Clinical Stage T2 Research Articles

Genomics Analysis and Nomogram Risk Predictionof Occult Lymph Node Metastasis in Non-Predominant Micropapillary Component of Lung Adenocarcinoma Measuring ≤ 3 cm.

BackgroundThe efficacy of sublobar resection and selective lymph node dissection is gradually being accepted by thoracic surgeons for patients within early-stage non-small cell lung cancer (NSCLC). Nevertheless, there are still some NSCLC patients develop lymphatic metastasis at clinical T1 stage. Lung adenocarcinoma with a micropapillary (MP) component poses a higher risk of lymph node metastasis and recurrence even when the MP component is not predominant. Our study aimed to explore the genetic features and occult lymph node metastasis (OLNM) risk factors in patients with a non-predominant micropapillary component (NP-MPC) in a large of patient’s cohort with surgically resected lung adenocarcinoma.MethodsBetween January 2019 and December 2021, 6418 patients who underwent complete resection for primary lung adenocarcinoma at the Qilu Hospital of Shandong University. In our study, 442 patients diagnosed with lung adenocarcinoma with NP-MPC with a tumor size ≤3 cm were included. Genetic alterations were analyzed using amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Abnormal protein expression of gene mutations was validated using immunohistochemistry. A nomogram risk model based on clinicopathological parameters was developed to predict OLNM. This model was invalidated using the calibration plot and concordance index.ResultsIn our retrospective cohort, the incidence rate of the micropapillary component was 11.17%, and OLNM was observed in 20.13% of the patients in our study. ARMS-PCR suggested that EGFR exon 19 del was the most frequent alteration in NP-MCP patients compared with other gene mutations (frequency: 21.2%, P<0.001). Patients harboring exon 19 del showed significantly higher risk of OLNM (P< 0.001). A nomogram was developed based on five risk parameters, which showed good calibration and reliable discrimination ability (C-index = 0.84) for evaluating OLNM risk.Conclusions.Intense expression of EGFR exon 19 del characterizes lung adenocarcinoma in patients with NP-MCP and it’s a potential risk factor for OLNM. We firstly established a nomogram based on age, CYFRA21-1 level, tumor size, micropapillary and solid composition, that was effective in predicting OLNM among NP-MCP of lung adenocarcinoma measuring ≤ 3 cm.

Sex differences in treatment patterns for non-advanced muscle-invasive bladder cancer: a descriptive analysis of 3484 patients of the Netherlands Cancer Registry

PurposeBladder cancer (BC) is a common malignancy with well-established differences in incidence, clinical manifestation and outcomes between men and women. It is unknown to what extent disparities in outcomes are influenced by differences in treatment approaches. This paper describes treatment patterns among men and women with muscle-invasive BC focusing on curative treatment (radical cystectomy or trimodal therapy).MethodsA retrospective population-based cohort study was performed with data from the Netherlands Cancer Registry. All patients newly diagnosed with muscle-invasive, non-advanced BC (MIBC, cT2-4a, N0/X, M0/X) in the years 2018, 2019 and 2020 were identified. Patient and tumor characteristics and initial treatment were compared between men and women with descriptive statistics and multivariable logistic regression analyses.ResultsA total of 3484 patients were diagnosed with non-advanced MIBC in 2018–2020 in the Netherlands, of whom 28% were women. Women had higher T-stage and more often non-urothelial histology. Among all strata of clinical T-stage, women less often received treatment with curative intent (radical cystectomy [RC] or trimodality treatment). Among RC-treated patients, women more often received neoadjuvant treatment (except for cT4a disease). After adjustment for pre-treatment factors, odds ratios were indicative of women having lower probability of receiving curative treatment and RC specifically, and higher probability to receive NAC when treated with RC then men, although not statistically significant.ConclusionsConsiderable differences in treatment patterns between men and women with MIBC exist. A more considerate role of the patient’s sex in treatment decisions could help decrease these differences and might mitigate disparities in outcomes.

Endoscopic balloon cryoablation against single instillation after transurethral resection of bladder cancer: A multicenter, randomized, controlled noninferiority trial.

e16561 Background: Cryotherapy is a prevalent percutaneous ablative therapy for solid tumors. However, studies on the clinical practice of endoscopic cryotherapy for intraluminal malignancies are lacking. We aim to explore the feasibility of endoscopic cryotherapy for bladder cancer. Methods: In this multicenter, randomized, parallel controlled, non-inferiority trial, we compared endoscopic balloon cryoablation (EBCA) with a single instillation (SI) of pirarubicin after transurethral resection (TUR).Men or women aged 18-85 years with a clinical diagnosis of bladder cancer (tumor number no more than 3 and maximal tumor size no more than 3 cm) were included. The exclusion criteria were as follows: locally advanced urinary bladder cancer (clinical stage T3 or T4), lymph node involvement (N1) or distant metastasis (M1), severe organ dysfunction, severe coagulation disorder, sepsis, concomitant neoplastic malignancy and other conditions unsuitable for surgery or intravesical chemotherapy. Women in pregnancy or lactation were also excluded. Eligible participants were randomly assigned (1:1) to the TUR-EBCA or TUR-SI group. The primary endpoint was the residual-free rate at repeated TUR. A non-inferiority test was used to compare the primary endpoint with a chosen margin of 10%. The secondary endpoints included the recurrence-free survival (RFS), progression-free survival (PFS) and adverse events. Results: We recruited 227 participants between November, 2017, and September, 2020. In total, 205 patients received EBCA or SI after TUR, of whom 163 completed all the required interventions and follow-up. In the per-protocol analyses, 75 (91.5%) of 82 patients had no residual tumor in the TUR-EBCA group compared with 61 (76.5%) of 81 in the TUR-SI group (risk difference 14.9%; 95% confidence interval [CI] 0.03 to 0.27, P &lt; 0.001), meeting the criteria for non-inferiority. Similar results were found in the after intention-to-treat analysis. After a median follow-up of 21 months, the TUR-EBCA group had better RFS(HR = 0.49; 95% confidence interval [CI] 0.24 to 0.99; Log-rank P = 0.046) and PFS (HR = 0.25; 95% confidence interval [CI] 0.08 to 0.77; Log-rank P = 0.0092). There were no significant differences in the SAEs rate (3.0% vs. 3.9%, p = 0.52). Conclusions: EBCA is a safe and effective adjuvant alternative to TUR for bladder cancer with the potential advantage of “energetically resecting” the tumor base. Clinical trial information: NCT02760953.

