bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing focality of dominant tumor on serial biopsy in an active surveillance cohort: Implications for focal therapy.
Authors: Fasulo Vittorio , Cowan Janet E. , Washington Samuel L. , Nguyen Hao Gia , Shinohara Katsuto , Casale Paolo , Carroll Peter
Published: February 2020

352

Background: Focal therapy (FT) has been proposed as an alternative to active surveillance (AS) for men with low/intermediate risk prostate cancer (PCa). We aim to understand progression within and outside the dominant tumor (DT) in terms of changes in focality, tumor volume and histologic grading on serial biopsy of the prostate (Bx) to identify reasonable candidates for FT. Methods: Men enrolled on AS at UCSF between 1996 and 2017 with low\intermediate risk PCa at diagnosis (PSA < 20ng\ml, stage cT1\2, Gleason score (GS) ≤3+4) and at least 1 Bx after diagnosis were included. All Bx were systematic. Changes in Bx laterality and/or grade were assessed over time. DT was defined as the tumor with highest GS and size on Bx confined to 1 or 2 contiguous sextants. Those with unifocal disease (Un), multifocal in contiguous sextants (Mc), or a small volume of GS 3+3 on the contralateral side were considered candidates for FT. Results: Among 1272 men, mean age was 62 years, median PSA was 5.42 ng\ml and median follow up was 78 months (IQR 46-108). Median number of Bx was 3 (min 2, max 12) and 18% had >5 Bx. At diagnosis 90% and 10% of patients had GS 3+3 and 3+4 disease respectively. At first surveillance Bx (fsBX) findings were negative in 20%, unchanged in 56% and upgraded in 24%. Findings were similar at the following 3 Bx. Across all biopsies 27% were negative and 7-year upgrade-free survival was 39%. At diagnosis, 88% of tumors were in locations viable for FT (50% Un and 38% Mc versus 12% multifocal in non-contiguous sextants (Mn-c)). At fsBX, 21% of Bx were negative and 85% of the remainder were viable for FT (29% Un and 56% Mc versus 15% Mn-c). Across all Bx DT remained stable in 592 (47%), changed prostate side or expanded to bilateral in 128 (10%), upgraded on the original dominant side in 407 (32%), and upgraded on the opposite side in 145 (11%). Of those upgraded on the non-dominant side, 74% were GS 3+4, 21% were GS 4+3 and 5% were GS ≥4+4. Conclusions: On serial biopsy, tumor location remains relatively stable and significant changes in grade and/or volume occur in the DT. A low percentage of patients show significant progression outside the DT. Such information is relevant when considering FT in this patient population.
Association of salvage cryoablation with decreased utilization of androgen deprivation therapy for recurrent prostate cancer after radiotherapy.
Authors: Parsons J Kellogg , Cotta Brittney , Rose Brent , Murphy James Don , Ryan Stephen T.
Published: February 2020

358

Background: Cryoablation is an established treatment for recurrent prostate cancer after primary radiotherapy, but outcomes data are mostly limited to uncontrolled case series. We assessed salvage cryoablation efficacy with a comparative analysis in a large national cohort. Methods: Patients with clinically localized prostate cancer treated with primary radiotherapy from 2000 to 2015 were identified in the Veterans Affairs Informatics and Computing Infrastructure (VINCI) dataset. Prostate-specific antigen (PSA) recurrence was defined as nadir + 2 ng/mL. Inclusion criteria included availability of serial PSA measures for ≥ 3 years after completion of radiotherapy and PSA < 10 ng/mL at recurrence. Salvage cryotherapy was identified with procedure- and fee-based billing codes. Chi square and Wilcoxon analysis was utilized for descriptive statistics; and Kaplan Meier analyses for time to androgen deprivation therapy (ADT). Results: Among 35,502 patients who underwent primary radiotherapy, 4,391 (12.3%) developed biochemical recurrence a median (IQR) of 4.5 (2.7, 6.9) years after treatment. Of these, 3889 (88.9%) had PSA < 10 ng/mL at time of recurrence, of whom 95 (2.4%) underwent salvage cryoablation. Cryoablation patients were younger at initial diagnosis (60 years versus 65 years, p < 0.01); had a lower pre-treatment PSA (6.6 ng/mL versus 7.8 ng/mL, p < 0.01); and had a lower PSA nadir (0.04 ng/mL versus 0.19 ng/mL, p<0.01). There were no between-group differences for clinical stage at initial diagnosis (p = 0.22) or African American prevalence (34.7% versus 29%, p =0.27). After recurrence, median (IQR) follow-up for those who did and did not receive cryoablation was 9.1 (7.2, 9.11) and 8.1 (5.4, 10.9) years, respectively. Cryoablation patients were less likely to receive ADT (40% versus 55%, p < 0.01); and, among those who did, time to ADT from recurrence was significantly longer compared to those who did not receive cryoablation (15.5 months versus 5.8 months, p<0.01). Conclusions: Salvage cryoablation is associated with decreased utilization of ADT in patients with biochemical recurrence after radiation.
Physical activity assessment among men undergoing genetic counseling for inherited prostate cancer: A teachable moment.
Authors: Giri Veda N. , Milliron Brandy-Joe , Sinclair Elizabeth , Obeid Elias , Smaltz Christa , Butryn Meaghan , Bruneau Michael
Published: February 2020

