T1a Tumors Research Articles

PIVOT-006: A phase 3, randomized study of cretostimogene grenadenorepvec versus observation for the treatment of intermediate risk non-muscle invasive bladder cancer (IR-NMIBC) following transurethral resection of bladder tumor (TURBT).

TPS715 Background: Guidelines for Intermediate Risk Non-Muscle Invasive Bladder Cancer (IR-NMIBC) recommend adjuvant intravesical (IVE) therapy or surveillance. Despite this, 30–60% of patients still recur, and these Guideline recommendations are lacking level-1 evidence. Thus, there is a considerable gap in knowledge and an unmet medical need for improved therapies in the adjuvant setting. Cretostimogene Grenadenorepvec is an oncolytic adenovirus designed to preferentially replicate in and kill cancer cells. The vector is transcriptionally regulated by the E2F promoter that is up-regulated in retinoblastoma (Rb) pathway-defective tumor cells, common in most IR-NMIBC bladder tumors. Additionally, the virus is engineered to selectively express GM-CSF, in order to induce a robust systemic anti-tumor immune response. PIVOT-006 is an open-label, multi-center, randomized Phase 3 study designed to assess the efficacy and safety of intravesical Cretostimogene after TURBT versus TURBT alone. Methods: Eligibility criteria: age ≥18 years, Eastern Cooperative Oncology Group performance status of 0-2, histologically confirmed IR-NMIBC with absence of nodal or metastatic disease at screening. IR-NMIBC, as defined by American Urologic Association-Society of Urologic Oncology Guidelines on NMIBC, is either a Low Grade (LG) stage Ta tumor that recurs within 12 months of prior LG or High Grade (HG) bladder cancer, a solitary LGTa tumor >3cm in size, multifocal LGTa tumors, primary HGTa lesion < 3cm in size, or a LGT1 tumor. Participants will be stratified by receipt of perioperative chemotherapy and tumor grade. Pts (N~450) will be randomized 1:1 to receive intravesical Cretostimogene (Cohort 1) adjuvant to TURBT or TURBT alone (Cohort 2). Single dose perioperative intravesical chemotherapy at the time of TURBT is permitted. If intravesical NMIBC recurrence is noted in Cohort 2, participants will be eligible to receive intravesical Cretostimogene. In Cohort 1, intravesical Cretostimogene will be instilled in combination with n-dodecyl-B-D-maltoside (DDM, an inactive detergent) for 6 weekly doses during the induction phase, followed by 3 weekly maintenance cycles at months 3 and 6, and culminating in single intravesical doses at months 9 and 12. Primary disease assessments include serial cystoscopy, urine cytology, axial imaging, and centralized review of pathologic samples. The primary outcome measure is recurrence free survival. Secondary outcome measures include safety, tolerability, progression free survival, and time to next intervention. Exploratory outcome measures include patient-reported quality of life, biomarker analyses, coxsackie adenovirus receptor and E2F promoter expression, neutralizing antibodies, and markers of immunogenicity. Clinical trial information: Pending.

Percutaneous cryoablation of 100 anterior renal tumors: safety and technical success.

To assess the safety, technical success, and clinical outcomes of percutaneous cryoablation (PCA) in patients with anterior renal tumors. A retrospective analysis of patients with anterior renal tumors, defined as tumors at or anterior to the level of the renal pelvis, treated with CT-guided PCA from 2008 to 2022. Summary statistics included demographics and baseline tumor attributes. Treatment and follow-up metrics included primary and secondary technical success, adverse events (AEs) according to the SIR classification, local recurrence, overall survival (OS), and cancer-specific survival (CSS)). 100 patients (60 males; mean age: 63, mean BMI: 33, mean Charlson comorbidity index:6) with 100 anterior renal tumors were included. 78% of tumors were T1a and 22% T1b with mean maximal tumoral dimension of 29mm (range: 6-62mm) and mean distance to nearest critical structure 9mm (range: 0-40mm). Mean follow-up was 20.9months (range: 3-103). 28% of PCAs required hydrodissection. Technical success was achieved in 92% of patients; with six remaining patients undergoing successful repeat PCA (secondary technical success: 98%). The remaining two patients without primary technical success were either surveilled or had a benign pathology on resulted concomitant biopsy. Four patients (4%) had major AEs (hemorrhage requiring prolonged admission, transfusion, or embolization (n = 3), perinephric abscess requiring drainage (n = 1)) and 27% had minor AEs. Eight patients (8%) had recurrence with a one-year OS of 94% and CSS of 100%. All recurrences underwent repeat ablation without additional recurrence and 3/8 (38%) were T1b and 5/8 (63%) were T1a tumors. PCA of anterior renal tumors can be performed safely with high rates of technical and oncologic success.

Risk factors associated with lymph node metastasis in early-stage distal gastric cancer.

