Clinical Stage T2 Research Articles

Evaluation of Patient- and Surgeon-Specific Variations in Patient-Reported Urinary Outcomes 3 Months After Radical Prostatectomy From a Statewide Improvement Collaborative

Understanding variation in patient-reported outcomes following radical prostatectomy may inform efforts to reduce morbidity after this procedure. To describe patient-reported urinary outcomes following radical prostatectomy in the diverse practice settings of a statewide quality improvement program and to explore whether surgeon-specific variations in observed outcomes persist after accounting for patient-level factors. This prospective population-based cohort study included 4582 men in the Michigan Urological Surgery Improvement Collaborative who underwent radical prostatectomy as primary management of localized prostate cancer between April 2014 and July 2018 and who agreed to complete validated questionnaires prior to surgery and at 3, 6, and 12 months after surgery. Data were analyzed from 2019 to June 2019. Radical prostatectomy. Patient- and surgeon-level analyses of patient-reported urinary function 3 months after radical prostatectomy. Outcomes were measured using validated questionnaires with results standardized using previously published methods. Urinary function survey scores are reported on a scale from 0 to 100 with good function established as a score of 74 or higher. For the 4582 men undergoing radical prostatectomy within the Michigan Urological Surgery Improvement Collaborative who agreed to complete surveys, mean (SD) age was 63.3 (7.1) years. Survey response rates varied: 3791 of 4582 (83%) responded at baseline, 3282 of 4137 (79%) at 3 months, 2975 of 3770 (79%) at 6 months, and 2213 of 2882 (77%) at 12 months. Mean (SD) urinary function scores were 88.5 (14.3) at baseline, 53.6 (27.5) at 3 months, 68.0 (25.1) at 6 months, and 73.7 (23.0) at 12 months. Regression analysis demonstrated that older age, lower baseline urinary function score, body mass index (calculated as weight in kilograms divided by height in meters squared) of 30 or higher, clinical stage T2 or higher, and lack of bilateral nerve-sparing surgery were associated with a lower probability of reporting good urinary function 3 months after surgery. When evaluating patients with good baseline function, the rate at which individual surgeons' patients reported good urinary function 3 months after surgery varied broadly (0% to 54.5%; P < .001). Patients receiving surgery from top-performing surgeons were more likely to report good 3-month function. This finding persisted after accounting for patient risk factors. In this study, patient- and surgeon-level urinary outcomes following prostatectomy varied substantially. Documenting surgeon-specific variations after accounting for patient factors may facilitate identification of surgical factors associated with superior outcomes.

Predicting Gleason sum upgrading from biopsy to radical prostatectomy pathology: a new nomogram and its internal validation

BackgroundTo explore the rate of Gleason sum upgrading (GSU) from biopsy to radical prostatectomy pathology and to develop a nomogram for predicting the probability of GSU in a Chinese cohort.MethodsWe retrospectively reviewed our prospectively maintained prostate cancer (PCa) database from October 2012 to April 2020. 198 patients who met the criteria were enrolled. Multivariable logistic regression analysis was performed to determine the predictors. Nomogram was constructed based on independent predictors. The receiver operating curve was undertaken to estimate the discrimination. Calibration curve was used to assess the concordance between predictive probabilities and true risks.ResultsThe rate of GSU was 41.4%, whilst GS concordance rate was 44.4%. The independent predictors are prostate specific antigen (PSA), greatest percentage of cancer (GPC), clinical T-stage and Prostate Imaging Reporting and Data System (PI-RADS) score. Our model showed good discrimination (AUC of 0.735). Our model was validated internally with good calibration with bias-corrected C-index of 0.726.ConclusionsUtilization of basic clinical variables (PSA and T-stage) combined with imaging variable (PI-RADS) and pathological variable (GPC) could improve performance in predicting actual probabilities of GSU in the 24-core biopsy scheme. Our nomogram could help to assess the true risk and make optimal treatment decisions for PCa patients.

Comparative Effectiveness Research in Localized Prostate Cancer: A 10-Year Follow-up Cohort Study

Long-term comparative effectiveness research on localized prostate cancer treatments is scarce, and evidence is lacking especially for brachytherapy. The aim of this study was to assess the long-term impact of the side effects of radical prostatectomy, brachytherapy, and external radiation therapy on patients with localized prostate cancer at 10 years, using propensity score analyses. This was a prospective observational study of a cohort of men who received a diagnosis of clinically localized prostate cancer (clinical stage T1 or T2, low and intermediate risk group) and were treated with radical prostatectomy (n = 139), brachytherapy (n = 317), or external radiation therapy (n = 194). Treatment decisions were jointly made by patients and physicians. Patient-reported outcome (PRO) evaluation included the Expanded Prostate Cancer Index Composite and Short Form-36, administered centrally by telephone interviews before and annually after treatment. The Expanded Prostate Cancer Index Composite covers urinary, bowel, sexual, and hormonal domains. To assess PRO changes over time, while accounting for correlation among repeated measures, generalized estimating equation models adjusted by propensity scores were constructed. The PRO completion rate at 10 years was 85.8%. Generalized estimating equation models showed that the pattern of radical prostatectomy side effects, with substantial urinary incontinence and sexual dysfunction, remained until 10 years after treatment (standard deviation [SD], -1.1 and -1.3, respectively). Brachytherapy produced late deterioration in urinary continence (SD, -0.4) and sexual function (SD, -0.9) that appeared midterm, but the differences from radical prostatectomy remained statistically significant at 10 years (P < .001 after adjusting by propensity score). External radiation therapy showed similar results to brachytherapy, but with bowel bother (SD, -0.3). Although late deterioration in radiation therapy groups attenuated differences from radical prostatectomy, relevant PRO differences still remained after 10 years. Our findings support that brachytherapy is the treatment option that causes the least impact on PROs; it is therefore an alternative to be considered when making evidence-based decisions on localized prostate cancer treatment.

