bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of caseload on survival of patients (pts) with localized prostate cancer (PC) after definitive radiation therapy (DRT).
Authors: Sadeghi Sarmad , Lara Primo , Tsao-Wei Denice D. , Aron Monish , Pinski Jacek K. , Quinn David I. , Gill Inderbir , Barzi Afsaneh
Published: February 2020

357

Background: We recently reported a significant all-cause mortality risk reduction associated with higher annual caseload for radical prostatectomy (RP)- (PMID 31398279). Here we explore this relationship in DRT. Methods: National Cancer Database (NCDB) was used to investigate outcomes of DRT in the United States. Beam radiation (BR), radioactive implant (RI) and both (BRRI) were included in analysis. Using overall survival (OS) as primary outcome, the relationship between facility annual caseload (FAC) for all PC pts and facility annual caseload (FARC) for those requiring DRT were examined using Cox model. Four volume groups (VG) were defined as VG1: <50th, VG2: 50th-74th, VG3: 75th-89th and VG4: top 10 percentile of caseload. Results: Between 2004 and 2014, 355,247 pts underwent DRT. At a median follow up of 70.1 (95% CI: 1.0 - 143.1) months (mo), the median OS was 137.3 mo (136.9, 138.1). Using FAC/FARC, 19/14, 27/24, 24/26, and 30/37 % of pts were treated at VG 1 through 4, respectively. For FARC, median OS was 136.8 mo (134.9, 142.2+) for VG1 and 139.7 (137.7, 141.8+) mo for VG4, adjusted hazard ratio (aHR) 1.06 (1.03-1.09), p <0.001. For FAC, median OS was 135.4 (134.1, 138.7) mo for VG1 and not reached for VG4, aHR 1.13 (1.09, 1.16), p <0.001. In subgroups, FARC aHR for VG1 vs VG4 were 1.20 (1.16-1.25) for BR, 0.99 (0.93-1.05) for RI, and 1.15 (1.02-1.31) for BRRI. These numbers for FAC were 1.10 (1.06, 1.14), 1.12 (1.05, 1.19), and 1.24 (1.12, 1.39), respectively. Conclusions: There is a statistically significant OS advantage to DRT at a high annual caseload facility. This effect is more pronounced for BR and is influenced more noticeably by facility all PC caseload rather than DRT.[Table: see text]
Treatment timing in localized high-risk prostate cancer treated with radiation and androgen deprivation therapy.
Authors: Hasan Shaakir , Lazarev Stanislav , Gorovets Daniel , Garg Madhur , Press Robert H. , Choi Isabelle , Simone Charles B.
Published: February 2020

359

Background: Data regarding the impact of overall treatment time in prostate radiotherapy predate the dose escalation era and is absent in high risk disease. We hypothesize that delays in initiating androgen deprivation therapy (ADT) and in completing fractionated radiotherapy (XRT) correlate with worse outcomes in high risk prostate cancer. Methods: Using the National Cancer Database, we identified 9,611 cases of localized high risk prostate cancer, defined as Grade groups 4 and 5 (Gleason 8-10), PSA < 40, and T1-T3N0M0, treated with conventionally fractionated XRT (74-81 Gy, median 78 Gy) and ADT between 2010-2014 with at least 12 months follow-up (median 40). Receiver operating characteristic (ROC) analyses determined a-priori values for days to initiation of treatment (ADT or XRT) and number of “missed” treatment days (number of days beyond the minimum required to complete XRT). Multivariable regression models with propensity matching conveyed the relative impact of these timing parameters on survival. Results: The median time from diagnosis to treatment intervention was 63 days and median missed XRT treatment days was 2.2. The greatest difference in survival was seen when intervention was initiated beyond 74 days from diagnosis (HR=1.21, P=0.045) and when more than 3 XRT treatment days were missed (HR=1.27, P=0.006). Only missed treatment days correlated with survival as a continuous variable (HR=1.028, P<0.001) on multivariable analysis. On a multivariable regression model propensity-matched for missed treatment days, independent predictors for worse survival include older age, higher comorbidity score, dose below 78 Gy, grade group 5, and PSA > 20. Greater than 3 missed treatment days remained an independent predictor; adjusted HR = 1.23 (P=0.002). The lone predictors of missed treatments was African American race (OR=1.21). Conclusions: Although outcomes in prostate cancer are not typically thought to be associated with treatment time, our study, the largest such analysis to date, revealed a strong independent correlation between timely completion of XRT and survival in high risk disease. The association between survival and time to initiating ADT was not nearly as strong.
Impact of overall survival (OS) as a function of facility caseload on feasibility of referral of radical prostatectomy (RP) to higher volume facilities.
Authors: Ahmadi Hamed , Barzi Afsaneh , Lara Primo , Quinn David I. , Klein Eric A. , Gill Inderbir , Sadeghi Sarmad
Published: February 2020