360

Background: Genetic counseling (GC) and genetic testing (GT) for prostate cancer (PCA) is growing rapidly for men with or at risk for PCA. GC provides opportunities to promote a healthy lifestyle and is understudied in men. To inform future lifestyle interventions, we assessed adherence to physical activity (PA) guidelines among a sample of men undergoing PCA GC/GT at two academic institutions. Methods: Participants enrolled in the Genetic Evaluation of Men study completed a structured lifestyle questionnaire to assess frequency of PA over the past year, including intensity of aerobic activity and strength-based activities. Data were evaluated as M±SD by PCA status, PCA aggressiveness (Gleason>7, T3, or metastatic disease), family history, and body mass index (BMI) with Chi-Square contingency analyses and adjusted residuals. Demographic characteristics predictive of PA adherence with current Department of Health and Human Services and American College of Sports Medicine PA guidelines were assessed using logistic regression analyses. Alpha levels were set a priori to p<.05. Results: Men with (n=158) or at risk (n=96) for PCA who underwent GC/GT were included; 84% were overweight or obese. Men with PCA had less adherence to engaging in moderate (p=.02) and vigorous (p=.01) PA than men without PCA. Men overall who reported engaging in strength-based PA did meet the recommended guideline of 2-3 days per week (p<.01). Lower BMI (p=.05) and higher education (p<.01) were found to be significant predictors for adherence to vigorous PA; older age (p=.02) and higher education (p<.01) were found to be significant predictors for adherence to strength-based PA; and, higher education (p=.02) was found to predict adherence to light and moderate PA (p<.05). Conclusions: High proportions of men undergoing PCA GC/GT were overweight/obese. Furthermore, men with PCA did not adhere to current PA guidelines. Age, BMI, and education were important predictors of PA engagement, which should be considered in intervention development. GC encounters represent “teachable moments” to promote healthy lifestyle among men, which may have additional benefit for survivorship and improved treatment experience.
Determinants of biochemical failure and distant metastases-free survival in high-risk prostate cancer patients treated with external beam radiotherapy.
Authors: Pilar Avinash , Bayley Andrew , Shehata Danny , Liu Zhihui (Amy) , Berlin Alejandro , Catton Charles N. , Kong Vickie , Rosewall Tara , Gospodarowicz Mary K. , Craig Tim , Helou Joelle , Warde Padraig Richard , Chung Peter W. M.
Published: February 2020

371

Background: Objectives were to1) identify predictors of biochemical failure(BCF) -free survival (FFS) & distant metastases free-survival (DMFS) in high-risk prostate cancer (HRPC) patients treated with external beam radiotherapy (EBRT) with or without androgen deprivation therapy (ADT); 2) assess the impact of nodal irradiation & escalation of dose to the nodal volumes in HRPC. Methods: Between Feb 2000 & May 2011, 462 patients with HRPC were treated with EBRT +/- ADT. This spanned an era of technical development; prior to 2002 conventional dose radiotherapy was routinely delivered, between 2002-2008, dose escalation to the prostate & pelvic lymph nodes was undertaken in a phase II trial & subsequently all patients were treated with a dose-escalated protocol. The disease characteristics included, a median PSA of 20ng/ml (range: 1-563), T3-T4 in 33% (n=158), & Gleason grade group (GGG) 3-5 in 72% (n=331). The majority (n=405, 88%) received ADT with EBRT & median duration of ADT was 36 months (range: 0-197). Dose escalated EBRT was utilized in 52% (n=241) & nodal irradiation in 69% (n=317); escalation of dose to nodal volumes was performed in 20% (n=93). Results: The median follow-up was 8.7yrs (range: 0.9-18.9). Median nadir PSA was < 0.05ng/ml (range: <0.05-5.78) with median time to nadir (TTN) of 11 months (range: 2-130). Cumulative incidence rates of BCF at 5 and 10-yrs were 23% & 45%; corresponding rates for DM were 6.6% & 14%, respectively. The 5 & 10-yr FFS rates were 75% & 51%; corresponding DMFS rates were 91.5% & 80%, respectively. On multivariate analysis, T stage (p<0.001), GGG (p<0.001), ADT (p=0.002), dose escalation to prostate (P=0.012) & median nadir PSA (p<0.001) were independent predictors of FFS. The GGG (p=0.007), median nadir PSA (p=<0.001) & Nodal RT (p=0.03) were independent predictors of DMFS. PSA of 20 & TTN predicted neither FFS nor DMFS. Conclusions: Nadir PSA level was an independent predictor of FFS & DMFS. Undetectable PSA level was associated with prolonged FFS & DMFS. Dose escalation to prostate resulted in an improved FFS & Nodal irradiation in an improved DMFS. Further studies are required to identify subgroups that may benefit the most from nodal irradiation.
Stereotactic radiotherapy +/- HDR boost for unfavorable-risk prostate cancer: Comparison of efficacy, survival, and late toxicity outcomes.
Authors: Loblaw Andrew , Cheung Patrick , Vesprini Danny , Liu Stanley K. , Chu William , Chung Hans T. , Morton Gerard , Musunuru Bindu , Deabreu Andrea , Davidson Melanie , Ravi Ananth , Helou Joelle , Ho Ling , Zhang Liying
Published: February 2020