Is neoadjuvant chemotherapy always justified in clinical T1 pancreatic ductal adenocarcinoma?

Introduction: Recently, several studies using neoadjuvant treatment have been actively conducted in patients with resectable pancreatic cancer. Neoadjuvant treatment usage in Stage I-II pancreatic cancer increased. These cases are needed to determine its effectiveness, especially clinical T1 stage. So we need to compare the survival benefit of preoperative neoadjuvant treatment in early T stage of pancreatic cancer.

Identification of Urinary Exosomal miRNAs for the Non-Invasive Diagnosis of Prostate Cancer.

BackgroundNovel and non-invasive biomarkers with higher sensitivity and specificity for the diagnosis of prostate cancer (PCa) is urgently needed. In this study, we used next-generation sequencing (NGS) to characterize the genome-wide exosomal miRNA expression profiling in urine specimens and explored the diagnostic potential of urinary exosomal miRNAs for PCa.MethodsUrinary exosomal microRNA expression profiling was performed by next-generation sequencing (NGS) and then validated by quantitative real-time PCR.ResultsSignificant downregulation of urinary exosomal miR-375 was observed in PCa patients compared with healthy controls, while the expression levels of urinary exosomal miR-451a, miR-486-3p and miR-486-5p were found to be significantly up-regulated in the PCa patients. Furthermore, the expression level of urinary exosomal miR-375 showed a significant correlation with the clinical T-stage and bone metastasis of patients with PCa (P<0.05). Receiver operator characteristic curve demonstrated that the urinary exosomal miR-375, miR-451a, miR-486-3p and miR-486-5p levels can be used to differentiate PCa patients from healthy controls, with area under the curves (AUCs) of 0.788, 0.757, 0.704 and 0.796, respectively. The urinary exosomal miR-375 was found to be superior in discriminating between localized and metastatic PCa with an AUC of 0.806. Moreover, PCa patients can be distinguished from patients with benign prostatic hyperplasia by using a panel combining urinary exosomal miR-375 and miR-451a with an AUC of 0.726.ConclusionThese findings demonstrate that the urinary exosomal miRNAs can serve as novel and non-invasive biomarkers for diagnosing and predicting the progression of PCa.

Development of an Indian nomogram for predicting extracapsular extension in prostate cancer.

Introduction:The aim of our study was to develop a new Indian nomogram to estimate pathologic extracapsular extension (ECE) risk in prostate cancer, by including PI-RADS v1-based magnetic resonance imaging (MRI) ECE risk score to the clinical variables used in the Partin nomogram (PN).Materials and Methods:We analyzed 273 patients who underwent MRI of prostate and radical prostatectomy (RP). Univariate and multivariate logistic regression analyses were performed to identify predictors of ECE. We calculated the area under the receiver operating characteristic curve (AUC) for three variables used in PN and MRI ECE risk score, and a new nomogram was designed using binary logistic regression. Calibration curves assessed the agreement between the actual ECE risk and the predicted probability of the new nomogram.Results:Out of 273 patients, 123 patients (45.1) had ECE on MRI, whereas 136 patients (49.8) had ECE on final pathology. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MRI for predicting ECE were 76.6, 66.9, 70.0, 73.9, and 71.7 (confidence interval 95), respectively. Multivariate logistic regression analyses showed that clinical T-stage (cT), Gleason score (GS), and MRI ECE risk score remained significant. The highest and the lowest values of the AUC for single variables were 0.748 (MRI ECE risk score) and 0.636 (cT stage), respectively, and AUC for PN was 0.67. New nomogram designed using R statistical package has higher predictive accuracy (0.826) compared to PN (0.67) and good calibration.Conclusions:MRI adds incremental value to PN. A new Indian nomogram can help in the decision-making process of nerve-sparing RP. This nomogram should be used with caution as validation is pending and will require further studies.

