Favorable Pathologic Features Research Articles

Clinicopathological characteristics and survival outcomes of women aged ≤45 and >45 years with endometrial adenocarcinoma in tertiary referral hospital: a 21-year cohort study

ObjectiveThis study aimed to compare clinicopathological characteristics and oncological outcomes in patients with endometrial cancer aged ≤45 and >45 years, with a focus on identifying distinct traits and prognostic factors...

A collaborative review of the microsatellite instability/deficient mismatch repair phenotype in patients with upper tract urothelial carcinoma.

To perform a collaborative review of the literature exploring the microsatellite instability/deficient mismatch repair (MSI/dMMR) phenotype in patients with upper tract urothelial carcinoma (UTUC). A collaborative review of the literature available on Medline was conducted by the Cancer Committee of the French Association of Urology to report studies describing the genetic mechanisms, investigation, prevalence and impact of the MSI/dMMR phenotype in UTUC patients. The predominant genetic mechanism leading to the MSI/dMMR phenotype in UTUC patients is related to the constitutional mutation of one allele of the MMR genes MLH1, MSH2, MSH6 and PMS2 within Lynch syndrome. Indications for its investigation currently remain limited to patients with a clinical suspicion for sporadic UTUC to refer only those with a positive testing for germline DNA sequencing to screen for this syndrome. With regard to technical aspects, despite the interest of MSIsensor, only PCR and immunohistochemistry are routinely used to somatically investigate the MSI and dMMR phenotypes, respectively. The prevalence of the MSI/dMMR phenotype in UTUC patients ranges from 1.7% to 57%, depending on the study population, investigation method and definition of a positive test. Younger age and a more balanced male to female ratio at initial diagnosis are the main specific clinical characteristics of UTUC patients with an MSI/dMMR phenotype. Despite the conflicting results available in the literature, these patients may have a better prognosis, potentially related to more favourable pathological features. Finally, they may also have lower sensitivity to chemotherapy but greater sensitivity to immunotherapy. Our collaborative review summarises the available data from published studies exploring the MSI/dMMR phenotype in UTUC patients, the majority of which are limited by a low level of evidence.

Lateral lymph node metastasis without mesenteric lymph node involvement in middle-low rectal cancer: Results of a multicentre lateral node collaborative group study in China

BackgroundCharacteristics and prognoses of lateral lymph node (LLN) metastasis but not mesenteric lymph node (LN) metastasis are poorly understood. This study explored patterns of mesenteric and LLN metastases in rectal cancer patients. MethodThis retrospective, multicentre study was conducted at three institutions and included patients who underwent total mesorectal excision (TME) with lateral lymph node dissection (LLND) for rectal cancer (n = 271). ResultsAmong the patients with LLN metastases, 210 patients (77.5 %) with clinical stage T3-4 disease and 157 patients (57.9 %) with clinical stage N1-N2 disease underwent TME as well as LLND. The prognoses of patients with metastasis confined to LLNs were significantly better than those of patients with both mesenteric and LLN metastases (3-year overall survival: 85.0 % vs. 51.0 %, p = 0.005; 3-year disease-free survival: 75.0 % vs. 26.5 %, p = 0.003) and were similar to those of patients with metastasis confined to mesenteric LNs (3-year overall survival: 85.0 % vs. 83.8 %, p = 0.607; 3-year disease-free survival 75.0 % vs. 68.8 %, p = 0.717). Patients with metastases confined to LLN had a lower proportion of poor histological types (20.0 % vs. 65.3 %, p = 0.002), lymphatic invasion (20.0 % vs. 59.2 %, p = 0.036) and number of LLN metastases (1.6 vs 2.7, p = 0.004), and all metastases were confined to the internal iliac or obturator region (100.0 % vs. 77.6 %, p = 0.008) compared to patients with both mesenteric and LLN metastasis. ConclusionsApproximately a quarter of patients with rectal cancer have LLN metastases but no mesenteric LN metastases. These patients have favourable pathological features and prognoses and can be managed and treated for mesenteric LN metastasis.

Breast cancer molecular subtype classification according to immunohistochemistry markers and its association with pathological characteristics among women attending tertiary hospitals in Tanzania