Association of DNA damage response (DDR) gene mutations (mts) and response to neoadjuvant cisplatin-based chemotherapy (chemo) in muscle-invasive bladder cancer (MIBC) patients (pts) enrolled onto SWOG S1314.

4522 Background: Neoadjuvant cisplatin-based chemo followed by radical cystectomy (RC) is a standard of care treatment for pts with MIBC. DDR gene mts, including within ERCC2, a DNA helicase implicated in cisplatin sensitivity in MIBC, have been associated with higher pathologic (path) downstaging ( &lt; pT2) and complete response (pT0) at RC and improved overall survival (OS) in retrospective series. S1314 randomized pts to one of 2 chemo regimens (dose dense MVAC or Gem/Cis) followed by RC. We sought to correlate ERCC2 and other DDR gene mts with response and survival in MIBC pts enrolled onto this prospective trial. Methods: Tumor and matched germline DNA from evaluable pts enrolled onto S1314 underwent exon capture sequencing of 505 cancer-associated genes (MSK-IMPACT). Both deleterious (del) mts and any mts in 9 DDR genes (ERCC2, ERCC5, BRCA1, BRCA2, RECQL4, ATM, ATR, RAD51C, FANCC) were correlated with clinical outcomes. The prespecified analyses included the association of mts with &lt; pT2 and pT0 by logistic regression analysis and with progression-free survival (PFS) and OS by Cox proportional hazards regression. Results: 179 patients (median 61 years, 85% male, 87% white, and 87% clinical stage T2) who received &gt;2 cycles of chemo and were evaluable for path response were included in the analysis. The pT0 rate was 28% and &lt; pT2 was 41%. Del mts in ERCC2 were detected in 26 (14%) pts followed by ATM (n = 12, 7%), ATR (n = 3) and BRCA2 (n = 2). ERCC2 mts were associated with statistically significantly higher path responses with a 54% pT0 rate and 62% downstaging rate. Patients with any del mts had higher path response rates (51% pT0, 56% &lt; pT2) and better PFS (Table) with a median follow-up of 53 months. There was a non-significant trend towards improved OS. Conclusions: In pts managed with neoadjuvant chemo and RC on S1314, both ERCC2 mts and del DDR gene mts correlated with pathologic response. Any del DDR gene mt was associated with improved PFS. These results are in line with retrospective analyses displaying a correlation between DDR gene mts and neoadjuvant chemosensitivity in MIBC and support ongoing genomically-informed organ sparing trials.[Table: see text]

Using customized PRO profiles to evaluate expected patient quality-of-life outcomes.

e18607 Background: Patient Reported Outcomes (PROs) are routinely employed in patient-focused drug development programs. However, PRO data are often under-utilized. Better approaches could employ trial data to describe expected patient outcomes. The objective of this work was to present a method for leveraging PRO-based patient profiles to project and thereby anticipate expected patient outcomes. Methods: A model-based approach to analyzing PRO scores allows for a more tailored approach to evaluating outcomes of interest. To demonstrate this approach, we analyzed PRO data from a Phase 3 trial of patients with prostate cancer randomized to either Hypofractionated 3D-CRT/MRT (experimental arm) or Conventionally Fractionated 3D-CRT/MRT (comparator arm). The outcome of interest was the difference between treatment arms on the Expanded Prostate cancer Index Composite (EPIC) urinary domain scores, defined on the sum of responses to 12 items. A longitudinal regression model was fit to EPIC scores at 6, 12, 24, and 60 months post-baseline. Patient profile variables (baseline EPIC urinary scores, treatment arm, age, race, clinical T-stage, and Gleason score) were included as predictors. For a particular patient profile of interest, expected EPIC urinary score at 6 months was estimated, as well as associated 95% confidence intervals, which allowed for an understanding of the range of likely outcomes for that particular patient profile. Results: n = 550 patients in the experimental arm and n = 542 patients in the comparator were analyzed. The difference in EPIC urinary scores between treatment arms at 6 and 12 months were computed, with higher scores reflecting greater symptom severity. The model estimated a difference of 2.12 points (p = 0.009) at 6 months and 2.16 points (p = 0.013) at 12 months, favoring the experimental arm. To illustrate how customized patient profiles can be used to better understand patient outcomes, a single profile is presented. At baseline, a patient receiving the experimental treatment, EPIC urinary score 98.0, age 57, white, clinical T-stage T2, Gleason score 6, could be expected to report an EPIC urinary score of 94.3 (92.06, 96.00) at 6 months based on the statistical model. In the observed trial data, one patient with this profile reported an EPIC urinary score of 93.8 at 6 months. The expected EPIC urinary score overestimated the observed score by only 0.53%, indicating the accuracy of the expected EPIC urinary scores. This corresponds to approximately one category decrease on two of the 12 domain items (i.e., a decrease in symptom severity). Conclusions: Well-established statistical methods can lead to improved clinician understanding of expected outcomes specific to a given patient profile. This would facilitate communication between clinician and patient regarding anticipated oncology treatment outcomes. Recommendations to support the use of these methods should be considered.