Discrepancy Between cTNM and pTNM in Patients with Oral Squamous Cell Carcinoma

<i>Objective</i>: To analyze discrepancy between cTNM and pTNM in patients with squamous cell carcinoma of oral cavity. <i>Study design</i>: Cross-sectional study. <i>Setting & Duration</i>: Cases of OSCC treated in Oral and Maxillofacial Surgery Department, Allied Hospital Faisalabad from December 2017 to November 2020 were included in the study. <i>Methodology</i>: Total 80 patients with biopsy proven OSCC were enrolled in the study. cTNM staging was based on clinical examination and CT/MRI. Primary tumor excision along with neck dissection was done in all patients. Postoperatively pTNM staging was done and compared to cTNM. The clinical, radiological and histopathological lymph node status of patients were compared. <i>Results</i>: Among 80 patients, male to female ratio was 1.6:1. The mean of age was 50.2±10.2 years. The most common site in our center was the lateral border of the tongue. The total coincidence rate between clinical T-stage and pathological T-stage was 57.5%. On comparison between the clinical and pathological N-stage the total coincidence rate was 40%. The total coincidence rate between cTNM and pTNM was 35% and the p-value was insignificant (p>0.05). The sensitivity of CT/MRI for N-stage was 53.3% and specificity was 60% and positive predictive value (PPV) was 53.3% and negative predictive value (NPV) was 60%. <i>Conclusion</i>: Disparity between cTNM and pTNM of OSCC exits that could affect the treatment planning and prognosis.

Effect of lateral lymph node dissection on the quality of life and genitourinary function after neoadjuvant chemoradiotherapy for rectal cancer.

PurposeThis study was performed to evaluate the quality of life and genitourinary function after total mesorectal excision with lateral lymph node dissection compared to those after total mesorectal excision alone following neoadjuvant chemoradiotherapy for rectal cancer.MethodsAmong patients who underwent rectal cancer surgery after completing neoadjuvant chemoradiotherapy between September 2011 and October 2018 at the National Cancer Center, Korea, patients who completed the validated questionnaires before initiation of neoadjuvant chemoradiotherapy and at 3 months and 1 year postoperatively were included in this study. The European Organization for Research and Treatment of Cancer (EORTC) core quality of life questionnaire (QLQ-C30), colorectal cancer-specific quality of life questionnaire (QLQ-CR38), and International Prostate Symptom Score (IPSS) questionnaire were used for collecting data.ResultsThe total mesorectal excision alone group and the total mesorectal excision with lateral lymph node dissection group included 52 and 38 patients, respectively. The second group included significantly younger patients (P = 0.024), had a higher incidence of clinical T4 stage disease (P = 0.033), estimated blood loss (P = 0.003), and longer operation time (P < 0.001). Significant differences were not observed between the groups with respect to the EORTC QLQ-C30, QLQ-CR38, and IPSS. Multivariable analysis showed that lateral lymph node dissection had no statistically significant association with postoperative urinary dysfunction (P = 0.953).ConclusionThe overall quality of life and urinary function after total mesorectal excision does not differ significantly when lateral lymph node dissection is performed as well.

Nefrectomía Parcial Laparoscópica

Currently, most kidney cancers are diagnosed locally in approximately 65% of cases. Partial nephrectomy versus radical nephrectomy reduces the risk of all-cause mortality by 19% and specific cancer by 29%. Partial nephrectomy can be performed open, laparoscopic, or robotic, depending on the availability, experience, preference, and skills of the surgeon. In studies with high volumes of patients and experienced surgeons, in which laparoscopic versus open partial nephrectomy was compared, no differences were found in progression-free survival and overall survival. Currently partial nephrectomy is indicated in patients with clinical stage T1 kidney cancer, and T2 in those cases that are technically feasible. This review article verifies and updates the most important aspects of partial nephrectomy, especially its indications, approach, scoring systems, and description of the surgical technique of the laparoscopic approach.

Prediction of lymph node metastases using pre-treatment PET radiomics of the primary tumour in esophageal adenocarcinoma: an external validation study.

To improve clinical lymph node staging (cN-stage) in oesophageal adenocarcinoma by developing and externally validating three prediction models; one with clinical variables only, one with positron emission tomography (PET) radiomics only, and a combined clinical and radiomics model. Consecutive patients with fluorodeoxyglucose (FDG) avid tumours treated with neoadjuvant therapy between 2010 and 2016 in two international centres (n = 130 and n = 60, respectively) were included. Four clinical variables (age, gender, clinical T-stage and tumour regression grade) and PET radiomics from the primary tumour were used for model development. Diagnostic accuracy, area under curve (AUC), discrimination and calibration were calculated for each model. The prognostic significance was also assessed. The incidence of lymph node metastases was 58% in both cohorts. The areas under the curve of the clinical, radiomics and combined models were 0.79, 0.69 and 0.82 in the developmental cohort, and 0.65, 0.63 and 0.69 in the external validation cohort, with good calibration demonstrated. The area under the curve of current cN-stage in development and validation cohorts was 0.60 and 0.66, respectively. For overall survival, the combined clinical and radiomics model achieved the best discrimination performance in the external validation cohort (X2 = 6.08, df = 1, p = 0.01). Accurate diagnosis of lymph node metastases is crucial for prognosis and guiding treatment decisions. Despite finding improved predictive performance in the development cohort, the models using PET radiomics derived from the primary tumour were not fully replicated in an external validation cohort. This international study attempted to externally validate a new prediction model for lymph node metastases using PET radiomics. A model combining clinical variables and PET radiomics improved discrimination of lymph node metastases, but these results were not externally replicated.