BackgroundBreast cancer immunohistochemistry is a biological characteristic of the tumour which has a role to diagnose molecular subtype, prognosticate and guide treatment and is categorised into 4 subtypes. Data in Tanzania was lacking and was based off data extrapolated from studies in Western Africa thus hypothesizing that women of African ancestry predominately develop Triple Negative Breast Cancer (TNBC). MethodsA retrospective cross-sectional study was carried out at two tertiary referral hospitals on participants who were recruited from the cancer registries from 2015 to 2022. Prevalence of each molecular subtype was determined and association between molecular subtype to demographic and pathological characteristics were evaluated. Predictors of molecular subtypes was then determined using logistic regression. ResultsTotal number of participants were 1214, median age was 50 (IQR: 41–61), median tumor size was 5 cm (IQR: 4–7) with lymph node positivity in 73.7 %. Immunohistochemistry studies showed estrogen, progesterone and Human Epidermal Growth Factor Receptor 2 (HER2) receptor positivity in 54.4 %, 34.4 % and 27.8 % of cases respectively. Molecular subtype classification prevalence for Luminal A was 21.17 % (95 % CI: 18.87–23.47), for Luminal B 35.75 % (95 % CI: 33.05–38.45), for HER2 enriched 11.86 % (95 % CI: 10.04–13.68) and for TNBC 31.22 % (95 % CI: 28.61–33.83). Significant association was seen between molecular subtype with age, tumor size, tumor grade and lymph node involvement. Predictors of Luminal tumors were larger tumor size (aOR 1.217, 95 % CI: 1.149–1.291) no lymph node involvement (aOR 0.429, 95 % CI: 0.313–0.589) while an advanced tumor grade reduced likelihood (aOR 0.041, 95 % CI: 0.011–0.019). ConclusionIn Tanzania Luminal B was most predominant subtype presenting at an earlier age and associated with more favorable pathological characteristics.

Long-term follow up of E3311, a phase II trial of transoral surgery (TOS) followed by pathology-based adjuvant treatment in HPV-associated (HPV+) oropharynx cancer (OPC): A trial of the ECOG-ACRIN Cancer Research Group.

6009 Background: E3311 is a phase II trial of TOS by credentialed surgeons with pathology-driven deintensified post-operative management in HPV+ OPC. Intermediate risk patients were randomized between standard and reduced dose radiation. We present mature outcome data, at median follow up of 52.4 months (m). Methods: Patients were eligible who had resectable cT1-2 stage III/IV AJCC7 p16+ OPC without matted neck nodes. Those with clear margins, 0-1 + nodes (LN), and no extranodal extension (ENE) were observed (Arm A, N=38); those with clear margins, 2-4 + LN, or ENE ≤1mm were randomized to 50Gy (Arm B, N=100) or 60Gy (Arm C, N=108); those with involved margins, >4 + LN, or >1mm ENE received weekly cisplatin 40 mg/m2 and 60-66Gy (Arm D, N=113). Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method and compared using a log-rank test, stratified by arm for comparisons of primary site and smoking history. Results: Among 359 evaluable patients, 54-m PFS and OS were 90.6% (90% CI: 87.2%, 93.1%) and 95.3% (90% CI: 93.0%, 96.9%). 54-m PFS by arm was: A 93.2% (90% CI: 79.6%, 97.8%); B 94.9% (90% CI: 89.7%, 97.5%); C 90.2% (90% CI: 82.7%, 94.6%) and D 85.5% (90% CI: 77.5%, 90.8%). 54-m OS by arm was: A 97.1% (90% CI: 85.7%, 99.4%); B 97.9% (90% CI: 93.5%, 99.3%), C 95.1% (90% CI: 90.1%, 97.6%) and D 92.5% (90% CI: 86.9%, 95.7%). Among patients in Arm A, 11 had N0 and 27 N1 stage. Median Arm A lymph node yield (LNY) was 29 (11 to 91 LN) and did not differ for patients with/without recurrence (p=0.83). All Arm A recurrences were in N1 patients: 1 at 18 m and 3 at > 40 m. No significant difference in PFS or OS was observed by prescribed radiation dose for intermediate risk patients (Arm B vs. C). Outcome did not differ by primary site of tonsil vs. other OPC (oOPC): 54-m PFS Tonsil 89.3% (90% CI: 84.9%, 92.5%) vs. oOPC 92.9% (90% CI: 87.0%, 96.2%), p=0.28, and 54-m OS Tonsil 94.6% (90% CI: 91.5%, 96.6%) vs oOPC 96.6% (90% CI: 92.4%, 98.5%), p=0.35. Smoking history also did not impact outcome. 54-m PFS was 89.9% (90% CI: 85.9%, 92.9%) for those with ≤10 pack-years (PY) tobacco exposure and 91.7% (90% CI: 83.9%, 95.9%) for those with >10 PY. Conclusions: TOS, neck dissection with deintensified risk-based post-operative management results in outstanding 54-m PFS and OS across all subsites of T1-2 p16+ OPC, irrespective of smoking history. Late recurrence is not increased when post-operative radiation is reduced from 60 to 50Gy for intermediate risk patients. Pathologic >1mm ENE (N=87), involved margin (N=12) or >4 involved LN (N=30) accurately identify patients at increased recurrence risk and outcomes were favorable among such patients. Among patients with favorable pathologic characteristics, a subset with N1 disease are at risk for late recurrence and further characterization of these patients is warranted. Clinical trial information: NCT01898494 .

Perineural Invasion is an Important Prognostic Factor in Patients With Radically Resected (R0) and Node-negative (pN0) Pancreatic Cancer.