This study was designed to explore the risk factors of lymph node metastasis (LNM) in distal gastric cancer with early stage, and to provide reference for the choice of treatment protocols. In this retrospective observational study, 824 early distal gastric cancer (EDGC) cases who treated at our unit from 2010 to 2020 were selected as research objects. Subsequently, univariate and multivariate logistic regression analyses were conducted to investigate the associations between LNM and clinicopathological features. Of these 824 EDGC cases, 140 (17.0%) developed LNM, including 72 N1 stage and 68 N2-3 stage LNM. Multivariate logistic regression analysis identified the tumor diameter ≥1.75cm (odds ratio (OR)=2.361, p<0.001), tumor location (OR=1.552, p=0.046), histological classification (p=0.004), tumor infiltration depth (OR=2.154, p=0.001), and vascular infiltration (OR=4.354, p<0.001) as independent predictors for LNM. Logistic regression analyses based on 756 N0-1 LNM cases identified the smoking history (OR=0.507, p=0.043), tumor diameter ≥1.75cm (OR=2.265, p=0.010), tumor location (OR=1.834, p=0.036), histological classification (p=0.018), tumor infiltration depth (OR=1.939, p=0.034), and vascular infiltration (OR=3.225, p<0.001) as independent predictors for N1 LNM. Moreover, preoperative hypoalbuminemia (OR=7.087, p=0.015), significant preoperative weight loss (OR=2.724, p=0.023), tumor diameter ≥1.75cm (OR=5.484, p=0.001), multiple tumors (OR=9.986, p=0.038), histological classification (p=0.029), and vascular infiltration (OR=33.704, p<0.001) were proved to be associated with LNM for T1a tumors. The tumor diameter, location and infiltration depth, histological classification, and vascular infiltration were expected to be used as predictors of LNM in EDGC, and preoperative hypoalbuminemia, significant weight loss, tumor diameter and number, histological classification, and vascular infiltration were associated with LNM for T1a tumors.

Evaluation of Volumetric Response Assessment From SABR for Renal Cell Carcinoma

PurposeStereotactic ablative radiotherapy (SABR) is increasingly used to treat renal cell carcinoma (RCC). However, the optimal method to assess treatment response is unclear. We aimed to quantify changes in both volume and maximum linear size of tumors after SABR, and evaluate the utility of the two approaches in treatment response assessment. Methods and MaterialsWe retrospectively studied patients with RCC treated with SABR at our institution between 2013 and 2020. All available follow-up CT scans were aligned, and tumors were contoured on all scans. Volume and maximum linear size were measured at each follow-up, relative to these measurements at the time of CT simulation. ResultsTwenty-four patients with 25 tumors were included. Median follow-up was 32 months (range: 16-67). Nineteen tumors (76%) had 30% volumetric response at a median time of 7 months after SABR, while 12 tumors (48%) had 30% decrease in maximum linear size at a median time of 16 months. Eighteen tumors (72%) decreased in volume on first follow-up scan and continued to shrink, while 5 tumors (20%) displayed transient growth after SABR (average 24% increase in volume). Compared to T1a tumors, T1b or larger tumors were more likely to have transient growth (8% vs 33%, p=0.16), and had higher average relative volume 24 months after SABR (0.47 vs 0.8, p=0.022). ConclusionsVolume measurement results in more pronounced and earlier change compared to linear size measurement when assessing response to SABR. These findings may provide guidance when assessing treatment response for patients with RCC treated with SABR.

OGC P63 The Influence of PET-CT on the Therapeutic Pathway of Oesophageal and Oesophago-Gastric Junction Cancers. A Clinical Audit in a High Volume UGI Cancer Unit in the UK

Abstract Background Patients with oesophageal and oesophago-gastric Junction (OGJ) cancers require accurate staging to decide on intent of treatment (curative or palliative). The literature reported higher accuracy (82% vs. 64%, P = 0.004) and sensitivity (74% vs. 47%) for PET-CT when compared to CT for detecting distant disease. Consequently, the National Institute for Health and Care Excellence (NICE) recommends PET-CT for all oesophageal and GOJ cancers except T1a tumors. This audit investigated how PET-CT affected the treatment plan of oesophageal and OGJ cancer patients and its impact on MDT decisions and patients’ waiting time before first treatment is started. Methods Retrospective data collection from our institutional electronic database for all oesophageal and OGJ cancer patients that had undergone PET-CT as part of cancer staging in the last 9 months. Data collected was basic demographics, waiting time for PET-CT and discrepancy between CT and PET-CT in finding distant metastasis or other incidental findings. The influence of this on the MDT outcomes was investigated and the delay in cancer treatment secondary to further investigations was recorded. Results A total of 44 oesophageal and OGJ cancer patients had staging PET-CT. Out of 44 patients, 33 (75%) were males. The average age was 67 (45-85) years. Average waiting time for PET-CT was 17(1-57) days. Fourteen (32%) patients had discrepancy between CT and PET-CT. In Group A, 5 (11%) patients, PET-CT reported distant metastasis. In Group B, 9 (20%) patients, PET-CT detected active uptake in colon (n=4), cervical LNs (n=2), thyroid (n=1), tonsils &amp; prostate (n=1) and spine (n=1). Further investigations (endoscopy, ultrasound, biopsy etc.) added a delay with an average of 15 (1-28) days. Conclusions It is proven that PET-CT is essential in staging non metastatic oesophageal and OGJ cancers. It is important for MDTs to be vigilant that PET-CT can delay the start of first treatment for those patients by picking up non UGI cancer related pathology. This initiates a cohort of further investigations, creating some delay. Therefore, timely PET-CT scanning and reporting is recommended e.g during pre-MDT referral triage meetings. Selecting patients for PET-CT may also be helpful based on accurate CT reporting of cancer TNM stage.