MP42-18 SOCIAL AND ENVIRONMENTAL RISK FACTORS FOR UNDERGOING RADICAL CYSTECTOMY FOR UROTHELIAL CARCINOMA IN RHODE ISLAND: 2000-2020

You have accessJournal of UrologyCME1 May 2022MP42-18 SOCIAL AND ENVIRONMENTAL RISK FACTORS FOR UNDERGOING RADICAL CYSTECTOMY FOR UROTHELIAL CARCINOMA IN RHODE ISLAND: 2000-2020 Borivoj Golijanin, Sarah Andrea, Justin Bessette, Rebecca Ortiz, Philip Caffery, Timothy O'Rourke, Christopher Tucci, Ali Amin, and Dragan Golijanin Borivoj GolijaninBorivoj Golijanin More articles by this author , Sarah AndreaSarah Andrea More articles by this author , Justin BessetteJustin Bessette More articles by this author , Rebecca OrtizRebecca Ortiz More articles by this author , Philip CafferyPhilip Caffery More articles by this author , Timothy O'RourkeTimothy O'Rourke More articles by this author , Christopher TucciChristopher Tucci More articles by this author , Ali AminAli Amin More articles by this author , and Dragan GolijaninDragan Golijanin More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002608.18AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Development of urothelial carcinoma (UC) has well documented risk factors including tobacco smoking and occupational exposure. Potentially upstream neighborhood-level factors are underexplored. We examined the association between sociodemographic and pollution composition and incidence of UC treated by radical cystectomy (RC) and overall survival (OS) in Rhode Island. METHODS: 484 patients underwent RC from 1/2000 to 12/2020 at Brown University affiliated hospitals. Patient addresses were linked to census tract level data on neighborhood sociodemographic composition and locations of leaking underground storage tanks, superfund sites, sanitary waste sites, and active solid waste facilities. Using Poisson and Cox proportional hazards models, we assessed incidence of RC and OS as a function of neighborhood pollution, area deprivation index (ADI), poverty, and racial composition quartiles in separate models adjusted for year and age at time of RC. RESULTS: Average age was 68 years, 73% men, and 90% white, with clinical stage T2 in 32%, Tis in 5%, Tx in 8%, and 3% had no information. Likelihood of RC positively correlated with greater neighborhood pollution (RR for 4th vs 1st quartile:1.39, 95% CI:1.08,1.79), predominance of white population (RR for 4th vs. 1st quartile:1.94, 95% CI:1.41,2.66) and negatively with greater poverty (RR for 4th vs. 1st quartile: 0.44, 95% CI:0.33, 0.58). Five-year OS rate was 56%, in neighborhoods with highest poverty rates (Q4) was 45%, and in neighborhoods with lowest rates of poverty (Q1) was 62%. Compared with Q1, the hazard ratio for those in Q4 poverty neighborhoods was 1.72 (95% CI:1.16,2.55). CONCLUSIONS: Inequalities in social determinants of health influence incidence and outcomes of UC patients undergoing RC. Patients undergoing RC were more likely to be white and living in affluent neighborhoods, however, this could be an artifact of selective survival. Those living in neighborhoods with greater number of pollutants underwent RC at greater rates. Risk of death in the first five years following RC was greatest for those living in neighborhoods with low socioeconomic status. Further research is needed to study contextual factors defining the differences in RC use and OS of patients with UC. Health policies and screening programs can target these high-risk UC hot-spots in order to improve earlier detection and patient outcomes. Source of Funding: Funded in part by DG and the Rhode Island Foundation © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e739 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Borivoj Golijanin More articles by this author Sarah Andrea More articles by this author Justin Bessette More articles by this author Rebecca Ortiz More articles by this author Philip Caffery More articles by this author Timothy O'Rourke More articles by this author Christopher Tucci More articles by this author Ali Amin More articles by this author Dragan Golijanin More articles by this author Expand All Advertisement PDF DownloadLoading ...

Is Robotic-assisted partial nephrectomy an efficacious and safe procedure for removal of stage T1 renal tumors?

Background Robotic surgery has now evolved as an emerging tool for better and easy operative techniques. The quest for trifecta comprising warm ischemia time less than 25 minutes, negative surgical margins and no perioperative complications seems to be better accomplished by robotic partial nephrectomy, which is likely to become the new standard for minimally invasive partial nephrectomy. Materials &amp; Methods It is a prospective observational study over 18 months in patients aged more &gt; 18 years with a renal tumour of clinical stage T1 coming for robotic partial nephrectomy. A total of 40 patients were included in the study who underwent robotic-assisted partial nephrectomy for renal tumours less than 7 cm in size. The duration of the study was from July- 2018 to December-2019 and their follow up period was 3 months post-surgery. Results Of the 40 patients, the mean age was 52.3 ± 11.91 years. 28 (70%) patients were males and remaining 12 (30%) were females. 11 (27.5%) tumours were situated in the anterior upper pole, 9 (22.5%) in the anterior lower pole, 8 (20%) in the posterior upper pole, 7 (17.5%) in the posterior lower pole and interpolar tumours were 5 in number (12.5%). 24 (60%) tumors were ≥ 50% exophytic, 11 (27.5%) were &lt; 50% exophytic and 5 (12.5%) were purely endophytic in nature. Maximum nephrometry score was 5a amounting to 10 (25%) patients and 5p tumours were the second most common amounting to 7 (17.5%) patients. The mean console time was noted to be 84.40± 12.05 mins. The mean total operative time was noted to be 167.00 ± 21.116 minutes. Mean Warm Ischemia Time (WIT) was recorded to be 27.28 ± 5.923 minutes. The mean blood loss was 145.75±61.075 ml. The mean length of hospital stay was 4.27 ± 0.78 days. None of the cases was converted to open partial/radical nephrectomy and none had positive surgical margins in the histopathology reports. Conclusion Our study shows that Robotic Assisted Partial Nephrectomy (RAPN) is an efficacious and safe surgery in stage T1 renal tumours (tumour size &lt;7 cm) to achieve complete oncological clearance by minimal access technique.