Laparoscopic Versus Open Distal Gastrectomy for Locally Advanced Gastric Cancer: Five-Year Update from the Class-01 Randomized Controlled Trial

BACKGROUND: It is not clear whether laparoscopic and open distal gastrectomy produce similar outcomes in patients with locally advanced gastric cancer. Data from a multicenter, randomized, controlled trial (CLASS-01) showed that laparoscopic distal gastrectomy did not result in inferior disease-free survival at 3 years compared with open distal gastrectomy. Here, we present 5-year overall survival data from this trial. METHODS: From September 2012 through December 2014, we randomly assigned 1056 patients with clinical stage T2, T3, or T4a gastric cancer (without bulky nodes or distant metastases) to undergo either laparoscopic distal gastrectomy or open distal gastrectomy with D2 lymphadenectomy in a 1:1 ratio. We compared 5-year overall survival between groups in the intent to treat population. RESULTS: We analyzed data from 1039 patients who received curative therapy. At 5 years, the overall survival rates were 72.6% in the laparoscopic distal gastrectomy group and 76.3% in the open distal gastrectomy group (log-rank P =0.19; hazard ratio [HR], 1.17; 95% CI, 0.93–1.48; P =0.187). After we compared for competing risk events, gastric cancer-related deaths (HR, 1.14; 95% CI, 0.87–1.49; P =0.34) and deaths from other causes (HR, 1.23; 95% CI, 0.74–2.05; P =0.42) did not differ significantly between groups. Overall rates of survival did not differ significantly between groups with each tumor stage. CONCLUSIONS: Laparoscopic distal gastrectomy with D2 lymphadenectomy results in similar 5-year overall survival compared to open distal gastrectomy in patients with locally advanced gastric cancer by experienced surgeons in high-volume specialized institutions. TRIAL REGISTRATION: ClinicalTrials.gov. number, NCT01609309 FUNDING STATEMENT: This work was supported by the National Natural Science of China, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, the Key Clinical Specialty Discipline Construction Program from the National Health and Family Planning Commission of China, and the Program of Global Medical Affairs Department of Johnson & Johnson Medical Ltd. DECLARATION OF INTERESTS: None. ETHICS APPROVAL STATEMENT: Each participating center obtained institutional review board approval, according to local regulations. Patients provided written informed consent.

The obesity paradox: defining the impact of body mass index and diabetes mellitus for patients with non-muscle-invasive bladder cancer treated with bacillus Calmette-Guérin.

To evaluate if the obesity paradox, wherein obesity portends worse overall prognosis for a disease but improved outcomes for patients receiving immunotherapy, exists for patients receiving bacillus Calmette-Guérin (BCG) in a contemporary cohort. We performed an Institutional Review Board-approved database review to identify patients with non-muscle-invasive bladder cancer (NMIBC) completing at least an induction course of BCG. Clinicopathological variables collected included: body mass index (BMI), medications, and diabetes mellitus (DM). Outcomes of interest included: recurrence-free (RFS), progression-free (PFS), cancer-specific (CSS), and overall survival (OS). Univariate and multivariate modelling were used to evaluate the association between outcomes and clinical factors. A total of 579 patients (median follow-up 4.6years) received BCG induction for NMIBC; 90% had high-grade disease (47.2% clinical stage T1). In all, 75.7% of patients were overweight or obese and 18% had DM. Aspirin, statins, metformin and β-blockers were used in 34%, 42%, 11%, and 29% of patients, respectively. Overweight and obese patients had improved PFS, CSS and OS. DM was associated with worse RFS. Medications of interest had no association with outcomes. Elevated BMI is associated with improved outcomes in patients with NMIBC treated with BCG immunotherapy. Patients with DM are at increased risk of recurrence. These findings support a potential obesity paradox in bladder cancer. Evaluation of the underlying mechanism and the role of global patient assessment, counselling, and risk factor modification are warranted.

Initial Observation of a Large Proportion of Patients Presenting with Clinical Stage T1 Renal Masses: Results from the MUSIC-KIDNEY Statewide Collaborative