Management of high-grade papillary Ta or T1 bladder cancer after restaging transurethral resection: A retrospective study comparing Bacillus Calmette–Guerin therapy upfront versus a third resection

PurposePerforming restaging transurethral bladder resection (reTURB) for high-risk non-muscle invasive bladder cancer (NMIBC) reduces the risk of recurrence and tumour understaging. Management of residual high-grade papillary Ta or T1 after reTURB has changed this last 10years in international recommendations. This study aimed to compare the recurrence free survival according to the different management procedures performed. Materials and methodsPatients who underwent reTURB for initial high-risk NMIBC between 2011 and 2020 were included. Patients with residual high-grade papillary Ta or T1 tumour after reTURB were divided into two groups: BCG instillations upfront versus BCG following a third-look resection (3TURB). Patient and tumour characteristics, BCG instillations, recurrence-free survival were retrospectively analysed. ResultsA total of 162 high-risk patients were included. Sixty-one (37.7%) had residual high-grade papillary Ta or T1 at reTURB: 35 (21.6%) had BCG instillations upfront, 18 (11.2%) had a 3TURB and 8 (5%) had other management. The mean follow-up was 34.2weeks±20.2. Recurrence-free survival was significantly better in patients who underwent BCG instillations upfront (P<0.0043). Recurrence after BCG therapy following reTURB was significantly lower in patients with no residual NMIBC at 6 (92.5% vs. 72.4%, P<0.004) and 12months (85% vs. 67.3%, P<0.03). ConclusionsThe efficacy of intravesical BCG is compromised in case of residual tumour following TURB. The role of a 3TURB following a positive reTURB is not yet determined. This study has confirmed that residual tumor following reTURB is a negative predictive factor but could not demonstrate the value of a 3TURB compared to upfront BCG. Level of evidence3.

Long-Term Outcomes and Risk Factors of Radiofrequency Ablation for T1N0M0 Papillary Thyroid Carcinoma

Radiofrequency ablation (RFA) has gained increasing interest as a minimally invasive procedure to treat low-risk papillary thyroid carcinoma (PTC). Considering the indolent nature of this disease, studies in large populations with long follow-up would be invaluable to further substantiate the effectiveness of RFA. To evaluate the long-term (58.5 months) outcomes of patients with T1N0M0 PTC who underwent RFA and investigate risk factors for local tumor progression (LTP). This cohort study included 1613 patients aged 18 years or older with T1N0M0 PTC who underwent ultrasonography-guided RFA between January 2014 and December 2020 at the Chinese People's Liberation Army General Hospital in Beijing, China. Included in the analysis were patients with PTC (confirmed by biopsy) with a maximum diameter of 20 mm or less; no evidence of extrathyroidal extension (capsular disruption or involvement of perithyroidal tissue), lymph node metastasis, or distant metastasis on ultrasonography or computed tomography; and no evidence of an aggressive subtype of PTC on biopsy. Patients with PTC larger than 2 cm, less than 12 months of follow-up, or inadequate follow-up information were excluded. Data were analyzed in April 2023. Long-term progression rate, disease-free survival, and complete tumor disappearance and their associations with patient and tumor characteristics. Disease-free survival was calculated using Kaplan-Meier analysis. Cox proportional hazards regression analyses were performed to assess risk factors for LTP and complete tumor disappearance. The study comprised 1613 patients (mean [SD] age, 43.3 [10.2] years; 1256 women [77.9%]) with 1834 T1N0M0 PTC tumors. During a mean follow-up of 58.5 months (range, 27 to 111 months), LTP was observed in 69 patients (4.3%), including 42 (2.6%) with tumor recurrence and 27 (1.7%) with tumor persistence. Cumulative disease-free survival rates at 1, 3, 5, and 8 years were 98.0%, 96.7%, 96.0%, and 95.7%, respectively. The overall complication rate was 2.0% (32 patients), with 6 (0.4%) major complications. Independent risk factors for LTP included subcapsular tumor location 2 mm or less from the capsule or trachea (hazard ratio [HR], 3.36; 95% CI, 2.02-5.59; P < .001) and multifocal tumors (HR, 2.27; 95% CI, 1.30-3.96; P = .004). Furthermore, 1376 patients (85.3%) showed complete tumor disappearance at follow-up ultrasonographic examination. Factors associated with complete tumor disappearance included age 40 years or less (HR, 0.78; 95% CI, 0.70-0.87; P < .001), stage T1a tumors (HR, 0.37; 95% CI, 0.31-0.45; P < .001), and unifocal tumors (HR, 0.50; 95% CI, 0.42-0.60; P < .001). In this cohort study, ultrasonography-guided RFA for T1N0M0 PTC had excellent long-term outcomes. Patients with unifocal T1N0M0 PTC and subcapsular tumor location more than 2 mm from the capsule or trachea may be the best candidates for RFA.

Intracanalicular vestibular schwannomas: facial and hearing outcomes according to the location of the tumor in relation to the nerves of the internal auditory canal.