Oncologic outcomes of pathologic T4 and T3 colon cancer patients diagnosed with clinical T4 stage disease using preoperative computed tomography scan

BackgroundThe diagnostic accuracy of computed tomography (CT) for colon cancer is low, and the preoperative risk factors for locally advanced colon cancer are unknown. This study aimed to evaluate the correlation between preoperative CT scan findings and oncologic outcomes and to identify risk factors associated with locally advanced colon cancer. Materials and methodsPatients diagnosed with clinical stage (cT) 4 colon cancer based on preoperative CT scan findings who underwent curative surgery between January 2005 and December 2015 were retrospectively studied. Patients were divided according to pathologic stage (pT) into pT3 (n = 114) and pT4 (n = 102). ResultsThe disease-free survival rate was significantly different between the pT3 and pT4 groups (88.6% vs. 68.6%, p < 0.001). The overall survival rate of the pT3 group was significantly higher than that of the pT4 group (91.2% vs. 76.5%, p = 0.002). Perineural invasion and tumor budding were identified as preoperative risk factors predisposing to pT4 staging (p = 0.044, p = 0.001). ConclusionThe survival rate of pT3 patients was significantly higher than that of pT4 patients with a preoperative cT4 diagnosis. This suggests that when planning for neoadjuvant chemotherapy in locally advanced colon cancer, preoperative CT scan findings may overestimate clinical staging and lead to inappropriate treatment. Thus, there is a need for a new modality to evaluate local advancement in colon cancer.

Treatment Implications for Complete Pathologic Responders to Neoadjuvant Immunotherapy

<h3>Purpose/Objective(s)</h3> Neoadjuvant immunotherapy is under increasing investigation for treatment of head and neck squamous cell carcinoma (HNSCC). Some patients have demonstrated strong pathologic responses to immunotherapy resulting in significant reductions in disease burden. However, evidence is lacking for how to treat patients for whom adjuvant therapy is indicated based on initial staging who go on to experience complete response to neoadjuvant immunotherapy. Here, we describe our experience with this subset of patients. <h3>Materials/Methods</h3> Here we report the outcomes of 5 patients with HNSCC enrolled in neoadjuvant immunotherapy trials at our institution with complete pathologic responses to treatment. Two patients received a combination of nivolumab + IDO inhibitor BMS986205 (Nivo+IDO) for a total of 8 weeks and one patient received nivolumab alone for 8 weeks. Two patients received a combination of nivolumab + PDE5 inhibitor (Nivo+tad) for 4 weeks. <h3>Results</h3> All three patients who were treated for 8 weeks of therapy were clinical stage T3 or above (T3N2c, T4aN0, T4aN0) with both T4 patients having bony cortical erosion of the mandible; all 3 patients were planned for adjuvant radiation based on their clinical staging. Pathologic evaluation in all 3 patients demonstrated T0N0 complete pathologic response. The two patients with T4 bony erosion on preoperative imaging declined the recommendation for adjuvant radiation, while the T3N2c patient completed radiation therapy. The two patients treated on the Nivo+tad trial for 4 weeks were clinically staged T2N1 (both HPV-positive) with multiple lymph nodes on imaging supporting the recommendation for adjuvant radiation. Both patients demonstrated complete pathologic response (T0N0). One patient declined adjuvant radiation; the other patient completed 2/3 of radiation therapy but discontinued due to adverse effects. All five patients are currently free of disease with follow-up ranging from 4-36 months and median follow up of 12 months, with no evidence of recurrence. <h3>Conclusion</h3> Neoadjuvant immunotherapeutic strategies continue to be of interest in HNSCCs. While this is a small case series, it highlights the potential for neoadjuvant strategies to modify adjuvant treatment algorithms. Longitudinal tracking and collating this unique patient group will help us guide our patients as they make treatment decisions. Clinical trials represented NCT03854032 and HCT03228265.

Prospective validation and extension of the Multimodality Prognostic Score for the treatment allocation of pleural mesothelioma patients.