363

Background: We recently reported a significant all-cause mortality (ACM) risk reduction associated with higher annual caseload for RP (PMID 31398279). Four volume groups (VG) were defined as VG1: <50th, VG2: 50th-74th, VG3: 75th-89th and VG4: top 10 percentile of caseload. The adjusted OS difference between VG1 and VG4 at 90th percentile survivorship reached 13.2 months, HR 1.30 (p<0.0001). Here we explore this economics of referral to VG4. Methods: Using a Markov model, we designed 4 scenarios (Sc) where 100,000 RPs were performed. In Sc 1 all RPs were performed at VG1; in Sc 2, 3 & 4, all RPs were performed at VG2, 3 &4 respectively. Subjects were followed for up to 20 years after RP. Survival and costs of care for each Sc were recorded. Probabilities of PSA recurrence (PSAR), development of metastatic disease (Met), cancer specific mortality (CSM) and ACM were adjusted for each VG according to the published HRs. Savings resulting from fewer recurrences, avoidance of salvage radiation therapy (SRT) and management of fewer Met were calculated. Standard discounting at 3% were applied to costs and benefits. Survival benefit and costs savings associated with making referrals from VG1, VG2, or VG3 centers to VG4 center were calculated. Using a willingness to pay (WTP) of $50K per life years gained (LYG), the maximum referral costs (MRC) were calculated. Results: Referral from a VG1 to a VG4 center was associated with highest OS benefit of 720 LYG at 20 years of follow up per 1000 referrals (PKR). Within a WTP of $50K, MRC of up to $37K was cost effective- Table. Conclusions: Given the survival benefit associated with performing RP at facility with high annual caseload, significant resources could be allocated to making a referral possible while still remaining within cost effectiveness boundaries.[Table: see text]
The efficacy and safety of radical prostatectomy and radiotherapy in high-risk prostate cancer: A systematic review and meta-analysis.
Authors: Wang Zhipeng , Ni Yuchao , Chen Junru , Sun Guangxi , Zhang Xingming , Zhao Jinge , Zhu Xudong , Zhang Haoran , Zhu Sha , Dai Jindong , Shen Pengfei , Zeng Hao
Published: February 2020

369

Background: The optimal treatment for patients with high-risk prostate cancer (PCa) remains debate and selection of patients to receive proper therapy is still an unsettled question. This systematical review was to compare the effectiveness of prostatectomy (RP) and radiotherapy (RT) in patients with high risk prostate cancer (PCa) and to select candidates for optimal treatment. Methods: PubMed, EMBASE, and Cochrane Central Register of Controlled Trials were searched for eligible studies. We extracted hazard ratios (HRs) and 95% CI of included studies. The primary outcomes were overall survival (OS) and cancer-specific survival (CSS); the secondary outcomes were biochemical recurrence-free survival (BRFS), metastasis-free survival (MFS) and clinical recurrence-free survival (CRFS). The meta-analysis was performed using Review Manager 5.3. Subgroup analyses were conducted according to GS, T stage and RT types. Quality of life (QOL) was compared with these two treatments. Results: A total of 25 studies were included. Overall, RP showed more survival benefits than RT on CSS (P=0.003) and OS (P=0.002), while RT was associated with a better BRFS (P=0.002) and MFS (P=0.004). Subgroup analyses showed RT was associated with similar or even better survival outcomes compared to RP in patients with high GS, high T stage or received external beam radiotherapy plus brachytherapy (EBRT+BT). As for QOL, RP was associated with poorer urinary and sexual function but better performance in the bowel domain. Conclusions: RP could prolong the survival time of patients with high risk PCa; however, RT could delay disease progression, and combined RT (EBRT+BT) even brought better CSS and similar OS than RP. RT might be the prior choice for patients with high T stage or high GS. RP could lead to poorer urinary and sexual function, while brought better performance in the bowel domain.
Overall survival (OS) in men with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) receiving bicalutamide (BIC) followed by enzalutamide (ENZA) or abiraterone (ABI).
Authors: George Daniel J. , Tagawa Scott T. , Lechpammer Stanislav , Russell Dave , Hong Agnes , Mardekian Jack , Huang Ahong , Wang Li , Janjan Nora , Ramaswamy Krishnan
Published: February 2020

40

Background: The objective of this study was to evaluate real-world OS in men with chemotherapy-naïve mCRPC treated with first-line ENZA or ABI or sequencing to these agents after treatment with BIC ( > 90 d). Methods: A retrospective analysis was performed using the Veterans Health Administration (VA) database. Men with mCRPC and ≥ 1 pharmacy claim for ABI or ENZA (1st claim date = index date) following surgical or medical castration and with no chemotherapy treatment 12 months pre-index date were identified from 01APR2014 to 31MAR2017. Men had continuous VA enrollment for ≥ 12 months pre- index date and were followed until death or study end. Cox proportional hazards regression models examined the impact of treatment on OS, and the impact of first using BIC ( > 90 d) vs first-line use of ABI and ENZA on OS. Adjusted Kaplan-Meier analysis was conducted to graphically describe OS. Results: This study included 1229 ENZA- and 1945 ABI-treated men with mCRPC with mean ages of 74 and 73 y, respectively. Median follow‐up was 548 and 572 d, and median OS was 892 and 786 d, respectively. ENZA and ABI were first-line treatment in 1068 and 1628 men, but BIC ( > 90 d) was first used before sequencing to ENZA or ABI in 161 and 317 men, respectively. Median duration of BIC treatment was similar in men subsequently treated with ENZA or ABI (251 v 246 d, respectively). Compared with first-line ABI, use of ABI following BIC led to shorter OS (hazard ratio [HR] = 1.30; 95% CI 1.11 -1.52). Compared with first-line ENZA, use of ENZA following BIC resulted in a nonsignificant effect on OS (HR = 0.92; 95% CI 0.72-1.19). In the Cox analysis, ENZA-treated men had longer OS compared with ABI-treated men (HR = 0.84; 95% CI 0.76-0.94). Conclusions: Use of BIC ( > 90 d) before sequencing to ENZA did not negatively effect OS, however BIC before ABI impacted OS adversely in men with chemotherapy-naïve mCRPC. There are significant differences in OS favoring ENZA compared with ABI regardless of prior BIC. Real-world observational data are nonrandomized, and markers for disease severity/volume are not available in the claims database. Further research is required to confirm these findings.
Thoracic radiotherapy for renal cell carcinoma metastases.
Authors: Stewart Glenn , Breen William , Stish Brad J. , Park Sean Sunghun , Olivier Kenneth R. , Costello Brian Addis
Published: February 2020