The objective was to evaluate whether the position of the nerves within the internal auditory canal (IAC) has any effect on preoperative and postoperative cochlear and facial nerve function in patients with intracanalicular vestibular schwannoma (VS) resected through the retrosigmoid transmeatal approach. Forty-four patients with sporadic intracanalicular VS, from a series of 710 patients with VS who underwent operations from January 1993 to April 2022, were retrospectively reviewed. The pattern of displacement of the cranial nerves and tumor within the IAC was recorded. Tumors were divided into 2 types: type T1A lesions had only anteriorly displaced nerves, and type T1B had posteriorly displaced vestibular nerves and anteriorly displaced facial and cochlear nerves. Differences in surgical outcomes between groups in terms of facial nerve function and hearing preservation were evaluated. Thirty-five cases (79.5%) were T1A tumors and 9 were T1B (20.5%). Gross-total resection and anatomical preservation of the facial and cochlear nerves were achieved in all patients. Postoperatively, all patients with T1A VS maintained normal facial nerve function; however, among T1B VS patients, 6 (67%) retained House-Brackmann grade I, 2 worsened to grade II, and 1 worsened to grade III at 6 months (p = 0.006). The 27 T1A VS patients with serviceable hearing maintained this status, and an additional patient with nonserviceable hearing improved to serviceable hearing; among T1B VS patients, only 2 of the 5 patients with serviceable hearing remained as such, 2 evolved to nonserviceable hearing, and 1 lost hearing after surgery (p = 0.0022). T1B VS patients had a 24-fold risk of facial nerve deterioration (relative risk [RR] 25.2, 95% CI 1.42-448.57, p = 0.028) and a 32-fold risk of hearing deterioration (RR 32.7, 95% CI 1.93-553, p = 0.016) after surgery. In intracanalicular VS, postoperative cochlear and facial nerve function are directly related to the location of the tumor in relation to the nerves, with worse outcomes in cases where the tumor is located between the vestibular and facial-cochlear nerves.

Percutaneous Ablation of T1 Renal Masses: Comparative Local Control and Complications after Radiofrequency and Cryoablation.

The efficacy and complication rates of percutaneous radiofrequency ablation (RFA) and cryoablation (CA) in the treatment of T1 renal masses in two Northern Italy hospitals were retrospectively investigated. Eighty-two patients with 80 T1a tumors and 10 T1b tumors treated with thermal ablation from 2015 through 2020 were included. A total of 43 tumors in 38 patients were treated with RFA (2.3 ± 0.9 cm), and 47 tumors in 44 patients were treated with CA (2.1 ± 0.8 cm). The mean follow-up observation period was 26 ± 19 months. The major complications and efficacy, as measured using the technical success and local tumor recurrence rates, were recorded. There were three (6.9%) technical failures with RFA and one (2.1%) with cryoablation (p = 0.30). Among the 40 tumors that were successfully treated with RFA, 1 tumor (2.5%) developed local tumor recurrence; 5/46 tumors that were treated with cryoablation (10.8%) developed local tumor recurrence (p = 0.17). T1b lesions (4.0 ± 0.7 cm) resulted in 1/6 technically unsuccessful cases with RFA and 0/4 with CA. No recurrent disease was detected in the T1b lesions. Major complications occurred after 2.3% (1/43) of RFAs and 0/47 of cryoablation procedures. RFA and cryoablation are both effective in the treatment of renal masses. Major complications with either procedure are uncommon.

Partial Nephrectomy Drives the Association Between High-volume Centers and Decreased Mortality: A Surveillance, Epidemiology, and End Results-Medicare Analysis

To better understand the association between high-volume surgical kidney cancer centers and decreased mortality. To identify quality metrics that mediate this association. We designed a cohort of 14,044 patients who were diagnosed with kidney cancer between 2004 and 2013 and underwent a partial or radical nephrectomy using SEER-Medicare data. Hospitals were divided into quartiles based on their total nephrectomy volume for the study period. We investigated 6 quality metrics as potential mediators of the association between hospital volume and mortality using a mediation model. At the highest volume centers, survival was higher at 1-, 3-, 5-, and 10-year time intervals, respectively (91% vs 89%, 80% vs 76%, 70% vs 66%, 45% vs 38%, P<.001) compared to the lowest quartile nephrectomy centers. Receipt of partial nephrectomy for stage ≤T1a tumors explains 52.3% of the total association between hospital nephrectomy volume and mortality. Additionally, patients at the highest-volume centers were more likely to be younger (20% vs 26% 80≤ years old, P<.001), white (82% vs 78%, P<.001), reside in more densely populated counties (≥1 million residents, 62% vs 42%, P>.001), have a shorter mean length of stay (5.03 vs 5.88days, P<.001) when compared to those in the lowest-volume quartile. This analysis of SEER-Medicare data is the first to suggest that partial nephrectomy in the setting of T1a tumors mediates the association between hospital volume and mortality. Quality metrics that reduce mortality should be harnessed to develop more efficient and higher-quality health systems.

Small arteriole sign: an imaging feature for staging T4a colon cancer.