OBJECTIVESPatient allocation to multimodality treatment in patients with malignant pleural mesothelioma remains a challenge. The aim of this study was to validate our previously established Multimodality Prognostic Score (MMPS) (tumour volume before chemotherapy, histological subtype, C-reactive protein before chemotherapy and tumour progression after chemotherapy) and to extend the score with additional blood parameters for better patient outcome.METHODSPatients with histologically proven malignant pleural mesothelioma and curative intended therapy with clinical stage T1–T3 N0–N2 M0 were eligible. The existing MMPS was validated and further additional blood markers (erythrocytes, neutrophils, monocytes, albumin, gamma-glutamyl transferase and alkaline phosphatase) were evaluated for potential incorporation.RESULTSFor the validation of the existing MMPS, as the first part of this analysis, 117 patients treated as of September 2011 were included. A total of 88 patients were treated with macroscopic complete resection, whereas 29 patients were treated with palliative or no surgery. Patients treated with macroscopic complete resection and a high MMPS showed statistically significant lower overall survival. In the second part, the extension of the MMPS with additional blood parameters was analysed. Albumin, the only parameter showing evidence for having influence on overall survival, was further added to the extended MMPS. When comparing the performance measures Area under the curve (AUC) and Brier score, the extended score performed better (higher AUC, lower Brier score) than the original MMPS.CONCLUSIONSThe extended score with albumin showed improved performance in comparison to the original score. The extended MMPS also may help allocating patients to surgery.

Non-organ confined stage and upgrading rates in exclusive PSA high-risk prostate cancer patients.

The pathological stage of prostate cancer with high-risk prostate-specific antigen (PSA) levels, but otherwise favorable and/or intermediate risk characteristics (clinical T-stage, Gleason Grade group at biopsy [B-GGG]) is unknown. We hypothesized that a considerable proportion of such patients will exhibit clinically meaningful GGG upgrading or non-organ confined (NOC) stage at radical prostatectomy (RP). Within the Surveillance, Epidemiology, and End Results database (2010-2015) we identified RP-patients with cT1c-stage and B-GGG1, B-GGG2, or B-GGG3 and PSA 20-50 ng/ml. Rates of GGG4 or GGG5 and/or rates of NOC stage (≥ pT3 and/or pN1) were analyzed. Subsequently, separate univariable and multivariable logistic regression models tested for predictors of NOC stage and upgrading at RP. Of 486 assessable patients, 134 (28%) exhibited B-GGG1, 209 (43%) B-GGG2, and 143 (29%) B-GGG3, respectively. The overall upgrading and NOC rates were 11% and 51% for a combined rate of upgrading and/or NOC stage of 53%. In multivariable logistic regression models predicting upgrading, only B-GGG3 was an independent predictor (odds ratio [OR]: 5.29; 95% confidence interval [CI]: 2.21-14.19; p < 0.001). Conversely, 33%-66% (OR: 2.36; 95% CI: 1.42-3.95; p = 0.001) and >66% of positive biopsy cores (OR: 4.85; 95% CI: 2.84-8.42; p < 0.001), as well as B-GGG2 and B-GGG3 were independent predictors for NOC stage (all p ≤ 0.001). In cT1c-stage patients with high-risk PSA baseline, but low- to intermediate risk B-GGG, the rate of upgrading to GGG4 or GGG5 is low (11%). However, NOC stage is found in the majority (51%) and can be independently predicted with percentage of positive cores at biopsy and B-GGG.

External beam radiation therapy with or without brachytherapy boost for low PSA, high-grade prostate cancer.

258 Background: Radiation dose escalation with the addition of a brachytherapy boost (BT) to external beam radiation therapy (EBRT) may be associated with improved survival in certain men with Gleason grade 5 (GG5) prostate cancer (PCa). However, low PSA, high-grade PCa has much worse outcomes, is associated with neuroendocrine genomic features, and may be more resistant to androgen suppression. It is unclear whether the addition of a BT boost in men with this disease subgroup is associated with a survival benefit and is the subject of this analysis. Methods: Men diagnosed with node-negative, non-metastatic GG5 PCa and treated with (1) EBRT plus ADT or (2) EBRT plus BT plus ADT between 2004 and 2015 were identified in the National Cancer Database (NCDB). The EBRT cohort received conventionally fractionated ≥ 74 Gy or moderately hypofractionated (2.5-3.0 Gy x 20-28 fractions) EBRT. EBRT plus BT cohort received external beam doses of conventionally fractionated ≥45 Gy or moderately hypofractionated (2.5 Gy x 15 – 18 fractions) radiation, and either LDR or HDR BT. Men receiving chemotherapy, immunotherapy, or any form of surgery were excluded. Patients were stratified into two groups based on whether the presenting PSA was above or below the normal threshold (≤4 and &gt; 4 ng/mL). OS was compared using the Kaplan-Meier and log-rank test. Multivariable analysis (MVA) using Cox proportional hazards regression modeling was performed, accounting for age, race, year of diagnosis, Charlson-Deyo comorbidity score, insurance status, treatment facility type, Gleason Score (9 versus 10), and clinical T-stage. Results: 8,260 men met study inclusion criteria of which 658 (8%) presented with PSA ≤4. 572 (87%) patients were treated with EBRT monotherapy and 86 (13%) patients were treated with EBRT + BT. 5-year OS for EBRT versus EBRT plus BT was 79.7 +/- 2.3% versus 86.9 +/- 5.0%, respectively (P = 0.49). On MVA analysis, EBRT plus BT was not associated with improved OS versus EBRT (adjusted HR 0.90, 95% CI 0.52-1.87; P = 0.62). In comparison, for men with PSA &gt; 4 and GG5 disease [EBRT: 6,780 patients (89.2%) &amp; EBRT plus BT: 822 patients (10.8%)], EBRT plus BT was associated with improved OS versus EBRT (adjusted HR 0.85, 95% CI 0.66-0.99; P = 0.044). Conclusions: Receipt of dose-escalated prostate radiation by means of a BT boost was not associated with improved survival in men with PSA ≤4 ng/mL and GG5 prostate cancer. By contrast, an association with improved survival was observed in men with GG5 disease and higher initial PSA. This low PSA, high-grade subgroup may represent a unique risk tier for which current treatment paradigms need further investigation, including study of escalated systemic therapy.