To investigate the association between perineural invasion (PNI) and overall survival (OS) in a nationwide cohort of patients with resected pancreatic ductal adenocarcinoma (PDAC), stratified for margin negative (R0) or positive (R1) resection and absence or presence of lymph node metastasis (pN0 or pN1-N2, respectively). Patients with R0 and pN0 resected PDAC have a relatively favorable prognosis. As PNI is associated with worse OS, this might be a useful factor to provide further prognostic information for patients counselling. A nationwide observational cohort study was performed including all patients who underwent PDAC resection in the Netherlands (2014-2019) with complete information on relevant pathological features (PNI, R status, and N status). OS was assessed using Kaplan-Meier curves, and Cox-proportional hazard analyses were performed to calculate hazard ratio's (HR) with corresponding 95% confidence intervals (CI). In total, 1630 patients were included with a median follow-up of 43 (interquartile range 33-58) months. PNI was independently associated with worse OS in both R0 patients (HR 1.49 [95%CI 1.18-1.88]; P<0.001) and R1 patients (HR 1.39 [95% CI 1.06-1.83]; P=0.02), as well as in pN0 patients (HR 1.75 [95%CI 1.27-2.41]; P<0.001) and pN1-N2 patients (HR 1.35 [95% CI 1.10-1.67]; P<0.01). In 315 patients with R0N0, multivariable analysis showed that PNI was the strongest predictor of OS (HR 2.24 [95% CI 1.52-3.30]; P<0.001). PNI is strongly associated with worse survival in patients with resected PDAC, in particular in patients with relatively favorable pathological features. These findings may aid patient stratification and counselling and help guide treatment strategies.

Trauma plays an important role in acral melanoma: A retrospective study of 303 patients.

Acral melanoma (AM) is the most common subtype of malignant melanoma in China, with a very poor prognosis. Despite the frequent reporting of trauma events in AM cases, the precise etiology of AM remains elusive. A retrospective analysis was conducted on a cohort of 303 AM patients at Nanjing Drum Tower Hospital. The patients were categorized into four distinct groups based on different patterns of disease onset: trauma type (Type 1), pigmented nevus type (Type 2), pigmented nevi with trauma (Type 3), and pigmented nevi with natural ulceration (Type 4). Differences in clinicopathological features, genetic alterations, and tumor immune microenvironment (TIME) were analyzed. Traumatic events accounted for a large proportion of AM cases. Among these categories, Type 1 patients displayed the least favorable pathological traits and an immunosuppressive TIME. Common copy number variations (CNVs) were observed in CCND1, RB1, FGF19, and IL7R, while CNVs in CDK4 and TERT occurred less frequently in patients with a history of trauma (Type 1 and Type 3). Type 2 patients exhibited the most favorable pathological characteristics and genetic profiles, and demonstrated the lowest incidence of CCDN1 and RB1 CNVs but had the highest CDK4 CNVs. In contrast, the pathological behavior of Type 3 and Type 4 patients was in between Type 1 and Type 2. And patients in Type 3 and Type 4 displayed a more favorable overall microenvironment. This study provides a clinical classification of Chinese AM based on diverse clinical onset characteristics and highlights the important role of trauma in AM. These findings may help to guide the diagnosis, treatment, and prognosis of AM patients. Further investigations are imperative to elucidate the underlying mechanisms governing the association between trauma and AM.

The impact of the Covid-19 pandemic on the stage of endometrial cancer at diagnosis

BackgroundEndometrial cancer generally presents at an early stage affording a high rate of surgical cure. Early in the Covid-19 pandemic it was suggested that treatment of tumors with favorable pathologic features might safely be delayed. ObjectiveWe hypothesized that disruption to health care services during the pandemic would impact the stage at presentation for these patients. Here we compare the stage at presentation of Endometrial Cancer in the months immediately preceding the pandemic to the stage at presentation during the pandemic. Study designCharts of patients presenting with Endometrial Cancer between January 1, 2018 and April 30, 2022 were reviewed. March 1, 2020 separated the “pre-pandemic” era from the “pandemic” era. Data was collected regarding patient age, body mass index (BMI), tumor stage, histology, grade, size, and depth of invasion. Results322 of 374 (86.09%) of surgically staged patients presented with FIGO stage I disease “pre-pandemic” compared to 263 of 329 (71.73%) of surgically staged patients in the “pandemic” cohort (p =.029). 2.08% pre-pandemic compared to 5.48% during the pandemic presented with FIGO stage IV (p =.015). ConclusionWe found a significant difference in the stage at presentation in endometrial cancer patients, a statistic which may be attributed to the disruption of healthcare services caused by the Covid-19 pandemic.

Renal cell carcinoma in native kidneys before transplantation - When will we stop waiting?

