bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prostate cancer screening: Have we tipped the seesaw?
Authors: Hobbs Matthew David , Norori Natalia , Harding Thomas , Rylance Amy 
Published: March 2023

43 Background: Screening for prostate cancer has been and remains contentious with evidence of harms and benefits finely balanced and inadequate to tip the see saw one way or another in order to give men clear, understandable guidance on PSA testing. In recent years the diagnostic pathway has changed significantly delivering a modern pathway that is likely to do far less harm and possibly more benefit. Our work quantifies the levels of harm and benefit at each stage of the entire pathway currently used in the UK from initial PSA through to biopsy-confirmed diagnosis of prostate cancer. Methods: Combining the full results of the most recent high quality diagnosis clinical trials, as well as real world evidence and practice patterns we have mapped each stage of the UK diagnostic pathway. Through this research we are able to quantify the number of men benefitting (i.e. those who move through the pathway correctly with an eventual diagnosis of clinically significant prostate cancer) and the number of men suffering harm (those who suffer biopsy side effects or who are subjected to unnecessary testing as they move through the pathway with no clinically significant cancer). Results: Initial results using clinical trial data and current practice patterns in the UK indicate that 10,000 men entering the diagnostic pathway with a PSA test would generate the following results. Diagnostic outcomes: 463 men would be diagnosed with a clinically significant (Gleason 3+4 or above) localised prostate cancer; 110 men would be diagnosed with a clinically insignificant (Gleason 3+3) prostate cancer; and 646 men would be taken through the entire diagnostic pathway with no diagnosis of prostate cancer. Harm: a maximum of 38 men would suffer clinical side effects from their biopsy. Healthcare costs: 10,000 PSA tests, 1,449 multiparametric MRI scans, and 1,207 biopsies would yield 463 significant cancers diagnosed. An estimated 1,258 clinically insignificant and 168 clinically significant cancers would remain undiagnosed using the current diagnostic pathway due to initial PSA below 3ng/ml. Conclusions: Rates of biopsy-related harm in modern practice are encouragingly low and likely to reduce further. A PSA-initiated diagnostic pathway misses a significant proportion of clinically important cancers. It is interesting to note the high conversion from MRI to biopsy in the data underpinning this model. Next steps will include analysis of the same outcomes in several centres in the UK to determine if actual practice matches expected outcomes (harms and benefits) from previous clinical trials.
Randomised phase II trial of adaptive image guided radiotherapy in muscle invasive bladder cancer: Late toxicity and cancer outcomes.
Authors: Huddart Robert A , Hafeez Shaista , Omar Abdullahi , Birtle Alison Jane , Cheung Ka Ching , Choudhury Ananya , Foroudi Farshad , Gribble Hannah , Griffin Clare , Henry Ann , Hindson Ben , Lewis Rebecca , McLaren Duncan , McNair Helen , Nikapota Ashok , Parikh Omi , Syndikus Isabel , Varughese Mohini Anna , Webster Amanda , Hall Emma 
Published: March 2023

446 Background: The bladder is a mobile, deformable structure which makes radiotherapy (RT) delivery challenging. Plan of the day (POD) adaptive image guided RT and tumour boost dose escalation can optimise treatment. We aimed to define a feasible, safe schedule for muscle invasive bladder cancer (BC) using these techniques. Methods: RAIDER (ISRCTN 26779187) is a 3-arm, international phase II trial. Participants (pts) had unifocal T2-T4a urothelial BC and were randomized (1:1:2) to: standard whole bladder RT (WBRT), standard dose adaptive tumour focused RT (SART) or dose escalated adaptive tumour boost RT (DART). Two fractionation (f) schedules recruited independently. WBRT and SART dose was 64Gy/32f or 55Gy/20f and DART was 70Gy/32f or 60Gy/20f. For SART and DART, POD (small, medium, large) was chosen daily. Neoadjuvant chemotherapy (NAC) and concomitant radiosensitising therapy (CTh) were permitted. Primary endpoint is proportion of pts with RT related CTCAE grade≥3 (G≥3) toxicity 6-18 months (m) after RT. A non-comparative design to rule out >20% G≥3 toxicity in DART pts required 57 evaluable DART pts in each fractionation cohort (90% power, 5% 1-sided alpha). Adverse events (AE) are treatment emergent with RT relatedness assessed blind to treatment allocation. In each fractionation cohort, toxicity analysis is by treatment received in the evaluable population (pts with at ≥1 toxicity assessment between 6-18m). 