BackgroundWhile surgical excision remains the principal management strategy for clinical T1 renal masses (cT1RMs), the rates of noninterventional approaches are not well known. Most single-institution and population-based series suggest rates below 10%. ObjectiveTo evaluate the use of observation for newly diagnosed cT1RM patients in academic and community-based practices across a statewide collaborative. Design, setting, and participantsThe Michigan Urological Surgery Improvement Collaborative—Kidney mass: Identifying and Defining Necessary Evaluation and therapY (MUSIC-KIDNEY) commenced data collection in September 2017 by recording clinical, radiographic, pathologic, and short-term follow-up data for cT1RM patients at 13 diverse practices. Patients with complete data were assessed at >90 d after initial evaluation as to whether observation or treatment was performed. Outcome measurements and statistical analysisRelationships with outcomes were analyzed using multivariable logistic regression, chi-square test, and Wilcoxon rank-sum test. Results and limitationsOut of 965 patients, observation was employed in 48% (n = 459), with practice-level rates ranging from 0% to 68%. Patients managed with observation (vs treatment) were significantly older (71.2 vs 62.8 yr, p < 0.0001) and had smaller tumors (2.3 vs 3.4 cm, p < 0.0001). Observation was used for 53.5% of cT1a renal masses, for 29.9% of cT1b renal masses, and for 42.5%, 53.7%, and 63.9% of radiographically solid, Bosniak III–IV cystic, and indeterminate cT1RMs, respectively. Factors significantly associated with observation in multivariable analysis included lesion type (Bosniak III–IV vs solid, p = 0.017), tumor stage (cT1a vs cT1b, p < 0.001), and higher age (p < 0.001). A short duration of follow-up limits the assessment of longer-term patient management. ConclusionsNoninterventional management of cT1RMs is common across the MUSIC-KIDNEY collaborative, with wide variability across practices. Factors associated with observation were advanced age, smaller tumor size, and cystic tumor type. Durability of the initial decision for observation (delayed intervention vs active surveillance vs less active surveillance) will be a focus of subsequent study. Patient summaryThe Michigan Urological Surgery Improvement Collaborative: Kidney mass: Identifying and Defining Necessary Evaluation and therapY (MUSIC-KIDNEY) quality improvement collaborative assessed the current utilization of initial observation of a renal mass ≤7 cm across a diverse group of urology practices and found it to be used in 48% of patients. We found that the factors predicting observation were advanced age, smaller tumor size, and cystic tumor type.

Impact of visceral adipose tissue on the accuracy of T-staging by CT in colon cancer

ObjectiveAccuracy of preoperative T-staging for colon cancer remains disappointing and may potentially influenced by patients’ individual characteristics including visceral adipose tissue (VAT). We sought to clarify the impact of VAT on the accuracy of T-staging by CT. MethodsThis study of 216 consecutive patients who underwent elective surgery was conducted in a single cancer center, to control other potentially confounding factors. Patients were divided into accurate- and mis-staging groups according to the comparison between preoperative CT-defined (cT) and postoperative pathologic T-stages (pT). Patients’ individual characteristics, including CT-based VAT at L2/L3 level, age, sex, body mass index (BMI), tumor location, present of bowel obstruction and pathologic subtype, were compared between the two groups. Association between VAT and mis-staging was assessed using multivariate logistic regression to adjust for confounders. ResultsOf the 216 patients, 84 (39%) were mis-staged by CT. The mean VAT in accurate-staging group was significantly higher than that in mis-staging group (146.8 ± 66.1 cm2 vs 98.1 ± 44.7 cm2, P < 0.001), with an optimal cutoff point of 122 cm2 for predicting mis-staging. After partial adjustment, a lower VAT (< 122 cm2, P < 0.001) and proximal location of tumor (P = 0.004) were independent factors associated with higher probability of mis-staging. Compared to VAT ≥ 122 cm2 as the reference, VAT < 122 cm2 exhibited an odds ratio of 2.701 (95% confidence intervals [CI], 1.618-3.907) for the probability of mis-staging. ConclusionA lower-VAT is associated with an increased probability of inaccurate clinical T-staging in colon cancer.

Robotic minimally invasive esophagectomy provides superior surgical resection.

Robotic minimally invasive esophagectomy (RMIE) and "traditional" minimally invasive esophagectomy techniques (tMIE) have reported superior outcomes relative to open techniques. Differences in the outcomes of these two approaches have not been examined. We hypothesized that short-term outcomes of RMIE would be superior to tMIE. The National Cancer Database was used to analyze outcomes of patients undergoing RMIE and tMIE from 2010 to 2016. Patients with clinical metastatic disease were excluded. Trends in the number of procedures performed with each approach were described using linear regression testing. Primary outcome of interest was 90-day mortality rate. Secondary outcomes of interest were positive surgical margin rate, number of lymph nodes (LN) removed, adequate lymphadenectomy (> 15 LNs), length of hospitalization (LOS), readmission rate, and conversion to open rate. Outcomes of RMIE and tMIE were compared using Wilcoxon rank sum test and chi square test as appropriate. Multivariable regression was also performed to reduce the impact of differences in the cohorts of patients receiving RMIE and tMIE. 6661 minimally invasive esophagectomies were performed from 2010 to 2016 (1543/6661 (23.2%) RMIE and 5118/6661 (76.8%) tMIE). Over the study period, the proportion of RMIE increased from 10.4% (64/618) in 2010 to 27.2% (331/1216) in 2016 (p < 0.001) (Fig.1). The primary outcome of 90-day mortality was similar between RMIE and tMIE (92/1170 (7.4%) vs 305/4148 (7.9%), p = 0.558) (Table 2). RMIE and tMIE also had similar readmission rate (6.3 vs 7%, p = 0.380). There was no difference between the cohorts based on sex, age, race, insurance, and tumor size. The cohorts of patients receiving RMIE and tMIE differed in that RMIE patients had lower rates of elevated Charlson scores, were more likely to be treated at an academic institution, had a higher rate of advanced clinical T-stage and clinical nodal involvement, and had received neoadjuvant therapy. In a univariate analysis, RMIE had a lower rate of positive margin (3.9 vs 6.1%, p = 0.001), more mean lymph nodes evaluated (16.6 ± 9.74 vs 16.1 ± 10.08 p = 0.018), lower conversion to open rate (5.4 vs 11.4%, p < 0.001), and a shorter mean length of stay (12.1 ± 10.39 vs 12.8 ± 11.18days, p < 0.001). In multivariable analysis, RMIE was associated with lower risk of conversion to open (OR 0.51, 95% CI: 0.37-0.70, p < 0.001) and lower rate of positive margin (OR 0.62, 95% CI: 0.41-0.93, p = 0.021).). Additionally, in a multivariable logistic regression, RMIE demonstrated superior adequate lymphadenectomy (> 15 LNs) (OR 1.18, 95% CI 1.02-1.37, p < 0.032). In the National Cancer Database, robotic esophagectomy is associated with superior rate of conversion to open and positive surgical margin status. We speculate enhanced dexterity and visualization of RMIE facilitates intraoperative performance leading to improvement in these outcomes.

