pT1 Tumors Research Articles

Obesity contributes to the stealth peritoneal dissemination of ovarian cancer: a multi-institutional retrospective cohort study.

The clinical significance of a higher BMI on the prognosis of ovarian cancer remains controversial; therefore, a more detailed analysis is demanded. This study investigated the impact of BMI on peritoneum-specific recurrence to clarify the involvement of adipose tissue in the proliferation of cancer cells at sites of peritoneal dissemination. Among 4,730 patients with malignant ovarian tumors, 280 diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage IIB to IIIC epithelial ovarian cancer and who underwent complete resection in the primary surgery were included in the present study. There were 42, 201, and 37 women in the low, normal, and high BMI groups, respectively. Peritoneum-specific recurrence-free survival and overall survival were both significantly shorter in patients with a high BMI than in those with a normal BMI (p=0.028 and 0.018, respectively). No significant differences were observed in the distribution of sites of recurrence between these two groups. A multivariate analysis identified obesity as an independent prognostic factor in addition to pT3 tumor staging and positive ascites cytology. Patients with a high BMI had a significantly worse prognosis than those with a normal BMI, and peritoneal adipose tissue may have contributed to this difference.

Effect of radioiodine therapy under thyroid hormone withdrawal on health-related quality of life in patients with differentiated thyroid cancer.

To investigate the effect of radioactive iodine therapy under thyroid hormone withdrawal in differentiated thyroid cancer patients on health-related quality of life. Patients who were diagnosed with differentiated thyroid cancer after thyroidectomy were involved in this study. All of them were managed with thyroid hormone withdrawal. Health-related quality of life was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and its thyroid cancer module at three different time points. Changes in health-related quality of life were evaluated by Wilcoxon and Kruskal-Wallis tests. Univariable logistic regression analysis was used to determine social-demographic and clinical factors associated with worse health-related quality of life. A total of 99 differentiated thyroid cancer patients were involved in this study. Changes in health-related quality of life at different time points showed that 1month post-radioactive iodine treatment, an improvement in nausea and vomiting, insomnia and appetite loss was observed. Impairments of global health, role, cognitive and social function and problems of discomfort in the head and neck, voice concerns, dry mouth, fatigue, pain, dyspnea, thyroid fatigue, fear, tingling or numbness, joint pain and shoulder function increased after radioactive iodine treatment. Univariable logistic regression analysis demonstrated potential factors associated with worse health-related quality of life. Thyroid stimulating hormone and parathyroid hormone levels were more sensible to changes in functional domain. Patients aged ≥55-year-old, with annual income under ¥50 000, low parathyroid hormone and pT4 tumour stage experienced higher changes in symptom scales after radioactive iodine treatment. After radioactive iodine treatment, differentiated thyroid cancer patients experienced negative health-related quality of life, and most of these impairments might not recover in the short term. Thyroid stimulating hormone and parathyroid hormone levels, annual income and pT tumours stage were independent risk factors for decreased health-related quality of life.

Особливості експресії молекул клітинної адгезії Е-кадгерину в різних молекулярних підтипах інвазивного протокового раку грудної залози

The purpose of the study was to determine the role of E-cadherin in the development and progression of molecular subtypes of invasive ductal breast cancer by assessing the expression of E-cadherin in various clinical and pathological prognostic parameters. Materials and methods. We demonstrated a comprehensive morphological, including immunohistochemical study of 193 cases of invasive ductal breast cancer with the molecular phenotype definition. General histological processing of samples was performed according to standard methods. Immunohistochemical studies for E-cadherin, ER, PR, c-erbB2, Ki-67 were performed according to standardized analytically validated protocols with the necessary controls. The grade of malignancy was determined according to the modified scheme of P. Scarff, H. Bloom and W. Richardson. E-cadherin expression level was quantified in 86 observations using the Qureshi counting system. Comparison of E-cadherin expression in different clinical and pathological parameters was evaluated using Pearson's test χ2. For all types of analysis, differences were considered significant at p <0.05. Results and discussion. E-cadherin expression in ductal breast cancer tissue is significantly lower in cases with lymph node metastases than without metastatic lymph node involvement (χ2 = 4.55, p = 0.031). Low expression of E-cadherin or its absence was associated with pT3 tumors, clinical stage 3, with G2 and G3 malignancies. Loss of E-cadherin expression has an unfavorable prognostic value. E-cadherin expression is associated with the molecular type of invasive breast ductal carcinoma. High E-cadherin expression was common in ER-positive tumors of the luminal A phenotype and was determined in patients of both premenopausal and postmenopausal age, suggesting that ER-positive expression may be involved in the regulation of E-cadherin expression. Low tumor activity of cells of invasive ductal breast cancer of the luminal subtype is accompanied by an increase in the adhesive properties of these cells due to the high level of expression of E-cadherin. E-cadherin is considered an independent marker of triple-negative breast cancer and is characterized by an unfavorable prognosis and short life expectancy. Triple-negative cancer was associated with a significant predominance of patients with low and negative E-cadherin expression (p = 0.011). Conclusion. Thus, E-cadherin is a potent tumor suppressor of breast cancer. According to this role in the progression of breast cancer, it was found that partial or complete loss of E-cadherin expression correlates with an unfavorable prognosis in patients