409

Background: For patients with metastatic renal cell carcinoma (RCC), metastasis-directed local therapies can delay progression and need to initiate/switch systemic therapy. We examined our experience treating lung or mediastinal metastases from RCC with radiotherapy (RT). Methods: We reviewed patients with lung or mediastinal metastases from RCC treated with RT. Overall survival (OS) and local control (LC) was measured from the start of RT using the Kaplan-Meier method. Results: Seventy-one patients were treated with RT for 89 lung or mediastinal metastases. Median follow-up was 2.0 years (range 0.02-11.4 years) after RT for surviving patients. Most patients were male (n=53, 74.6%). Median age was 58.4 years at initial diagnosis. Histology was most frequently clear cell carcinoma (n=62, 89.9%). At the time of treatment, 18 patients (25.4%) had 1-3 metastases, and the remainder (74.6%) had 4 or more metastases. Forty-one patients (57.5%) received systemic therapy prior to thoracic radiation. Initial systemic therapy was most commonly sunitinib (45%) or pazopanib (32.5%). Median time from starting systemic therapy to initiation of radiation was 2.0 years. Fifty-eight lung metastases and 31 mediastinal metastases were treated with a median 5 fractions (range 1-40), to a median total dose of 4800 cGy (range 400-7000), with a median fraction size of 500 cGy (range 150-2000). Thirty-three lesions were treated with concurrent systemic therapy, which was most commonly nivolumab (n=16). Of 89 treated lesions, 11 (12%) had local tumor recurrence, at a median of 1.6 years (range 0.4-2.9 years) after initiation of radiation. 1, 3, and 5 year MC (metastasis control) were 96.6%, 83.5% and 67.9%, respectively. Nine patients were treated with radiation in order to delay initiation of systemic therapy. Of these, 3 eventually received systemic therapy, initiated at a median 2.5 years after radiation. At last follow-up, 41 patients (57.7%) had died. Median OS was 2.6 years. Survival at 1, 3, and 5 years was 65.2%, 48.5%, and 38%, respectively. Conclusions: Radiation achieves high metastasis control rates for lung and mediastinal metastases from RCC, potentially delaying the need for systemic therapy.
Serum microRNA-371a-3p levels to predict viable germ cell tumor in chemotherapy-naïve patients undergoing retroperitoneal lymph node dissection.
Authors: Singla Nirmish , Lafin John T. , Woldu Solomon L. , Lotan Yair , Lewis Cheryl , Majmudar Kuntal , Savalyeva Anna , Kenigsberg Alexander P. , Kapur Payal , Margulis Vitaly , Strand Douglas , Murray Matthew , Amatruda James F. , Bagrodia Aditya
Published: February 2020

417

Background: Serum microRNAs are candidate biomarkers for diagnosing and monitoring germ cell tumors (GCTs). The ability of miRNA to inform treatment in low-stage chemotherapy-naïve patients is unexplored. We sought to evaluate the performance characteristics of serum miRNA levels to predict viable GCT in chemotherapy-naïve patients undergoing primary retroperitoneal lymph node dissection (RPLND). Methods: We prospectively collected presurgical serum samples and clinicopathologic characteristics from consecutive chemotherapy-naïve GCT patients undergoing primary RPLND from 2016-2019. Serum miRNAs (-367-3p/-371a-3p/-372-3p/-373-3p/-375) were isolated and quantified. RPLND histopathology was categorized as benign, viable GCT, or teratoma; miRNA levels were compared among groups. Performance characteristics, including receiver operating characteristic (ROC) curves, assessed the discriminative ability of each miRNA signature to predict viable GCT. Results: 24 patients with stage I-II GCT underwent RPLND, revealing viable GCT in 11 (46%), teratoma in 3 (13%), and benign pathology in 10 (42%) patients. miR-371a-3p was the most discriminatory serum miRNA for viable GCT, exhibiting ~13,000-fold increase in expression over teratoma or benign pathology. On ROC analysis, miR-371a-3p had AUC = 0.965, with sensitivity and specificity of 100% and 92%, respectively. The AUC for other serum miRNAs in predicting viable GCT were 0.874 (miR-367-3p), 0.846 (miR-372-3p), and 0.720 (miR-373-3p). These serum miRNAs were not predictive of pure teratoma. Potential limitations include small cohort size and no post-RPLND sera for comparison. Conclusions: Serum miRNAs, particularly miR-371a-3p, can accurately differentiate small-volume viable GCT from benign processes or teratoma in patients with negative serum tumor markers undergoing primary RPLND. If validated, these data suggest a basis to implement precision medicine strategies in treating patients with early-stage GCT.
Clinicopathologic predictors of outcomes in children with stage I germ cell tumors: A pooled post hoc analysis of trials from the Children’s Oncology Group.
Authors: Singla Shyamli , Wong Justin , Singla Nirmish , Krailo Mark D. , Huang Li , Shaikh Furqan , Billmire Deborah F. , Rescorla Frederick J. , Ross Jonathan H. , Dicken Bryan J. , Amatruda James F. , Frazier A. Lindsay , Bagrodia Aditya
Published: February 2020

