Receipt Of Neoadjuvant Chemotherapy Research Articles

OGC P32 Prognostic impact of clinicopathological features following metastectomy for metachronous pulmonary metastasis from oesophageal cancer: a systematic review and meta-analysis

Abstract Background Disease recurrence following treatment for oesophageal cancer (OC) remains common despite incremental gains from receipt of neoadjuvant chemotherapy. The lung is a common site of distant metastasis following definitive OC treatment. Clinicopathological features of the primary oesophageal tumour have implications on the development of metastatic disease and overall survival. This systematic review sought to identify the prognostic impact of clinicopathological features of the primary oesophageal tumour following treatment of metachronous pulmonary metastasis from OC. Methods A search of the major reference databases (PubMed, Medline, Cochrane) was performed with no time limits up to March 2022. Results were screened in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies reporting on the clinical and pathological features of the primary OC tumour among patients undergoing treatment for metachronous pulmonary metastasis were included. A random effects meta-analysis model was used to compare the impact of gender (male vs female), primary OC pathological T-stage (pT1/2 vs pT3/4) and pathological N-stage (N0 vs N1+), on 5-year survival following pulmonary metastectomy. Results Seven non-randomised studies comprising 110 patients undergoing pulmonary metastectomy for metastatic OC were included. Gender did not have an impact upon 5-year survival (Risk Ratio (RR) =0.65; 95% confidence interval(CI):0.37–1.15; p=0.14). A lower primary OC T-stage (T1/2) was associated with improved 5-year survival following pulmonary metastectomy compared to advanced T-stages (T3/4), though this did not reach statistical significance (RR= 1.76; 95% CI:0.96–3.20; p=0.07). The absence of nodal disease (N0) in the primary disease did not confer a survival benefit over those patients with nodal involvement (N1+) proceeding to pulmonary metastectomy (RR= 1.45; 95% CI:0.86–2.46; p=0.18). Conclusions Patient gender and pathological T- and N-stages of the primary tumour do not impact upon prognosis following metastectomy for metachronous pulmonary metastasis from OC. However, current evidence from smaller non-randomised studies remains weak owing to variation in the treatment of the primary oesophageal tumour, limiting outcome assessment.

Perioperative and Oncologic Outcomes Associated with Simultaneous Radical Cystectomy and Nephroureterectomy

To compare the perioperative and oncologic outcomes associated with RCNU to a matched cohort undergoing RC alone. Simultaneous radical cystectomy and nephroureterectomy (RCNU) for synchronous upper tract and bladder urothelial carcinoma is an uncommon procedure. Sparse literature exists comparing outcomes in patients treated with radical cystectomy (RC) alone versus RCNU. Adults treated with RCNU for urothelial carcinoma of the bladder (UCB) and upper tract urothelial carcinoma (UTUC) between 1980 and 2020 were identified. Patients were matched 2:1 to patients undergoing RC alone for UCB based on age (+/- 5 years), gender, BMI (+/- 5), Charlson Comorbidity Index, pathologic staging (stage ≤pT2 vs >pT2), and receipt of neoadjuvant chemotherapy. Outcomes included overall survival (OS), recurrence free survival (RFS), cancer specific survival (CSS), 30-day complications, length of stay (LOS), operative time, and estimated blood loss (EBL). A total of 39 patients undergoing RCNU were identified and matched to 74 patients undergoing RC. There were no significant differences in LOS, EBL, or 30-day complication rates. Operative time was significantly longer in the RC cohort. OS (HR 0.58, CI 0.35-0.97, P=.036) was significantly better for patients undergoing RC alone, while no significant difference was noted in RFS (HR 0.65, 0.34-1.24) and CSS (HR 0.58, CI 0.31-1.08, P=.08). Patients undergoing RCNU had significantly lower OS compared to a matched group of patients undergoing RC alone. Perioperative outcomes between the groups did not differ significantly. This data can inform patient counseling for treatment of this rare disease state.

Hand-Assisted Versus Pure Minimally-Invasive Distal Pancreatectomy: Is There a Downside to Lending a Hand?

Hand-assisted laparoscopic distal pancreatectomy (HALDP) is suggested to offer similar outcomes to pure laparoscopic distal pancreatectomy (LDP). However, given the longer midline incision, it is unclear whether HALDP increases the risk of postoperative hernia. Our aim was to determine the risk of postoperative incisional hernia development after HALDP. We retrospectively collected data from patients undergoing HALDP or LDP at a single center (2012-2020). Primary endpoints were postoperative incisional hernia and operative time. All patients had at minimum six months of follow-up. Outcomes were compared using unadjusted and multivariable regression analyses. Ninety-five patients who underwent laparoscopic distal pancreatectomy were retrospectively identified. Forty-one patients (43%) underwent HALDP. Patients with HALDP were older (median, 67 vs. 61years, p = 0.02). Sex, race, Body Mass Index (median, 27 vs. 26), receipt of neoadjuvant chemotherapy, gland texture, wound infection rates, postoperative pancreatic fistula, overall complications, and hospital length-of-stay were similar between HALDP and LDP (all p > 0.05). In unadjusted analysis, operative times were shorter for HALDP (164 vs. 276min, p < 0.001), but after adjustment, did not differ significantly (MR 0.73; 0.49-1.07, p = 0.1). Unadjusted incidence of hernia was higher in HALDP versus LDP (60% vs. 24%, p = 0.004). After adjustment, HALDP was associated with an increased odds of developing hernia (OR 7.52; 95% CI 1.54-36.8, p = 0.014). After propensity score matching, odds of hernia development remained higher for HALDP (OR 4.62; 95% CI 1.28-16.65, p = 0.031) p = 0.03). Compared with LDP, HALDP was associated with increased likelihood of postoperative hernia with insufficient evidence that HALDP shortens operative times. Our results suggest that HALDP may not be equivalent to LDP.