Long-term outcomes after extra-levator versus conventional abdominoperineal excision for low rectal cancer

PurposeExtralevator (ELAPE) and abdominoperineal excision (APE) are two major surgical approaches for low rectal cancer patients. Although excellent short-term efficacy is achieved in patients undergoing ELAPE, the long-term benefits have not been established. In this study we evaluated the safety, pathological and survival outcomes in rectal cancer patients who underwent ELAPE and APE.MethodsOne hundred fourteen patients were enrolled, including 68 in the ELAPE group and 46 in the APE group at the Beijing Chaoyang Hospital, Capital Medical University from January 2011 to November 2020. The baseline characteristics, overall survival (OS), progression-free survival (PFS), and local recurrence-free survival (LRFS) were calculated and compared between the two groups.ResultsDemographics and tumor stage were comparable between the two groups. The 5-year PFS (67.2% versus 38.6%, log-rank P = 0.008) were significantly improved in the ELAPE group compared to the APE group, and the survival advantage was especially reflected in patients with pT3 tumors, positive lymph nodes or even those who have not received neoadjuvant chemoradiotherapy. Multivariate analysis showed that APE was an independent risk factor for OS (hazard ratio 3.000, 95% confidence interval 1.171 to 4.970, P = 0.004) and PFS (hazard ratio 2.730, 95% confidence interval 1.506 to 4.984, P = 0.001).Conclusion Compared with APE, ELAPE improved long-term outcomes for low rectal cancer patients, especially among patients with pT3 tumors, positive lymph nodes or those without neoadjuvant chemoradiotherapy.

Translation of IDEA trial results into clinical practice: Analysis of the implementation of a new guideline for colon cancer.

The IDEA trial showed no clinical relevant differences in efficacy between 3 and 6 months of oxaliplatin‐based adjuvant chemotherapy (ACT) in colon cancer (CC), while toxicity was substantially lower in the 3 months regimen. Therefore, in 2017 the Dutch colorectal cancer guideline was revised and currently recommends 3 months of oxaliplatin‐based ACT. Furthermore, the definition of high‐risk stage II CC was restricted to pT4 tumors. We analyzed changes in ACT between 2015 and 2019. From the Netherlands Cancer Registry all 16 721 patients ≥18 years with resected high‐risk stage II and stage III CC during 2015 to 2019 were selected. Differences in patient and treatment characteristics were analyzed per calendar year according to stage and age. Mean duration of oxaliplatin‐based ACT decreased from 18.6 (±8.0) to 9.5 (±3.8) weeks between 2015 and 2019. In patients receiving ACT (n = 8170), the proportion treated with oxaliplatin increased from 74% to 83%. The proportion of patients receiving ACT was stable, 61% to 69% in stage III and 26% to 29% in pT4 stage II. ACT in previous high‐risk pT3N0 disease decreased from 15% to 3%. Use of oxaliplatin increased from 27% to 49% in patients aged ≥75 years. The revised guideline was rapidly implemented and led to an increase in oxaliplatin‐based ACT in the elderly and increased guideline‐adherence in high‐risk stage II CC.

Prognostic significance of additional histologic features for subclassification of pathological T3 colon cancer

BackgroundAdditional histologic features of T3 colon cancer, such as tumour depth invasion beyond muscularis propria and elastic lamina invasion (ELI), have taken interest for a more accurate staging.MethodsPatients with pT3 and pT4a (control group) colon adenocarcinoma were retrospectively collected from our institutional database. The study group was divided according to depth of tumour invasion < 5 mm and ≥ 5 mm, and into ELI − and ELI + . Chi-square test was used to compare the clinicopathological characteristics. OS and DFS were estimated using Kaplan–Meier method and compared with the log-rank test. Univariable and multivariable Cox proportional hazard models were employed to assess the effect on OS and DFS.ResultsOut of 290 pT3 tumours, 168 (58%) had a depth of tumour invasion < 5 mm and 122 (42%) ≥ 5 mm. The 5-year OS and DFS were 85.2, 68.7 and 60.9%, and 81.4, 73.9 and 60.1% in pT3 < 5 mm, pT3 ≥ 5 mm, and pT4a respectively (p = 0.001, p = 0.072). Considering ELI − (n = 157, 54%) and ELI + (n = 133, 46%), the 5-year OS and DFS were 78.9, 76.7, and 60.9%, and 75.5, 81.5, and 60.1% in ELI − , ELI + and pT4a respectively (p = 0.955, p = 0.462). At multivariable analysis, the depth of invasion was found to be an independent predictive factor for OS (HR 2.04, 95%CI 1.28–3.24, p = 0.003) and DFS (HR 1.98, 95%CI 1.24–3.18, p = 0.004), while ELI did not result a prognostic factor for OS nor DFS.ConclusionIn pT3 colon cancer, depth of tumour invasion ≥ 5 mm is an independent risk factor for OS and DFS, whereas ELI did not result a prognostic factor affecting OS nor DFS.