418

Background: Patients with clinical stage I (CS I: cN0M0) germ cell tumors (GCT) exhibit favorable oncologic outcomes. While prognostic features can help inform treatment in adults with CS I GCT, we lack reliable means to predict relapse among pediatric patients. We sought to identify predictors of relapse in children with CS I GCT. Methods: We performed a pooled post hoc analysis on pediatric CS I GCT patients enrolled in 3 prospective trials: INT-0097 (phase II), INT-0106 (phase III), and AGCT0132 (phase III). Pathology was centrally reviewed. Patient demographics, pT stage, serum tumor markers, margin status, histology, relapse, and survival were compiled. Cox regression analyses were used to identify predictors of outcomes. Results: 88 patients were identified with histologic data available. Most patients were pT1-2 stage. Yolk sac tumor was present in 75%, while 16% had embryonal carcinoma, and 9% had choriocarcinoma. When evaluable, lymphovascular invasion (LVI) was present in 36/66 (55%) of patients. Over a median follow-up of 5.0 years, no patients died and 24 patients (27%) relapsed (median relapse-free survival not reached). Predictors of relapse included presence of choriocarcinoma (HR 4.3, p=0.004), embryonal carcinoma (HR 3.8, p=0.002), pT3 stage (HR 6.9, p=0.027), and age >12 years (HR 3.1, p=0.011). LVI (HR 2.4, p=0.072), serum tumor markers, and dominant tumor size did not reach significance. Pediatric CS I GCT patients exhibit remarkable 5-year survival. Conclusions: Using combined data from multiple prospective trials, our study identifies clinicopathologic features that predict relapse and potentially inform personalized treatment for these patients.
Differential expression of melanoma-associated antigen A3/6 and associated immune molecules prior to and post treatment with immune checkpoint inhibitors (ICI) in patients with mUC.
Authors: Faiena Izak , Funt Samuel Aaron , Astrow Stephanie H. , Dorff Tanya B. , Adhikary Sabina , Gorgan Tristan , Rosenberg Jonathan E. , Elashoff David , Pantuck Allan J. , Drakaki Alexandra
Published: February 2020

433

Background: MAGE is an attractive target for IO given its expression restricted to carcinomas and the testes. Engineered T-cell targeting MAGE A3/6 has shown promise. However, successful treatment is dependent on circumventing the potentially hostile immune microenvironment in metastatic tumors. In this study, we aim to assess the effects of ICI on the immune microenvironment in patients who progressed on ICI. Methods: We obtained FFPE tissue from 16 patients with mUC across 3 institutions. Samples from the primary or metastatic tumor prior to treatment with PD1/PD-L1 inhibitors (ICI) were paired with samples from metastatic sites post-treatment. Differential mRNA expression was assessed using NanoString PanCancerIO360 panel for the main genes of interest ( MAGEA3/6, CD274, HLADP, HLAA, B2M and PDCD1) in addition to immune profiling of the tumor samples. Also, IHC was done on the paired samples to assess DE for the genes of interest using an H-score analyzed via the paired T-test. p-values <0.05 were considered significant and FDR corrected. Results: MAGEA3/A6 mRNA expression was unchanged in the post-treatment samples. In addition, time to progression was not influenced by the mRNA DE. Similarly, IHC expression was not decreased post-treatment. The other genes of interest were also similarly expressed pre and post treatment. Immune cell localization genes CPA3,TPSAB1/B2, HDC, MS4A2 were significantly downregulated post treatment. Genes implicated in cancer cell killing ( MX1,KIT) were similarly downegulated whereas CD276, TLR1 were upregulated. Expression in the post treatment tissue of PTPN1, CES3, ACVR1C, and BAD were associated with increased progression. LY9, PTPRC, CTLA4, HLA-DMA, IL10RA, HLA-DMB, ITGAL, CD48 were associated with decreased progression. Conclusions: Prior ICI treatment does not decrease expression of MAGE A3/6, suggesting that salvage treatments targeting this antigen remain a viable strategy. Suggestion of immune microenvironment alterations were also noted. More work is necessary to understanding the tumor microenvironment in order to design rational treatment combinations and sequences.
Impact of 18FDG-PET CT in the management of invasive bladder cancer.
Authors: Bertolaso Pauline , Brouste Véronique , Cazeau Anne Laure , De Clermont-Gallerande Henri , Bladou Franck , Cabart Mathilde , Ravaud Alain , Gross-Goupil Marine
Published: February 2020

444

Background: Guidelines do not recommend FDG-Positron Emission Tomography (PET) Computed Tomography (CT) for the staging of Muscle Invasive Bladder Cancer (MIBC), but rather CT scan for lymph node (LN) and metastatic staging, despite its low accuracy. We performed a retrospective analysis of patients (pts) with MIBC who had a FDG-PET CT for staging, indicated by multidisciplinary team, in two centers, and analyzed its utility in this setting. Methods: All pts who had a FDG-PET CT performed at the time of diagnosis of MIBC from 01/2005 to 12/2017 in Bordeaux (Bergonie Institute and University Hospital) were retrospectively reviewed. Nodal and metastatic staging on CT and FDG-PET CT were done independently according to the 8th TNM classification. The aims of the study were to evaluate the accuracy of the FDG-PET CT for LN staging and to determine the rate of treatment modification (neoadjuvant chemotherapy for curative intent, no surgery for metastatic disease), according to FDG-PET CT results. Results: Among the 130 pts included, with a median age of 65 years, 74% were considered free from nodal metastasis (N0) by CT whereas only 44% were N0 from FDG-PET CT. Based on CT results, 88% of pts were free from distant metastasis (M0) but only 75% were classified M0, on FDG-PET CT. Accuracy of LN staging for CT and FDG-PET CT at initial diagnosis were analyzed for 85 pts (including 70 pts treated with neoadjuvant chemotherapy) and compared to pathological examination of resected LN. Sensitivity of FDG-PET CT was better than CT (respectively 80.8% versus 26.9%) but the specificity was low (respectively 54.2% versus 83.1%). Youden index was better for FDG-PET CT (0.35; 0.1 for CT), being more accurate for determining LN staging of MIBC. FDG-PET CT findings allowed a treatment decision modification in 34/130 pts (26.1%): therapeutic intensification in 12 pts (9.2%), including surgery not previously indicated, modified radiotherapy; or de-escalation in 22 pts (16.9%), mostly avoiding surgery. Conclusions: FDG-PET CT is more sensitive to detect LN involvement at initial diagnosis of MIBC than standard CT scan. Moreover, in the present study, treatment decisions were modified, according to FDG-PET CT results, in a quarter of pts according to LN and distant metastatic staging.
Patient and caregiver benefit-risk preferences for treatment in advanced urothelial carcinoma.
Authors: Apolo Andrea B. , Cambron-Mellott M. Janelle , Will Oliver , Seal Brian S. , Maculaitis Martine C. , Bernstein Andrew , Epperson Megan , Jeffress Mara Lisa , Doleh Yunes
Published: February 2020