Kidney transplantation requires immunosuppression, traditionally regarded as a risk factor for progression in all malignancies. Based on the Cincinnati Registry, a waiting period before transplantation is therefore mandatory. However, recent evidence suggests this increased risk is restricted to particular tumors, whereas others like renal cell carcinoma (RCC) are not negatively affected. We aimed to compare oncological outcomes of RCC in native kidneys of end-stage renal disease (ESRD) patients, according to their transplantation or dialysis status. Retrospective analysis of all ESRD patients diagnosed with RCC between 2010 and 2020 in our center. Recurrence-free survival (RFS) and overall survival (OS) were estimated with Kaplan-Meier curves. Multivariable Cox regression model was used to evaluate their association with kidney transplantation. Clinical and pathological characteristics were similar between groups. Kidney transplant recipients had similar risk of recurrence (hazard ratio [HR] 0.40, 95% confidence interval [CI) 0.04-4.46, p = 0.458) and overall survival (HR 0.34, 95%CI 0.07-1.77, p = 0.202) as dialyzed patients. On multivariable Cox regression model, presence or absence of transplantation was not significantly associated with RFS (p = 0.479) or OS (p = 0.236). Time on dialysis was the only independent predictor of worse survival (HR 1.86, 95%CI 1.18-2.93, p = 0.008). Most RCC in native kidneys of ESRD patients are low-grade, low-stage and exhibit favourable pathological and outcome features. Immunosuppression does not seem to have an impact on oncological outcomes, but an increased time on dialysis seems to be associated with worse overall survival. Therefore, waiting time for transplantation for these tumors could be reduced.

Nondisparate Survival of Non-Hispanic Black Women With Breast Cancer Despite Less Favorable Pathology: Effect of Access to and Provision of Care Within a Military Health Care System.

Breast cancer mortality rates are 40% higher in non-Hispanic Blacks (NHBs) than in non-Hispanic White (NHWs) in the United States. All women treated within the Murtha Cancer Center at Walter Reed National Military Medical Center (MCC/WRNMMC) have health insurance and are provided multidisciplinary health care. Pathological factors and outcomes of NHBs and NHWs treated within the MCC/WRNMMC were evaluated to determine whether equal-access health care reduces disparate phenotypes and survival between the racial groups. Between 2001 and 2018, 368 NHB and 819 NHW women were diagnosed with breast cancer at MCC/WRNMMC. Differences between NHBs and NHWs in epidemiological and pathological characteristics were evaluated. Overall and breast cancer-specific 5- and 10-year survival rates were compared between races. Compared with NHWs, NHBs were significantly more likely to have a body mass index ≥30 kg/m2, to be unmarried, to have tumors of higher grade, later stage, with lymph node metastases, and to be hormone receptor negative (HR-)/human epidermal growth factor receptor 2 positive (HER2+) or triple negative. After adjustment for demographic factors, NHBs remained significantly more likely to have tumors diagnosed at a higher grade and later stage, and to be HR-/HER2+ or triple negative. Neither 5- nor 10-year overall or breast cancer-specific survival differed significantly between the racial groups after adjusting for demographic and pathological variables. Despite having tumors with less favorable pathological characteristics, overall and disease-free survival disparities were not observed for NHBs treated at MCC/WRNMMC. These data suggest that survival disparities of NHBs with breast cancer can be diminished with provision of quality care.

B7-H4 Further Stratifies Patients With Endometrial Cancer Exhibiting a Nonspecific Molecular Profile.

Endometrial cancer is classified into 4 molecular subtypes: DNA polymerase epsilon ultramutated, mismatch repair deficient, p53 mutant, and nonspecific molecular profile (NSMP). Additional biomarkers are urgently needed to better characterize the NSMP subtype, the largest group with heterogeneous pathologic features and prognoses. To investigate the expression of B7 homolog 3 (B7-H3), B7 homolog 4 (B7-H4), and V-set and immunoglobulin domain containing 3 (VSIG-3, a ligand for B7-H5) in 833 patients with endometrial cancer and determine their associations with clinicopathologic and molecular features as well as survival outcomes. Molecular classification was determined by polymerase epsilon sequencing and immunohistochemical staining for p53 and mismatch repair proteins. B7-H3, B7-H4, VSIG-3, and programmed death ligand-1 (PD-L1) were detected via immunohistochemistry. The positivity rates for B7-H3 in each of the tumor and immune cells, B7-H4 (exclusively in tumor cells), and VSIG-3 (exclusively in tumor cells) were 89.0%, 42.3%, 71.5%, and 99.8%, respectively. B7-H3 and B7-H4 positivity in tumor cells was associated with favorable pathologic features and prognosis. In contrast, B7-H3 expression in immune cells was frequent in samples with unfavorable pathologic features; those with p53-mutant subtype, PD-L1 positivity, and a high density of CD8+ T cells; and in patients with poor prognoses. Positive B7-H4 expression was a predictor of improved survival in patients with the NSMP subtype independent of tumor stage or pathologic features. The NSMP subgroup of endometrial cancer can be further stratified by B7-H4 status. Incorporating B7-H4 status into the molecular classification of NSMP could improve the ability to predict disease relapse.

Upregulated Ubiquitin D is a Favorable Prognostic Indicator for Rectal Cancer Patients Undergoing Preoperative Concurrent Chemoradiotherapy.