The probability of residual tumor detection in the second transurethral resection of pT1 urothelial bladder cancer according to the risk factors

ObjectiveTo analyze the predictive factors for residual tumors in the second resection after the initial transurethral resection of bladder tumor (TUR-BT) in patients with pT1 tumors and to develop a simple method to predict the probability of residual tumor detection. Material and MethodsPatients with pT1 bladder cancer who underwent a second resection within two to six weeks after the initial TUR-BT were included in our retrospective study. The patients’ demographics and the tumor characteristics of the initial and second resections were recorded. ResultsA total of 144 patients were included in our analysis with a 53-month follow-up. In the univariate logistic regression analysis, tumor grade, concomitant carcinoma in situ (CIS), macroscopic appearance of the tumor (solid vs papillary), and presence of a variant histology, were significant risk factors for residual tumor. In the multivariate analysis, tumor grade was the only independent predictor of residual tumor at second TUR (OR: 5.62, 95% CI: 1.228–25.708, p = 0.026). According to our findings, the patients with the highest risk have a 90.9% residual tumor detection probability at the second resection, and the patients with the lowest risk have 25.4%. ConclusionsTumor grade, macroscopic appearance of the tumor (solid vs papillary), and concomitant CIS, were important predictors of residual tumors at second resection of primary pT1 NMIBC patients. We were able to calculate the probability of residual tumor which helped us determine risk adapted strategies according to these probabilities.

Abstract 3097: Patient-derived renal cell carcinoma xenografts engraftment identifies patients at risk of disease relapse, progression and death

Abstract Renal cell carcinoma (RCC) represents up to 90% of all kidney tumors, with 30% of patients presenting metastasis at diagnosis while 20-50% of those treated for curable localized disease experience recurrence. A better understanding of RCC biology is necessary to define the most efficient and personalized treatment or develop better antineoplastic drugs. Patient-derived xenografts (PDX) have emerged as one of the most promising approaches for that. This tool was generated by using surgical specimens of 87 patients implanted in immunodeficient NOD/SCID/gamma (NSG) mice, 17 of those subcutaneously and 70 at the renal subcapsular space. A total of 19 PDX developed only after orthotopic implantation and included 15 cases of clear cell RCC subtype, 3 cases of papillary subtype, and one unclassifiable tumor. One case of a PDX of a clear cell RCC recapitulated the phenotype of vena cava tumor thrombus extension that had been diagnosed in the source patient. The overall take rate was 27%, and the time to observed tumor growth varied from 5 to 13 months. An association between tumor growth and take rate was suggested by increasing take rates of 18%, 36%, and 100% among pT1 (pT1a + pT1b), pT3a, and pT3b stage tumors, respectively. PDX take rate was unrelated to tumor size (p =0.071). Patients whose tumor fragments engrafted experienced worse overall survival (OS) than those whose tumor fragments did not engraft (p = 0.003). Data also suggested a similar trend of association with metastasis-free survival (MFS) (p = 0.063). The median MFS for patients with successful PDX was 21.6 months (95% CI: 14.9, 28.3;), compared to a median of 34.4 months (95% CI: 30.4, 38.5 p = 0.003) among PDX engraftment-negative patients. PDX characterization by immunohistochemistry and targeted sequencing of the 21 most frequently mutated genes in the kidney indicated that all PDXs preserved RCC identity and major molecular alterations. From 19 PDX, the sequences of 13 patients’ tumor samples were compared with their respective PDX. In most patients (92% - 11/12), at least one mutation in patients’ tumor was identified in the PDX and in one case, no alterations were mapped. The most frequently mutated genes were VHL (50% - 6/12) and PBRM1 (41.7% - 5/12), followed by SETD2 (25% - 3/12), BAP1 and KDM5C (both 16.7% - 2/12), and ARID1A (8.3% - 1/12), indicating that all PDXs preserved RCC identity and major molecular alterations. These findings suggest that tumor engraftment capacity can identify patients at increased risk of relapse or death. Furthermore, pT1 stage tumors with the ability to engraft could also facilitate the identification of risk factors related to the rare pT1 cases with disease progression. These results suggest that the orthotopic xenograft model of RCC represents a suitable tool to study RCC biology, identify biomarkers, and test therapeutic candidates. Citation Format: Vilma Regina Martins, Adriano Beserra, Ethiene C. Estevan, Stephania Bezerra, Giovana T. Torrezan, Amanda Ikegani, Dellê Humberto, Isabela V. Cunha, Isabella T. Meira, Dirce M. Carraro, Primo N. Lara, Stenio Zequi, Tiago G. Santos. Patient-derived renal cell carcinoma xenografts engraftment identifies patients at risk of disease relapse, progression and death [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3097.