Breast Cancer Presenting with Intravascular Tumor Emboli in Axillary Soft Tissue: Recurrence Risk and Radiotherapy Outcomes

<h3>Purpose/Objective(s)</h3> Intravascular tumor emboli in axillary soft tissue (ITE) is a rare pathologic finding in breast cancer and is associated with higher axillary nodal disease burden. The independent prognostic and predictive value of this biomarker is unknown, as is the role of radiotherapy for ITE. <h3>Materials/Methods</h3> We analyzed breast cancer patients treated at our institution from 1992-2020, excluding those over 90 years of age at diagnosis, primary tumors >5cm in size, receipt of neoadjuvant chemotherapy, or those with synchronous bilateral breast cancers. A 1:3 propensity score match was performed between patients with ITE and those without. Matching was based on age, pathologic T stage, number of positive nodes removed, receipt of radiotherapy or chemotherapy, and biologic subtype. Disease free survival (DFS) was evaluated using a Cox regression analysis. Locoregional recurrence (LRR) and distant recurrence were evaluated using competing risks methods. These endpoints were compared between patients with versus without ITE. Among those with ITE, we evaluated whether radiotherapy (RT) improved outcomes using the same methods with a six-month landmark. <h3>Results</h3> We identified 127 patients with ITE, of whom, 103 (81%) were propensity score matched to 309 without ITE. Median follow up from surgery was 6.9 years (IQR 2.5, 10). 5-year DFS for those with ITE was 68% (95% CI 57%-82%) versus 78% (95% CI 73%-84%) for those without ITE (HR 1.37, 95% CI 0.82-2.30, p = 0.2). ITE was associated with increased likelihood of distant recurrence (p=0.02; 5-year cumulative incidence 26%, 95% CI 16%-38% and 14%, 95% CI 10%, 19%, respectively), but was not associated with LRR (p=0.97; 5-year cumulative incidence 5.4%, 95% CI 1.3%-14% and 8.7%, 95% CI 5.6%-12%, respectively). Among those with ITE, 5-year DFS was 74% (95% CI 63%-87%) for those receiving RT versus 32% (95% CI 10%-98%) among those not receiving RT (HR 0.33, 95% CI 0.12-0.91, p=0.03). <h3>Conclusion</h3> Patients with intravascular tumor emboli in axillary soft tissue exhibited higher rates of distant recurrence compared to a propensity score matched control group. Among patients with ITE, those who received RT demonstrated improved DFS.

562. PROGNOSTIC IMPACT OF CLINICOPATHOLOGICAL FEATURES FOLLOWING METASTECTOMY FOR METACHRONOUS PULMONARY METASTASIS FROM ESOPHAGEAL CANCER: A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract Disease recurrence following treatment for esophageal cancer (EC) remains common despite incremental gains from receipt of neoadjuvant chemotherapy. The lung is a common site of distant metastasis following definitive EC treatment. Clinicopathological features of the primary EC tumour have implications on the development of metastatic disease and overall survival. This systematic review sought to identify the prognostic impact of clinicopathological features of the primary esophageal tumour following treatment of metachronous pulmonary metastasis from EC. A search of the major reference databases (PubMed, Medline, Cochrane) was performed with no time limits up to March 2022. Results were screened in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies reporting on the clinical and pathological features of the primary EC tumour among patients undergoing treatment for metachronous pulmonary metastasis were included. A random effects meta-analysis model was used to compare the impact of gender (male vs female), primary EC pathological T-stage (pT1/2 vs pT3/4) and pathological N-stage (N0 vs N1+), on 5-year survival following pulmonary metastectomy. Seven non-randomised studies comprising 110 patients undergoing pulmonary metastectomy for metastatic EC were included. Gender did not have an impact upon 5-year survival (Risk Ratio (RR) =0.65; 95% confidence interval (CI):0.37-1.15; p=0.14). A lower primary EC T-stage (T1/2) was associated with improved 5-year survival following pulmonary metastectomy compared to advanced T-stages (T3/4), though this did not reach statistical significance (RR= 1.76; 95% CI:0.96-3.20; p=0.07). The absence of nodal disease (N0) in the primary EC tumour did not confer a survival benefit over those patients with nodal involvement disease (N1+) proceeding to pulmonary metastectomy (RR= 1.45; 95% CI:0.86-2.46; p=0.18). Patient gender and pathological T- and n-stages of the primary tumour do not impact upon prognosis following metastectomy for metachronous pulmonary metastasis from EC. However, current evidence from smaller non-randomised studies remains weak owing to variation in the treatment of the primary EC, limiting outcome assessment.

Systemic Therapy Is Associated with Improved Oncologic Outcomes in Resectable Stage II/III Intrahepatic Cholangiocarcinoma: An Examination of the National Cancer Database over the Past Decade.

Simple SummaryIntrahepatic cholangiocarcinoma (ICC) is a primary liver cancer that currently has limited treatment options and an overall poor prognosis. Evidence-based guidelines for the management of resectable ICC are lacking. We investigated three treatment strategies for resectable ICC using a large cancer registry and compared their use and oncologic outcomes. Our findings suggest a benefit of both neoadjuvant and adjuvant therapy for patients with high-risk resectable ICC. Prospective and randomized studies are needed to better define patients who may benefit from systemic therapy and to clarify the most appropriate sequencing of treatment for resectable ICC.Limited evidence-based management guidelines for resectable intrahepatic cholangiocarcinoma (ICC) currently exist. Using a large population-based cancer registry; the utilization rates and outcomes for patients with clinical stages I-III ICC treated with neoadjuvant chemotherapy (NAT) in relation to other treatment strategies were investigated, as were the predictors of treatment regimen utilization. Oncologic outcomes were compared between treatment strategies. Amongst 2736 patients, chemotherapy utilization was low; however, NAT use increased from 4.3% to 7.2% (p = 0.011) over the study period. A higher clinical stage was predictive of the use of NAT, while higher pathologic stage and margin-positive resections were predictive of the use of adjuvant therapy (AT). For patients with more advanced disease, the receipt of NAT or AT was associated with significantly improved survival compared to surgery alone (cStage II, p = 0.040; cStage III, p = 0.003). Furthermore, patients receiving NAT were more likely to undergo margin-negative resections compared to those treated with AT (72.5% vs. 62.6%, p = 0.027), despite having higher-risk tumors. This analysis of treatment strategies for resectable ICC suggests a benefit for systemic therapy. Prospective and randomized studies evaluating the sequencing of treatments for patients with high-risk resectable ICC are needed.