372

Background: The ASCO/CCO guidelines recommend brachytherapy boost for all eligible intermediate- or high-risk localized prostate cancer patients. Stereotactic body radiotherapy (SBRT) is an emerging treatment for prostate cancer but its use in high risk disease is limited. We compare efficacy, survival and late toxicity outcomes in patients treated on 2 prospective, phase 2 protocols that both use pelvic SBRT and androgen deprivation therapy (ADT). One used MR-guided HDR brachytherapy boost (SPARE) and the other uses a SBRT boost (SATURN). Methods: SPARE was a phase I/II study where intermediate (IR) or high-risk (HR) prostate cancer patients received HDR-BT 15Gy x 1 to the prostate and up to 22.5Gy to the MRI nodule and followed by gantry-based SBRT 25Gy in 5 weekly fractions delivered to pelvis. ADT was used for 6-18 months. SATURN was a phase II study where high risk patients received 40Gy to prostate and 25Gy to pelvis along in 5 weekly fractions with 12-18 months ADT. CTCAEv3 was used to assess toxicities and was captured q6months x 5 years. Biochemical failure (BF; nadir + 2 definition), nadir PSA, proportion of patients with PSA < 0.4 ng/ml at 4 years (4yPSARR), incidence of salvage therapy, cause specific survival were calculated. Day 0 was first day of RT for all time-to-event analyses. Results: Thirty-two patients (NCCN 3% favorable IR, 47% unfavorable IR (UIR), 50% HR) completed SPARE while 30 patients (7% UIR, 93% HR) completed SATURN. Median follow-up of 50 and 48 months, respectively. Actuarial 4-year BF was 11.5% and 0%. Median nPSA was 0.02 ng/ml for both studies. 4yPSARR was 69% and 93%. 4-year cause-specific survival was 96% and 100%. Toxicities are listed in Table. Conclusions: In the context of SBRT pelvis and ADT, SBRT boost provides similar efficacy for unfavorable risk prostate cancer with acceptable but worse toxicities compared to HDR boost. A randomized study is recommended to answer this question. Clinical trial information: 01953055. [Table: see text]
Clinical characteristics and treatment adherence among men with testicular germ cell tumors: Real-world data from a referral center in Mexico.
Authors: Salazar-Mejía Carlos Eduardo , Zayas-Villanueva Omar , Gutiérrez Adriana González , Martinez Rolando Jacob , GUERRA CEPEDA ABRAHAM , Wimer-Castillo Blanca Otilia , Rodríguez-Calvillo Héctor Alejandro , Chapa-Montalvo Lourdes Paola , Samaniego-Sáenz Brenda Alejandra , Hernández-Barajas David , Vidal-Gutiérrez Oscar
Published: February 2020

393

Background: Notwithstanding excellent oncological outcomes reported by pivotal trials in patients with testicular germ cell tumors (TGCT), adherence to medical treatment and follow-up remains a major issue in developing countries. Studies that describe the clinical characteristics and treatment adherence of Mexican men with TGCT are lacking. Methods: We performed a retrospective analysis of all men with newly diagnosed TGCT treated at an oncology referral center in Northeast Mexico from 2014 to 2018. Results: In the analysis, 195 patients were included. Median age at diagnosis was 28 years; median time from diagnosis to first evaluation by an oncologist was 26 days. Distribution according to the laterality of the primary tumor was right, 56%; left, 43%; and bilateral, 1%. There were 14 oncological emergencies at presentation; the most frequent was choriocarcinoma syndrome, described in 5 patients. Thirty-five percent of cases were seminomatous germ cell tumors (SGCT) and 65% nonseminomatous germ cell tumors (NSGCT). The clinical stages at diagnosis were I, 36%; IS, 8%; II, 18%; and III, 38%. After risk stratification according to the International Germ Cell Cancer Collaborative Group (IGCCCG), 90% of SGCT had a good risk and 10% an intermediate risk. In NSGCT, the risk distribution was 65, 10, and 25% for good, intermediate, and poor-risk disease, respectively. After proposing treatment, the adherence rate was 81%. Of the total, 58% were lost to medical follow-up with a median time of adherence of 11.5 months. Conclusions: Despite coverage by the Mexican public health insurance system “Seguro Popular”, treatment adherence and medical follow-up abandonment is a problem among men with TGCT, which could negatively impact their prognosis. Measures must be implemented to optimize adherence in this group of patients.
The use of DNA promoter methylation testing for prostate cancer diagnosis in the Department of Veterans Affairs.
Authors: Lee Kyung Min , Jones Jeffrey A. , Efimova Olga , DuVall Scott L. , Lynch Julie Ann
Published: February 2020

394

Background: It is essential to study real-world evidence of novel molecular diagnostic tests to measure their impact on clinical decision-making and health outcomes. Studying test utilization within the Department of Veterans Affairs (VA) informs about clinical validity in a racially diverse population. This study analyzed the impact of DNA promoter methylation (ConfirmDx), on the diagnostic workup of Veterans. Methods: The VA Corporate Data Warehouse (CDW) was used to identify all incident prostate biopsies and cancers from 1/2014-10/2019. We captured patient clinical characteristics, including number and date of biopsies, date of cancer diagnosis, dates and values of PSA tests, comorbidities, demographics, whether the patient underwent DNA promoter methylation testing, and the results of that test. Results: Each year an average of 25,299 biopsies are conducted in the VA. Between 2014 and 2019, 151,794 biopsies were performed. 98,155 (70%) Veterans underwent first-time biopsies and 54,447 (55%) were positive for carcinoma. 8,062 (8.2%) underwent multiple biopsies, among whom 3,589 (44%) were subsequently diagnosed with cancer. 34 Veterans underwent 5 or more biopsies before being diagnosed. 33,878 (35%) did not undergo another biopsy in the study period. 328 (0.3%) of the 98,155 Veterans underwent the DNA promoter methylation test. 55 (17%) of these Veterans were eligible for Medicare coverage of the test. Of the 328 tested for DNA methylation, 217 (66%) were minorities. 132/328 (40%) tested positive for carcinoma and 168/328 (51%) were negative. Conclusions: Most Veterans referred for prostate biopsy have detectable cancer, and a large number are minorities with potential increased prostate cancer risk. DNA promoter methylation may improve care by reducing the need for multiple biopsies, limiting exposure to infection, and reducing time to diagnosis and treatment.
Do men want to perform testicular self-examination?
Authors: Dason Shawn , Beebe Sarah , Scimeca Alicia , Posid Tasha
Published: February 2020