High-risk MSI-H stage II colon cancer: Treatment patterns and outcomes.

e15587 Background: For resected stage II MSI-high (MSI-H) colorectal cancer (CRC) without high-risk features (HRF), standard of care recommendation per NCCN guidelines is observation. For tumors with HRF, the prognostic significance and impact of adjuvant therapy remains uncertain. The NCDB was queried to assess outcomes. Methods: Adult patients with stage II MSI-H CRC, surgically resected between 2010 and 2017, were identified in the NCDB. Univariate and multivariate Cox proportional hazards models and Kaplan Meier survival curves were generated to assess impact of HRF, clinical and demographic variables, and chemotherapy use on overall survival (OS). Results: 9634 patients with stage II MSI-H CRC who met criteria were identified. In multivariate analysis T4 tumor status, &lt; 12 lymph nodes (LN) examined, perineural invasion (PNI) and positive margins were associated with worse OS, as were older age and increased comorbidity index (CDCC). Poor differentiation and lymphovascular invasion (LVI) were not associated with OS. No OS difference was observed between T4a vs T4b tumors or based upon tumor sidedness, tumor size, or sex. Excluding poor differentiation (33%) and LVI (17%), HRFs were present in 26% of cases: 21% (n = 2033) had 1 HRF and 5% (n = 505) had &gt; 1 HRF. HRFs were associated with decreased 5-year OS. For 1 HRF OS was 66% (HR 1.48, p &lt; 0.0001) and for &gt; 1 HRF OS was 54% (HR 2.31, p &lt; .0001), compared to 77% with 0 HRFs. HRF presence was associated with increased chemotherapy use: 46% for &gt; 1 HRF, 26% for 1 HRF, and 8% with 0 HRFs. pT4 tumors (T4b &gt; T4a) and younger age were also associated with increased chemotherapy use. By age group, chemotherapy was utilized in 31% of those &lt; 50, 27% of those 51-60, 17% of those 61-70 and 6% of those &gt; 70 years old. In the overall population, chemotherapy administration was associated with improved OS on multivariate analysis compared with no treatment (N = 1344; HR 0.76, p &lt; 0.0001). 69% of patients received multi-agent chemotherapy. However, survival was similar between those receiving single-agent vs multi-agent chemotherapy (HR 1.2, p = 0.2016). In patients &lt; 60 years old, chemotherapy use was associated with decreased OS (HR 1.4, p = 0.0156). Conclusions: In this retrospective, uncontrolled large database survey, HRFs are associated with decreased OS in stage II MSI-H CRC. This data indicates that poor differentiation and LVI do not independently worsen outcomes, but that the presence of multiple HRFs bears relevance. Though chemotherapy was associated with improved OS, the association is reversed in the &lt; 60 year old population; this analysis cannot fully control for extent of disease and PS, among other factors. Chemotherapy should be judiciously administered in Stage II MSI-H CRC with HRFs. Immunotherapy trials are justified.[Table: see text]

Importance of accurate clinical staging in patients with early stage HER2+ and triple negative breast cancer.

e12631 Background: Comprehensive radiological evaluation in early-stage breast cancer is essential for accurate staging and subsequent therapeutic decisions. This is especially important in early-stage human epidermal receptor -2 (HER2) positive and triple negative breast cancer (TNBC). For these tumors, current guidelines suggest a neoadjuvant approach for ≥cT2 disease. Standard diagnostic modalities have oftentimes failed to confirm the correct size of these tumors. Misrepresentation of their true size may lead to patients being treated with upfront surgery and potentially missing the added benefits of residual treatment if they were later found to have &gt;T2 disease. Methods: We conducted a retrospective analysis via electronic medical record review of a large institutional database from 2008 to 2020. We reviewed all patients with a diagnosis of early-stage breast cancer (Stage I - III) with triple negative or HER2 positive tumors. Patients who received neoadjuvant chemotherapy were excluded. Data on demographics, comorbidities, receptor status, clinical staging, pathological staging, and mortality were collected. Results: Electronic charts from 448 patients were reviewed. 153 patients had ≤cT1 disease. 33 (21.6%) of the 153 patients were upstaged from cT1 to ≥pT2 tumors. Combined imaging modality with mammogram + ultrasound (US) yielded a statistically significant accuracy in clinical staging compared to US alone (82.6 vs. 44.4%; p = 0.02). Comparisons between other imaging methods were not statistically significant (mammogram + US vs. mammogram only, 74.1 vs. 82.6%, p = 0.41 and mammogram only vs. US only, 74.1 vs. 44.4%, p = 0.13). Magnetic Resonance Imaging (MRI) was only utilized on 2 patients with 50% accuracy. Conclusions: Significant discordance (&gt; 20%) exists between radiological staging and pathological staging of T1 TNBC and HER2 positive breast cancers at our institution. This data has considerable therapeutic implications as landmark studies such as the CREATE-X and KATHERINE trials have provided better survival data with the use of drugs such as capecitabine and trastuzumab emtansine (T-DM1), respectively, in patients with residual disease who have undergone neoadjuvant chemotherapy followed by surgery. Combined imaging with mammography and US yielded the most accurate staging. MRI was utilized on only two patients. MRI has shown to be helpful in evaluation of patients for preoperative systemic therapy, defining the extent of disease, assessing response to treatment and the potential for breast conserving surgery. Several studies have also demonstrated the accuracy of MRI for staging breast cancer. Given the significant discordance seen at our institution, one possible solution may be to employ MRI for staging on patients with inherently aggressive early-stage tumors such as TNBC and HER2+ breast cancers. Further prospective studies are required to validate our findings.