448

Background: Checkpoint blockade therapy has demonstrated improved survival in second-line urothelial carcinoma and is also active as first-line (1L) therapy in locally advanced / metastatic urothelial carcinoma (mUC) patients (PTs) who are cisplatin-ineligible / PD-L1 high or platinum-ineligible regardless of PD-L1 level. This study quantified trade-offs between efficacy and adverse events (AEs) associated with 1L treatments for mUC that PTs and caregivers (CGs) are willing to make. Methods: PTs with mUC and CGs were recruited via advocacy groups to complete a cross-sectional online survey assessing treatment preferences with a discrete choice experiment (DCE) employing descriptive language. In a series of tasks, PTs and CGs chose their preferred option from two alternative treatment profiles varying on six select attributes: overall survival (OS), progression-free survival (PFS), and AEs including: all grades (AG) neuropathy; and G3/4 nausea/vomiting, fatigue, and diarrhea. Hierarchical Bayesian modelling estimated preference weights for each attribute level. Results: PTs (N=152) had a mean age of 60 years; 68% had Stage 4 UC. CGs (N=151) had a mean age of 53 years and cared for PTs with a mean age of 62; most CGs (67%) cared for a PT with Stage 4 UC. While attributes had the same rank order of importance for both PTs and CGs, improving OS from 10 to 22 months was 31% more important than improving PFS from 2 to 10 months for PTs, whereas OS and PFS were more similarly valued by CGs. CGs placed less importance than PTs on OS relative to the importance of G3/4 nausea/vomiting, G3/4 diarrhea, and AG neuropathy (all P<0.01). Despite these differences, OS was at least twice as important than reduction in AEs for both cohorts. To accept increases in G3/4 nausea/vomiting by 21%, G3/4 fatigue by 23%, G3/4 diarrhea by 7%, and AG neuropathy by 5%, OS would need to improve by 2.2, 2.3, 1.2, and 0.5 months (PTs) and 6.6, 5.5, 3.0, and 1.1 months (CGs), respectively. Conclusions: Trade-offs made between efficacy and specific AEs for mUC are nuanced between PTs and CGs, with CGs desiring larger OS benefits to accept higher AE risk. These findings suggest a need for deeper discussions between PTs, CGs and physicians about treatment decisions.
Intravesical irrigation to prevent early bladder recurrence in patients undergoing laparoscopic radical nephroureterectomy for upper urinary tract cancer.
Authors: Tamura Takaaki , Sakamoto Shinichi , Yamamoto Satoshi , Maimaiti Maihulan , Imamura Yusuke , Komiya Akira , Nagata Maki , Ichikawa Tomohiko
Published: February 2020

454

Background: The bladder carcinoma recurrence rate after nephroureterectomy is known to be high. Here we studied the clinical benefit of Intravesical irrigation during laparoscopic radical nephroureterectomy in upper urinary tract cancer (UUTUC) patients. Methods: This study enrolled 197 UUTUC patients who receive laparoscopic radical nephroureterectomy at Chiba University Hospital and Yokohama Rosai Hospital between 2001 and 2019. Association between the various clinical factors and postoperative recurrence rates within two years were statistically analyzed. Intravesical irrigation was carried out only during surgery and by using distilled water or saline. Results: Bladder recurrence was confirmed for 79 of the 197 patients. Irrigation was carried out in 75 cases (distilled water, 49 cases; saline, 26 cases). Tumor grade (G1-2 vs G3; p=0.0029) and irrigation (with vs. without; p<0.0001) were related to bladder recurrence on univariate analysis. Even on multivariate analysis, both tumor grade (p=0.0094) and irrigation ( p<0.0001) remained as independent factors. Comparison between the irrigation and non-irrigation groups showed that bladder recurrence rates were significantly lower in the irrigation groups (irrigation group vs non-irrigation group: 29.3% vs 46.7%, p=0.015). There was no prognostic difference between the type of irrigation (distilled water vs saline, p=0.177). Conclusions: Intravesical irrigation prevented early bladder recurrence in patients undergoing radical nephroureterectomy for UUTUC. [Table: see text]
Cancer stage and quality of life in bladder cancer.
Authors: McCloskey Hannah , McCabe Sean , Gessner Kathryn , Filippou Pauline , Hamad Judy , Deal Allison Mary , Smith Angela , Gore John L.
Published: February 2020