Improved survival with combination chemotherapy and external beam radiation therapy in uterine carcinosarcoma

ObjectivesTo evaluate differences in survival and recurrence patterns in stage I–IV uterine carcinosarcoma patients treated with surgery followed by adjuvant chemotherapy alone, radiation alone, or a combination of both chemotherapy...

Efficacy and safety of niraparib as maintenance treatment in patients with newly diagnosed advanced ovarian cancer using an individualized starting dose (PRIME Study): A randomized, double-blind, placebo-controlled, phase 3 trial (LBA 5)

<b>Objectives:</b> Niraparib, a potent poly(adenosine diphosphate [ADP]–ribose) polymerase (PARP) inhibitor, demonstrated statistically significant improvement in progression-free survival (PFS) in advanced ovarian cancer (OC) patients (pts) with complete or partial response (CR/PR) after first-line platinum-based chemotherapy (1L CT) regardless of biomarker status in the global phase 3 PRIMA study. The PRIME study was conducted to evaluate the efficacy and safety of niraparib using an individualized starting dose as a maintenance treatment following CR/PR to 1L CT in Chinese pts with advanced OC. <b>Methods:</b> In this double-blind, placebo (PBO)-controlled, multicenter phase 3 study, pts with newly diagnosed, advanced (stage III-IV) OC (including high-grade serious or endometrioid ovarian, primary peritoneal, or fallopian tube cancer) with CR/PR to 1L CT were randomized 2:1 to niraparib or PBO once-daily. A starting dose of 200 mg once daily (QD) was used, except in pts with a baseline body weight of ≥ 77 kg and platelet count ≥ 150,000/μL who received 300 mg QD. Pts were stratified by gBRCA status (mutated [m]/non-gBRCAm), tumor HRD status (HRDpos, HRDneg [including not determined, missing] by BGI Genomics assay, receipt of neoadjuvant chemotherapy (yes/no), and best response to 1L CT (CR/PR). All randomized pts remained on assigned treatment until disease progression, unacceptable toxicity, death, withdrawal of consent, or lost to follow-up. The primary endpoint was PFS assessed by blinded independent central review, analyzed using a stratified log-rank test and a Cox proportional hazards model. The secondary endpoint included overall survival (OS). All efficacy outcome measures were analyzed based on the intention-to-treat (ITT) population. <b>Results:</b> Of the 384 randomized pts (niraparib, n=255; PBO, n=129); 125 (32.6%) were gBRCAm, 257 (66.9%) were HRd population (HRDpos/non-gBRCAm or gBRCAm) (data cutoff [DCO], 30 September 2021). The median follow-up was 27.5 months. Median PFS was significantly longer among pts who received niraparib compared with PBO (24.8 <i>vs</i> 8.3 months; hazard ratio [HR] 0.45; 95% confidence interval [CI] 0.34–0.60; <i>P</i><0.001; Figure 1). All subgroup analysis demonstrated consistent treatment benefit with HRd population (HR 0.48) and HRp (HR 0.41). OS data was immature (as of DCO, number of OS events: 65[16.9 %] occurred; HR, 0.63; 95% CI, 0.38-1.03). The most common grade ≥ 3 adverse events in niraparib arm were anemia (18.0%), neutrophil count decreased (17.3%), and platelet count decreased (14.1%), 1.6%, 1.6%, and 0.8% in placebo arm, respectively. <b>Conclusions:</b> The PRIME study is the first phase 3 study to confirm the efficacy and safety of niraparib as a single agent in Chinese pts with newly diagnosed advanced OC as 1L maintenance therapy. Pts who received niraparib had a clinically meaningful and statistically significant improvement in PFS compared to those who received PBO, regardless of biomarker status. Niraparib was well tolerated and no new safety signals were identified.Fig. 1

Chronic kidney disease and radical cystectomy for bladder cancer: perioperative and oncologic outcomes in 1,214 patients.

To assess the impact of chronic kidney disease (CKD) on outcomes after radical cystectomy (RC) in patients with bladder cancer treated within a high-volume tertiary referral center. We identified 1,214 patients who underwent RC with intent to cure from 2009 to 2019. The Modification of Diet in Renal Disease (MDRD) GFR (ml/min/1.73 m²) was calculated and patients were categorized by baseline GFR: Group A = GFR > 60, Group B = GFR > 30-59 and Group C = GFR < 30. Pre-, intra- and postoperative characteristics, oncological outcomes, and 90-day perioperative outcomes were compared. Multivariable logistic regression was used to control for confounding variables. We identified 722 (59.5%) patients in Group A, 448 (36.9%) in Group B, and 44 (3.6%) in Group C. Patients with worse CKD were older and had significantly worse overall comorbidity (all P < 0.001). Neoadjuvant chemotherapy was used in 352 patients (29%), including 182 (25.2%) in Group A, 153 in Group B (35.3%), and 12 in Group C (27.3%). On univariate analysis, worse CKD was associated with higher pathologic stage, lymph node metastases and positive soft tissue margins (all P < 0.0001). The rates of blood transfusion, 90-day complications and readmissions were higher in patients with worse CKD (P < 0.0001, P = 0.02, P = 0.04, respectively). Patients with worse CKD had worse overall survival (77% vs. 73% vs. 55%, P < 0.0001). On multivariable analysis, worse CKD was independently associated with adverse pathology (≥pT3 or node positive) (OR = 6.96, 95%CI 3.20-15.12), 90-day readmissions (OR 2.09, 95%CI 1.11-3.94) and perioperative transfusion (OR 2.08, 95%CI 1.05-4.11). Receipt of neoadjuvant chemotherapy was significantly associated with a decreased risk of adverse pathology (OR 0.51, 95%CI 0.36-0.74) and increased risk of transfusion (OR 2.24, 95%CI 1.70-2.96), but not with mortality, complications, readmissions or length or stay. CKD is prevalent in patients undergoing radical cystectomy. We found CKD to be independently associated with a higher likelihood of adverse pathology, 90-day readmissions, and transfusion.