By analyzing the distribution of existing and newly proposed staging imaging features in pT1-3 and pT4a tumors, we searched for a salient feature and validated its diagnostic performance. Preoperative multiphase contrast-enhanced CT images of the training cohort were retrospectively collected at three centers from January 2016 to December 2017. We used the chi-square test to analyze the distribution of several stage-related imaging features in pT1-3 and pT4a tumors, including small arteriole sign (SAS), outer edge of the intestine, tumor invasion range, and peritumoral adipose tissue. Preoperative multiphase contrast-enhanced CT images of the validation cohort were retrospectively collected at Beijing Cancer Hospital from January 2018 to December 2018. The diagnostic performance of the selected imaging feature, including accuracy, sensitivity, and specificity, was validated and compared with the conventional clinical tumor stage (cT) by the McNemar test. In the training cohort, a total of 268 patients were enrolled, and only SAS was significantly different between pT1-3 and pT4a tumors. The accuracy, sensitivity, and specificity of the SAS and conventional cT in differentiating T1-3 and T4a tumors were 94.4%, 81.6%, and 97.3% and 53.7%, 32.7%, and 58.4%, respectively (all p < 0.001). In the validation cohort, a total of 135 patients were collected. The accuracy, sensitivity, and specificity of the SAS and the conventional cT were 93.3%, 76.2%, and 96.5% and 62.2%, 38.1%, and 66.7%, respectively (p < 0.001, p = 0.021, p < 0.001). Small arteriole sign positivity, an indirect imaging feature of serosa invasion, may improve the accuracy of identifying T4a colon cancer. Small arteriole sign helps to distinguish T1-3 and T4a colon cancer and further improves the accuracy of preoperative CT staging of colon cancer. • The accuracy of preoperative CT staging of colon cancer is not ideal, especially for T4a tumors. • Small arteriole sign (SAS) is a newly defined imaging feature that shows the appearance of tumor-supplying arterioles at the site where they penetrate the intestine wall. • SAS is an indirect imaging marker of tumor invasion into the serosa with a great value in distinguishing between T1-3 and T4a colon cancer.

Investigation of Early-Stage Non-Small Cell Lung Cancer Patients with Different T2 Descriptors: Real Word Data From a Large Database.

The current study evaluated a large cohort of T2N0M0 NSCLC patients with different T2 descriptors to investigate the prognostic disparities and further externally validate the T category of these patients. The Kaplan-Meier Method with the log-rank test was used to plot survival curves. The propensity score matching (PSM) method was used to reduce bias. Univariable and multivariable Cox analyses were used to determine prognostic factors. A total of 13,015 eligible T2N0M0 NSCLC patients were included. There were 5,287, 2,577 and 5,151 patients in the T2a, T2b and non-sized determined T2N0M0 (T2non-sized) groups, respectively. Before PSM, the survival of T2non-sized patients was comparable to that of T2a patients (P = 0.080) but was superior to that of T2b patients (P < 0.001). After PSM, the survival of T2non-sized patients was inferior to that of T2a patients (P = 0.028) but was similar to that of T2b patients (P = 0.325). The T category was further subdivided based on the specific non-sized T2 descriptors and tumor size. The results of the multivariate Cox analysis found that the prognosis of T2 tumors with visceral pleural invasion (size: 0-30mm) was better than that of T2a tumors, and the prognosis of T2 tumors with visceral pleural invasion (size: 30-40mm) was inferior to that of T2a tumors but comparable to that of T2b tumors. T2 tumors with visceral pleural invasion (size: 30-40mm) should be assigned to the T2b category, and those with a size interval of 0-30mm should be assigned to a better prognostic T2a category.

Prognosis and trends in chemotherapy use for patients with stage IA triple-negative breast cancer (TNBC): A population-based study.

510 Background: Outcomes for patients with stage IA TNBC in the modern era remain poorly characterized, and the benefit and utilization of adjuvant chemotherapy (chemo) in this setting remains controversial. Methods: We analyzed data from women diagnosed with pathological stage IA TNBC in the Surveillance, Epidemiology, and End Results (SEER) database during 2010 to 2019. We evaluated the associations of adjuvant chemo with breast-cancer specific survival (BCSS) stratified by tumor size, using multivariate cox models adjusted for tumor size (overall cohort only), age at diagnosis, race, tumor grade, histology, radiation, marital status, income, and rurality. Frequency of chemo use over time was examined by tumor size. Multivariate logistic regression assessed variables associated with chemo administration. Results: In total, we examined data from 8,601 women with stage IA TNBC. Median age at diagnosis was 62 years. Most patients had high-grade tumors (70.1%), ductal histology (92.8%), and received adjuvant chemo (61.6%). Median follow up was 48 months (IQR: 20 – 83). The use of chemo significantly increased during 2010-2019 for both T1b tumors (p for trend = 0.001) and T1c tumors (p for trend &lt; 0.001), with 52.5% and 63% of the patients with T1b and T1c TNBCs receiving chemo in 2010, respectively, compared with 60.5% and 71.1% in 2019. No significant differences were observed in the use of chemo for T1mic (p for trend = 0.567) and T1a (p for trend = 0.637) tumors, with low utilization seen in both cohorts (9.5% overall in T1mic, 22.5% overall in T1a). Variables associated with chemo use included younger age, white race, married status, higher income, more recent diagnosis, higher tumor grade, ductal histology, and larger tumor size (all p &lt; 0.02). Overall, 5-year BCSS was high across T groups ( &gt; 90%; Table). Receiving chemo (vs. none/unknown) was associated with an improved 5-year BCSS (adjusted HR for BCSS = 0.70, p = 0.006). For T1c tumors specifically, adjuvant chemo (vs. none/unknown) was also associated with BCSS (adjusted HR 0.64, p = 0.002). The small number of BCSS events precluded comparisons for other tumor size subgroups. Table shows sample sizes and 5-year BCSS rate by chemo receipt for each T group. Conclusions: In a large population-based cohort of patients with stage IA TNBC, we observed excellent 5-year BCSS outcomes, supporting the good prognosis of this patient population. The use of adjuvant chemo increased over time for T1b and T1c TNBCs, and was associated with improved BCSS for T1c tumors, although evaluation of benefit is limited by the inherent treatment bias in registry data. [Table: see text]