395

Background: Early detection of testicular cancer (TC) may reduce the required burden of therapy. The long-term adverse effects of therapy in TC survivors are becoming increasingly recognized. The U.S. Preventive Services Task Force (USPSTF) currently recommends against testicular self-examinations (TSE) for TC screening due to a low incidence and lack of data to support a benefit. Our objective was to better understand the baseline knowledge and practices of men in the general population regarding TC/TSE in an effort to understand whether current screening guidelines reflect their viewpoint. Methods: This was a prospective survey study (51 questions). Participants (N=250; MAge=33 years, IQR: 28-39) were recruited via Amazon Mechanical Turk, a crowdsourcing platform used recruit minimally compensated participants. This platform has been extensively validated in US populations as being concordant with surveys conducted by other methods. Results: Most respondents were white (65.6%), had a college degree (76.4%), and did not work in a medical field (89.6%). Men rated themselves as “somewhat unknowledgeable” about testicular cancer, with no respondents considering themselves “very knowledgeable”. Only 26.4% of men knew that testicular cancer was curable most of the time. Despite 90.8% of men feeling that their doctor had at least some role in discussing TC/TSE, only 17.2% had actually discussed these topics with their doctor. Even after being informed of the rationale behind USPSTF recommendations, only 8% of men thought that potential false positives of TSE would be more important than the rare chance of finding early testicular cancer. Conclusions: Based on the largest survey of American men regarding testicular self-examination since the 2009 USPSTF recommendations, men don’t feel knowledgeable about testicular cancer, have a favorable attitude towards testicular self-examination, and want their doctor to discuss these topics. Shared decision making regarding testicular cancer screening is warranted given the low risk of harm and patient interest.
Tumor immune microenvironment alterations in penile squamous cell carcinoma using multiplex immunofluorescence and image analysis approaches.
Authors: Chahoud Jad , Netto Frederico , Lazcano Segura Rossana , Parra Cuentas Edwin Roger , Lu Xin , Rao Priya , Wistuba Ignacio Ivan , Pickering Curtis R. , Pettaway Curtis Alvin
Published: February 2020

4

Background: Penile Squamous Cell Carcinoma (PSCC) is a rare but often fatal disease. In this study, we characterize the poorly understood immune microenvironment using multiplex immunofluorescence (mIF) and image analysis approaches in 54 patients with PSCC. Methods: Representative blocks of 54 PSCC patients were stained for six immune markers: CD3, CD8, CD68, PD-1, PD-L1, Pancytokeratin and DAPI. Two experienced pathologists using an image analysis system (InForm 2.2.4) divided them into the tumor and stroma compartment and assessed the different densities of cell phenotypes using R studio with results expressed as cells/mm2. The statistical correlations were performed using Fisher’s exact test, Pearson and Log-rank test for Kaplan Meyer plots. Results: 54 patients with confirmed diagnosis of PSCC had a median age of 62 (IQR 50-70). All samples were from the primary penile tumor with the majority of cases being HPV(–) (62%). We observed significantly higher stromal cytotoxic T cells in HPV(+) cases compared to HPV(–) ( P=0.04). Using the mean macrophage count as cutoff for positivity, high densities of total tumor macrophages CD68+ were associated with significantly improved estimated median cancer specific survival (CSS) (NA, P=0.04), median overall survival (OS) (68mos vs NA P=0.02) and lower risk of regional recurrence ( P=0.04). On the other hand, the high densities of stromal cytotoxic T cells antigen-experienced (CD3+CD8+PD-1+), was associated with significantly worse median OS (27 vs 102mos P=0.05) and median disease free survival (DFS) (18.2mos vs NA P= 0.07). Also, high densities of stromal T cells antigen-experienced (CD3+PDL-1+), were associated with significantly better CSS (NA, P=0.06) and better median OS (142.1 vs 68.8mos P=0.14). Conclusions: Using novel multiplex image analysis to assess the immune microenvironment in primary PSCC, we showed that high macrophage levels were associated with lower risk of recurrence and improved survival outcomes. Moreover, a low level of exhausted stromal cytotoxic PD-1+ T cells was associated with improved PSCC survival. Further characterization of T cell subsets in relation to tumor HPV status is ongoing.
Causes and patterns of mortality in patients with lethal germ cell tumor (GCT).
Authors: Hamid Anis , Funt Samuel Aaron , Markt Sarah C. , Bromberg Maria , O'Donnell Devon , Adra Nabil , Taza Fadi , Albany Costantine , Krailo Mark D. , Frazier A. Lindsay , Einhorn Lawrence H. , Feldman Darren R. , Sweeney Christopher
Published: February 2020