Are We Overtreating Patients With T1a HER2+ Breast Cancer? An Analysis of the National Cancer Database

IntroductionThe potential benefit of systemic therapy in patients with T1a HER2+ cancers is not well understood, and no consensus guidelines exist. We sought to investigate practice patterns of chemotherapy use in this population. MethodsFrom the National Cancer Database (2013-2018), we identified female patients with HER2+ cancers staged as cT1aN0 or pT1aN0 and stratified by receipt of chemotherapy. Using univariate and multivariable analyses we assessed the clinicopathologic features associated with the receipt of chemotherapy. We also compared rates of overall survival (OS). ResultsOf 5176 women with cT1aN0 HER2+ cancers, 88 (2%) received neoadjuvant chemotherapy. Younger age and hormone-receptor (HR) negative tumors were factors independently associated with receipt of neoadjuvant chemotherapy (all P < .001). Of 11,688 women with pT1aN0 HER2+ cancers, 5,588 (48%) received adjuvant chemotherapy. Rates of use increased over the analysis period from 39% in 2013 to 53% in 2018 (P < .001). Factors independently associated with receipt of adjuvant chemotherapy included younger age, having a poorly differentiated tumor, exhibiting lymphovascular invasion, undergoing adjuvant radiation (all P < .001). There were no differences in OS when comparing those who did and did not receive chemotherapy in either group. ConclusionsThe use of chemotherapy in patients with HER2+ T1a cancers is increasing over time and is, as expected, more common among patients with unfavorable clinicopathologic features. Since no prognostic algorithm currently exists, more prospective data is needed to understand which of these patients may derive benefit from systemic therapy and which may safely avoid the morbidity of chemotherapy.

Implications for pelvic lymph node irradiation in definitive chemoradiotherapy of node negative muscle invasive bladder cancer based on predictive factors of clinicopathologic discrepancy.

To identify pre-surgical imaging predictive value and factors associated with the clinicopathologic discrepancy for implication of definitive pelvic radiotherapy in clinically node-negative bladder cancer. The documented data of bladder cancer patients who underwent radical cystectomy plus pelvic lymphadenectomy were collected retrospectively. Patients' characteristics, last imaging, pathology reports, disease-specific survival and overall survival were retrieved. From 142 patients, pre-surgical imaging had a sensitivity of 76.4%, specificity of 73.7%, positive predictive value (PPV) of 94.9%, and negative predictive value (NPV) of 32.6% (p value < 0.0001) for detection of muscle invasion. Also, for detection of positive lymph nodes, imaging had a sensitivity of 31.8%, specificity of 85.7%, PPV of 50%, and NPV of 73.7% (p value: 0.022). 44.4% of study population were upstaged after surgery (24.6% associated with N-upstaging) and 18.3% were downstaged (12% associated with N-downstaging). Receipt of neoadjuvant chemotherapy and T-stage were not correlated with N-upstaging. On multivariate analysis, lymphovascular invasion (LVI) maintained its significance for independent prediction of upstaging (OR 3.3, 95% CI 1.5-7.5, p value: 0.004) and inversely with downstaging (OR 0.34, 95% CI 0.12-0.96, p value: 0.04). Older age (OR 1.03, 95% CI 1.0-1.05, p value 0.047), positive margins (OR 2.1, 95% CI 1.2-3.8, p value 0.011), presence of LVI (OR 2.5, 95% CI 1.4-4.7, p value 0.003), perineural invasion (OR 2.0, 95% CI 1.2-3.4, p value 0.013), and lymph node ratio (OR 1.011, 95% CI 1.001-1.021, p value 0.03) were associated with worse survival. Also, N-upstaging independently predicted a worse survival after controlling for surgical pathology stage (OR 2.3, 95% CI 1.2-4.5, p value 0.011). The optimal target volume in definitive chemoradiotherapy of node-negative bladder cancer patients remains to be established. Since then, customizing the treatment is considered especially for positive LVI in TURBT specimen.

Comparing Minimally Invasive and Open Pancreaticoduodenectomy for the Treatment of Pancreatic Cancer: a Win Ratio Analysis

IntroductionDespite its rising adoption, the use of minimally invasive (MIS) pancreaticoduodenectomy (PD) in the treatment of pancreatic cancer remains controversial. We sought to compare MIS and open PD for pancreatic cancer resection in terms of short-term, long-term, and oncologic outcomes using the win ratio, a novel statistical approach. MethodsPatients undergoing PD for pancreatic adenocarcinoma 2010–2016 were identified from the National Cancer Database (NCDB). Patients were paired based on age, sex, race, tumor size, Charlson-Deyo score, and receipt of neoadjuvant chemotherapy. The win ratio was calculated based on 30-day and 3-year mortality, receipt of adjuvant chemotherapy, surgical margin status, examination of at least 11 lymph nodes, extended length of stay, and 30-day readmission. ResultsAmong 18,936 patients, median age was 67 (IQR: 60–74); most patients had stage II disease at diagnosis (n = 16,530, 87.3%) and tumor size ≥ 2 cm (n = 15,880, 83.9%). The majority of patients underwent open PD (n = 16,409, 86.7%) versus MIS PD (n = 2527, 13.3%). For every matched patient-patient pair, the odds of the patient undergoing MIS PD “winning” were 1.14 (95%CI 1.13–1.15) higher versus open PD. The benefits of MIS PD were most pronounced among patients with tumor size < 2 cm (WR 1.21, 95%CI 1.13–1.30 versus ≥ 2 cm, WR 1.13, 95%CI 1.12–1.14) and patients who received neoadjuvant chemotherapy prior to resection (WR 1.28, 95%CI 1.23–1.32 versus no neoadjuvant chemotherapy, WR 1.13, 95%CI 1.11–1.14). ConclusionsMIS PD may be preferable to open PD based on a hierarchical composite outcome that considered short-term, long-term, and oncologic outcomes.