Abstract B021: Spatial dynamic transcriptomic characterization of response patterns to neoadjuvant chemotherapy in muscle-invasive bladder cancer

Abstract Defined by a high mutational burden and a heterogeneous tissue landscape, muscle-invasive bladder cancer (MIBC) is an aggressive disease with a 5-year mortality rate of approximately 50%. To lower the risk of relapse and improve survival, cisplatin-based combination neoadjuvant chemotherapy (NAC) is recommended prior to radical cystectomy, but response rates are limited to only 30-50% of patients. Importantly, patients in whom NAC treatment induces a pathological downstaging of the primary tumor to pT0/pTis have a significantly increased 5-year mortality of 85% compared to 43% for patients with resistant ≥ pT2 tumors. Thus, the current inability to stratify patients who are most likely to benefit from NAC treatment results in a considerable overtreatment of non-responders. The effectiveness of chemotherapy can be influenced by numerous factors, including intrinsic or acquired tumor resistance mechanisms or the selection of pre-existing treatment-resistant clones. Previous literature on MIBC has recognized several tumor characteristics associated with chemosensitivity, including somatic mutations in DNA repair-associated genes, chromosomal alterations, immune cell infiltration, and distinct variant histologies, but no robust biomarkers have yet been implemented in clinical routine. Thus, further in-depth characterization of the tumor architecture of MIBC is highly needed. We aim to perform a comprehensive spatial mapping of the transcriptomic landscape of MIBC through analysis of longitudinal tumor tissue samples from patients (n=15) treated for MIBC at Skåne University Hospital, Sweden, with divergent response patterns to NAC. Multiregional sampling from pre-NAC tissue specimens derived from transurethral resection of the bladder tumor (TURBT) and post-NAC radical cystectomy will be performed and incorporated into tissue microarrays. GeoMx Digital Spatial Profiler Cancer Transcriptome Atlas panel (Nanostring Technologies) will be applied for high-plex compartment-specific expression of genes covering important aspects of tumor biology and tumor-immune interaction, as well as a customized panel including RNA-binding motif protein 3 (RBM3), a gene previously associated to cisplatin sensitivity in several cancer types including urothelial cancer. Gene expression will be quantified through next-generation sequencing and related to clinical and pathological data. Hereby, we aim to gain insights into mechanisms of chemosensitivity and durable response that could potentially refine treatment protocols towards more tailored approaches. Citation Format: Sara Wahlin, Karolina Boman, Björn Nodin, Gottfrid Sjödahl, Karin Jirström. Spatial dynamic transcriptomic characterization of response patterns to neoadjuvant chemotherapy in muscle-invasive bladder cancer [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr B021.

Long-Term Oncological Outcomes of Papillary Thyroid Cancer and Follicular Thyroid Cancer in Children: A Nationwide Population-Based Study

IntroductionPediatric thyroid carcinoma is a rare malignancy and data on long-term oncological outcomes are sparse. The aim of this study was to describe the long-term oncological outcomes of pediatric papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) in a national cohort, and to identify risk factors for recurrence.MethodsWe conducted a nationwide, retrospective cohort study, in which we combined two national databases. Patients aged <18 years, diagnosed with PTC or FTC in the Netherlands between 2000 and 2016, were included. pT-stage, pN-stage, multifocality and angioinvasion were included in a Cox-regression analysis for the identification of risk factors for recurrence.Results133 patients were included: 110 with PTC and 23 with FTC. Patients with PTC most often presented with pT2 tumors (24%) and pN1b (45%). During a median follow-up of 11.3 years, 21 patients with PTC developed a recurrence (19%). Nineteen recurrences were regional (91%) and 2 were pulmonary (9%). No risk factors for recurrence could be determined. One patient who developed pulmonary recurrence died two years later. Cause of death was not captured. Patients with FTC most often presented with pT2 tumors (57%). One patient presented with pN1b (4%). In 70%, no lymph nodes were collected. None of the patients with FTC developed a recurrence or died.ConclusionPediatric PTC and FTC are two distinct diseases. Recurrence in pediatric PTC is common, but in FTC it is not. Survival for both pediatric PTC and FTC is very good.