PurposeFor locally advanced rectal cancer, neoadjuvant concurrent chemoradiotherapy (CCRT) allows tumor downstaging and makes curative radical proctectomy possible. However, we lack a genetic biomarker to predict cancer prognosis or treatment response. We investigated the association between ubiquitin D (UBD) expression and clinical outcomes in rectal cancer patients receiving CCRT.Patients and MethodsWe analyzed the genes associated with the protein modification process (GO:0036211) and identified the UBD gene as the most relevant among the top 7 differentially expressed genes associated with CCRT resistance. We collected tissue specimens from 172 rectal cancer patients who had received CCRT followed by a curative proctectomy. We examine the relationship between UBD expression and patient characteristics, pathological findings, and patient survival, such as metastasis-free survival (MeFS) and disease-specific survival.ResultsUpregulated UBD expression was associated with lower pre-CCRT tumor T stage (P = 0.009), lower post-CCRT tumor T stage (P < 0.001), lower post-CCRT nodal stage (P < 0.001), less vascular invasion (P = 0.015), and better tumor regression (P < 0.001). Using univariate analysis, we found that high UBD expression was correlated with better disease-free survival (DFS) (P < 0.0001), local recurrence-free survival (LRFS) (P < 0.0001) and MeFS (P < 0.0001). Moreover, multivariate analysis demonstrated that high UBD expression was associated with superior DFS (P < 0.001), LRFS (P = 0.01), and MeFS (P = 0.004).ConclusionUBD upregulation was linked to better clinical prognosis, favorable pathological features, and good treatment response in rectal cancer patients undergoing CCRT. These results suggest UBD is a biomarker for rectal cancer.

Prognosis of isolated tumor cells and the utility of molecular classification in early stage endometrioid endometrial cancer (243)

<b>Objectives:</b> To assess the prognosis of isolated tumor cells (ITCs) within sentinel lymph nodes (SLN) compared with node-negative (NN) disease in early-stage endometrioid endometrial cancer and to perform additional evaluation by molecular classification. <b>Methods:</b> Patients (pts) who underwent primary surgical management of uterine cancer from 2007-2019 with a final diagnosis of Stage IA, IB, and II endometrioid endometrial cancer were identified. All SLN underwent ultrastaging per institutional protocol. Cytokeratin-positive cells, ITCs with micrometastasis, and ITCs with macrometastasis were excluded. Clinical-pathologic variables were reviewed. Tumors were classified as POLE, MSI-H, CN-high, or CN-low, based on the TCGA, by utilizing MSK-IMPACT next-generation sequencing (NGS) results and tumor IHC staining. Appropriate statistical analyses were performed. <b>Results:</b> We identified 1381 pts who met the inclusion criteria: 1256 NN (91%) and 125 ITCs (9%). Adjuvant treatment was given to 85% of pts with ITCs compared to 40% of NN pts (p<0.01). Compared to NN patients, the presence of ITCs had a greater association with myoinvasion ≥50% (41% vs 13%, p<0.01), lymphovascular space invasion (77% vs 23%, p<0.01), and chemotherapy +/- radiation (62% vs 7%, p<0.01). The Median follow-up time was 36.5 months (0.4-167 months). There was no significant difference in survival when comparing node status (3-yr PFS: 94% ITC vs 90% NN, p=0.09; 3-yr OS: 98% ITC vs 96% NN, p=0.6). Progression-free survival of ITC-positive pts was not significantly different among those receiving no treatment, chemotherapy +/- radiation, or radiation (p=0.3; Figure 1). TCGA classification was available for 34 ITC and 300 NN pts. Distribution by molecular classification for ITC pts was 3% POLE, 35% MSI-H, 9% CN-high and 53% CN-low; for NN pts, 16% POLE, 36% MSI-H, 4% CN-high, and 43% CN-low (p=0.2). Molecular-based survival outcomes were performed for pts who underwent MSK-IMPACT prior to documented recurrence. There was a significant difference in survival when stratifying the entire cohort by molecular classification, with CN-high having worse outcomes (3-yr PFS: 73% vs 90-95%, p=0.046; 3-yr OS: 78% vs 94-100%, p=0.02). Nine NN patients and two ITC patients were classified as CN-high. Statistics were not applied due to limited numbers. <b>Conclusions:</b> ITCs are associated with less favorable pathologic features than NN disease but are not statistically significantly associated with survival outcomes. Molecular classification type does not have a significant association with the presence of ITCs, but CN-high remains a poor prognostic indicator that may be of clinical value. The role of postoperative therapy in the presence of ITCs or CN-high requires further investigation.