KRAS variant allele frequency, but not mutation positivity, associates with survival of patients with pancreatic cancer.

KRAS mutation is a major driver of pancreatic carcinogenesis and will likely be a therapeutic target. Due to lack of sensitive assays for clinical samples of pancreatic cancer with low cellularity, KRAS mutations and their prognostic association have not been fully examined in large populations. In a multi‐institutional cohort of 1162 pancreatic cancer patients with formalin‐fixed paraffin‐embedded tumor samples, we undertook droplet digital PCR (ddPCR) for KRAS codons 12/13/61. We examined detection rates of KRAS mutations by clinicopathological parameters and survival associations of KRAS mutation status. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) for disease‐free survival (DFS) and overall survival (OS) were computed using the Cox regression model with adjustment for potential confounders. KRAS mutations were detected in 1139 (98%) patients. The detection rate did not differ by age of tissue blocks, tumor cellularity, or receipt of neoadjuvant chemotherapy. KRAS mutations were not associated with DFS or OS (multivariable HR comparing KRAS‐mutant to KRAS‐wild‐type tumors, 1.04 [95% CI, 0.62–1.75] and 1.05 [95% CI, 0.60–1.84], respectively). Among KRAS‐mutant tumors, KRAS variant allele frequency (VAF) was inversely associated with DFS and OS with HRs per 20% VAF increase of 1.27 (95% CI, 1.13–1.42; p trend <0.001) and 1.31 (95% CI, 1.16–1.48; p trend <0.001), respectively. In summary, ddPCR detected KRAS mutations in clinical specimens of pancreatic cancer with high sensitivity irrespective of parameters potentially affecting mutation detections. KRAS VAF, but not mutation positivity, was associated with survival of pancreatic cancer patients.

Neoadjuvant chemotherapy is associated with improved outcomes in patients with stage 1A and 1B pancreatic cancer undergoing surgery: An NCDB study.

4157 Background: The use of neoadjuvant chemotherapy (NAC) for pancreatic ductal adenocarcinoma (PDAC) has shown clear advantages in locally advanced and borderline resectable disease. The benefit in upfront resectable PDAC is debated. Moreover, in early clinical stages IA/IB, potential benefits including improved R0 resection rate, decreased tumor upstaging, and survival, are not clear. We hypothesize that NAC will be associated with improved outcomes and survival compared to adjuvant therapy in patients with clinical stage IA/IB PDAC. Methods: The National Cancer Database (NCDB) PUFs (2004-2017) were used to perform a retrospective review of patients with clinical stage IA or IB PDAC undergoing surgery. Treatment groups were selected based on timing of chemotherapy. Patients receiving chemotherapy or surgery alone were excluded. Results: We identified 6,613 patients with clinical stage IA or IB PDAC who underwent surgery. The neoadjuvant therapy group (NAT) included 1,533 patients who received neoadjuvant or perioperative chemotherapy, and the adjuvant therapy group (AT) contained 5080 patients who received chemotherapy after surgery. Patients in the NAT had higher rates of T1 and T2 disease and lower rates of T3 pathology compared to the AT (pT1: 18.7% vs 7.8%; pT2: 20.1 vs 18.6%; pT3: 59.3% vs 72.1%, p&lt;0.0001). Additionally, the NAT had significantly higher rates of N0 disease and less N1 pathology (pN0: 54.6% vs 37.5%; pN1: 45.4% vs 62.5%, p&lt;0.0001). The R0 resection rate was higher in the NAT (83.2% vs 62.3%, p=0.0197) and there was less lymphovascular invasion (LVI) compared to the AT (34.8% vs 48.1%, p&lt;0.0001). Using Kaplan Meier estimates, the NAT was associated with improved overall survival (OS) compared to the AT (median OS: 33.4 vs 27.5 months, p&lt;0.0001). On multivariable analysis, R0 resection (HR=0.715, CI: 0.619-0.825, p&lt;0.0001), LVI (HR=1.126, 95% CI: 1.038-1.222, p=0.0043) but not receipt of NAC (HR=0.94, 95% CI: 0.852-1.038, p=0.2229) were independent risk factors for OS. Conclusions: NAC is beneficial in patients with stage IA/IB PDAC undergoing surgical resection as it is associated with improved oncologic outcomes including increased R0 resection rate, decreased tumor upstaging, lymph node metastasis, and LVI. Furthermore, patients receiving NAC were found to have improved survival over those getting adjuvant therapy. Based on these results, we recommend all patients diagnosed with PDAC be considered for NAC prior to surgery. [Table: see text]

Efficacy of niraparib maintenance therapy in patients with newly diagnosed advanced ovarian cancer in phase 3 PRIME study: A subgroup analysis by response to first-line platinum-based chemotherapy.