3m local control was assessed by cystoscopic biopsy. Cancer outcomes are analysed by intention-to-treat with fractionation cohorts combined. Results: 345 pts were randomised (Oct 2015 - Apr 2020): 46/41 WBRT, 46/41 SART and 90/81 DART pts in 32f/20f cohorts respectively. Baseline characteristics for 32f/20f were median age 73 years (IQR 67, 79)/ 72 (67, 79); 83%/ 78% T2; 46%/ 52% had NAC and 71%/ 70% CTh. Median follow-up was 32f: 38.2m (IQR 26.2, 50.2), 20f: 42.1m (35.6, 50.1). 3588/6222 (58%) fractions delivered to SART and DART pts used small or large POD. Late toxicity outcomes are shown in table. RT related G≥3 in 20f DART was 1/58 (90% CI 0.1, 7.9) and in 32f DART was 0/57. 3m local control was achieved in 44/51 (86%) WBRT, 45/53 (85%) SART and 82/92(89%) DART. 2 year survival was 79% (95% CI: 69, 86) WBRT, 74% (63, 82) SART and 80% (73, 85) DART. Conclusions: Late G≥3 toxicity was low in all treatment groups. 20f and 32f DART was safe and feasible to deliver with toxicity rates below predefined thresholds. Local control for image guided (chemo)RT was good. CTCAE G≥3 and G≥2 treatment emergent toxicity 6-18m after RT. Clinical trial information: 26779187 . [Table: see text]
Patterns of failure after radiotherapy (RT) in patients with prostate cancer re-staged with 18F-DCFPyL PSMA-PET: A regional cohort analysis.
Authors: Mesci Aruz , Mukherjee Sneha , Gouran-Savadkoohi Mohammad , Kapoor Anil , Bauman Glenn , Lukka Himu , Dayes Ian S. , Schnarr Kara , Goldberg Mira , Quan Kimmen , Zukotynski Katherine A. , Tsakiridis Theodoros 
Published: March 2023

45 Background: In Ontario, PSMA-PET is available to patients with prostate cancer who experience biochemical failure after definitive primary RT (pRT) or salvage/adjuvant RT (sRT) through a provincial registry study (PREP protocol). Here we review patterns of PSMA-PET-detected failure after primary (pRT) or salvage/adjuvant RT (sRT) radiotherapy (RT) in cohorts of PREP-registry patients from the Local Health Integration Network (LHIN) 4 region. Methods: With ethics approval, we retrospectively analyzed patients imaged with PSMA-PET in Hamilton, Ontario, Canada, after biochemical failure, following pRT or sRT. Demographic, clinical and treatment parameters as well as PSMA-PET results were collected. Results: Between April 2019 and December 2021, 104 pRT and 91 sRT patients were imaged with 18F-DCFPyL PSMA-PET. Median PSA (ng/mL) before PSMA-PET for the two groups was 5.0 (IQR:3.1-8.9) and 1.3 (IQR:0.6-3.4). The percentages of Prostate or Prostatic bed RT alone (Pr-RT) and Pr + pelvic Lymph Node RT (Pr+LN-RT) RT treatments, were Pr-RT:76% vs Pr+LN-RT:24% for the pRT group and Pr-RT:49.4% vs Pr+LN-RT:50.6% for the sRT group, respectively. Rates of PSMA-PET detected local, pelvic lymph node and distant recurrence are shown. In the pRT group, increasing D’Amico risk category (low to high risk) was associated with lower risk for local and increased risk for pelvic and distant metastasis. Pelvic RT was associated with reduce risk for local recurrence in the pRT but not in the sRT group. Conclusions: In this cohort of patients PSMA-PET detected a considerable risk for local recurrence in patient treated with pRT. A high number of patients are detected with pelvic-only disease recurrence, but pelvic RT seems to be associated with reduction in this risk only in the pRT population. Studies with PSMA-PET at baseline, before pRT or sRT, may help discern better patients that would benefit from pelvic RT and systemic therapy.[Table: see text]
Clinical significance of squamous differentiation in upper tract urothelial carcinoma treated with radical nephroureterectomy.