What are the determinants of parametrial invasion in patients with early stage cervical cancer: A cross sectional study

IntroductionThere was an increase in number of patients presented with early-stage cervical cancer (CC). Tumors with favorable pathological features might be candidates for less radical surgery. MethodsWe retrospectively reviewed 700 patients with histologically confirmed CC between January 2011 and March 2020. Chi-square, Fisher's exact tests and multivariate logistic regression analysis were used to assess relations between parametrial involvement (PI) and clinic-pathological variables. ResultsTotal number of 132 patients with stage IA to IIA were eligible to participate. Squamous cell carcinoma was reported in 100 (75.8%) patients, adenocarcinoma and other tumor pathologies were found in 24(18.2%) and 8(6.1%), respectively. Considering the 2018 FIGO stage, 11 (8.4%) patients had IA, 111 (83%%) IB and 10 (7.6%) IIA. Nine patients (6.8%) had PI on permanent pathologic report. Univariate analysis demonstrated that following variables were statistically different between patients with and without PI: age ≥50, tumor size ≥ 3 cm, lower segment involvement, poorly differentiated pathology, deep stromal invasion, pelvic lymph node, lympho-vascular involvement and positive surgical margin (all p values < 0.05). Among these variables only tumor size ≥3 cm (OR: 2.1, 95% CI: 1.11–4.16, p value: 0.02), deep stromal invasion (OR: 2.2, 95% CI: 1.9–7.43, p value: 0.02) and positive surgical margin (OR: 5.1, 95% CI: 3.97–11.15, p value: 0.008) were independent risk factor of PI in multivariate analysis. ConclusionsEarly stage CC might be surgically approached in a more conservative manner if patients have tumor size <3 cm and do not have deep stromal invasion in conization.

Tumor genomic landscape in younger compared to older patients (pts) with metastatic clear cell renal cell carcinoma (mccRCC).

373 Background: Renal cell carcinoma is predominant in 6th to 8th decade of life. Younger pts are more likely to have symptomatic tumors on presentation but with favorable pathological features and disease specific survival (PMID: 17092632). Herein, we hypothesized that the genomic landscape for pts with onset of renal cell cancer at a younger age is distinct from those with late age of onset. Methods: In this IRB-approved retrospective study, pts with mccRCC and tumor comprehensive genomic profiling (CGP) available from a CLIA-certified laboratory were evaluated. Among these, the pts in the first and fourth quartiles of age were included in this study. Variants of unknown significance and gene with alterations (GA) present in less than 5% of pts were excluded from the analysis. A chi-square test was used to compare gene aberration frequency and p-values were adjusted for false discovery rate (FDR) using Benjamini-Hochberg (BH) correction. The median number of genomic aberrations per pt was compared using Wilcoxon rank-sum test. Results: 78 pts were eligible and included: first quartile (Range: 25-53 years; n=54) and fourth quartile (Range: 68-77 years; n=38); male vs female: 30/13 vs 20/15. The genomic aberrations observed in both groups is listed in the table. GA in VHL and PBRM1 were the most commonly observed in both groups . Most commonly observed genomic alterations in first quartile was TP53, BAP1, CDKN2B and TSC1; and fourth quartile of age was SETD2, TSC1, KDM5C and TP53. Tumor mutation burden and the frequency of gene aberrations was similar across both the cohorts. Conclusions: In these hypothesis generating data, there was no significant difference in prevalence of targetable genomic aberrations, tumor mutational burden and frequency of genomic alterations in younger vs older pts with mccRCC. The numerically higher GA in KDM5C and SETD2 (both of which contribute to epigenetic dysregulation) in older pts warrant interrogation in a larger data set. Future directions may include the investigation of epigenomic changes and transcriptomic profiling. Detailed genomic landscape of these pts will be presented in the meeting.[Table: see text]

Final results of a multicenter prospective phase II clinical trial of gemcitabine and cisplatin as neoadjuvant chemotherapy in patients with high-grade upper tract urothelial carcinoma.

440 Background: Neoadjuvant chemotherapy (NAC) has proven survival benefits for invasive urothelial carcinoma of the bladder, yet its role in upper tract urothelial carcinoma (UTUC) remains undefined. We conducted a phase II multicenter trial of NAC with gemcitabine and cisplatin (GC) in patients with high-risk UTUC prior to extirpative surgery to evaluate major outcomes of response, survival, and tolerability. Methods: Eligible patients with defined criteria for high-risk localized UTUC received four cycles of GC prior to surgical resection and lymph node dissection. The primary study endpoint was pathologic response rate (defined as &lt; pT2N0). Patients with progressive disease prior or unable to proceed to surgery were considered treatment failures. Secondary endpoints included time to disease progression (PFS), overall survival (OS), and safety and tolerability. Results: Among 57 patients evaluated, 36 (63%) demonstrated pathologic response, meeting the primary endpoint of the study. A complete response was noted in 11 patients (19%), defined as pT0N0. Forty patients (70%) tolerated all four cycles of GC, and all patients proceeded to surgery. The 90-day ≥ grade 3 surgical complication rate was 7.0%. With a median follow up of 42.3 months among survivors, six patients succumbed to disease. Two and five-year PFS were 76% (95% CI 66, 89) and 61% (95% CI 47, 78). Two and five-year OS were 93% (95% CI 86, 100) and 79% (95% CI 67, 94). Patients demonstrating pathologic response had improved PFS and OS compared to those who did not (two-year PFS 91% vs 52%, log-rank p &lt; 0.001, two-year OS 100% vs 80%, log-rank p &lt; 0.001). Conclusions: NAC for high-risk UTUC demonstrates outcomes of favorable pathologic response, is well tolerated requiring minimal delay to surgery without significant perioperative complication risk, and thus should be considered a new standard of care option for patients with high-risk UTUC. Better survival outcomes in patients with favorable pathologic features after NAC indicate a potential clinical benefit to this approach. Clinical trial information: NCT01261728.