466

Background: Bladder cancer requires treatment and surveillance which varies in intensity by disease stage. Our objective was to evaluate stage-specific differences in generic and bladder cancer-specific quality of life (QOL) among a large bladder cancer cohort. Methods: We performed a cross-sectional survey of bladder cancer patients using the Bladder Cancer Advocacy Network Patient Survey Network and Inspire platforms to determine generic and bladder cancer-specific QOL using the EORTC QLQ-C30 and Bladder Cancer Index. Patients were also queried regarding demographic, socioeconomic and clinical characteristics. We present descriptive statistics and a multiple linear regression model to identify factors independently associated with QOL domain score. Results: 972 respondents self-identified as patients with bladder cancer. Among respondents, 41% were female and 97% were white. The mean age was 67.6 years (range 29 to 93 years). Patients identified as having non-muscle-invasive bladder cancer (NMIBC, n=578 [63%]), MIBC (n=270, 30%), and metastatic bladder cancer (n=63, 7%). On bivariable analysis ( Table), lower stage was significantly associated with better generic (p<0.01) and bladder-cancer specific QOL (p<0.01). This associated persisted on multivariable analysis adjusted for age, sex, race, years since diagnosis, and comorbidity (p<0.01 for generic, urinary, sexual, and bowel QOL). Conclusions: Disease stage significantly impacts generic and bladder cancer-specific QOL among bladder cancer survivors. Differential impact by stage may be important for the development of tailored interventions to improve QOL for bladder cancer patients. [Table: see text]
Resource utilization analysis of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (DD-MVAC) versus gemcitabine-cisplatin (GC) as neoadjuvant chemotherapy (NAC) for muscle invasive bladder cancer (MIBC).
Authors: Montazeri Kamaneh , Dranitsaris George , Curran Catherine , Thomas Jonathan David , Ingham Matthew D. , Preston Mark A. , Steele Graeme S. , Kilbridge Kerry L. , Wei Xiao X. , McGregor Bradley Alexander , Mossanen Matthew , Sonpavde Guru
Published: February 2020

474

Background: DD-MVAC and GC are commonly used NAC regimens for MIBC. While efficacy across studies appears similar, the resource utilization burdens have not been compared. Methods: We assessed the resource utilization and cost effectiveness of NAC with GC vs DD-MVAC for MIBC patients (pts) treated at Dana-Farber. Data on chemotherapy administered, supportive medications, relevant procedures, hospitalizations, clinic, infusion, and emergency room visits were collected retrospectively. Results: 147 patients were included, 51 in the DD-MVAC and 86 in the GC group. The two groups had similar baseline pt characteristics except lower mean age (59 vs 67 years, p<0.001) and higher proportion of ECOG-PS=0 (96.1% vs 60.5%, p<0.001) in the DD-MVAC group. The mean cumulative cisplatin dosages were similar (DD-MVAC=284 mg/m2, GC= 257 mg/m3). The DD-MVAC group exhibited a greater use of G-CSF analogues (100% vs 32.6%, p < 0.001), central line placement (28.6% vs 11.8%, p = 0.017), infusion visits/pt (12 vs 8), ER visits (35% vs 18%, p = 0.048), and cardiac imaging (0.98 vs 0.58/pt, p<0.001). Patients receiving GC were more likely to experience delayed chemotherapy cycles (30.2% vs 9.8%, p = 0.008) and required more frequent clinic visits (9 vs 5/pt). The frequency and duration of hospitalization (23.6% vs 13.7% and 0.88 vs 0.49 days/pt, p = 0.46) and rate of grade ≥3 toxicities (32.6% vs 45.1%, p = 0.18) were numerically but not statistically different between the GC and DD-MVAC group. Cost efficacy analysis is pending and will be presented. Conclusions: DD-MVAC and GC exhibit different characteristics in terms of resource utilization as NAC for MIBC. Importantly, excess resource utilization did not clearly favor one of the regimens, although the DD-MVAC group was younger with better ECOG-PS. Given that similar overall delivery of cumulative cisplatin dosage was feasible with both regimens, the values and costs affixed to different resources may impact the selection of DD-MVAC vs GC in different regions of the world.
Pembrolizumab with chemoradiotherapy as treatment for muscle invasive bladder cancer: A planned interim analysis of safety and efficacy of the PCR-MIB phase II clinical trial (ANZUP 1502).
Authors: Weickhardt Andrew James , Foroudi Farshad , Lawrentschuk Nathan , Galleta Laura , Seegum Amanda , Herschtal Alan , Link Emma , McJannett Margaret Mary , Liow Elizabeth Chien Hern , Grimison Peter S. , Zhang Alison Yan , Patanjali NItya , Ng Siobhan , Goodwin Robert , Tang Colin , Chen Colin , Hovey Elizabeth J. , Hruby George , Guminski Alexander David , Davis Ian D. ,   Australia and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP)
Published: February 2020

485

Background: In patients (pts) with muscle invasive bladder (MIBC) suitable for curative definitive chemoradiotherapy (CRT), we hypothesise that the addition of pembrolizumab may be safe and improve efficacy. A pre-planned safety analysis was performed after the first 10 of planned 30 pts were enrolled and completed treatment. Methods: Patients with maximally resected non-metastatic MIBC and ECOG 0-1, who desire bladder preservation or are ineligible for cystectomy were treated with 64Gy in 32 daily radiation fractions to the whole bladder alone over 6.5 weeks in combination with 6 concurrent doses of weekly cisplatin at 35mg/m2 IV. Pembrolizumab was commenced concurrently with radiation and given flat-dose 200mg IV q21 days for 7 doses. Surveillance cystoscopy, urine cytology and CT chest-abdomen-pelvis were performed 12 & 24 weeks post CRT. The primary endpoint is feasibility, defined by a satisfactory low rate of unacceptable toxicity of a) G3-4 non-urinary adverse events (AE) or b) failure of completion of planned CRT according to defined parameters. Secondary endpoints include complete cystoscopic response without metastatic disease at 12 & 24 weeks, loco-regional PFS, metastatic DFS, and overall survival. A 2-stage design was planned, with accrual to be halted if >5 of the first 10 pts experienced unacceptable toxicity up to 12 weeks post treatment. Results: All 10 pts completed the course of CRT and pembrolizumab without alteration in radiation dose or schedule. 1 patient had a dose of cisplatin withheld. 4/10 pts experienced G3-4 non-urinary adverse events within 12 weeks of completing treatment. One immune related AE interrupted pembrolizumab delivery (G2 nephritis). By week 24, 9/10 pts achieved a complete cystoscopic response to treatment post CRT and were free of distant metastatic disease. Conclusions: Interim results indicate that pembrolizumab and CRT shows satisfactory safety, and promising efficacy. There were no unexpected safety signals. Follow up of these and additional pts will better define the efficacy and safety of the combination. Enrolment is ongoing with 20 pts recruited out of a planned total of 30. Clinical trial information: NCT02662062.
Association of area social determinants of health with prostate cancer mortality.
Authors: Henegan John Clark
Published: February 2020

