80‐57.63, P = 0.080).ConclusionsLymph node recurrence frequently involved the elective nodal irradiation field, with recurrent nerve lymph nodes being common metastasis sites. The high incidence of nodal recurrence for T1b tumors with lymphovascular invasion highlights a need for new strategies for treating this subset of superficial esophageal squamous cell carcinomas.

Multimodal therapy in the management of lacrimal gland adenoid cystic carcinoma

BackgroundTo evaluate the prognosis of Chinese patients with lacrimal gland adenoid cystic carcinoma treated with eye-sparing surgery and adjuvant multimodal therapy.MethodsThe study included 24 consecutive patients with lacrimal gland adenoid cystic carcinoma treated at the Ninth People’s Hospital of Shanghai from May 2008 to September 2017. All patients underwent eye-sparing surgical tumor resection and 20 (83.3%) of the 24 patients in the cohort received postoperative RT. Eight (41.7%) patients in the cohort received chemotherapy. Each patient’s medical records were reviewed.ResultsThe study included 13 male and 11 female patients. The median follow-up time after surgery was 33.5 months. Fifteen (62.5%) patients experienced local recurrence. The 1-, 3-, and 5-year recurrence rates were 27.9, 60.0, and 80.0%, respectively. Eleven (45.8%) patients developed metastasis. The 1-, 3-, and 5-year metastasis rates were 8.7, 48.5, and 66.9%, respectively. Eight (33.3%) patients died of lacrimal gland adenoid cystic carcinoma, with a median survival duration of 34.0 months. The 1-, 3-, and 5-year tumor-related mortality was 4.5, 28.1, and 58.0%, respectively. More advanced T stage (≥ T3a) was a risk factor for local recurrence (hazard ratio [HR]: 5.374, P = 0.02), distant metastasis (HR: 8.585, P < 0.01), and tumor-related survival (HR: 9.654, P < 0.01).ConclusionsEye-sparing tumor resection protocol followed by adjuvant therapy seems to be associated with high rates of local recurrence, metastases and death. In addition, greater attention should be paid to patients with lacrimal gland adenoid cystic carcinoma with ≥ T3a tumors.

AGA Clinical Practice Update on the Utility of Endoscopic Submucosal Dissection in T1b Esophageal Cancer: Expert Review

AGA Clinical Practice Update on the Utility of Endoscopic Submucosal Dissection in T1b Esophageal Cancer: Expert Review

JAAD Game Changers: Variability in mitotic figures in serial sections of thin melanomas

Capsule Summary•A rigorous approach to accurately capture mitotic activity and expected density of mitoses in T1b melanomas is needed.•We describe the variability in mitoses between serial sections and the minimum number of sections to review (5 sequential sections).•This will increase accuracy and should help prevent under diagnosis.How did this article change the practice of dermatology?Looking back at this article in 2018, these authors were ahead of their time in demonstrating the difficulty in determining the mitotic rate in melanomas.1 The American Joint Committee on Cancer evaluated survival outcome of melanomas with <0.8-mm tumor thickness (Breslow) and determined that primary ulceration and tumor thickness were more important than mitotic rate in determining prognosis, and mitotic rate no longer is considered in staging of these tumors. T1a tumors are nonulcerated melanomas <0.8 mm in thickness, and T1b tumors are (1) 0.8 to 1.0 mm in thickness regardless of ulceration status or (2) ulcerated melanomas <0.8 mm in thickness.1

Disease-Free Survival for Patients with Thin Melanomas according to the American Joint Committee on Cancer 8th Edition

Background: The recently implemented AJCC 8th edition TNM staging system for malignant melanoma (MM) changed the definition for T1a and T1b tumours. Objectives: To analyse differences in disease-free survival (DFS) among patients with thin MM staged according to both AJCC 7th and 8th editions. Methods: An observational study including 285 patients with cutaneous thin MM (thickness ≤1 mm). Cases were staged as T1a and T1b using both 7th and 8th editions. Neither regional nor visceral diseases were present at diagnosis. DFS curves were generated according to the Kaplan-Meier method. Results: An 8% shift of patients from a T1a towards a T1b stage group was observed after applying the AJCC 8th edition. According to this 8th edition, DFS for T1a patients was significantly longer than for T1b patients (log-rank test; p = 0.005); 5-year DFS for T1a and T1b was 100 and 95%, respectively (Wilcoxon test; p = 0.002). According to the AJCC 7th edition, DFS did not significantly differ for T1a and T1b patients; 5-year DFS for T1a and T1b was 99 and 97%, respectively (p > 0.05). Conclusions: The AJCC 8th edition seems to be a better tool for staging thin melanomas.

