bluuebunny/crossref_metadata_2025 huggingface dataset:
Synchronous double primary malignancies of the pancreatic body and extrahepatic bile duct treated with pancreatoduodenectomy and splenic artery resection following neoadjuvant chemotherapy with gemcitabine plus nab-paclitaxel: a case report
Authors: Murokawa Takahiro , Okabayashi Takehiro , Sui Kenta , Tabuchi Motoyasu , Iwata Jun
Published: February 2022

Background

Primary pancreatic cancer with synchronous primary tumors in other organs is a rare condition, and its treatment largely depends on the progression of pancreatic cancer. Here, we describe a rare case of double primary malignancies involving borderline resectable pancreatic body and extrahepatic bile duct cancers that were successfully resected after neoadjuvant chemotherapy (NAC), subsequently avoiding total pancreatectomy.

Case presentation

A 61-year-old Japanese male was referred to our hospital by his general practitioner after presenting with elevated liver enzymes during a routine check-up for type 2 diabetes mellitus. He was diagnosed with synchronous borderline resectable pancreatic cancer in the body of the pancreas and lower extrahepatic bile duct cancer with obstructive jaundice. Abdominal computed tomography (CT) confirmed a hypovascular mass in the pancreatic body with partial encasement of the common hepatic artery, left gastric artery, celiac artery, and splenic artery and invasion of the splenic vein. Endoscopic retrograde cholangiopancreatography and bile duct biopsy confirmed lower bile duct cancer. Following multidisciplinary discussion, endoscopic retrograde biliary drainage was performed, and neoadjuvant chemotherapy comprising gemcitabine plus nanoparticle albumin-bound paclitaxel (GEM + nab-PTX) was administered. After a total of seven cycles of chemotherapy, follow-up CT showed that the size of the pancreatic lesion reduced, following which the patient underwent pancreatoduodenectomy with splenic artery resection. The postoperative course was uneventful without any surgical complications or intensive hypoglycemic treatment. The pathological diagnosis was pancreatic ductal adenocarcinoma (ypT3N1aM0 ypStage IIB/UICC 8th) with synchronous extrahepatic cholangiocarcinoma (ypT2N1M0 ypStage IIB/UICC 8th). R0 pancreatic resection was performed with an Evans grade III response to neoadjuvant chemotherapy. The patient was followed up and had no tumor recurrence at 22 months after surgery with adjuvant S-1 chemotherapy, however, died after 32 months after surgery due to multiple liver metastasis and para-aortic lymph node metastasis despite salvage GEM + nab-PTX chemotherapy.

Conclusion

In our case, neoadjuvant chemotherapy for borderline resectable pancreatic cancer and function-preserving pancreatoduodenectomy (R0 resection) for double primary malignancies achieved balanced patient survival and postoperative quality of life.
START-online: acceptability and feasibility of an online intervention for carers of people living with dementia
Authors: Loi Samantha M. , Tropea Joanne , Gaffy Ellen , Panayiotou Anita , Capon Hannah , Chiang Jodi , Bryant Christina , Doyle Colleen , Kelly Michelle , Livingston Gill , Dow Briony
Published: February 2022

Background

With increasing numbers of people living with dementia relying on family to care for them at home, there is an urgent need for practical and evidence-based programs to support carers in maintaining their mental health and well-being. The objective of this study was to evaluate the acceptability and feasibility of a modified STrAtegies for RelaTives (START) program delivered online (START-online).

Method

A mixed-methods non-blinded evaluation of START-online (using Zoom as videoconferencing platform) for acceptability and feasibility (completion rates and qualitative feedback through surveys and focus groups) and quantitative evaluation. This occurred at the National Ageing Research Institute, in metropolitan Victoria, Australia.

Results

Twenty-nine eligible carers were referred, 20 (70%) consented to the study. Of these, 16 (80%) completed all 8 sessions, 2 completed only 3 sessions, and 2 withdrew. Carers’ qualitative feedback indicated that the therapist interaction was valued, content and online delivery of the program was acceptable. Feedback was mixed on the appropriate stage of caring.

Conclusion

START-online was feasible and acceptable for carers, including those living outside of metropolitan areas who might otherwise be unable to access face-to-face programs. With the recent COVID-19 pandemic necessitating social distancing to avoid infection, interventions such as this one have increasing relevance in the provision of flexible services.
Particulate matter-induced hypomethylation of Alu and LINE1 in normal human bronchial epithelial cells and epidermal keratinocytes
Authors: Lee Ji Yun , Lee Won Kee , Kim Dong Sun
Published: February 2022

Background

Airborne particulate matter (PM), a complex mixture of organic and inorganic compounds, is a major public health concern due to its adverse health effects. Understanding the biological action of PM is of particular importance in the improvement of public health. Differential methylation of repetitive elements (RE) by PM might have severe consequences for the structural integrity of the genome and on transcriptional activity, thereby affecting human health. This study aimed to evaluate the effect of inhaled and non-inhaled PM (PM2.5, PM10, and PM10-PAH) exposure on DNA methylation. We quantitatively measured the methylation content of Alu and LINE1 in PM-treated normal human bronchial epithelial cells (NHBE) and normal human epidermal keratinocytes (NHEK) by using whole-genome bisulfite sequencing and pyrosequencing.