Survival outcomes in men with unfavorable intermediate-risk and high-risk prostate cancer treated with prostate-only versus whole pelvic radiation therapy.

264 Background: Men with unfavorable intermediate-risk (UIR-PCa) or high-risk prostate cancer (HR-PCa) are often treated with definitive external beam radiotherapy (EBRT) plus androgen deprivation therapy (ADT). Treatment is frequently intensified by electively treating the pelvic lymph nodes with whole pelvis radiotherapy (WPRT), but practice patterns differ and the benefits of WPRT are not clearly defined, with mixed results from clinical trials. The recent POP-RT trial showed improved biochemical control with WPRT but most patients were staged with PET/CT scan. We hypothesized that men treated with WPRT would have improved overall survival (OS) relative to men treated with prostate-only radiotherapy in patients staged using conventional imaging. Methods: Men diagnosed between 2008-2015 with UIR or high-risk prostate cancer were retrospectively reviewed from the National Cancer Database (n = 28,724). Patients with involved nodes or distant metastases were excluded. Men received EBRT to a dose of 72-86.4 Gy and either prostate-only RT ± ADT (n = 13,549) or WPRT plus prostate RT ± ADT (n = 15,175). WPRT was delivered using a dose range of 40-50.4 Gy (1.8 – 2.0 Gy/fraction). The MSKCC nomogram was used to calculate risk of lymph node involvement. Unweighted or inverse probability of treatment weighting (IPTW) was used to perform multivariable analysis (MVA) using Cox regression modeling to compare OS hazard ratios, accounting for age, race, year of diagnosis, Charlson-Deyo comorbidity score, insurance status, education, income, treatment facility type, PSA, Gleason score, clinical T-stage, use of ADT, lymph node risk score, and radiation dose. Results: 53% of men received WPRT, with national utilization of WPRT increasing from 2008 to 2015. For every 1% increase in risk of lymph node involvement, there was a 1% increased risk of death ( P&lt;.001). WPRT trended toward improved OS in all men with UIR or high-risk (Hazard Ratio (HR): 0.95 [95% Confidence Interval: 0.90-1.006], P=.07). WPRT correlated with improved OS in men with grade group 5 (GG5) disease (HR: 0.87 [0.78-0.98]. P=.02) or risk of lymph node involvement ≥ 10% (HR: 0.93 [0.87-0.99], P=.03). Conclusions: WPRT is associated with improved OS in men with a lymph node risk score ≥ 10% or GG5 disease. These results complement the recent POP-RT randomized trial in mostly PET/CT-staged patients, demonstrating that a more heterogenous population of men staged without functional imaging appears to benefit from WPRT.

No axillary surgical treatment for lymph node-negative patients after ultra-sonography [NAUTILUS]: protocol of a prospective randomized clinical trial

BackgroundFollowing sentinel lymph node biopsy (SLNB), the axillary recurrence rate is very low although SLNB has a false-negative rate of 5–10%. In the ACOSOG Z0011 trial, non-sentinel positive-lymph nodes were found in more than 20% of the axillary dissection group; the SLNB only group did not have a higher axillary recurrence rate. These findings raised questions about the direct therapeutic effect of the SLNB. SLNB has post-surgical complications including lymphedema. Considering advances in imaging modalities and adjuvant therapies, the role of SLNB in early breast cancer needs to be re-evaluated.MethodsThe NAUTILUS trial is a prospective multicenter randomized controlled trial involving clinical stage T1–2 and N0 breast cancer patients receiving breast-conserving surgery. Axillary ultrasound is mandatory before surgery with predefined imaging criteria for inclusion. Ultrasound-guided core needle biopsy or needle aspiration of a suspicious node is allowed. Patients will be randomized (1:1) into the no-SLNB (test) and SLNB (control) groups. A total of 1734 patients are needed, considering a 5% non-inferiority margin, 5% significance level, 80% statistical power, and 10% dropout rate. All patients in the two groups will receive ipsilateral whole-breast radiation according to a predefined protocol. The primary endpoint of this trial is the 5-year invasive disease-free survival. The secondary endpoints are overall survival, distant metastasis-free survival, axillary recurrence rate, and quality of life of the patients.DiscussionThis trial will provide important evidence on the oncological safety of the omission of SLNB for early breast cancer patients undergoing breast-conserving surgery and receiving whole-breast radiation, especially when the axillary lymph node is not suspicious during preoperative axillary ultrasound.Trial registrationClinicalTrials.gov, NCT04303715. Registered on March 11, 2020.

MRI Radiomics Model Predicts Pathologic Complete Response of Rectal Cancer Following Chemoradiotherapy.