421

Background: Most metastatic GCTs are cured with cisplatin-based chemotherapy. Clinical factors of adverse GCT-specific survival have been identified, however patterns of death are not well-defined and would inform clinical care and biological investigation. Methods: This multi-institutional study pooled data of male pts with death related to GCT from high-volume adult GCT academic centers (Dana-Farber Cancer Institute, Memorial Sloan Kettering Cancer Center, Indiana University) over 20 years (1997-2017). Pts were annotated for site, stage, IGCCC risk, histology, primary therapy and relapse variables (including relapse histology, metastatic (met) burden, salvage and palliative therapies), and detailed cause of GCT death. Cox regression assessed associations with survival. Results: The pooled cohort of 620 pts comprised 90% non-seminoma, 21% mediastinal primary and at diagnosis, 59% were stage III, 64% poor risk; 48% received high-dose chemotherapy plus transplantation. Median survival (OS) from first relapse after metastasis was 12.0 mos. Leading causes of death were chemorefractory GCT (83.1%), secondary somatic malignancy (SSM) arising from teratoma (9.4%), acute toxicity (4.5%), late toxicity (2.3%) and progressive untransformed pure teratoma (0.8%). Late relapse (relapse >2 years after 1st-line therapy) occurred in 11.3% at a median of 5.9 yrs. Of these pts, 1/3 were stage I at initial diagnosis and 75% were good or intermediate risk at met diagnosis, and were more likely to have SSM histology/death vs early relapse. Late relapsing disease (HR 0.48, p<0.0001) and presence of SSM (HR 0.74, p=0.017) were associated with longer OS from first relapse after metastasis. Brain metastasis at any time occurred in 29.8%, associated with poorer OS. Conclusions: Comprehensive characterization of GCT-related death reveals a predominant pattern of mortality marked by de novo metastatic, poor-risk disease with subsequent early relapse and death due to chemorefractory non-teratomatous GCT. By contrast, a subset of pts with late-relapsing disease are more likely to have SSM-teratoma and a protracted clinical course. Lethal late relapses frequently occurred beyond 5 years, emphasizing the importance of long-term follow-up.
Safety and efficacy of intravesical nadofaragene firadenovec for patients with high-grade, BCG unresponsive nonmuscle invasive bladder cancer (NMIBC): Results from a phase III trial.
Authors: Boorjian Stephen A. , Dinney Colin P.N. ,   SUO Clinical Trials Consortium
Published: February 2020

442

Background: Patients (pts) with BCG-unresponsive NMIBC are at significant risk for disease recurrence and progression. While cystectomy can be curative, many such pts are unwilling or unable given the attendant morbidity of surgery. To date, effective salvage intravesical therapies in this setting remain lacking. Nadofaragene firadenovec is a novel intravesical gene-mediated therapy that delivers the human IFNα2b gene resulting in IFNα2b expression that provided durable responses in a previous Phase 2 trial. Herein, we report the results from a follow-up Phase III trial of this agent for pts with BCG unresponsive NMIBC. Methods: This multicenter, open-label Phase 3 study investigated nadofaragene for high-grade NMIBC (CIS ± Ta/T1, or Ta/T1 alone) unresponsive to BCG. Nadofaragene (3X1011 vp/mL [75 mL]) was administered once every 3 months for up 4 doses in the initial 12 months, with additional dosing at the investigator’s discretion. The primary endpoint was complete response (CR) at any time in pts with carcinoma in situ (CIS). Results: A total of 157 pts (safety population, n=157; efficacy population, n=151) were enrolled. Among pts with CIS (n=103), 55 (53.4%) (95% CI, 43.3-63.3) achieved CR, all by month 3 after treatment. Of these 55 CIS CR pts, 25 (45.5%) remained free of high-grade recurrence at month 12, confirmed on protocol-mandated biopsy. For pts with HG Ta/T1 alone, 35 (72.9%) and 21 (43.8%) were free from recurrence at 3 and 12mos, respectively. Most treatment-emergent adverse events (TEAEs) were transient in nature: instillation site discharge 33.1%; fatigue 23.6%; bladder spasm 19.7%; micturition urgency 17.8%; hematuria 16.6%. There were 2 Gr4 TEAEs (sepsis and anaphylactic reaction, neither related to study drug) and no Gr5 TEAEs. Conclusions: Nadofaragene achieved CR in 53.4% of pts with BCG-unresponsive CIS, and was well tolerated. Responses were noted early and remained durable to one year. These data represent a potentially significant management advancement for a historically difficult to treat disease state. Clinical trial information: NCT02773849.
Bladder cancer caregiver quality of life and patient cancer severity.
Authors: Gessner Kathryn , McCabe Sean , Filippou Pauline , McCloskey Hannah , Hamad Judy , Deal Allison Mary , Gore John L. , Smith Angela
Published: February 2020