PD59-03 ADJUVANT THERAPY AFTER SURGICAL RESECTION OF NONMETASTATIC RENAL-CELL CARCINOMA: ONE SIZE DOES NOT FIT ALL

You have accessJournal of UrologyCME1 May 2022PD59-03 ADJUVANT THERAPY AFTER SURGICAL RESECTION OF NONMETASTATIC RENAL-CELL CARCINOMA: ONE SIZE DOES NOT FIT ALL Zine-Eddine Khene, Axel Bex, and Karim Bensalah Zine-Eddine KheneZine-Eddine Khene More articles by this author , Axel BexAxel Bex More articles by this author , and Karim BensalahKarim Bensalah More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002644.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Keynote 564 was a double-blind randomised phase 3 trial comparing adjuvant pembrolizumab versus placebo for up to one year in patients who had a completely resected ccRCC considered at high risk of recurrence. The interim analysis has sparked enthusiasm in the onco-urological community since the primary endpoint (investigator assessed disease free survival (DFS)) was reached. However, In the Keynote-564 trial, inclusion criteria were very heterogeneous. The trial included patients who were considered at “intermediate-high risk” (pT2 and G4 or sarcomatoid, pT3) and “high risk” (pT4, N1) of recurrence. Our objective was to investigate the real risk associated with these prognostic groups in a cohort of patients treated in a “real life” setting outside of a clinical trial. METHODS: Patients who underwent radical or partial nephrectomy for a localized ccRCC between 2010 and 2020 were analyzed. We exclusively focused on patients with pT2 and G4 or sarcomatoid, pT3, pT4 and N1 (i.e., whose characteristics matched Keynote 564 prognostic classification). We excluded patients who received adjuvant or neo-adjuvant treatment. we plotted the survival curves using the Kaplan Meier estimates to make a direct visual comparison between groups. RESULTS: 400 patients were included in the analysis. Kaplan-Meier curves for DFS (A) and OS (B) according to Keynote-564 inclusion criteria are clearly separating (Figure 1). Patients with the best outcome are those with pT2 and pT3a tumours, whereas pT3b-c, pT4 and N1 patients have a far worse prognosis. Following this observation, we conducted an exploratory analysis by dividing our cohort into two prognostic groups: 1) pT2 and G4 or sarcomatoid, pT3a N0 and 2) pT3b-c, pT4 and N1 and found a very significant difference (p<0.05). CONCLUSIONS: The patients included in Keynote 564 have heterogenous disease stages that will exhibit different natural histories. It is therefore questionable to consider them all equally eligible for an adjuvant treatment. Moreover, including patients with a good prognosis in the trial and thus the primary analysis may obscure the benefit of adjuvant therapy for patients with a poor prognosis. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e1019 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Zine-Eddine Khene More articles by this author Axel Bex More articles by this author Karim Bensalah More articles by this author Expand All Advertisement PDF DownloadLoading ...

Peritumoral histopathologic findings in patients with chronic viral hepatitis-associated hepatocellular carcinoma.

Data on peritumoral histopathologic findings in patients with hepatocellular carcinoma (HCC) is limited. In this retrospective study, we evaluated the peritumoral histopathologic changes in patients with chronic viral hepatitis (CVH)-associated HCC (CVH-HCC) and their prognostic value. 61 consecutive cirrhotic patients who underwent liver transplantation due to CVH-HCC were included. Histopathologic features within 1 cm distance of the tumor, and their association with clinicopathological characteristics and prognosis were evaluated. A random representative slide of cirrhotic parenchyma unrelated to invasive and/or dysplastic foci was also evaluated for the same histopathologic criteria. The majority (85%, n = 52) were male with a median age of 55 ± 6.38 (range, 39-67). The etiologic agent was only HBV in 90% (n = 55). The most common peritumoral findings were portal inflammation (100%; n = 61), ductular reaction (100%; n = 61) and sinusoidal dilatation (95%; n = 58). Macrovascular invasion was observed only in four cases (7%) with mild peritumoral portal inflammation. Neutrophilic infiltration of the peritumoral portal tracts (n = 18; 30%) was significantly associated with pT4 tumor stage, tumor grade, macrovascular invasion, and pretransplant therapy. Patients with moderate or severe peritumoral sinusoidal dilatation tended to have worse prognosis, albeit not significantly. Peritumoral ballooning degeneration was associated with multifocality, recurrence and recurrence-free survival in both uni- and multivariate analysis. Peritumoral histopathologic changes in CVH-HCC can be classified as: changes related to pathogenesis, changes indirectly affecting prognosis, and changes directly affecting prognosis. Peritumoral prominent ballooning degeneration may be a predictor of recurrence while portal neutrophilic infiltration and sinusoidal dilatation seem to indicate poor prognosis.