Authors: Minato Akinori , Noguchi Hirotsugu , Kimuro Rieko , Tomisaki Ikko , Harada Kenichi , Fujimoto Naohiro 
Published: March 2023

451 Background: Upper tract urothelial carcinoma (UTUC) involving the renal pelvis/ureter is histologically similar to bladder cancer in morphological diversity. Although squamous differentiation (SD) is the most common variant in UTUC, the clinical significance of SD in UC has yet to be comprehensively elucidated given the rarity of the disease compared to bladder cancer. To assess the impact of SD on the prognosis of patients with UTUC undergoing radical nephroureterectomy (RNU). Methods: Among the 244 consecutive patients who underwent RNU at our single institution from May 2005 to October 2019, only patients who had histologically confirmed pure UC or UC with SD (UCSD) were included. SD required the presence of intercellular bridges or keratinization for diagnosis. Metastasis-free survival (MFS) and overall survival (OS) rates were retrospectively evaluated using Kaplan–Meier analysis and Cox regression analysis. Results: We identified 197 (87.9%) and 27 (12.1%) patients with pure UC and UCSD, respectively. No significant differences in age, sex, concomitant carcinoma in situ and tumour grade were observed between the groups. UCSD was significantly associated with an advanced tumour stage and a higher rate of lymphovascular invasion. With a median follow-up time of 58 months, the pure UC and UCSD groups had a 5-year MFS rate of 65.2% and 40.9% ( p=0.005) and a 5-year OS rate of 74.4% and 49.0% ( p=0.002), respectively. Multivariate analyses revealed that the presence of SD was significantly associated with MFS [hazard ratio (HR), 1.88; p=0.027] and OS (HR, 1.70; p=0.048). Conclusions: The patients with UCSD are at high risk for disease metastasis and short-term survival. SD in UC could be an independent predictor of poor prognosis after RNU for UTUC.
Racial and geographical disparities in pivotal bladder cancer clinical trials.
Authors: Padua Tiago Costa de , Marandino Laura , Patanè Damiano Alfio , Raggi Daniele , Necchi Andrea 
Published: March 2023

454 Background: According to population-based studies, there is a significant racial difference in patient characteristics, incidence, and survival among bladder cancer patients. Non-Hispanic whites have the highest incidence rate, followed by blacks. However, racial clinical trial disparities in clinical research are a critical problem around the world, with an underrepresentation of the black population. In the last years, multiple phase 2/3 trials have introduced the use of immunotherapy and targeted therapy in the treatment of bladder cancer. We aimed to assess the enrollment disparities in pivotal BC clinical trials. Methods: Published clinical trials were identified from the Bladder Cancer European Society of Medical Oncology (ESMO) guideline, considering the approved drugs and availability in clinical practice. The characteristics of participants, including race and geographic location, were collected. Results: A total of 1 phase 2 or 3 trials were identified, evaluating pembrolizumab, atezolizumab, avelumab, erdafitinib, durvalumab +/- tremelimumab and enfortumab vedotin, with a total of 7748 patients. The table summarizes the findings. Race information is available only in 8 of them, 4 in the original report and 4 in the results section of clinicaltrials.gov, with a pooled sample of 6573 patients. White, Asian and Black patients comprised 71.74% (4716 pts), 19.9% (1313 pts), and 0.66% (44 pts) of all patients, respectively. The percentage of white patients ranged from 51.6% to 88.6%, whereas the black population varied from 0.3% to 2.2%. Geographical location information is available only for 2 clinical trials, with a predominance of patients from the United States and Europe and an under-representation of patients from other continents. Conclusions: We observed a low rate of race reporting in bladder cancer published trials and a very significant under-representation of non-white participants in the pivotal trials for bladder cancer, with just 0.66% of black patients. Based on these finding, there are insufficient data to confirm the effectiveness or safety of new drugs in minority groups, especially blacks. To provide generalizable results, race reporting should be always included in licensing trials, and recruitment of black and other minority population to trials should be stimulated.[Table: see text]
Whole-body diffusion-weighted magnetic resonance imaging to assess bone response in patients with hormone-sensitive metastatic prostate cancer randomly assigned to receive androgen deprivation + enzalutamide ± zoledronic acid.