Background Preoperative assessment of pathologic complete response (pCR) in locally advanced rectal cancer (LARC) after neoadjuvant chemoradiotherapy (nCRT) is increasingly needed for organ preservation, but large-scale validation of an MRI radiomics model remains lacking. Purpose To evaluate radiomics models based on T2-weighted imaging and diffusion-weighted MRI for predicting pCR after nCRT in LARC and compare their performance with visual assessment by radiologists. Materials and Methods This retrospective study included patients with LARC (clinical stage T3 or higher, positive nodal status, or both) who underwent post-nCRT MRI and elective resection between January 2009 and December 2018. Surgical histopathologic analysis was the reference standard for pCR. Radiomic features were extracted from the volume of interest on T2-weighted images and apparent diffusion coefficient (ADC) maps from post-nCRT MRI to generate three models: T2 weighted, ADC, and both T2 weighted and ADC (merged). Radiomics signatures were generated using the least absolute shrinkage and selection operator with tenfold cross-validation. Three experienced radiologists independently rated tumor regression grades at MRI and compared these with the radiomics models' diagnostic outcomes. Areas under the curve (AUCs) of the radiomics models and pooled readers were compared by using the DeLong method. Results Among 898 patients, 189 (21%) achieved pCR. The patients were chronologically divided into training (n = 592; mean age ± standard deviation, 59 years ± 12; 388 men) and test (n = 306; mean age, 59 years ± 12; 190 men) sets. The radiomics signatures of the T2-weighted, ADC, and merged models demonstrated AUCs of 0.82, 0.79, and 0.82, respectively, with no evidence of a difference found between the T2-weighted and merged models (P = .49), while the ADC model performed worse than the merged model (P = .02). The T2-weighted model had higher classification performance (AUC, 0.82 vs 0.74 [P = .009]) and sensitivity (80.0% vs 15.6% [P < .001]), but lower specificity (68.4% vs 98.6% [P < .001]) than the pooled performance of the three radiologists. Conclusion An MRI-based radiomics model showed better classification performance than experienced radiologists for diagnosing pathologic complete response in patients with locally advanced rectal cancer after neoadjuvant chemoradiotherapy. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Taylor in this issue.

The Effect of Maximum Tumor Diameter by MRI on Disease Control in Intermediate and High-risk Prostate Cancer Patients Treated With Brachytherapy Boost.

Larger maximum tumor diameter (MTD) has been associated with worse prostate cancer (PCa) outcomes. However, the impact of MTD in PCa treated with external beam radiotherapy and brachytherapy boost (EBRT+BB) remains unknown. Patients with PCa treated with EBRT+BB were identified from an institutional database. Clinical data including MTD, age, androgen deprivation therapy (ADT) use, prostate specific antigen (PSA), International Society of Urologic Pathology (ISUP) group, clinical T-stage, and presence of adverse pathology on imaging were retrospectively collected. Multivariable and univariable cox proportional hazards models for biochemical failure (BF) and distant metastasis (DM) were produced with MTD grouped by receiver operating characteristic (ROC) cut-point. Cumulative hazard functions for BF and DM were compared with log-rank test and stratified by ISUP group. Of 191 patients treated with EBRT+BB, 113 had MTD measurements available. Larger MTD was associated with increased ADT use and seminal vesicle involvement. ROC optimization identified MTD of 24 mm as the optimal cut-point for both BF and DM. MTD was independently associated with both BF (HR 8.61, P=.048, 95% CI 1.02-72.97) and DM (HR 8.55, P=.05, 95% CI 1.00-73.19). In patients with ISUP group 4 to 5 disease, MTD > 24 mm was independently associated with increased risk of DM (HR 10.13, P=.04, 95% CI 1.13-91.12). This is the first study to evaluate MTD in the setting of EBRT+BB. These results demonstrate that MTD is independently associated with BF and metastasis. This suggests a possible role for MTD in risk assessment models and clinical decision-making for men receiving EBRT+BB.

Effect of peri-operative chemotherapy regimen on survival in the treatment of locally advanced oesophago-gastric adenocarcinoma – A comparison of the FLOT and ‘MAGIC’ regimens

BackgroundPeri-operative chemotherapy improves survival in patients with locally advanced oesophago-gastric adenocarcinoma. Two regimens with proven survival benefits are epirubicin, cisplatin plus capecitabine or fluorouracil (Medical Research Council Adjuvant Gastric Infusional Chemotherapy, MAGIC) and fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT). This study aimed to compare the effect of these regimens on survival (primary aim) and pathological response, surgical complications, adverse events and chemotherapy completion rates. MethodsCohort study including 946 patients treated with FLOT (n = 257) or MAGIC (n = 689) who underwent surgical resection for oesophageal (n = 743) or gastric (n = 203) adenocarcinoma between 2002 and 2021 at St Thomas’ Hospital or The Royal Marsden Hospital, London, UK. Survival analysis was performed using multivariable Cox regression, providing hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for age, sex, clinical T-stage, clinical N-stage, tumour grade and presence of signet ring cells. ResultsPatients treated with FLOT had better overall survival (HR = 0.69, 95% CI 0.50–0.94) and disease-free survival (HR = 0.75, 95% CI 0.58–0.98) than MAGIC. Patients treated with FLOT were more likely to have a complete pathological response (9.5% FLOT versus 5.5% MAGIC, p = 0.027) and were less likely to have a positive resection margin (19.1% FLOT versus 32.2% MAGIC, p < 0.001). The stratified analysis revealed similar results for oesophageal and gastric tumours. Rates of surgical complications, chemotherapy-associated adverse events and completion were similarly distributed between treatment groups. ConclusionsPatients with oesophageal or gastric adenocarcinoma treated with peri-operative FLOT had better survival and pathological response than those treated with peri-operative MAGIC. Rates of surgical complications, adverse events and chemotherapy completion were comparable.

Validation of models predicting lymph node involvement probability in patients with prostate cancer.