PD45-07 RISK OF RECURRENCE AND SURVIVAL OF DIALYZED AND TRANSPLANT PATIENTS WITH RENAL CELL CARCINOMA OF NATIVE KIDNEYS

You have accessJournal of UrologyRenal Transplantation & Vascular Surgery II (PD45)1 Sep 2021PD45-07 RISK OF RECURRENCE AND SURVIVAL OF DIALYZED AND TRANSPLANT PATIENTS WITH RENAL CELL CARCINOMA OF NATIVE KIDNEYS Jorge Correia, Mariana Madanelo, Sofia Mesquita, Gonçalo Mendes, Avelino Fraga, and Miguel Silva-Ramos Jorge CorreiaJorge Correia More articles by this author , Mariana MadaneloMariana Madanelo More articles by this author , Sofia MesquitaSofia Mesquita More articles by this author , Gonçalo MendesGonçalo Mendes More articles by this author , Avelino FragaAvelino Fraga More articles by this author , and Miguel Silva-RamosMiguel Silva-Ramos More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002059.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Renal transplantation requires immunosuppression, which was regarded as a risk factor for tumor progression in all types of malignancy. Therefore, until recently, based on the Cincinnati registry a waiting period before transplantation was mandatory in any patient with a history of cancer. However, this registry doesn’t take into account current staging, disease biology or advances in treatments, and there is growing evidence that the increased tumor risk by immunosuppression is restricted to particular subgroups of malignancy, whereas others such as renal cell carcinoma (RCC) are not negatively influenced. Our objective was to compare the risk of recurrence of RCC of native kidneys and death in patients with end-stage renal disease (ESRD), according to their dialysis or transplantation status. METHODS: We performed a retrospective analysis of all patients with ESRD diagnosed with RCC between 2010 and 2019 in our center, and stratified them according to their dialysis (D) or kidney transplantation (KT) status.Patients’ characteristics were compared by using Chi-square (or Fischer) and t-tests. Survival was assessed by Kaplan-Meier and Cox proportional hazards model. RESULTS: 40 patients were followed for a median of 41 months [IQR 22-71], 22 KT and 18 D. KT had a lower ASA score (p<0.001) and lower grade of tumor (p=0.014). All other clinical and pathological characteristics were similar between groups. The risk of RCC recurrence was similar between them (HR=0.402; p=0.458). 5-year recurrence-free survival was 96% in KT and 89% in D (p=0.443). All recurrences were on the contralateral kidney, without impact on patient or graft survival. In multivariable Cox regression analysis, no predictor was significantly associated with the risk of recurrence, including presence of KT. No cancer-related deaths were seen during follow-up, with the majority of deaths being related to cardiovascular disease (100% in KT and 60% in D). 5-year overall survival was 91% and 72% for KT and D, respectively (p=0.181). KT did not have a lower survival compared to D patients (HR=0.343; p=0.202). In multivariable analysis the presence of a renal transplant had no effect on survival (HR=0.002; p=0.167). Time on dialysis was the only independent predictor of overall survival (HR=1.058; p=0.049). CONCLUSIONS: Most RCCs in renal transplant recipients are low-grade and exhibit many favorable pathological characteristics. Immunosuppression doesn’t seem to have an impact on outcomes, but an increased time on dialysis seems to be associated with worse survival. As so, waiting time for low stage/low grade RCC could be reduced. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e744-e745 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jorge Correia More articles by this author Mariana Madanelo More articles by this author Sofia Mesquita More articles by this author Gonçalo Mendes More articles by this author Avelino Fraga More articles by this author Miguel Silva-Ramos More articles by this author Expand All Advertisement Loading ...

Intraductal Papillary Mucinous Carcinoma Versus Conventional Pancreatic Ductal Adenocarcinoma: A Comprehensive Review of Clinical-Pathological Features, Outcomes, and Molecular Insights.