Report of a Large Cohort of Intermediate-Risk Prostate Cancer Patients Treated with Cs-131 Brachytherapy

The intermediate-risk (IR) group of prostate cancer patients is extremely heterogenous. Patients are sub-classified into favorable-IR (FIR) and unfavorable-IR (UIR) groups due to variable prognoses, leading to significant treatment variations. We sought to evaluate our institutional outcomes utilizing Cs-131 prostate brachytherapy (PB) for IR patients and elucidate which factors are important for driving more aggressive treatment. We reviewed a prospectively collected database of men treated with Cs-131 PB between 2006-2019. Patients with less than 24-months follow-up were excluded. Patients were classified as IR if they had one of the following factors: Gleason Score 7, prostate specific antigen (PSA) >10 but < 20 ng/mL, or T2b-c on clinical exam. We defined UIR patients as having either Grade Group (GG) 3 or >1 IR factors. Our general treatment schema was to treat FIR with PB alone (115 Gy) and UIR with combined external beam radiation therapy (EBRT) to 45 Gy + PB boost (85 Gy), though this was somewhat variable. The Kaplan-Meier method was used to estimate actuarial event-time probabilities for biochemical failure (BF). BF was defined as a serum PSA at least 2 ng/mL greater than posttreatment nadir PSA. Cox regression analysis was performed to identify predictors for BF. These factors included: GG, UIR subgroup, treatment (PB alone vs combined modality), ADT use, age (≤67 vs >67), clinical T-stage, PSA (<10 vs ≥10-20), and >1 IR factors. A total of 327 patients with a median follow-up of 70.6 months (IQR 45.9-102.7 months) were identified. Median age was 67 (IQR 62-72). ADT was used in 12.5% of patients. Most patients (57.5%) were classified as FIR. Of the 139 patients in the UIR subgroup, 69.1% met UIR criteria by virtue of GG 3 only and 30.9% by having >1 IR factor. Twenty-eight patients (20.1%) had a GG 3 and >1 IR factor. FIR patients had a 5-year BF rate (BFR) of 2.5% (SE 0.012). The 5-year BFRs for FIR patients treated with PB alone (81.4%) and combined modality (18.6%) were 1.7% (SE 0.012) and 5.0% (SE 0.035), respectively (p = 0.18). UIR patients had a 5-year BFR of 10.9% (SE 0.030) and were most commonly treated with EBRT+PB (61.9%). Five-year BFRs were 14.0% (SE 0.078) and 10.1% (SE 0.032) for UIR patients treated with PB alone and combined modality, respectively (p = 0.91). UIR patients by virtue of GG 3 only (n = 68) had a 5-year BFR of 13.0% (SE 0.047). The 5-year BFR for UIR due to >1 IR factors (n = 71) was 8.9% (SE 0.038). Six patients had 3 IR factors with a 5-year BFR of 50% (SE 0.25). On multivariate analysis, UIR subgroup was the only significant predictor for BF (p = 0.02; HR 2.49, 95% CI 1.15-5.41). The FIR subgroup is a distinct entity from the UIR subgroup with excellent outcomes when treated with Cs-131 PB alone. UIR patients have excellent outcomes with combined EBRT + PB. The majority of UIR patients do not require ADT, though the group that would benefit still needs to be defined.

Association Between T-Stage and Cancer-Specific Mortality among Men with High-Risk Prostate Adenocarcinoma