49

Background: Validated clinical nomograms prognosticate survival for men with metastatic castrate resistant prostate cancer. In addition to clinical factors, significant disparities in survival in advanced prostate cancer are associated with social determinants of health (SDH). We performed a study of county-level data to evaluate SDH associated with prostate cancer mortality. Methods: County-level data regarding prostate cancer crude mortality rate (dependent variable) and crude incidence rate was extracted from the ten states with information at www.cancer-rates.info for the years 2006-2015. The 2014 Robert Wood Johnson County Health Rankings dataset was used for information regarding county demographics, clinical information, and available SDH(independent variables). A correlation analysis was performed between independent variables and only one variable was analyzed if a criterion of a correlation of ≥ 0.65 was present. All counties with ≤ 30 death in the specified time period or with incomplete independent variable information were excluded from analysis. A univariate linear regression analysis was performed. All individual independent variables with a statistically significant (p ≤ 0.05) association with the dependent variable were included in a multivariate linear regression model. Results: 275 counties were available for analysis. On multivariate analysis, independent variables statistically significantly associated with the crude rate of prostate cancer mortality included household income and the percentage of: a population ≥ 65 years of age, the population < 18 years of age, African Americans, the population classified as rural, women reporting a screening mammography, smokers, and uninsured patients. The multivariate model was associated with a R-squared of 0.62. Conclusions: In addition to differences in baseline clinical factors, prostate cancer quality metrics that evaluate survival should account SDH. Information from this study, if validated in subsequent work, could be used to develop a stepwise model to adjust for both clinical factors and SDH when measuring survival as a quality metric.
Analysis of clinical outcomes according to response status in prospective clinical trials of atezolizumab (atezo) in pretreated locally advanced/metastatic urothelial carcinoma (mUC).
Authors: Bedke Jens , Merseburger Axel Stuart , Loriot Yohann , Castellano Daniel , Choy Ernest , Duran Ignacio , Rosenberg Jonathan E. , Petrylak Daniel Peter , Dreicer Robert , Perez-Gracia Jose Luis , Hoffman-Censits Jean H. , Van Der Heijden Michiel Simon , Degaonkar Viraj , Thiebach Lars , de Ducla Sabine , Fear Simon , Powles Thomas , Sternberg Cora N.
Published: February 2020

492

Background: Atezo is an approved therapy for mUC based on the IMvigor210 (IM210) and IMvigor211 (IM211) phase 2 and 3 trials. The single-arm phase 3b SAUL study in a broader patient (pt) population showed consistent efficacy and safety. The value of complete response to immunotherapy is well recognized, but less is known about the benefit of partial response (PR) or stable disease (SD). We performed post hoc analyses of outcomes in pts with PR/SD in atezo trials. Methods: Pts with mUC received atezo 1200 mg q3w until disease progression (PD) or unacceptable toxicity. Baseline characteristics, efficacy and safety were analyzed in pts achieving PR or SD in IM210 cohort 2 (2nd line), IM211 (atezo and chemotherapy [CT] arms analyzed separately) and SAUL. Data cutoffs were 5/5/15, 3/13/17 and 9/16/18, respectively. Results: The analysis population included 229 PR and 583 SD pts (183 and 421, respectively, treated with atezo); ~40% of pts had 0 Bellmunt risk factors. Baseline characteristics were generally similar between trials. PD-L1 IC 2/3 was more common in PR than SD pts in atezo-treated (41% vs 26%) and CT-treated (37% vs 23%) pts. Median time to best response (PR or SD) was 2.1 mo across trials and treatments. In PR pts, disease control (DC) and overall survival (OS) durations were longer with atezo than CT (Table). Durations of DC and OS were shorter in SD than PR pts; OS was numerically longer with atezo than with CT in the SD population. Presence of more Bellmunt risk factors was associated with worse OS with CT but showed only a weak (SD pts) or no (PR pts) association in atezo-treated pts. Conclusions: Pts achieving a PR or SD have meaningful OS expectancy; pts with PR on atezo have sustained DC. Clinical trial information: NCT02108652 ; NCT02302807 ; NCT02928406 . [Table: see text]
Efficacy of immune checkpoint inhibitors (ICIs) in rare histological variants of bladder cancer.
Authors: Philip Errol James , Wright Francis , Kim Daniel Myung , Kwon Daniel , Ho Hansen , Ho Son , Cheung Edna , Chan Emily , Porten Sima P. , Wong Anthony C. , Borno Hala , Desai Arpita , Chou Jonathan , Oh David Yoonsuk , Aggarwal Rahul Raj , Fong Lawrence , Small Eric Jay , Friedlander Terence W. , Koshkin Vadim S
Published: February 2020