Pembrolizumab (pembro) for patients (pts) with high-risk (HR) non–muscle invasive bladder cancer (NMIBC) unresponsive to Bacillus Calmette-Guérin (BCG): Updated follow-up from KEYNOTE-057.

4530 Background: Upregulation of the PD-1 pathway has been observed in BCG-unresponsive NMIBC, suggesting that pembro may be beneficial. Efficacy and safety of pembro in pts with HR, BCG-unresponsive NMIBC was evaluated in the single-arm phase 2 KEYNOTE-057 study (NCT02625961); updated results for pts with carcinoma in situ (CIS) with or without papillary tumors (cohort A) are reported. Methods: Pts with histologically confirmed HR, BCG-unresponsive CIS with or without papillary tumors who received adequate BCG therapy and were unable/refused to undergo radical cystectomy received pembro 200 mg Q3W for 24 mo or until recurrence, progression, or unacceptable toxicity. Pts who developed HR NMIBC or progressive disease during treatment were required to discontinue. Key end points were complete response rate (CRR), duration of response, and safety. Results: 102 pts (median age, 73 years; CIS alone, 63.7%; median number of prior BCG instillations, 12) had enrolled in cohort A as of enrollment cutoff. Median (range) duration of follow-up was 15.8 mo (4.6-28.2) ; 3-mo CRR was 40.2% (95% CI, 30.6-50.4) by central assessment. Among 41 pts who had CR at 3 mo, median CR duration was 12.7 mo (range, 0+ to 20.5+ mo); 75.4% had a CR duration ≥ 6 mo; 52.6% had a CR duration ≥12 mo (Kaplan-Meier method); 24 pts (58.5%) maintained CR at last follow-up, and 15 (36.6%) experienced recurrent NMIBC after CR; at the time of analysis, none progressed to muscle-invasive or metastatic disease. CRR was 44.6% for pts with CIS alone (n = 65), 41.7% for CIS with T1 tumors (n = 12), and 28.0% for CIS with high-grade Ta tumors (n = 25). Treatment-related adverse events (AEs) occurred in 66 (64.7%) pts; most frequent (≥10%) were pruritus (10.8%), diarrhea (10.8%), and fatigue (9.8%). Grade 3/4 treatment-related AEs occurred in 13 (12.7%) pts. Immune-mediated AEs occurred in 19 (18.6%) pts. Conclusions: Pembro continued to show encouraging antitumor activity in pts with HR, BCG-unresponsive CIS with or without papillary tumors and a safety profile consistent with that of previous experience. Updated data using additional follow-up will be presented. Clinical trial information: NCT02625961.

Bone Pseudometastasis on 18F-FDG PET in Japanese Patients With Esophageal Cancer.

False-positive bone lesions mimicking bone metastases (bone pseudometastasis) on F-FDG PET/CT have often been reported in patients with esophageal cancer. We aimed to evaluate the prevalence and features of these lesions in Japanese patients with esophageal cancer. In this retrospective study, we analyzed 83 FDG PET/CT studies for initial staging of esophageal cancer, and extracted patients with 1 or more localized high uptake sites with no subsequent progression, which were therefore judged to be bone pseudometastasis. The FDG PET/CT imaging features of the bone pseudometastasis were evaluated, and other available imaging and clinical features reviewed. Of the 83 patients, 7 had bone pseudometastasis. All 7 were males diagnosed with squamous cell cancer, of which 5 had T1a tumors. Bone pseudometastasis showed normal or ill-defined hyperdense (nonosteolytic) sites compared with the surrounding area on the CT. Additionally, accumulation in the upper vertebral levels of each case was contiguously high compared with the lumbar spines (we named this finding "contiguous accumulation"). On MRI, these findings were visualized as low signals on T1-weighted imaging (T1WI) and T2WI images but were unclear on fat-suppressed T2WI images. Among all PET/CT performed for staging of esophageal cancer, 8.3% demonstrated bone pseudometastasis characterized by heterogeneous distribution with severe fatty degeneration of bone marrow accompanied by contiguous accumulation. Caution is required during diagnoses of bone lesions in esophageal cancer patients in Japan to prevent inappropriate therapeutic choices.