Authors: Dalla Volta Alberto , Valcamonico Francesca , Zivi Andrea , Procopio Giuseppe , Sepe Pierangela , Del Conte Gianluca , Di Meo Nunzia , Foti Silvia , Zamboni Stefania , Messina Caterina , Lucchini Eleonora , Rizzi Anna , Ravanelli Marco , Milella Michele , Calza Stefano , Simeone Claudio , Maroldi Roberto , Farina Davide , Berruti Alfredo 
Published: March 2023

46 Background: Bone is frequently involved in metastatic hormone sensitive prostate cancer (mHSPC). Whole-body diffusion-weighted magnetic resonance imaging (WB-DW-MRI) is a promising imaging technique for the assessment of bone response in prostate cancer. It is not known whether the addition of antiresorptive agents can improve disease response in bone in mHSPC patients undergoing next generation hormonal agents. Methods: In this multicenter phase II study patients with de novo or relapsed mHSPC and bone metastases at bone scan were randomly allocated with a 1:1 ratio to receive either androgen deprivation therapy (ADT) plus Enzalutamide (E arm) or the same combination with the addition of Zoledronic Acid (EZ arm). The study was designed to observe a significant increase in bone response rate in the experimental arm after 12 months of treatment, as assessed through WB-DW-MRI. WB-DW-MRI was performed centrally at baseline and after 6 and 12 months and images were evaluated by the same radiologist. Results: From February 2018 to June 2021, 126 mHSPC patients were randomized, 64 in EZ arm and 62 in E arm. A total of 111 patients, 54 from E arm and 57 from EZ arm, were eligible for WB-DW-MRI assessment (15 patients were excluded because of the absence of bone target lesions at MRI or specific contraindications to MRI). Bone response at 6 months was observed in 41 patients (76%) in E arm and 41 patients (72%) in EZ arm; the corresponding bone response at 12 months were 44 (82%) and 44 (77%), respectively (OR 0.77; 95%IC 0.30-1.93; p = 0.6). Complete response was the best overall bone response after 12 months in 9 patients (17%) from E arm and in 11 patients (19%) from EZ arm. In the same period, treatment was interrupted due to disease progression in 7 (13%) and 7 (12%) patients in E and EZ arm, respectively. Conclusions: The addition of Zoledronic Acid to Enzalutamide and ADT did not improve bone disease response in patients with mHSPC. WB-DW-MRI was able to detect bone responses in a great proportion of patients. Clinical trial information: NCT03336983 .
Real-world treatment and quality of life (QOL) in locally advanced or metastatic urothelial carcinoma (la/mUC) in Saudi Arabia, Singapore, South Korea, Taiwan, and Turkey.
Authors: Cheng Li-Jen , Kim Janet , Mukherjee Apurba , Milloy Neil , Unsworth Mia , Ng Daniel 
Published: March 2023

462 Background: Little is known about treatment and QOL of la/mUC in Saudi Arabia, South Korea, Turkey, and Taiwan. Therefore, this study assessed patient (pt), tumor, and disease characteristics; treatment sequencing; and QOL in pts with la/mUC treated in these countries. Methods: Data were drawn from the Adelphi mUC Disease-Specific Programme, a real-world, multinational, point-in-time study using validated methodology (Anderson et al. Curr Med Res Opin. 2008;24:3063-72) and included physician surveys, chart reviews, and pt questionnaires (Saudi Arabia, Turkey, and Taiwan only). Data were collected (12/2021–3/2022) from oncologists and urologists and adult pts with confirmed la/mUC. EQ-5D visual analogue scale (VAS; scores: 0 [worst health] to 100 [best health]) and the global health status (QL2) from the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 (scores: 0 [low functioning] to 100 [high functioning]) questionnaires were used to assess QOL. Results: Data were provided by 175 physicians for 988 pts (Turkey, n=300; Saudi Arabia, n=240; South Korea, n=298; Taiwan, n=150) with la/mUC. Mean pt age was 66.3 y; 77% were men. Most (77%) pts had no family history of urothelial carcinoma (UC); 30% recorded no risk factors (eg, genetic risk, smoking, occupational exposure). At initial UC diagnosis, the bladder was the initial tumor location in 82% of pts, of whom 67% had la/mUC, and 83% of pts had an Eastern Cooperative Oncology Group performance status 0–2. At data collection, the most common metastatic sites were the lymph nodes (53%), lungs (29%), liver (27%), and bone (21%). Biomarker/tumor testing was not done in 45% of pts. In pts initially diagnosed with nonmetastatic UC (n=346), 28% received neoadjuvant and 31% received adjuvant therapy. Of pts receiving ≥1 line of therapy (LOT) for la/mUC (n=988), 74% received gemcitabine, 60% received cisplatin, 18% received carboplatin, 17% received a programmed cell death protein 1/ligand 1 (PD-1/L1) inhibitor, and 4% received best supportive care (BSC) in the first-line (1L) setting; mean duration of therapy (DOT) in 1L was 5.7 mo. Of pts receiving ≥2 LOTs for la/mUC (n=290), 63% received a PD-1/L1 inhibitor and 35% received chemotherapy in the second-line (2L) setting; mean DOT in 2L was 4.9 mo. Of pts receiving ≥3 LOTs for la/mUC (n=87), 59% received chemotherapy (most often cisplatin [46%] or gemcitabine [38%]), 34% received a PD-1/L1 inhibitor, and 10% received BSC only in the third-line (3L) setting; mean DOT in 3L was 4.3 mo. Questionnaires were available for 319 pts. Mean (SD) EQ-5D VAS score was 51.8 (15.6); EORTC QL2 score was 44.6 (19.9). Conclusions: Pts with la/mUC in this multinational study generally received 1L platinum-based and 2L PD-1/L1 inhibitor therapies. These results highlight the need for therapies that improve clinical and QOL outcomes.