502

Background: ICIs are effective agents in metastatic urothelial carcinoma in both platinum-refractory and frontline settings. Responses in patients (pts) with non-urothelial histological variants are not well defined. Methods: We undertook a retrospective analysis of pts with metastatic bladder cancer treated with ICI monotherapy. Pts were identified as having a variant histology if any non-urothelial component was present. Fisher’s exact test was used to assess differences in ORR by histology. Results: Between 12/2014 and 10/2019, 102 pts received ICI monotherapy, of whom 93 were evaluable for response and 33 had variant histology. Median age was 70 yrs, 66% were male, 50% received prior platinum-based chemotherapy. Most received pembrolizumab (66%) or atezolizumab (33%). ORR in the overall cohort was 26% (15% PR, 11% CR), with 12% having SD. Histology breakdown and responses are shown in Table. Although twice as many responses were seen in urothelial pts as in pts with variant histologies (ORR 31% vs 15%), this difference was non-significant (p = 0.14). Conclusions: In this large single-institution cohort, ORR in a heterogeneous population of bladder cancer pts was consistent with data previously reported in clinical trials. Pts with variant histologies had numerically lower responses relative to pure urothelial histology, but this difference was not statistically significant. Clinical benefit to ICIs was seen across multiple variant histologies suggesting potential efficacy in this patient population that should be confirmed prospectively.[Table: see text]
Safety and efficacy of neoadjuvant chemotherapy (NAC) with accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (aMVAC) in patients (pts) with muscle invasive bladder cancer (MIBC) as a function of age.
Authors: Zibelman Matthew R. , Lewis Bianca , Ross Eric A. , Anari Fern , Ghatalia Pooja , Plimack Elizabeth R. , Geynisman Daniel M.
Published: February 2020

506

Background: NAC improves survival in pts with MIBC eligible to receive cisplatin-based chemotherapy. Prospective data supports the use of aMVAC, however concerns about toxicity limits usage compared to gemcitabine and cisplatin, especially in the elderly. We investigated the safety and efficacy of aMVAC as a function of age. Methods: We conducted a retrospective analysis of pts with MIBC at Fox Chase Cancer Center who received NAC with aMVAC from 2008-2017. Pts were excluded for non-urothelial histology, non-muscle-invasive or primary upper tract disease, or if final pathology was not available. Clinicopathologic variables were extracted from charts and pts were grouped into 3 cohorts by age ( < 65, 65-74, ≥75). Associations between age group (gp) and categorical/continuous factors were evaluated using Fisher’s exact/Wilcoxon rank sum tests. Results: A total of 90 pts ( < 65: 40; 65-74: 28; ≥75: 22) were evaluable for safety and 84 for efficacy. The majority of pts were male (72%), PS 0 ( < 65: 85%; 65-74: 85%; ≥75: 68%) and Caucasian (90%). Baseline clinical staging was cT2 in 50%, cT3 in 27% and > cT3 in 14%, with 9% lacking clinical staging. Mean number of aMVAC cycles delivered was numerically similar between age gps, though statistically different (3.1 v 2.8 v 2.6; p = 0.01). There were no statistically significant differences in dose reductions, treatment interruptions, or time to surgery (10.7 v 10.7 v 10.1 wks, p = 0.91) by age. Grade ≥3 AEs were most frequent in the youngest age gp (14.4% v 2.2% v 8.9%, p = 0.018). Split-dose cisplatin was increasingly used in advanced age (2.5% v 17.9% v 31.8%, p = 0.003). Although glomerular filtration rate (GFR) at baseline inversely correlated with age (105 v 93 v 63 ml/min, p < 0.0001), there was no difference in % GFR decline at 90 days or 1 year. The downstaging rate to < pT2N0 disease was similar in all age gps (41.0% v 29.6% v 38.9%; p = 0.41). At median follow-up of 20 months, recurrence rates were 30.0% v 25.9% v 28.6% (p = 0.95). Conclusions: NAC with aMVAC yields similar safety and efficacy outcomes regardless of age, thus age should not be a factor in determining treatment eligibility.
Results after two years of follow up after intravesical thermochemotherapy with heated mitomycin 40 in patients with high-risk superficial bladder cancer.
Authors: Voegeli Thomas Alexander , Frank Eric , Bach Christian , Nzeh Catejan
Published: February 2020

512

Background: Standard management of high risk TCC is either BCG or radical cystectomy, alternative treatment options are limited. It is known that the anti-tumor effect of heated mitomycin is 10 fold higher than at room temperature, which is the standard of intravesical therapy. We herein report the first 2 year follow up (FU) after intravesical therapy with heated mitomycin in a cohort of patients with high risk superficial bladder cancer (TCC). Methods: Treatment was performed for 1 hour with machine bladder irrigation (COMBAT) which maintaines temperature of mitomycin (40 mg) exactly at 43 C. Patients underwent therapy with a 6 week course of weekly treatment and were than followed by cystoscopy every 3 month and if necessary biopsy. Results: We identified 62 patients out of a total group of 108 patients who met the inclusion criteria for high risk TCC according to the EAU Guidelines and who got the complete 6 courses of treatment. 2 were lost of follow up, 1 died due to cardiac problems and 1 from metastatic prostate carcinoma. The remaining 58 patients had a mean FU of 26 month (16-54 m) and included 20 non-responders to BCG. 48/58 patients had CIS or pT1 Tumors or both, 10 patients had pTa+CIS. There were 5 recurrences, all superficial stage pTa, one in the rigth ureter, all could be managed without cystectomy. 8 patients had progressive or recurrent CIS/pT1 or were progressive to pT2 after therapy and underwent cystectomy. Conclusions: In this high risk cohort of 58 patients with a high rate of BCG non-responders only 8 patients had to undergo cystectomy during a 2 year follow up. Intravesical therapy with heated mitomycin is safe and well tolerated and may be an additional alternative treatment before cystectomy is performed in high risk patients with high risk TCC or BCG non responders.