456

Background: Bladder cancer patients’ care is often managed by caregivers, yet caregiving can create a physiologic and emotional burden that compromises the caregivers’ own quality of life (QOL). Our objective was to determine the impact of disease stage on caregiver QOL among a large national cohort of bladder cancer patients. Methods: We performed a cross-sectional survey of bladder cancer caregivers using the Bladder Cancer Advocacy Network Patient Survey Network and Inspire platforms to determine caregiver QOL using the CareGiver QOL questionnaire (CarGOQoL). Caregivers were also queried regarding demographic, socioeconomic and clinical characteristics of their loved one. We present descriptive statistics and a multiple linear regression model to identify factors independently associated with QOL domain score. Results: 132 respondents self-identified as caregivers of patients with bladder cancer. Among respondents, 85% were a spouse, 86% were female, and 97% were white. The mean age was 63 years (range 34 to 72 years) and 73% of respondents completed college. The highest cancer stage for patients was non-invasive in 42%, muscle-invasive in 33%, and metastatic in 24%. On bivariable analysis, stage was associated with leisure and social support but was not associated with global QOL, psychologic or physical well-being, burden, relationship with healthcare, administration and finances, coping, self-esteem or private life. However, on multivariable analysis controlling for age, race, years since diagnosis, and comorbidity, stage was significantly associated with Caregiver QOL (p=0.04). Conclusions: Disease stage significantly impacts QOL among bladder cancer caregivers. As the caregiver is increasingly considered as a stakeholder in survivorship efforts, future interventions should consider targeting social support among caregivers of patients with advanced bladder cancer.
The impact of physician specialty on general and bladder cancer-specific quality of life among patients with muscle invasive bladder cancer.
Authors: McCloskey Hannah , McCabe Sean , Gessner Kathryn , Filippou Pauline , Hamad Judy , Deal Allison Mary , Gore John L. , Smith Angela
Published: February 2020

462

Background: Treatment delivery for muscle invasive bladder cancer (MIBC) may involve general urologists, urologic oncologists or a multidisciplinary team that includes medical oncology and radiation oncology. Our objective was to evaluate differences in general and bladder cancer-specific quality of life (QOL) based on treating physician among MIBC patients. 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 general and bladder cancer-specific QOL using the EORTC QLQ-C30 and Bladder Cancer Index, respectively. Patients were also queried regarding demographic, socioeconomic and clinical characteristics. Patients were asked whether they sought care from a general urologist, urologic oncologist, medical oncologist and/or radiation oncologist. We present descriptive statistics and a multiple linear regression model to identify factors independently associated with QOL domain score. Results: 270 respondents identified as MIBC patients. Among MIBC respondents, 38% were female and 97% were white. The mean age was 67.4 years (range 30 to 93 years). Respondents were highly educated (67% completed college). Among MIBC patients, 17% sought care from a general urologist only, 33% from a urologic oncologist only, and 50% from a multidisciplinary team that included either a medical or radiation oncologist. Physician specialty was not associated with generic, sexual, or bowel QOL. Patients seeing a general urologist had—on average—better urinary function compared with those seeing a urologic oncologist or multidisciplinary team. On multivariable analysis, physician specialty remained a significant predictor of urinary function (p = 0.02), controlling for age, sex, race, recurrence, and comorbidity. Conclusions: Among MIBC patients, physician specialty does not substantially impact general QOL but may be associated with urinary function. This may relate to cancer severity or other unmeasured patient characteristics.
The impact of age on general and bladder cancer-specific quality of life among bladder cancer survivors.
Authors: Filippou Pauline , McCabe Sean , McCloskey Hannah , Gessner Kathryn , Hamad Judy , Deal Allison Mary , Smith Angela , Gore John L.
Published: February 2020

463

Background: Quality of life among cancer survivors has been shown to vary by age. Our objective was to evaluate differences in general and bladder cancer-specific quality of life based on age among a large cross-sectional 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 general and bladder cancer-specific quality of life (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, of whom 41% were female and 97 % were white. The mean age was 67.6 years (range 29 to 93 years). Respondents were highly educated (67% completed college). 63% of patients identified as having non-invasive (NMIBC) cancer (n=578), 30% had MIBC (n=270), and 7% had metastatic bladder cancer (n=63). On multivariable analysis, older age was significantly associated with better generic QOL and urinary function ( Table), but not sexual function (p=0.19) or bowel function (p=0.73), controlling for sex, race, stage, comorbidity and years since diagnosis. Conclusions: Higher general and domain-specific QOL scores are more common among older bladder cancer patients. Differential impact by age may be important for the development of tailored interventions to improve QOL for bladder cancer patients. [Table: see text]
Gender and quality of life in bladder cancer.
Authors: Gessner Kathryn , McCabe Sean , Filippou Pauline , McCloskey Hannah , Hamad Judy , Deal Allison Mary , Gore John L. , Smith Angela
Published: February 2020

464

Background: Quality of life among cancer survivors has been shown to vary by gender. Our objective was to evaluate differences in generic and bladder cancer-specific quality of life (QOL) based on gender 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. The survey was advertised. 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). Respondents were highly educated (67% completed college). 63% of patients identified as having non-invasive (NMIBC) cancer (n=578), 30% had MIBC (n=270), and 7% had metastatic bladder cancer (n=63). On multivariable analysis ( Table), female gender was significantly associated with worse generic QOL (p<0.001), bowel function (p=0.001), and sexual function (p=0.02), and women trended toward worse urinary function (p=0.06), controlling for age, race, stage, comorbidity and years since diagnosis. Conclusions: Lower generic and domain-specific QOL scores are more common among female bladder cancer patients. Differential impact by gender may be important for the development of tailored interventions to improve QOL for bladder cancer patients. [Table: see text]
Feasibility of neobladder reconstruction after pelvic irradiation.
Authors: Vassantachart April , Miranda Gus , Daneshmand Siamak , Schuckman Anne K. , Djaladat Hooman , Ballas Leslie
Published: February 2020