There are many models to predict lymph node involvement in patients with prostate cancer. We aimed to externally validate several models in a Japanese cohort. We considered patients who were treated with robotic-assisted radical prostatectomy with extended pelvic lymph node dissection for prostate cancer. The risk of lymph node involvement was calculated for each patient in several models. Model performance was assessed by calculating the receiver operating characteristic curve and the area under the curve, calibration plots, and decision curve analyses. We identified lymph node involvement in 61 (18.4%) of the 331 considered patients. Patients with lymph node involvement had a higher prostate-specific antigen level, percentage of positive biopsy cores, primary Gleason grade, Gleason group grade, and clinical T-stage category. The Memorial Sloan Kettering Cancer Center web calculator presented the highest area under the curve (0.78) followed by the Yale formula area under the curve (0.77), the updated version of Briganti nomogram of 2017 area under the curve (0.76), and the updated version of the Partin table by Tosoian etal. had an area under the curve of 0.75. However, the 95% confidence interval for these models overlapped. The calibration plot showed that the Memorial Sloan Kettering Cancer Center web calculator and the updated version of the Briganti nomogram calibrated better. In the decision curve analyses, all models showed net benefit; however, it overlapped among them. However, the Memorial Sloan Kettering Cancer Center web calculator and the updated Briganti nomogram presented the highest net benefit for lymph node involvement risks <35%. Models predicting lymph node involvement were externally validated in Japanese men. The Memorial Sloan Kettering Cancer Center web calculator and the updated Briganti nomogram of 2017 were the most accurate performing models.

Imbalanced Data Correction Based PET/CT Radiomics Model for Predicting Lymph Node Metastasis in Clinical Stage T1 Lung Adenocarcinoma

ObjectivesTo develop and validate the imbalanced data correction based PET/CT radiomics model for predicting lymph node metastasis (LNM) in clinical stage T1 lung adenocarcinoma (LUAD).MethodsA total of 183 patients (148/35 non-metastasis/LNM) with pathologically confirmed LUAD were retrospectively included. The cohorts were divided into training vs. validation cohort in a ratio of 7:3. A total of 487 radiomics features were extracted from PET and CT components separately for radiomics model construction. Four clinical features and seven PET/CT radiological features were extracted for traditional model construction. To balance the distribution of majority (non-metastasis) class and minority (LNM) class, the imbalance-adjustment strategies using ten data re-sampling methods were adopted. Three multivariate models (denoted as Traditional, Radiomics, and Combined) were constructed using multivariable logistic regression analysis, where the combined model incorporated all of the significant clinical, radiological, and radiomics features. One hundred times repeated Monte Carlo cross-validation was used to assess the application order of feature selection and imbalance-adjustment strategies in the machine learning pipeline. Prediction performance of each model was evaluated using the area under the receiver operating characteristic curve (AUC) and Geometric mean score (G-mean).ResultsA total of 2 clinical parameters, 2 radiological features, 3 PET, and 5 CT radiomics features were significantly associated with LNM. The combined model with Edited Nearest Neighbors (ENN) re-sampling methods showed strong prediction performance than traditional model or radiomics model with the AUC of 0.94 (95%CI = 0.86–0.97) vs. 0.89 (95%CI = 0.79–0.93), 0.92 (95%CI = 0.85–0.97), and G-mean of 0.88 vs. 0.82, 0.80 in the training cohort, and the AUC of 0.75 (95%CI = 0.57–0.91) vs. 0.68 (95%CI = 0.36–0.83), 0.71 (95%CI = 0.48–0.83) and G-mean of 0.76 vs. 0.64, 0.51 in the validation cohort. The combination of performing feature selection before data re-sampling obtains a better result than the reverse combination (AUC 0.76 ± 0.06 vs. 0.70 ± 0.07, p<0.001).ConclusionsThe combined model (consisting of age, histological type, C/T ratio, MATV, and radiomics signature) integrated with ENN re-sampling methods had strong lymph node metastasis prediction performance for imbalance cohorts in clinical stage T1 LUAD. Radiomics signatures extracted from PET/CT images could provide complementary prediction information compared with traditional model.

Impact of COVID-19 on the oncological outcomes of colorectal cancer surgery in northern Italy in 2019 and 2020: multicentre comparative cohort study.

BackgroundThis study compared patients undergoing colorectal cancer surgery in 20 hospitals of northern Italy in 2019 versus 2020, in order to evaluate whether COVID-19-related delays of colorectal cancer screening resulted in more advanced cancers at diagnosis and worse clinical outcomes.MethodThis was a retrospective multicentre cohort analysis of patients undergoing colorectal cancer surgery in March to December 2019 versus March to December 2020. Independent predictors of disease stage (oncological stage, associated symptoms, clinical T4 stage, metastasis) and outcome (surgical complications, palliative surgery, 30-day death) were evaluated using logistic regression.ResultsThe sample consisted of 1755 patients operated in 2019, and 1481 in 2020 (both mean age 69.6 years). The proportion of cancers with symptoms, clinical T4 stage, liver and lung metastases in 2019 and 2020 were respectively: 80.8 versus 84.5 per cent; 6.2 versus 8.7 per cent; 10.2 versus 10.3 per cent; and 3.0 versus 4.4 per cent. The proportions of surgical complications, palliative surgery and death in 2019 and 2020 were, respectively: 34.4 versus 31.9 per cent; 5.0 versus 7.5 per cent; and 1.7 versus 2.4 per cent. Cancers in 2020 (versus 2019) were more likely to be symptomatic (odds ratio 1.36 (95 per cent c.i. 1.09 to 1.69)), clinical T4 stage (odds ratio 1.38 (95 per cent c.i. 1.03 to 1.85)) and have multiple liver metastases (odds ratio 2.21 (95 per cent c.i. 1.24 to 3.94)), but were not more likely to be associated with surgical complications (odds ratio 0.79 (95 per cent c.i. 0.68 to 0.93)).ConclusionColorectal cancer patients who had surgery between March and December 2020 had an increased risk of advanced disease in terms of associated symptoms, cancer location, clinical T4 stage and number of liver metastases.