Evaluation of a novel Re-VASC score to differentiate malignant and benign T1a renal masses.

e16548 Background: Early characterization of renal cell carcinoma (RCC) is pertinent for cancer prognosis and patient treatment. However, characterization of renal masses as benign or malignant on computed tomography (CT) remains a difficult clinical challenge. Angiogenesis plays a major role in RCC progression and assessing neovascularity in tumor-burdened kidneys with Re-VASC scoring has been shown to aptly predict tumor pathology and staging. In the current study, we evaluated if Re-VASC can reliably differentiate between malignant T1a ( &lt; 4cm) RCC and benign T1a renal masses. Methods: All eligible patients had a diagnosis of T1a from pathologic or clinical evaluation. The inclusion criteria for malignant masses included a diagnosis of RCC by pathology after partial or radical nephrectomy. Our T1a benign group was comprised of patients with a diagnosis of a non-malignant renal mass (angiomyolipoma or oncocytoma) established via histopathology or CT imaging (fat containing lesions). Re-VASC score was calculated on axial preoperative contrast enhanced CT utilizing the system described below: 0 = No visible neovascularization 1 = visualized single new vessel &lt; 3mm in diameter 2 = visualized single new vessel ≥3mm in diameter 3 = visualized multiple new vessels &lt; 3mm in diameter 4 = visualized multiple new vessels and at least one vessel ≥3mm in diameter. Results: A total of 64 benign and 69 malignant T1a tumors were included. Comparison of the two groups demonstrated no significant differences with regards to age, sex, ASA, and BMI. The average Re- VASC scores was 0.159 and 0.753 for benign and malignant masses respectively (p &lt; 0.001). Additionally, the tumor size for benign masses was 2.373 and for malignant masses was 2.546 (p = 0.210). There was no significant difference in Re-VASC score between the contralateral kidneys of malignant and benign kidney masses (p &lt; 0.508). Additionally, the sensitivity, specificity and positive predictive values were 26%, 86% and 74% respectively, when utilizing a Re-VASC score of 1 as a cutoff for malignancy. Conclusions: Our results show a significantly higher Re-VASC score in T1a malignant tumors and T1a benign tumors. While biopsy remains the gold standard for confirmation of malignant tumors such as RCC, radiological evaluation with tumor scoring systems like Re-VASC may offer a useful clinical decision-making tool in a less-invasive manner. Because renal biopsy carries non-negligible risk of complications, reducing volume of biopsies among low-risk patients may lead to better overall care. The Re-VASC score shows potential as a confirmatory test with a specificity of 86%. We would like to apply the Re-VASC score to an expanded multi-center trial, in order to assess its translatability to the general population.

An in-progress phase 2 window of opportunity (WOO) trial of targeted therapy with erdafitinib for patients with recurrent FGFR3-altered non–muscle-invasive bladder cancer (NMIBC).

TPS4614 Background: Alterations to FGFR3 are the most common somatic mutations in non-muscle invasive bladder cancer (NMIBC), present in 40-60% of high-grade Ta and &gt; 80% of recurrent low grade Ta tumors. FGFR3 mutations are also known to be associated with a “cold” tumor microenvironment (TME) that may mediate BCG resistance. Erdafitinib, a targeted inhibitor of FGFR 1-4, is the first FDA approved targeted therapy for locally advanced/metastatic bladder cancer. As FGFR3 mutations are present 3-5x more commonly in NMIBC than metastatic disease, erdafitinib is a logical therapeutic candidate for FGFR3-altered NMIBC. Through this ongoing phase II trial, we seek to determine the safety and efficacy of erdafitinib for the treatment of intermediate and high risk FGFR3-altered NMIBC after prior intravesical therapy. Methods: To address the need for expanded targeted therapeutics for NMIBC,, we launched an investigator-initiated phase II window of opportunity (WOO) trial of erdafitinib (NCT04917809, PI Pietzak). We are currently enrolling patients with intermediate or high risk NMIBC with history of ≥1 or more induction courses of BCG and/or intravesical chemotherapy who present with a clinically staged Ta papillary recurrence on office cystoscopy. Patients are also required to have an oncogenic FGFR3 mutation or fusion, as confirmed by OncoKB on MSK-IMPACT, to be included in the trial. Trial patients are treated with 6 mg oral erdafitinib daily for 28 days during the “window of opportunity” time period between office cystoscopy and transurethral resection of the recurrent bladder tumor (TURBT). The primary outcome is the rate of objective response, defined as complete (no visible tumor) or partial ( &gt; 50% reduction of measured diameter by Response Evaluation Criteria for Tumors of the Bladder [RECIT-Bladder]) as compared to cystoscopy at TURBT. We are employing an optimal Simon two-stage binomial design, assuming an objective response of &gt; 15% would and &lt; 2% would not be worthy of further study. We plan to enroll 16 patients in the first stage and 9 in the second (87% power). Secondary outcomes include safety (CTAE 5.0), patient reported outcomes, and recurrence-free survival. Correlative studies will be conducted with urine, blood, and tumor tissue samples. Urine and blood are collected before (day 1), during (day 14) and after treatment (day 28) and will undergo immune and molecular studies to understand shifts in the microenvironment in the setting of response and resistance. This trial is being conducted in parallel with a co-clinical trial of patient derived organoid/xenograft models (MSK 19-015, PI Pietzak) to further refine the understanding of FGFR3 mutational resistance to standard treatment and the effects of targeted immunotherapy on tumor clinicogenomics. Clinical trial information: NCT04917809 .