COVID-19 vaccines in patients with urothelial cancers receiving immune checkpoint inhibitors.
Authors: Gilbert Danielle , Hu Junxiao , Lam Elaine T. 
Published: March 2023

491 Background: COVID-19 vaccination recommendations for cancer patients (pts) are similar to the general population. The interaction between checkpoint inhibitors (CPI) and Sars-COV-2 vaccines has been understudied. One potential complication in pts receiving CPI is the occurrence of immune-mediated adverse events (irAEs) resulting from overactivation of the immune system. This retrospective study examined the incidence of severe irAEs in pts with bladder urothelial cancer (UC) treated with CPI therapy who received concurrent vaccinations against Sars-CoV-2. Methods: Following IRB approval, UC pts who received any approved CPI treatment since FDA authorization of the first COVID-19 vaccine in December 2020 were identified via institutional electronic health record. Pts who received 1 or more doses of an authorized vaccine within 60 days of CPI treatment were included. The primary endpoint was to evaluate the incidence of severe irAE (defined as one or more of the following: grade 3 AE or above, multi-system involvement, need for hospitalization). Secondary endpoints included time between CPI and vaccination, need for immunosuppressive therapy, and rate of discontinuation. Data was analyzed using descriptive statistics. Results: Forty pts were included in our analysis with a median age of 72.5 years (IQR: 66.0-79.2); 82% pts were male. At the time of vaccination, 37 pts (92.5%) received CPI monotherapy, 2 pts (5.0%) received combination (combo) CPI therapy, and 1 pt (2.5%) received combo platinum-based chemotherapy and CPI. The vaccine manufacturer was Pfizer Bio-N-Tech in 22 pts (55.0%), Moderna in 17 pts (42.5%), and Johnson and Johnson in 1 pt (2.5%). Number of vaccinations received was >/= 3 in 27 pts, 2 in 11 pts, and 1 in 2 pts. Six pts (15.0%) experienced severe irAEs following vaccination, including nephritis, colitis, pneumonitis, DKA, and infusion-related reaction. Rates of severe irAEs were 16.2% (6/37) with CPI monotherapy, no severe irAEs occurred in the combo CPI and combo CPI-chemo groups. Severe irAEs occurred after the first vaccine dose in 1 pt (16.7%), second dose in 3 pts (50.0%), and third dose in 2 pts (33.3%) pts. The median time between CPI treatment and vaccination in this group was 22.0 days (IQR: 15.8-36.5. Hospitalization was required for all 6 patients (100%). Three pts (50.0%) required immunosuppressive therapy with a median therapy duration of 64.0 days (IQR 47.0-83.5). Five pts (83.3%) discontinued CPI therapy following severe irAEs. Conclusions: In this retrospective study, we observed a 15% rate severe irAE in UC pts receiving CPI concurrently with COVID-19 vaccines. Further investigation in pts with additional cancer types is warranted to help determine best practice guidelines for COVID-19 vaccination in cancer patients receiving CPI. NCI University of Colorado Cancer Center Support Grant 5P30CA046934-30, Health Data Compass Data Warehouse project (healthdatacompass.org).