479

Background: To assess the effects of pelvic radiotherapy (RT) on orthotopic neobladder reconstruction (ONR), this review presents retrospective data of surgical outcomes following prior RT. Methods: Our institutional IRB approved bladder cancer database was queried for all patients who underwent radical cystectomy and ONR between 1980 and 2018. Radiation data was abstracted from the electronic medical record (EMR) with inclusion of patients receiving >40 Gy to the pelvis prior to surgery. Surgical outcomes including estimated blood loss (EBL), operative time, margin status, overall survival (OS), and need for subsequent surgeries were evaluated. Results: Of 2117 ONRs performed, 96 patients received prior RT. Of those, RT details could be obtained on 24 patients. Fifteen patients underwent definitive bladder RT with a median dose of 6480 cGy (range, 4500 - 8640 cGy); 7 of these patients received concurrent chemoradiotherapy, 2 received chemotherapy and RT with timing uncertain, and 6 received RT alone. Eight patients had prior prostate RT (median 7200 cGy) and one patient underwent prior cervical RT (7910 cGy). The median time interval between bladder RT and ONR was 7 months (range, 2 – 116 months) verses a median of 29 months between other pelvic RT and ONR (range, 6 – 163 months). Median EBL was 875 cc (range, 200-3000 cc) in patients with prior pelvic RT. Median operative time was 355 minutes (range, 231-600) in those who had prior RT compared with 354 minutes (range, 111-778) in those who underwent ONR without prior RT. Twenty-three patients had negative margins on surgical resection and one had a positive ureteral or urethral margin. The median OS following surgery was 50 months. Two patients died within 1 year due to disease progression. Seven patients (29%) required a surgical intervention after ONR: two patients developed fistulas (both with pouch to cutaneous fistulas), four patients had artificial urinary sphincters placed, and one developed small bowel obstruction due to adhesions. One patient required urethrectomy for recurrent disease. Conclusions: Orthotopic ileal neobladder reconstruction after pelvic irradiation is feasible with acceptable functional results.
A phase II trial of regorafenib for advanced urothelial cancer (aUC) following prior chemotherapy.
Authors: Naik Gurudatta , Vaishampayan Ulka N. , Nabell Lisle , De Shazo Mollie R. , Nandagopal Lakshminarayanan , Grivas Petros , Morgan Charity , Hardwick Pamela , Sonpavde Guru
Published: February 2020

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Background: Salvage therapy options for aUC following platinum-based chemotherapy and immune checkpoint inhibitors (ICIs) have modest activity. Regorafenib is a multitargeted TKI that targets VEGF and Tie2 receptors among others, which is approved for multiple malignancies. Both VEGF and Tie2 inhibitors have preliminarily exhibited activity in aUC. Hence, a rationale was made to evaluate regorafenib in aUC progressing following chemotherapy. Methods: We conducted a single arm, non-randomized Phase II study (NCT02459119) of regorafenib for aUC following chemotherapy. All patients (pts) started at 120 mg po qd for one cycle (28 days) before escalating to 160 mg po qd in the absence of intolerable regorafenib related toxicities. Pts who had progressed after 1-3 prior chemotherapy regimens and exhibited measurable disease by RECIST 1.1 were selected. The primary objectives was progression free survival at 6 months (PFS-6) and the secondary objectives were objective response rates (ORR), overall survival (OS) and toxicities. PFS6 of ≥20% was considered of interest and the target accrual was 32 evaluable pts. The treatment was continued until progression or intolerable adverse events. Results: We enrolled 17 pts across 3 institutions (UAB, Wayne State and Cleveland Clinic) between May 2015 and May 2019. Of these, 14 patients were male (82%) and the median age was 67 years. Pts received a median of 2 prior therapies including chemotherapy. 9 pts had received a prior ICI. 13 pts (76.5%) experienced treatment related adverse events (AE), and 7 pts (41.2%) had grade 3 toxicities including–anemia, thrombocytopenia, myalgia, hypophosphatemia, abdominal pain and fatigue. Treatment was discontinued for patients who suffered grade 3 myalgia and abdominal pain. There were no treatment related deaths. 3 patients attained PFS6 (18%) who also displayed minor regressions and 1 of them had received a prior ICI. Conclusions: Although the trial was halted for slow accrual, regorafenib appeared to demonstrate activity in heavily pretreated pts with aUC who had received chemotherapy or ICI. Further evaluation may be warranted in less heavily pretreated pts and in combination with rational agents with non-overlapping toxicities. Clinical trial information: NCT02459119.
Concurrent or layered treatment (Tx) with radium-223 (Ra-223) and enzalutamide (Enza) or abiraterone plus prednisone/prednisolone (Abi/pred): A retrospective study of real-world clinical outcomes in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Shore Neal D. , Sartor Oliver A. , Sternberg Cora N. , Saad Fred , TOMBAL Bertrand F. , Miller Kurt , Kalinovsky Jan , Jiao Xiaolong , Tangirala Krishna , Higano Celestia S.
Published: February 2020