5551 Background: In PRIME (NCT03709316), niraparib significantly reduced the risk of disease progression or death versus placebo (PBO) (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.34–0.60) in Chinese patients (pts) with newly diagnosed, advanced ovarian cancer (OC), regardless of biomarker status. As response to chemotherapy is deemed to be associated with prognosis in OC, this subgroup analysis of the PRIME study aims to better understand niraparib treatment effect in pts based on response to first-line platinum-based chemotherapy (1L CT). Methods: This randomized, double-blind, PBO-controlled, phase 3 trial enrolled adults with newly diagnosed, stage III or IV OC who achieved a complete response (CR) or partial response (PR) to 1L CT and received primary or interval cytoreductive surgery, irrespective of residual disease status after surgery. Pts were randomized (2:1) to receive niraparib or PBO, whose starting doses were individualized based on baseline bodyweight and platelet count, with stratification according to status of germline BRCA mutations (yes or no), tumor homologous recombination status (deficient or proficient), receipt of neoadjuvant chemotherapy (yes or no), and clinical response to 1L CT (CR or PR). This prespecified exploratory analysis reports progression-free survival (PFS) and HRs based on clinical response to 1L CT. The data cut-off date was 30 September 2021. Results: Of the 384 pts randomized, 315 (82.0%) and 69 (18.0%) had a CR (212 niraparib, 103 PBO) or PR (43 niraparib, 26 PBO) to 1L CT, respectively. Baseline characteristics are presented in the Table. The overall PFS median follow-up was 27.5 months. Niraparib significantly extended PFS compared with PBO: the median PFS was 29.4 months for niraparib versus 8.3 months for PBO (HR=0.45; 95% CI, 0.32–0.61; P&lt;0.001) in the CR group and was 19.3 months for niraparib versus 8.3 months for PBO (HR=0.45; 95% CI, 0.23–0.86; P=0.014) in the PR group. Conclusions: In pts with newly diagnosed advanced OC, PFS was substantially prolonged with niraparib versus PBO, regardless of response to chemotherapy and biomarker status. Moreover, pts who achieved a CR appeared to receive larger PFS benefit from niraparib than those with a PR. Clinical trial information: NCT03709316. [Table: see text]

MP56-06 ASSOCIATIONS BETWEEN SKELETAL MUSCLE GAUGE AND SURVIVAL FOLLOWING RADICAL CYSTECTOMY FOR BLADDER CANCER: A NOVEL ASSESSMENT OF MUSCLE MASS AND QUALITY

MP56-06 ASSOCIATIONS BETWEEN SKELETAL MUSCLE GAUGE AND SURVIVAL FOLLOWING RADICAL CYSTECTOMY FOR BLADDER CANCER: A NOVEL ASSESSMENT OF MUSCLE MASS AND QUALITY

MP23-07 PREVALENCE AND IMPACT OF FEAR OF RECURRENCE ON BLADDER CANCER PATIENTS AFTER RADICAL CYSTECTOMY

You have accessJournal of UrologyCME1 May 2022MP23-07 PREVALENCE AND IMPACT OF FEAR OF RECURRENCE ON BLADDER CANCER PATIENTS AFTER RADICAL CYSTECTOMY Justin Badal, Brady Miller, Nora Ruel, Airybelle Uchida, Kelly Franklin, Sumanta Pal, and Bertram Yuh Justin BadalJustin Badal More articles by this author , Brady MillerBrady Miller More articles by this author , Nora RuelNora Ruel More articles by this author , Airybelle UchidaAirybelle Uchida More articles by this author , Kelly FranklinKelly Franklin More articles by this author , Sumanta PalSumanta Pal More articles by this author , and Bertram YuhBertram Yuh More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002562.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The recurrence rate for bladder cancer is high. Over 30% of those with muscle invasive bladder cancer have a recurrence within 5 years representing a source of persistent anxiety and distress. Fear of cancer recurrence (FCR) is well characterized in other malignancies such as breast, thyroid, and brain cancers. It has been characterized in prostate, renal, and testis cancer. This study describes the prevalence and impact of FCR among patients with bladder cancer who have had cystectomy. METHODS: A phone survey was conducted using the Fear of Cancer Recurrence-7 index in patients who had previously undergone radical cystectomy for bladder cancer. From the period of 2015 to 2020, 145 patients were eligible to undergo the phone survey. 75 patients agreed to being surveyed. We evaluated patients based on factors such as time since surgery, clinical and pathologic stage, receipt of neoadjuvant chemotherapy, ASA status, and length of stay. RESULTS: The median age for participants was 70. 83% of respondents were male. 84% of respondents were white. 39 patients had muscle invasive disease at presentation and 17 patients had muscle invasive disease on pathologic staging. Median time since surgery was 28 months. 17% of patients had high (FCR7 ≥17) scores. Those with lower clinical and pathologic stage disease had higher FCR7 scores. 12/58 (21%) patients with ≤PT1 reported a high FCR while only 1/17 (6%) of patients with ≥pT2 disease reported high FCR (p=0.11). Their FCR7 score was more likely to be ≥17 in the 2nd or 3rd year from surgery. Patients who underwent Indiana Pouch urinary diversion were more likely to have a FCR7≥17 when compared to ileal conduit or Studer neobladder (44.4% vs 13.6%, p=0.022). CONCLUSIONS: Fear of cancer recurrence in patients with bladder cancer is a phenomenon that should be considered when counseling patients in the preoperative as well as surveillance stages of their cancer care. Even after several years, patients who have FCR continue to exhibit persistent fear. Patients with certain forms of urinary diversion may also have differing FCR. Though not statistically significant, patients with lower stage disease may require closer psychologic monitoring through their cancer treatment journey. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e383 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Justin Badal More articles by this author Brady Miller More articles by this author Nora Ruel More articles by this author Airybelle Uchida More articles by this author Kelly Franklin More articles by this author Sumanta Pal More articles by this author Bertram Yuh More articles by this author Expand All Advertisement PDF DownloadLoading ...