New concept in urologic surgery: The total extended genital sparing radical cystectomy in women

The aim of the study was to evaluate genital sparing radical cystectomy surgery in female patients from the point of view of both oncologic and functional outcomes (with emphasis on urinary and sexual outcomes) in a single high-volume center for the treatment of muscular invasive bladder cancer. Between January 2014 and January 2018, 14 female patients underwent radical cystectomy with preservation of genital organs (the entire vagina, uterus, fallopian tubes, ovaries) and orthotopic urinary neobladder (Padua neobladder). Inclusion criteria were recurrent T1G3 tumors; refractory tumors after BCG therapy without associated carcinoma in situ (CIS); T2 or T3a tumors entirely resected at endoscopic transurethral resection of the bladder and not involving urethra/bladder trigone. Exclusion criteria were: T3b or higher bladder cancer, associated CIS and involvement of urethra or bladder trigone. Oncological and histopathological outcomes (Overall Survival - OS, Recurrence Free Survival - RFS), urinary outcomes (day and night incontinence, intermittent catheterization use, Sandvik Score) and sexual outcomes (Female Sexual Function Index 19 FSFI-19) were considered. The average follow-up time was 56 months. Considering oncological outcomes, histologic examination reported urothelial carcinoma in 13/14 patients; 8/13 patients (61.5%) had high grade T1 stage, 3/13 patients (23%) had high grade T2 stage and finally 2/13 patients (15.5%) had high-grade T3 stage. One patient presented with embryonal rhabdomyosarcoma completely excised after surgery (PT2aN0M0). No patient developed local or metastatic recurrence (RFS 100%); OS was 100%. Considering urinary continence outcomes, 12/14 patients retained daytime and nighttime continence (85.5%); 2/14 (14.5%) complained of low stress urinary incontinence daily and nighttime urinary leakage. The Sandvik Score showed complete continence in 7/14 patients (50%); mild degree incontinence in 6/14 patients without use of incontinence devices (43%); moderate degree of incontinence in one patient (7%). The FSFI administered at 1 year from the surgery showed sexual desire in all patients (100%); subjective arousal, achievement of orgasm and sexual satisfaction in 12/14 patients (85.5%); sufficient lubrication in 11/14 patients (78.5%). Only one patient (7%) complained about dyspareunia during sexual intercourse. Our study aims to demonstrate that genital-sparing radical cystectomy is a safe surgery in terms of oncologic outcomes and, most importantly, that it is beneficial in terms of urinary and sexual function. Indeed, patients' quality of life together with their psychological and emotional health should be put on the same level as oncological safety. However, it is a treatment reserved for selected patients who are strongly motivated to preserve fertility and sexual function and thoroughly informed about the benefits and complications of such a procedure.

Microwave ablation of the T1a small renal mass: expanding beyond 3cm.

To compare the oncological and renal function outcomes for patients receiving microwave ablation (MWA) in tumors < 3 and 3-4cm. Retrospective analysis of a prospectively maintained database identified patients with < 3 or 3-4cm renal cancers undergoing MWA. Radiographic follow-up occurred at approximately 6months post-procedure and annually thereafter. Serum creatinine and estimated glomerular filtration rate (eGFR) were calculated before and 6-months post-MWA. Local recurrence-free survival (LRFS) was estimated using the Kaplan-Meier method. Tumor size was evaluated as a prognostic factor using Cox proportional-hazards regression. Predictors for change in eGFR and chronic kidney disease (CKD) stage were modeled using linear and ordinal logistic regression. A total of 126 patients fit the inclusion criteria. Overall recurrences were 2/62 (3.2%) and 6/64 (9.4%) for < 3 versus 3-4cm. Both recurrences in the < 3cm group were local, 4/6 in the 3-4cm group were local and 2/6 were metastatic without local progression. For < 3 versus 3-4cm, cumulative LRFS at 36months was 94.6% versus 91.4%. Tumor size was not a significant prognostic factor for LRFS. Renal function did not change significantly after MWA. Patient comorbidities and RENAL nephrometry score significantly affected change in CKD. With comparable oncological outcomes, complication rates, and renal function preservation, MWA is a promising management strategy for renal masses of 3-4cm in select patients. Our findings suggest that current AUA guidelines, which recommend thermal ablation for tumors < 3cm, may need review to include T1a tumors for MWA, regardless of size.