Intraductal papillary mucinous neoplasms (IPMN) are common and one of the main precursor lesions of pancreatic ductal adenocarcinoma (PDAC). PDAC derived from an IPMN is called intraductal papillary mucinous carcinoma (IPMC) and defines a subgroup of patients with ill-defined specificities. As compared to conventional PDAC, IPMCs have been associated to clinical particularities and favorable pathological features, as well as debated outcomes. However, IPMNs and IPMCs include distinct subtypes of precursor (gastric, pancreato-biliary, intestinal) and invasive (tubular, colloid) lesions, also associated to specific characteristics. Notably, consistent data have shown intestinal IPMNs and associated colloid carcinomas, defining the “intestinal pathway”, to be associated with less aggressive features. Genomic specificities have also been uncovered, such as mutations of the GNAS gene, and recent data provide more insights into the mechanisms involved in IPMCs carcinogenesis. This review synthetizes available data on clinical-pathological features and outcomes associated with IPMCs and their subtypes. We also describe known genomic hallmarks of these lesions and summarize the latest data about molecular processes involved in IPMNs initiation and progression to IPMCs. Finally, potential implications for clinical practice and future research strategies are discussed.

Abstract PS7-38: Pathologic characteristics of African American women with breast cancer treated at the DoD’s Murtha Cancer Center: Understanding why survival cancer is not disparate to European American women when treated within the US Military Healthcare System

Abstract Background: In the United States, breast cancer mortality rates in African American women (AAW) are significantly higher than in European American women (EAW). In contrast, within the Department of Defense Military Healthcare System (DoD MHS) healthcare system, overall survival did not differ significantly between AAW and EAW with early-stage breast cancer. In this study, we evaluated pathological factors of AAW treated within the Murtha Cancer Center at Walter Reed National Military Medical Center to identify factors associated with this lack of disparate outcomes within the DoD MHS. Methods: Between 2001-2018, 345 AAW and 759 EAW treated at MCC/WRNMMC enrolled in the Clinical Breast Care Project (CBCP). Extracted demographic data included BMI, Charlson comorbidity index (CCI), education level and marital and smoking status. All diagnoses were performed by a single breast pathologist and included stage, grade, size, lymph node, hormone receptor and HER2 status. Statistical analyses included odds ratio (OR) and log-rank analyses. Results: Within this cohort, AAW were not at increased risk for having higher CCI scores, cigarette use or a college education, however, AAW were significantly more likely to be obese (OR 2.07, 95% CI 1.5, 2.9) and unmarried (OR 2.4, 95% CI 1.8, 3.2). The average age at diagnosis was 56.1 years in AAW and 57.5 years in EAW with 11% of AAW and 8% of EAW diagnosed &amp;lt;40 years of age. AAW were more likely to have higher stage (OR 1.6, 95% CI 1.3, 2.1), high-grade (OR 2.6, 95% CI 1.9, 3.6), larger (OR 1.6, 95% CI 1.2, 2.1) tumors. AAW were at increased risk for having triple negative tumors (OR 2.1, 95% CI 1.5, 2.9). Neither 5-year nor 10-year survival differed significantly between populations. Conclusion: While a previous study found no overall survival difference in early-stage AAW and EAW treated within the DoD MHS, this study found that across all stages of breast cancer breast cancer-specific survival was not inferior for AAW treated at MCC/WRNMMC. Critically, AAW did not have disparate survival despite having tumors with less favorable pathological characteristics, similar to those seen in the US general population. Evaluation of pre- and post-diagnostic care within DoD MHS should be performed to determine how breast care is provided to AAW within an equal-access healthcare setting and the results used as a model of care template to reduce breast cancer disparities within the US general population. The contents of this publication are the sole responsibility of the author(s) and do not necessarily reflect the views, opinions or policies of Uniformed Services University of the Health Sciences (USUHS), The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., the Department of Defense (DoD) or the Departments of the Army, Navy, or Air Force. Mention of trade names, commercial products, or organizations does not imply endorsement by the U.S. Government. Citation Format: Rachel Ellsworth, Leann Lovejoy, Craig Shriver. Pathologic characteristics of African American women with breast cancer treated at the DoD’s Murtha Cancer Center: Understanding why survival cancer is not disparate to European American women when treated within the US Military Healthcare System [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-38.

Gastro-entero-pancreatic neuroendocrine neoplasia: The rules for non-operative management

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) with favorable pathological and clinical features may be considered as indolent lesions, and therefore be amenable to conservative management. According to the primary tumor site, different non-aggressive approaches, based on endoscopic resection or simple active surveillance, can be proposed to selected patients fulfilling specific criteria. Tumor size, Ki67 proliferative index and depth of invasion are markers that can be used in order to identify these subjects. Patients with type I gastric NENs <1 cm as well as those with non-ampullary duodenal NENs <1 cm with no associated syndrome can be safely managed by endoscopic resection. On the other hand, an active surveillance approach is preferred over surgery for patients with asymptomatic, non-functioning pancreatic NENs ≤2 cm without dilation of the main pancreatic duct or bile duct. As far as NENs of the appendix are concerned, appendectomy should be considered as curative when a R0 resection has been achieved in the presence of a tumor ≤1.5 cm, graded as G1 and without lymphovascular invasion. Finally, G1 rectal NENs ≤1 cm without invasion of the muscular layer can be safely treated by endoscopic resection. Therefore, surgeons should be aware of the existence of indolent GEP-NENs, in order to avoid unnecessary operations with associated postoperative complications.