PD10-05 PERIOPERATIVE BLOOD TRANSFUSION IS ASSOCIATED WITH INCREASED RISK OF VENOUS THROMBOEMBOLISM AFTER RADICAL CYSTECTOMY

You have accessJournal of UrologyCME1 May 2022PD10-05 PERIOPERATIVE BLOOD TRANSFUSION IS ASSOCIATED WITH INCREASED RISK OF VENOUS THROMBOEMBOLISM AFTER RADICAL CYSTECTOMY Amanda Myers, Igor Frank, Paras H. Shah, Robert F. Tarrell, Giovanni A. Gonzalez, R. Jeffrey Karnes, Houston Thompson, Matthew K. Tollefson, Stephen A. Boorjian, and Timothy D. Lyon Amanda MyersAmanda Myers More articles by this author , Igor FrankIgor Frank More articles by this author , Paras H. ShahParas H. Shah More articles by this author , Robert F. TarrellRobert F. Tarrell More articles by this author , Giovanni A. GonzalezGiovanni A. Gonzalez More articles by this author , R. Jeffrey KarnesR. Jeffrey Karnes More articles by this author , Houston ThompsonHouston Thompson More articles by this author , Matthew K. TollefsonMatthew K. Tollefson More articles by this author , Stephen A. BoorjianStephen A. Boorjian More articles by this author , and Timothy D. LyonTimothy D. Lyon More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002536.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Venous thromboembolism (VTE) is increasingly used as a quality indicator after radical cystectomy (RC). However, the role of perioperative blood transfusion (PBT) in VTE risk adjustment remains unclear. While transfusion has been associated with an increased risk of VTE in administrative datasets, these analyses are limited by inability to adjust for several risk factors for VTE including cancer stage and receipt of neoadjuvant chemotherapy which may confound the observed associations. The objective of this study was to examine whether perioperative blood transfusion is associated with VTE following RC after adjusting for both patient- and disease-related factors. METHODS: Patients who underwent RC for bladder cancer from 1980-2020 were identified in the Mayo Clinic cystectomy registry. PBT was defined as intraoperative and/or postoperative blood transfusion during the initial hospital stay. The primary outcome was VTE within 90 days of RC, inclusive of either deep venous thrombosis or pulmonary embolism. Perioperative VTE prophylaxis varied according to institutional standard at the time, but generally consisted of sequential compression devices and subcutaneous heparin while inpatient. In April 2013, we began using intraoperative tranexamic acid, and in May 2014, we began prescribing outpatient extended duration VTE prophylaxis with enoxaparin in all patients without contraindications. Associations between clinicopathologic variables and 90-day VTE were assessed using multivariable logistic regression. PBT was analyzed as both a categorical and a continuous variable. RESULTS: We identified 3958 patients with RC, of whom 162 (4%) experienced a VTE within 90 days of RC. 2244 patients (57%) received a PBT, with a median of 1 (range: 0-69, IQR: 0-3) unit transfused. Median follow up among survivors was 6.7 years (IQR 2.4-12.7). On multivariable analysis adjusting for year of surgery, BMI, robotic approach, neoadjuvant chemotherapy, diversion type, pathologic tumor stage and pathologic nodal stage, the receipt of PBT remained significantly associated with an increased risk of VTE (adjusted OR 1.46, 95% CI 1.01-2.09, p=0.04). When further analyzed as a continuous variable, each unit of blood was associated with 6% higher odds of a VTE (adjusted OR 1.06, 95% 1.01-1.10, p=0.01). CONCLUSIONS: PBT was independently associated with VTE within 90 days of RC after adjusting for disease-related factors. Each unit transfused was associated with higher odds of a VTE. Continued effort to limit blood transfusion in these patients is warranted. Source of Funding: none © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e185 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Amanda Myers More articles by this author Igor Frank More articles by this author Paras H. Shah More articles by this author Robert F. Tarrell More articles by this author Giovanni A. Gonzalez More articles by this author R. Jeffrey Karnes More articles by this author Houston Thompson More articles by this author Matthew K. Tollefson More articles by this author Stephen A. Boorjian More articles by this author Timothy D. Lyon More articles by this author Expand All Advertisement PDF DownloadLoading ...

MP25-16 CLINICAL IMPLICATIONS OF THE URINARY DIVERSION MICROBIOME AFTER RADICAL CYSTECTOMY

You have accessJournal of UrologyCME1 May 2022MP25-16 CLINICAL IMPLICATIONS OF THE URINARY DIVERSION MICROBIOME AFTER RADICAL CYSTECTOMY Saum Ghodoussipour, Seyedeh Sanam Ladi Seyedian, David Nusbaum, Shane Pearce, Hiren Patel, Aishani Prem, Wendy Ullmer, Sumeet Bhanvadia, Hooman Djaladat, Anne Schuckman, Gangning Liang, and Siamak Daneshmand Saum GhodoussipourSaum Ghodoussipour More articles by this author , Seyedeh Sanam Ladi SeyedianSeyedeh Sanam Ladi Seyedian More articles by this author , David NusbaumDavid Nusbaum More articles by this author , Shane PearceShane Pearce More articles by this author , Hiren PatelHiren Patel More articles by this author , Aishani PremAishani Prem More articles by this author , Wendy UllmerWendy Ullmer More articles by this author , Sumeet BhanvadiaSumeet Bhanvadia More articles by this author , Hooman DjaladatHooman Djaladat More articles by this author , Anne SchuckmanAnne Schuckman More articles by this author , Gangning LiangGangning Liang More articles by this author , and Siamak DaneshmandSiamak Daneshmand More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002568.16AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: We use bacterial 16S rRNA and fungal ITS sequencing to identify the UD microbiome after radical and clinical implications of taxonomic and microbial diversity differences. METHODS: We enrolled patients who underwent RC and UD with either ileal conduit or neobladder under an IRB-approved protocol. A catheterized urine specimen from the native bladder and a swab of the ileal segment used to create the UD were collected in the operating room. We then collected sequential catheterized specimens from the UD until 1-year after surgery. Preoperative antibiotic prophylaxis was administered according to an institutional ERAS protocol. Microbial 16S rRNA and ITS sequencing and profiling were performed. RESULTS: We included 20 patients (75% male, 30% had neoadjuvant chemotherapy). The 90-day complication rate was 60% (n=12), including infectious in 25% (n=5). The average bacterial count, estimated by gene copy number, was higher in the bowel swab (1.38 x 108 cells/ml) than native bladder (7.23 x 106 cells/ml) as was alpha diversity, which measures the number of different species in each sample (mean species richness = 50 ± 26 in bowel and 29 ± 25 in native bladder). The average UD bacterial count and alpha diversity was high on post-operative day 1 (1.38 x 108 cells/ml and 31 ± 19, respectively), but over time, alpha diversity decreased while bacterial counts tended to increase (11 ± 12 and 4.54 x 108 cells/ml at 1 year, respectively). High fungal cell counts (>1,000 cells/ml) were noted in 7 patients and Candida species were abundant in all but one. Principal coordinate analysis showed microbial profiles of the native bladder and ileum clustering in distinct patterns, but the UD microbiome varied between patients (Figure). Age, gender, receipt of neoadjuvant chemotherapy and type of diversion did not predict similarities in the UD microbiome. There were no significant differences in microbial diversity or bacterial count amongst patients with and without complications. However, a high fungal count was associated with any complication in the first month (p<0.01) and first year (p<0.05). CONCLUSIONS: The UD microbiome differs from the native bladder and ileum and varies widely between patients. High fungal loads are associated with patients having any complication, potentially implicating Candida species as a pathogenic organism. Source of Funding: Zymo Research Corp © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e434 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Saum Ghodoussipour More articles by this author Seyedeh Sanam Ladi Seyedian More articles by this author David Nusbaum More articles by this author Shane Pearce More articles by this author Hiren Patel More articles by this author Aishani Prem More articles by this author Wendy Ullmer More articles by this author Sumeet Bhanvadia More articles by this author Hooman Djaladat More articles by this author Anne Schuckman More articles by this author Gangning Liang More articles by this author Siamak Daneshmand More articles by this author Expand All Advertisement PDF DownloadLoading ...