50

Background: In clinical practice, Ra-223 is often combined with Enza or Abi/pred. ERA 223 (NCT02043678) showed increased fracture risk with concurrent Ra-223+Abi/pred. We assessed real-world symptomatic skeletal events (SSEs) and overall survival (OS) of pts with mCRPC who received concurrent or layered Ra-223+Enza or Abi/pred. Methods: Patients with mCRPC treated with Ra-223 in US cancer clinics from 1/01/2013 to 6/30/2017 were identified from a Flatiron prostate cancer registry of electronic health records. Tx initiation defined subgroups: concurrent (both started within 30 days) or layered (1 started ≥30 days after the other). Baseline (BL) was the first dose of Ra-223. Descriptive analysis was performed for BL characteristics, SSEs, and OS (Kaplan–Meier). Results: Of 625 pts treated with Ra-223, 48% received Ra-223+Enza or Abi/pred. Layered Tx was more common (73%) than concurrent (27%). BL characteristics and clinical outcomes were summarized [Table]. Conclusions: Ra-223+Enza or Abi/pred Tx was mainly layered. SSE rates with layered vs concurrent Ra-223+Abi/pred varied between subgroups; results must be treated cautiously given small pt numbers and a non-randomized study. The ongoing PEACE III trial is investigating concurrent Ra-223+Enza; a Phase III study (ESCALATE) exploring layered Ra-223+Enza is planned. Clinical trial information: NCT02043678. [Table: see text]
Patterns of use of chemotherapy with radiotherapy in the treatment of muscle-invasive bladder cancer: Data from the RAIDER randomized trial of adaptive radiotherapy.
Authors: Huddart Robert A. , Lewis Rebecca , Griffin Clare , Alonzi Roberto , Birtle Alison Jane , Choudhury Ananya , Cresswell Joanne , Foroudi Farshad , Hafeez Shaista , Henry Ann , Hindson Ben , McLaren Duncan , Mitra Anita , Nikapota Ashok , Parikh Omi , Rimmer Yvonne L. , Syndikus Isabel , Varughese Mohini Anna , Hall Emma ,   on behalf of Raider Trial Management Group
Published: February 2020

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Background: Level 1 evidence exists for the use of both neoadjuvant chemotherapy (NAC) and concomitant radiosensitization (CRS) to improve outcomes in patients receiving radical radiotherapy (RT) for muscle invasive bladder cancer, but uptake has been patchy. We report here the current patterns of usage in an ongoing trial of adaptive radiotherapy. Methods: RAIDER is an international randomized phase II trial recruiting patients with unifocal T2-T4a urothelial carcinoma of the bladder suitable for RT (ISCRTN:26779187). Patients are randomized in a 1:1:2 ratio to one of 3 arms: Standard whole bladder RT (control); Standard dose adaptive tumour focused RT; Dose escalated (DE) adaptive tumour boost RT. Standard dose patients are treated to either 64Gy/32f or 55Gy/20f and DE patients to 70Gy in 32f or 60Gy in 20f. Patients are encouraged to receive NAC and CRS. The primary endpoint is the rate of late toxicity 6-18 months post treatment in arm 3, with secondary endpoints of patient reported and disease related outcomes. Results: To August 2019, 285 patients had been recruited. Median age is 72 years (IQR 67-79). Stage of disease is T2 79%, T3 19%, T4 2%; 19% have hydronephrosis. Patients receiving NAC were more likely to be PS 0 at trial entry (70% v 45%). Variation in frequency of CRS use is seen across sites, with some offering to >90% of participants and some <50%. Data on NAC and CRS use is available for 249 patients recruited to date is shown in table. Conclusions: In this ongoing clinical trial the majority of patients are receiving NAC and/or CRS. However, uptake is not universal with ~30% of patients not receiving low dose CRS, including some who have received NAC. Clinical trial information: 26779187. [Table: see text]
Marker lesion study of oral FGFR inhibitor BGJ398 in patients with FGFR3-altered intermediate-risk nonmuscle-invasive bladder cancer.
Authors: Cha Eugene K. , Iyer Gopa , Funt Samuel Aaron , Regazzi Ashley Marie , Francis Jasmine , Heinemann M.H. , Ostrovnaya Irina , Dalbagni Guido , Bajorin Dean F. , Bochner Bernard H. , Rosenberg Jonathan E.
Published: February 2020

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Background: FGFR3 alterations are prevalent in non-muscle-invasive bladder cancer (NMIBC). We conducted a marker lesion study of the oral FGFR inhibitor BGJ398 in patients with intermediate-risk NMIBC. Methods: Patients with recurrent clinical high-grade papillary NMIBC following intravesical BCG were eligible. FGFR3 alteration status was determined via testing of pre-treatment or archival tumor tissue. BGJ398 was administered at 125 mg PO daily for a 3 week on, 1 week off schedule (1 cycle). Response was determined after 2 cycles (at 7 weeks). Patients with a complete response (CR) had the option to continue therapy. Results: We enrolled four patients on trial, which we closed secondary to low accrual. Three patients had a CR at the 7-week evaluation. The other patient had a smaller, necrotic lesion after prematurely discontinuing treatment at 4 weeks. Clinically significant toxicities included eye disorders, skin and nail disorders, and elevations in LFTs. Two patients required dose reductions for toxicities. Two patients discontinued treatment before the 7-week evaluation, one for Grade 2 skin toxicity and the other for Grade 3 LFT elevation. All other toxicities were Grades 1 and 2. The other two patients continued treatment beyond a CR at 7 weeks but stopped after 3 and 4 cycles (after 11 and 16 weeks) for vision/skin toxicities and nail infection/mucositis, respectively. Conclusions: The oral FGFR inhibitor BGJ398 showed antitumor activity in a marker lesion study of patients with recurrent high-grade papillary NMIBC. Treatment was discontinued secondary to toxicities in all subjects, after a range of 4 to 16 weeks. Further investigation may be warranted for lower doses of oral BGJ398 or other formulations, such as intravesical delivery. Clinical trial information: NCT02657486. [Table: see text]