Benchmarking Survival Outcomes Following Surgical Management of pT3 and pT4 Cutaneous Squamous Cell Carcinoma of the Head and Neck

BackgroundpT3/4 head and neck cutaneous squamous cell carcinomas (HNcSCCs) are associated with poor outcomes, including local recurrence, metastasis and death. Whilst surgery remains the standard treatment for advanced HNcSCC, novel systemic therapies, such as immunotherapy, are being used earlier in the treatment paradigm. It is imperative that the clinical outcomes of surgery are clearly described so that conventional and emerging treatment modalities can be better integrated and sequenced in the management of pT3/4 HNcSCC.MethodsPatients with confirmed pT3/4 HNcSCC undergoing curative surgical resection between 2014-2020 were identified retrospectively from a prospectively maintained research database. The primary outcomes of interest were locoregional control (LRC), disease-specific survival (DSS), and overall survival (OS). The secondary outcome was surgical complication rate.ResultsA total of 104 patients (median age 74, range 41–94 years) were included, 90% of which had pT3 tumors; 36.5% received adjuvant radiotherapy. Median follow-up was 24.3 (range 1.0–84.3) months. LRC at 5 years was 62.0%, DSS at 5 years was 83.7%, and OS at 5 years was 71.9%. Median time to recurrence was 8.4 months. LRC was reduced in the presence of margin involvement and previous treatment (radiotherapy/surgery). The major surgical complication rate was 9.6%.ConclusionsMore than 60% of patients treated surgically for pT3/4 head and neck cSCC were alive and free of disease at 5 years posttreatment. High-risk features such as margin involvement and having had previous treatment (radiotherapy/surgery) should be used to guide adjuvant therapy.

Prognostic Impact of Primary Tumor Extent and Postoperative Radiation Facility Location in Major Salivary Gland Malignancies.

IntroductionThe treatment of primary salivary malignancies often requires a multimodality approach. The purpose of this analysis was to evaluate the interaction between primary tumor extent and the treatment location of postoperative radiotherapy (PORT) in patients with primary salivary malignancies with respect to survival outcomes.MethodsPatients with primary salivary malignancies who underwent upfront surgery followed by radiation were queried in the National Cancer Database (NCDB). Patients were stratified by pathologic T stage and whether PORT was performed at the same or different facility as the definitive surgery. Survival outcomes were compared using the Kaplan-Meier method and Cox proportional hazards regression.ResultsA total of 5,553 patients were selected, of which 1,159 had pathologic T4 (pT4) tumors. Patients who received PORT at the same facility compared with a different facility demonstrated superior overall survival (OS) on log-rank analysis (p=0.003). On subgroup analysis, patients with pT4 tumors had superior OS (p=0.015), whereas patients with smaller T1-3 tumors did not. PORT receipt at the same surgical facility was not a significant predictor of OS on multivariable analysis when all patients were included (p=0.057). However, among patients with pT4 tumors, OS was improved in patients who got PORT at the same facility as their surgery (p=0.015), with 10-year survival rates of 38.3 (95% confidence interval (CI): 33%-44%) versus 31% (95%CI: 24%-38%).ConclusionOS was improved in patients with primary salivary malignancies who received PORT at the same facility as their surgery, but the difference appears to be primarily driven by patients with pT4 primary tumors.

Assessment of positive surgical margins in the management of patients after radical prostatectomy for pT2 prostate cancer

Few data are available regarding positive surgical margins (PSM) in patients who underwent surgery for localized prostate cancer (PC). Our objective was to evaluate the impact of PSM on biochemical recurrence-free survival (BRFS) for patients who underwent PC for pT2 tumor without adjuvant treatment. We included each patient who underwent radical prostatectomy for pT2N0 PC between 1988 and 2018. Primary endpoint was biochemical recurrence (BR). BRFS was calculated using Kaplan-Meier method. Univariate and multivariate analyses were used to determine factors associated with BR and PSM. Overall, 2429 patients were included whom 420 patients had PSM (17.3%). Median follow-up was 116 months. BRFS at 10 years was 66.6% in case of PSM, and 84% in the negative margins group (P<0.0001). Parameters associated with BR were preoperative PSA level (P<0.0001), Gleason score (P<0.0001), tumor volume in biopsies, and margins length (P<0.04). PSM in pT2N0 CP are associated with poor prognosis in terms of BR. Nevertheless, only a small number of pT2R1 cancer will present biological recurrence. The use of adjuvant radiotherapy in these patients therefore represents a risk of overtreatment, with the risk of adverse effects inherent to irradiation. Clinical and biological monitoring in case of PSM seems acceptable.

Thymic Mucoepidermoid Carcinoma: A Clinicopathologic and Molecular Study.