Staging Accuracy and Lymph Node Involvement in Superficial Adenocarcinoma and Squamous Cell Carcinoma of the Esophagus—a Multicenter Case Series Analysis

AbstractAt an early stage, esophageal cancer can be removed surgically or endoscopically. T1a tumors are removed by endoscopic resection, whereas T1b tumors are preferably surgically removed (esophagectomy) due to possible lymph node involvement. However, the diagnostic tools (endoscopic ultrasonography (EUS) and CT/PET-CT) used to distinguish between T1a and T1b tumors and to detect malignant lymph nodes are imprecise. This study aimed to review the accuracy of preoperative locoregional staging in superficial esophageal cancer in a Danish setting. This was a retrospective, multicenter study including patients with a cT1 esophageal tumor, both adenocarcinoma and squamous cell carcinoma. Patients receiving neoadjuvant treatment were excluded. Results from the preoperative diagnostics tools were compared with the pathology report to determine the diagnostic accuracy. Sixty-eight patients were included, 34 patients underwent esophagectomy, and 34 patients underwent endoscopic resection. The positive predictive value (PPV) of PET-CT (or CT) (when staged as a T1 tumor) was 77% (95%CI: 0.59–0.88), and the PPV of EUS (when staged as a T1a or T1b tumor) was 52% (95%CI: 0.32–0.72) and 60% (95%CI: 0.36–0.82), respectively. Six patients had malignant lymph nodes in the surgical specimen; none of them was identified before surgery. In conclusion, neither CT/PET-CT nor EUS is a precise tool to distinguish mucosal from submucosal esophageal tumors. Furthermore, in superficial malignant lesions, lymph node involvement is rare, but when present, it is rarely detected before surgery. To improve staging accuracy, all patients with cT1 tumors could be referred for a diagnostic endoscopic resection prior to possible other treatments.

International Opinions on Grading of Urothelial Carcinoma: A Survey Among European Association of Urology and International Society of Urological Pathology Members

BackgroundGrade of non–muscle-invasive bladder cancer (NMIBC) is an important prognostic factor for progression. Currently, two World Health Organization (WHO) classification systems (WHO1973, categories: grade 1–3, and WHO2004 categories: papillary urothelial neoplasm of low malignant potential [PUNLMP], low-grade [LG], high-grade [HG] carcinoma) are used. ObjectiveTo ask the European Association of Urology (EAU) and International Society of Urological Pathology (ISUP) members regarding their current practice and preferences of grading systems. Design, setting, and participantsA web-based, anonymous questionnaire with ten questions on grading of NMIBC was created. The members of EAU and ISUP were invited to complete an online survey by the end of 2021. Thirteen experts had previously answered the same questions. Outcome measurements and statistical analysisThe submitted answers from 214 ISUP members, 191 EAU members, and 13 experts were analyzed. Results and limitationsCurrently, 53% use only the WHO2004 system and 40% use both systems. According to most respondents, PUNLMP is a rare diagnosis with management similar to Ta-LG carcinoma. The majority (72%) would consider reverting back to WHO1973 if grading criteria were more detailed. Separate reporting of WHO1973-G3 within WHO2004-HG would influence clinical decisions for Ta and/or T1 tumors according the majority (55%). Most respondents preferred a two-tier (41%) or a three-tier (41%) grading system. The current WHO2004 grading system is supported by a minority (20%), whereas nearly half (48%) supported a hybrid three- or four-tier grading system composed of both WHO1973 and WHO2004. The survey results of the experts were comparable with ISUP and EAU respondents. ConclusionsBoth the WHO1973 and the WHO2004 grading system are still widely used. Even though opinions on the future of bladder cancer grading were strongly divided, there was limited support for WHO1973 and WHO2004 in their current formats, while the hybrid (three-tier) grading system with LG, HG-G2, and HG-G3 as categories could be considered the most promising alternative. Patient summaryGrading of non–muscle-invasive bladder cancer (NMIBC) is a matter of ongoing debate and lacks international consensus. We surveyed urologists and pathologists of European Association of Urology and International Society of Urological Pathology on their preferences regarding NMIBC grading to generate a multidisciplinary dialogue. Both the “old” World Health Organization (WHO) 1973 and the “new” WHO2004 grading schemes are still used widely. However, continuation of both the WHO1973 and the WHO2004 system showed limited support, while a hybrid grading system composed of both the WHO1973 and the WHO2004 classification system may be considered a promising alternative.

Overall survival among patients who undergo resection does not differ significantly between T1a and T1b hepatocellular carcinoma based on the 8th American Joint Commission on Cancer.

The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for hepatocellular carcinoma (HCC) has been used since 2018. However, whether any significant difference in overall survival (OS) exists between patients with T1a and T1b HCC who undergo resection has been controversial. We aim to clarify this issue. We consecutively enrolled newly diagnosed HCC patients who underwent liver resection (LR) from 2010 to 2020 at our institution. OS was estimated using the Kaplan-Meier method and compared using log-rank tests. Prognostic factors for OS were identified by multivariate analysis. This study enrolled 1250 newly diagnosed HCC patients who underwent LR. No significant differences in OS were identified between patients with T1a and T1b tumors among all patients (p = 0.694), cirrhotic patients (p = 0.753), non-cirrhotic patients (p = 0.146), patients with alpha-fetoprotein (AFP) > 20ng/ml (p = 0.562), patients with AFP ≤ 20ng/ml (p = 0.967), patients with Edmondson grade 1 or 2 (p = 0.615), patients with Edmondson grade 3 or 4 (p = 0.825), patients positive for hepatitis B surface antigen (HBsAg; p = 0.308), in patients positive for anti-hepatitis C virus (HCV) antibody (p = 0.781), or patients negative for both HBsAg and anti-HCV antibody (p = 0.125). Using T1a as the reference, multivariate analysis showed that T1b is not a significant predictive factor for OS (hazard ratio (HR): 1.338; 95% confidence interval (CI):0.737-2.431; p = 0.339). No significant difference in OS was observed between patients who underwent LR to treat T1a and T1b HCC tumors.