Risk group stratification identifies men with high-risk prostate adenocarcinoma (Gleason 8-10, PSA > 20 ng/mL, or cT3-T4) who benefit from more intense treatment. However, many patients are classified as high-risk with only one high-risk feature. Although many trials that are the basis for 2-3 years of androgen deprivation therapy (ADT) studied patients with mostly cT3/T4 disease, PSA-detected, non-palpable T1c disease is currently the most commonly detected. We assessed whether within localized high-risk prostate cancer, survival differences existed based on T-stage. Data from men with high-risk N0M0 prostate adenocarcinoma from the 2004 to 2015 Surveillance, Epidemiology, and End Results database were used. Ten-year PCSM was estimated using Fine-Gray competing-risk regression. The independent variable of interest was clinical T-stage (cT1/2 vs. cT3/4); adjustments were made for PSA, Gleason score, treatment with radical prostatectomy (RP) and radiation (RT), and relevant demographic factors. A second analysis assessed PCSM only among men who received RP, with pathologic T-stage as co-variate (pT2 vs. pT3/4). The average of 12 prostate cancer prognostic signatures, including Decipher prostate cancer signature, compared genomic risk score by pT-stage. For 63,319 men included (median follow-up 6.4 years, median age 68 years), 56,322 (89.0%) had cT1/2, and 6,997 (11.1%) had cT3/4 disease. Ten-year PCSM for men with cT1/2 disease was 12.5%, and for men with cT3/4 disease was 17.5% (competing risk regression HR 0.55, 95CI 0.51—0.60, P<0.001). Greater PSA and greater Gleason score were associated with greater PCSM; receipt of RP, RT, being married, greater income, and later year of diagnosis were associated with lower PCSM. African American and Other race were also associated with lower PCSM. Of the 20,409 men who received radical prostatectomy, 9,953 (48.8%) had pT2 disease and 10,456 (51.2%) had pT3/4 disease. Ten-year PCSM for post-RP men with pT2 disease was 3.5%, and for men with pT3/4 disease was 11.9% (competing risk regression HR 0.29, 95CI 0.24—0.35, P<0.001). Greater PSA, Gleason score, receipt of radiation, and earlier year of diagnosis were associated with worse PCSM. Within a high-risk prospective RP cohort (n = 10,419) from the Decipher GRID registry (NCT02609269), patients with pT3/4 had significantly higher genomic risk scores than patients with pT2 (p<0.001). Men with cT1/2 disease had improved cancer-specific outcomes compared to men with cT3/4. Among men treated with RP, pT2 disease was associated with lower PCSM compared to pT3/4. Genomic risk scores validated these findings. Therefore, treatment paradigms given clinically relevant sub-classification of high-risk tumors based on size merit further study, with a focus on shorter-duration ADT among men with high-risk but T1/2 disease. As cT1c disease is most commonly diagnosed, more men with smaller tumors should be included in trials.

Improved Survival With The Addition Of Pelvic Radiotherapy To Chemotherapy In Patients With Metastatic Urothelial Carcinoma

There is little data on the benefit of local therapy to the bladder for patients with metastatic urothelial carcinoma of the bladder (mUC). We hypothesized that high-dose pelvic radiotherapy (RT) to the bladder plus chemotherapy (CT) improves overall survival (OS) vs. CT alone. We queried the NCDB for newly diagnosed mUC cases (cT1-4 N0-3 M1) from 2004-2015. We included all patients who received CT and excluded patients who received partial, total, or radical cystectomy. The RT cohort included patients who received external beam RT ≥ 45 Gy to the bladder +/- pelvic soft tissues. To account for lead time bias, we excluded patients with <2 months of follow-up or who died within 2 months of diagnosis. Logistic regression was used to identify factors associated with receipt of RT. We performed multivariable Cox proportional hazards analyses with propensity-score matching and landmark estimation to evaluate overall survival and treatment effects. We identified 3289 patients with newly diagnosed mUC who received either CT+ RT (n = 229) or CT alone (n = 3,060). Median follow-up time was 10.9 months (range 2-150), and median OS for CT+RT was 14.5 months (95% CI, 11.9-17.2) vs. 10.5 months (95% CI, 10.7-11.4) for CT alone (P<0.0001). The use of RT was associated with advanced age, higher T-stage, and treatment at a non-academic center (P<0.05). We did not identify significant associations with the receipt of RT and comorbidity score, cN stage, or local surgery (none, excisional biopsy, other). Median RT dose was 59.4 Gy (interquartile range, 50.4 – 64.8 Gy). On our unmatched multivariable analysis (MVA), RT was independently associated with improved OS (HR, 0.70; 95% CI, 0.60-0.80; P<0.0001) after adjusting for age, sex, year of diagnosis, facility type/location, insurance status, Charlson-Deyo comorbidity index, cT/N stage, number of CT agents, and type of local surgery. Increasing age, comorbidity score, and clinical T-stage were all associated with worse OS (P<0.02). On our propensity matched analysis (229 CT+RT patients matched with 229 CT patients), we observed improved OS with CT+RT vs. CT alone (median OS 14.5 months vs. 10.9 months; P = 0.001; MVA HR 0.72, 95% CI 0.59-0.87, P = 0.001). Landmark analysis for patients living ≥6 months (median OS 17.0 months for CT+RT vs. 13.8 months for CT, P = 0.007) and ≥12 months (median OS 24.2 months for CT+RT vs 17.1 months for CT, P = 0.025) also demonstrated improved outcomes for patients treated with CT+RT. In this large contemporary retrospective analysis, patients with newly diagnosed mUC who received local RT plus CT had improved OS compared to CT alone. The magnitude of the effect persisted even with a 12-month landmark analysis which should mitigate the effect of selection bias. The findings are hypothesis-generating; a prospective trial evaluating the impact of bladder RT in mUC is warranted.