Thymic mucoepidermoid carcinoma (MEC) is a rare tumor, and its characteristics remain to be clarified. Here we investigated 20 cases of thymic MEC to systematically characterize its clinical, histopathologic, and molecular features. The median age of the patients was 56 years (range, 19 to 80 y), there was a slight male predilection (3:2), and 44% of the patients were asymptomatic at diagnosis. The median tumor size was 6.8 cm in diameter, 55% were pT1 tumors, and 50% were TNM stage I tumors. When 4 tumor grading systems for salivary MEC (Armed Forces Institutes of Pathology, Brandwein, modified Healey, and the Memorial Sloan-Kettering) were employed, low-grade, intermediate-grade, and high-grade tumors accounted for 35% to 70%, 5% to 25%, and 25% to 50%, respectively. Many histologic variants were noted, and 70% of the cases were classified as nonclassic variants. MAML2 rearrangement was detected in 56% of cases, and the fusion partner was CRTC1 in all cases. CRTC1-MAML2 fusion was associated with lower pT classification and lower TNM stage. The overall survival rate of all patients was 69% and 43% at 5 and 10 years, respectively. Worse overall survival was associated with higher pT stage, higher TNM stage, residual tumors, greater tumor size, high-grade tumor histology (Armed Forces Institutes of Pathology and Memorial Sloan-Kettering, but not the other 2), and with the absence of CRTC1-MAML2 fusion. Of note, none of the patients with CRTC1-MAML2 fusion-positive tumors died during the follow-up. In conclusion, the clinicopathologic and molecular findings of thymic MEC presented here are expected to contribute to the management of this rare tumor.

Reclassifying pT3 renal pelvic urothelial carcinoma with renal parenchyma invasion to pT2 improves correlation with overall survival

The American Joint Cancer Committee pT categorization in renal pelvic carcinoma defines pT3 as invasion of renal parenchyma, invasion of peripelvic fat, or both. However, survival heterogeneity within the pT3 category has been demonstrated. This investigation sought to compare survival between pT categories of renal pelvic urothelial carcinoma and identify modifications to improve correlation with survival. Pathology reports from nephroureterectomies performed at our institution from 2010 to 2019 were analyzed to identify primary renal pelvic urothelial carcinoma (n=146). Tumors were stratified based on pT, pN, and invasion of renal parenchyma vs invasion of peripelvic fat with or without renal parenchyma invasion. Kaplan-Meier survival curves and Cox regression multivariate analysis were used to compare overall survival between groups. Similar survival curves were observed for pT2 and pT3 tumors. Multivariate analysis confirmed overlapping hazard ratios (HRs) for pT2 (HR=2.64, 95% confidence interval [CI] = 0.69, 10.06)and pT3 (HR=4.42, 95% CI = 2.08, 9.37). pT3 tumors with peripelvic fat invasion, regardless of renal parenchyma involvement, had a 3.3-fold worse overall survival than pT3 tumors with only renal parenchyma involvement. Additionally, pT3 tumors with only renal parenchyma invasion had similar survival compared to pT2, while pT3 tumors with peripelvic fat invasion had worse overall survival (p=0.00091). Reclassifying renal parenchyma invasion as pT2 yielded greater survival curve separation and greater difference in HRs. For renal pelvic urothelial carcinoma, modifying the pT3 category to only include tumors with peripelvic fat invasion and expanding the pT2 category to include renal parenchyma invasion may improve pT correlation with overall survival.

Germline and sporadic mTOR pathway mutations in low-grade oncocytic tumor of the kidney

Low-grade oncocytic tumor (LOT) of the kidney is a recently described entity with poorly understood pathogenesis. Using next-generation sequencing (NGS) and complementary approaches, we provide insight into its biology. We describe 22 LOT corresponding to 7 patients presenting with a median age of 75 years (range 63–86 years) and male to female ratio 2:5. All 22 tumors demonstrated prototypical microscopic features. Tumors were well-circumscribed and solid. They were composed of sheets of tumor cells in compact nests. Tumor cells had eosinophilic cytoplasm, round to oval nuclei (without nuclear membrane irregularities), focal subtle perinuclear halos, and occasional binucleation. Sharply delineated edematous stromal islands were often observed. Tumor cells were positive for PAX8, negative for CD117, and exhibited diffuse and strong cytokeratin-7 expression. Six patients presented with pT1 tumors. At a median follow-up of 29 months, four patients were alive without recurrence (three patients had died from unrelated causes). All tumors were originally classified as chromophobe renal cell carcinoma, eosinophilic variant (chRCC-eo). While none of the patients presented with known syndromic features, one patient with multiple bilateral LOTs was subsequently found to have a likely pathogenic germline TSC1 mutation. Somatic, likely activating, mutations in MTOR and RHEB were identified in all other evaluable LOTs. As assessed by phospho-S6 and phospho-4E-BP1, mTOR complex 1 (mTORC1) was activated across all cases but to different extent. MTOR mutant LOT exhibited lower levels of mTORC1 activation, possibly related to mTORC1 dimerization and the preservation of a wild-type MTOR copy (retained chromosome 1). Supporting its distinction from related entities, gene expression analyses showed that LOT clustered separately from classic chRCC, chRCC-eo, and RO. In summary, converging mTORC1 pathway mutations, mTORC1 complex activation, and a distinctive gene expression signature along with characteristic phenotypic features support LOT designation as a distinct entity with both syndromic and non-syndromic cases associated with an indolent course.