Risk of Melanoma Recurrence After Diagnosis of a High-Risk Primary Tumor

With emerging new systemic treatments for metastatic melanoma, early detection of disease recurrence is increasingly important. To investigate the risk of melanoma recurrence in patients with a localized melanoma at a high risk of metastasis. A total of 1254 patients with newly diagnosed, histologically confirmed tumor category T1b to T4b melanoma in Queensland, Australia, were recruited prospectively between October 1, 2010, and October 1, 2014, for participation in a cohort study. Data analysis was conducted from February 8, 2018, to February 20, 2019. We used Cox proportional hazards regression analysis to examine associations between patient and tumor factors and melanoma recurrence. Disease-free survival (DFS) by melanoma tumor category defined by the 7th vs 8th editions of the AJCC Cancer Staging Manual (AJCC 7 vs AJCC 8). Melanoma recurrences were self-reported through follow-up questionnaires administered every 6 months and confirmed by histologic or imaging findings. Of 1254 patients recruited, 825 individuals (65.8%) agreed to participate. Thirty-six were found to be ineligible after providing consent and a further 89 patients were excluded after reclassifying tumors using AJCC 8, leaving 700 participants with high-risk primary melanoma (mean [SD] age, 62.2 [13.5] years; 410 [58.6%] men). Independent predictors of recurrence were head or neck site of primary tumor, ulceration, thickness, and mitotic rate greater than 3/mm2 (hazard ratio, 2.36; 95% CI, 1.19-4.71). Ninety-four patients (13.4%) developed a recurrence within 2 years of diagnosis: 66 tumors (70.2%) were locoregional, and 28 tumors (29.8%) developed at distant sites. After surgery for locoregional disease, 37 of 64 patients (57.8%) remained disease free at 2 years, 7 patients (10.9%) developed new locoregional recurrence, and 20 patients (31.3%), developed distant disease. Two-year DFS was similar when comparing AJCC 7 and AJCC 8, for T1b (AJCC 7, 253 [93.3% DFS]; AJCC 8, 242 [93.0% DFS]) and T4b (AJCC 7 and AJCC 8, 50 [68.0% DFS] category tumors in both editions. Patients with T2a to T4a tumors who did not have a sentinel lymph node biopsy (SLNB) at diagnosis had lower DFS than patients with the same tumor category and a negative SLNB (T2a: 136 [91.1%; 95% CI, 86.4-95.9] vs 96 [96.9%; 95 % CI, 93.4-100.0]; T4a: 33 [78.8%; 95% CI, 64.8-92.7] vs 6 [83.3; 95% CI, 53.5-100.0]). These findings suggest that 13.4% of patients with a high-risk primary melanoma will experience disease recurrence within 2 years. Head or neck location of initial tumor, SLNB positivity, and signs of rapid tumor growth may be associated with primary melanoma recurrence.

Optimal Lymph Node Examination and Adjuvant Chemotherapy for Stage I Lung Cancer

ObjectiveTo determine the optimal number of lymph nodes (LNs) examined and the role of adjuvant chemotherapy in stage I lung cancer. MethodsThe National Cancer Database was queried for surgically treated patients with pathologic stage I lung cancer between 2006 and 2014 (N = 65,438). The optimal LN numbers were determined in the multivariate Cox model and were further validated in the cohort with clinical stage I disease (N = 117,112) in terms of nodal upstaging and prognostic stratification. The role of adjuvant chemotherapy in patients with suboptimal staging (number of LNs examined was less than than the optimum) was evaluated in each T stage. ResultsThe number of LNs examined correlated with tumor size (p < 0.001). There were increasing survival benefits with each additional LN examined—up to eight, nine, 10, and 11 nodes for patients with T1a, T1b, T1c, and T2a, respectively. Validation from the cohort with clinically staged disease showed that the threshold of eight to 11 LNs was an independent predictor of nodal upstaging (OR = 1.706, 95% confidence interval [CI] 1.608–1.779) and survival outcome (hazard ratio = 0.890, 95% CI: 0.865–0.916). After propensity matching, adjuvant chemotherapy was associated with improved survival in patients with stage T2a disease having suboptimal staging (hazard ratio = 0.841, 95% CI: 0.714–0.990), but not in patients with stage T1a to T1c disease. ConclusionLN evaluation was important for accurate staging and adequate treatment, and examinations of an increasing number of nodes for progressively higher T components (i.e., eight, nine, 10, and 11 nodes for T1a, T1b, T1c, and T2a tumors, respectively) seemed crucial to predict upstaging and survival outcomes. Adjuvant chemotherapy might be beneficial to patients with stage T2a disease who have suboptimal nodal staging.

MP42-20 A COMPARISON OF LONG-TERM OUTCOMES BETWEEN PARTIAL NEPHRECTOMY AND RADICAL NEPHRECTOMY FOR CLINICAL STAGE T1B AND T2A RENAL TUMORS

INTRODUCTION AND OBJECTIVES:Partial nephrectomy (PN) for T1b and T2a tumors has not been established as the reference standard treatment due to unclear functional benefit at the expense of increase...