Adjuvant Radiation Therapy for Pleural Mesothelioma after Extrapleural Pneumonectomy (EPP) or Pleurectomy and Decortication (P+D)

The optimal treatment sequence for localized malignant pleural mesothelioma (MPM) is controversial. We hypothesized that pleurectomy and decortication (P+D) followed by adjuvant intensity modulated radiation therapy (IMRT) has equivalent cancer control with less morbidity than extrapleural pneumonectomy (EPP) followed by adjuvant radiation therapy (RT). Forty-four patients treated with curative intent surgery and adjuvant RT for MPM at a single institution were included. Prior to September 2013, patients were treated with EPP followed by adjuvant RT (n = 24, 54%). After September 2013, standard treatment was P+D followed by adjuvant IMRT (n = 20, 45%). We compared oncologic outcomes and toxicities (CTCAE version 5.0) between these two approaches. Median age at diagnosis was 64 years (range 26-76); patients receiving EPP were significantly younger (median age 60 vs. 70, p<0.01). Most patients were AJCC 8th edition clinical stage T1 (80%) and N0 (91%). Thirty-seven patients (84%) received neoadjuvant chemotherapy. At surgery, pathologic T stage was most commonly T3 (64%), with 30% node positive. Forty-two patients (95%) had epithelioid histology at surgery, and the remaining two had biphasic histology (5%). Median total RT dose to the entire pleura was 45 Gy (range 30-60 Gy), delivered over a median 27 fractions (range 20-33). Median follow-up for the entire cohort was 3.9 years (range 0.6-20.0 years). Median OS was 2.6 years for P+D compared to 1.1 years for EPP (HR: 0.52, 95% CI: 0.25-1.09, p = .08). Two-year OS was 63% for P+D versus 21% for EPP. On univariate analysis, male sex, pre-operative FEV1% <80, and clinically positive nodes were significantly associated with risk of death. There was no difference in locoregional control (LRC) or progression-free survival (PFS) between P+D and EPP. LRC at 2 and 5 years for the entire cohort was 48% and 39%. PFS at 2 and 5 years was 34% and 17%. Acute Grade 2+ pneumonitis was seen in 0% of EPP patients compared to 35% for P+D, with one grade 3 (5%), one grade 4 (5%), and no grade 5 (0%) pneumonitis. Mean lung dose was significantly associated with development of any grade pneumonitis (odds ratio: 1.46, 95% CI: 1.02-2.11, p = 0.04). Patients who developed pneumonitis had a mean total lung mean dose of 20.4 Gy, compared to 12.9 Gy in those who did not. Total lung V20% was also significantly associated with development of any grade pneumonitis (odds ratio: 1.11, 95% CI: 1.01-1.22, p = 0.03). Mean total lung V20% was 38% for those who developed pneumonitis, compared to 20% for those who did not. FEV1% declined by 27% after P+D and 32% after EPP, while DLCO% declined by 22% after P+D and 28% after EPP. Modern treatment with pleurectomy and decortication followed by adjuvant hemithoracic IMRT appears to provide favorable survival compared to EPP followed by RT, though more non-fatal pneumonitis was seen after P+D with adjuvant IMRT.

Prediction Of Local Pathologic Findings Based On MRI-Based Clinical Staging In Prostate Cancer: A Radiation Oncologist Perspective

Predicting the risk of extracapsular extension (ECE) and seminal vesicle invasion (SVI) is critical for definitive radiotherapy in prostate cancer. Preoperative magnetic resonance imaging (MRI) is known for its predictive value for those findings. This study aimed to develop a model for predicting pathologic findings integrating MRI-based clinical T-staging (cTMRI, cT1c–cT3b). A total of 1915 treatment-naive patients between 2006–2016 who underwent preoperative MRI before radical prostatectomy met the inclusion/exclusion criteria. We performed a multivariate logistic regression analysis as well as a Bayesian Network (BN) modeling based on possible confounding factors. The BN model was further validated by a 5-fold validation. On multivariate logistic regression analysis, initial PSA (iPSA) (β = 0.050; p<0.001), percentage of positive biopsy cores (PPC) (β = 0.033; p<0.001), both lobe involvement on biopsy (β = 0.359; p-0.009), Gleason score (GS) (β = 0.358; p<0.001), and cTMRI (β = 0.259; p<0.001) were significant factors for ECE. For SVI, iPSA (β = 0.037; p<0.001), PPC (β = 0.024; p<0.001), GS (β = 0.753; p<0.001), and cTMRI (β = 0.507; p<0.001) showed statistical significance. BN models to predict ECE and SVI were also successfully established. PPC (normalized MI, 8.22%; p<0.001) and cTMRI (normalized MI, 9.85%; p<0.001) were the most important factors in each BN model for ECE and SVI, respectively, in G-test. The overall AUC/accuracy of BN models were 0.76/73.0% and 0.88/89.6% for ECE and SVI, respectively. Two models to predict pathologic ECE and SVI integrating cTMRI were established. These models will be installed on a separate website for public access to guide radiation oncologists in the future.