MP23-06 NEOADJUVANT CHEMOTHERAPY BEFORE RADICAL CYSTECTOMY FOR MUSCLE-INVASIVE BLADDER CANCER: PATIENT, PROVIDER, AND CLINICAL ETIOLOGIES FOR LACK OF UTILIZATION

You have accessJournal of UrologyCME1 May 2022MP23-06 NEOADJUVANT CHEMOTHERAPY BEFORE RADICAL CYSTECTOMY FOR MUSCLE-INVASIVE BLADDER CANCER: PATIENT, PROVIDER, AND CLINICAL ETIOLOGIES FOR LACK OF UTILIZATION Hiten D. Patel, Ushasi Naha, Victor S. Chen, Caitlyn Ko, Rachel Yang, Aleksander Druck, Goran Rac, and Marcus L. Quek Hiten D. PatelHiten D. Patel More articles by this author , Ushasi NahaUshasi Naha More articles by this author , Victor S. ChenVictor S. Chen More articles by this author , Caitlyn KoCaitlyn Ko More articles by this author , Rachel YangRachel Yang More articles by this author , Aleksander DruckAleksander Druck More articles by this author , Goran RacGoran Rac More articles by this author , and Marcus L. QuekMarcus L. Quek More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002562.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Neoadjuvant chemotherapy (NAC) represents a standard of care prior to radical cystectomy for muscle-invasive bladder cancer (MIBC; ≥cT2). While NAC utilization has increased over time in the United States, many patients may not receive NAC due to reasons that are difficult to identify in administrative or registry data. We aimed to assess utilization of NAC and etiologies for lack of NAC receipt among consecutive patients at a single institution. METHODS: Patients diagnosed with bladder cancer and undergoing radical cystectomy at Loyola University Medical Center (2005-2021) were included. Clinical variables included age, sex, race, comorbidities, prior intravesical therapy, hydronephrosis, histology, clinical stage, and surgical approach. Patients were categorized by stage and receipt of NAC. Early and recent time periods were evaluated among all ≥cT2 patients and after exclusion of non-candidates. Reasons for no NAC were categorized. Overall survival (OS) was evaluated with Kaplan-Meier curves and multivariable Cox proportional hazards regression models. RESULTS: Of 589 evaluable patients, 380 (64.5%) had ≥cT2 disease and 209 (35.5%) <cT2. Among ≥cT2 patients, a total of 155 (40.8%) received NAC with significant increase in utilization from the early to recent time periods (22.8% to 67.8%, p <0.001). Utilization of NAC was similar for open and robotic approach (p=0.15). Among 225 patients not receiving NAC, reasons included renal dysfunction (28.0%), patient symptoms (9.3%), concern for disease progression (8.4%), salvage setting (3.1%), patient preference/refusal (24.4%), and provider recommendation (26.7%). Provider recommendation was related to comorbidities (18/60 (30.0%); e.g. prior chemotherapy, hearing loss, non-renal comorbidity), histology (20/60 (33.3%); e.g. squamous or adenocarcinoma histology), or not mentioned (22/60 (36.7%)). After excluding non-candidates for NAC, increase in utilization from the early to recent time periods was 34.2% to 85.8% (p <0.001). Patient preference/refusal decreased from 29.0% to 8.2% in the early to recent time periods (p <0.001). NAC was associated with improved OS (HR 0.54, p=0.003). Patients with reasons to forgo NAC had worse OS including due to renal dysfunction (HR 1.98, p=0.007), symptoms (HR 2.27, p=0.03), or provider recommendation (HR 2.35, p=0.002). CONCLUSIONS: NAC utilization increased over time with change in estimates before and after exclusion of non-candidates. Renal dysfunction, patient preference, and provider recommendation based on histologic or clinical concerns were primary etiologies for lack of NAC prior to radical cystectomy for muscle-invasive bladder cancer. Fewer patients refused NAC in recent years leading to a potential ceiling for NAC utilization. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e383 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hiten D. Patel More articles by this author Ushasi Naha More articles by this author Victor S. Chen More articles by this author Caitlyn Ko More articles by this author Rachel Yang More articles by this author Aleksander Druck More articles by this author Goran Rac More articles by this author Marcus L. Quek More articles by this author Expand All Advertisement PDF downloadLoading ...