Results

All PMs exposure significantly lowered Alu and LINE1 methylation in both cells than in mock-treated controls. Hypomethylation was more prominent in PM10-PAH exposed-NHBE and PM10 exposed-NHEK. Alu and LINE1 methylation change exhibited different sensitivity according to the subfamily evolutionary ages, with stronger effects on the oldest L1-M and Alu J in NHBE, and oldest L1-M and youngest Alu S in NHEK.

Conclusions

These results demonstrate that the differential susceptibility of PM-induced hypomethylation of Alu and LINE1 depends upon RE evolutionary age and PM type.
Staff support in a National Health Service mental health trust in response to the COVID-19 pandemic: qualitative study
Authors: Smith Holly , Zhang Shuo , Jones Abbeygail , Dorrington Sarah , Winter Helen , Beck Alison
Published: February 2022

Background

The COVID-19 pandemic has highlighted the impact work can have on healthcare workers and the importance of staff support services. Rapid guidance was published to encourage preventive and responsive support for healthcare workers.

Aims

To understand mental healthcare staff's help-seeking behaviours and access to support at work in response to the COVID-19 pandemic, to inform iterative improvements to provision of staff support.

Method

We conducted a formative appraisal of access to support and support needs of staff in a National Health Service mental health trust. This involved 11 semi-structured individual interviews using a topic guide. Five virtual staff forums were additional sources of data. Reflexive thematic analysis was used to identify key themes.

Results

Peer-based, within-team support was highly valued and sought after. However, access to support was negatively affected by work pressures, physical distancing and perceived cultural barriers.

Conclusions

Healthcare organisations need to help colleagues to support each other by facilitating open, diverse workplace cultures and providing easily accessible, safe and reflective spaces. Future research should evaluate support in the evolving work contexts imposed by COVID-19 to inform interventions that account for differences across healthcare workforces.
Longitudinal trends of "manels" and gender representation at the ASCO Genitourinary Cancers Symposium.
Authors: Huynh Melissa Jessica , Ghosh Anushka , Yeap Beow Y. , Zietman Anthony L. , Vapiwala Neha , Kamran Sophia C.
Published: February 2022

2

Background: Gender disparity in academic medicine has been a longstanding issue. Efforts have been made to recognize this imbalance and increase inclusivity. Despite this, a recent study examining the prevalence of all-male panels (“manels”) found that female faculty are significantly underrepresented at urology meetings, and nearly two-thirds of the sessions were manels. Therefore, we aimed to investigate the prevalence and longitudinal trends of manels and gender representation across genitourinary oncology disciplines at the ASCO Genitourinary Cancers Symposium (GU ASCO). Methods: GU ASCO online programs from 2018-2021 were used to obtain faculty information. Data collected included perceived gender, medical specialty, and panel role (chair/moderator vs. non-chair/non-moderator). For year 2021, additional data about the panelists, including the number of publications, H-index, citations, and academic rank, was collected. The primary outcomes were the percentage of manels and proportion of female panelists over time. Additionally, female representation among chair/moderators and specialties were evaluated. Results: Among 83 sessions involving 317 faculty members, 227 (71.6%) were males (p<0.001), and 28 panel sessions (33.7%) were manels. Between 2018 and 2020, there was a decrease in the prevalence of manels from 45% to 21.7%, but in 2021, it rose to 32.0%. The proportion of female panel members increased over time from 17.1% in 2018 to 35.7% in 2021 (p=0.012). The role of chair/moderator was predominantly represented by males (67.2%, p<0.001). The proportion of male panelists was particularly high in urology (91.2%, p<0.001) and radiation oncology (81.8%, p=0.002) compared to medical oncology (54.6%). In 2021, male speakers held higher academic rank (i.e. professor, associate, assistant) (p=0.020) and had a greater number of publications (p=0.003), H-index (p=0.009), citations (p=0.014) than females (Table). Conclusions: Over time, the number of female panelists increased with a corresponding decrease in proportion of manels, with the exception of 2021. Future studies that include data on meeting participant demographics will provide insight on whether panelists are over/under-represented in proportion to the audience. While improvements in male and female representation have been made over the years, meeting organizers should strive for representation that reflects a diversity of expertise and perspectives. [Table: see text]
Clinical results of PERICLES: A phase II trial investigating atezolizumab +/- radiotherapy for advanced squamous cell carcinoma of the penis.
Authors: de Vries Hielke Martijn , De Feijter Jeantine , Bekers Elise , Lopez-Yurda Marta , Pos Floris J. , Horenblas Simon , Jordanova Ekatarina S. , Brouwer Oscar R. , Schaake Eva E. , Van Der Heijden Michiel Simon
Published: February 2022

3

Background: Patients (Pts) with advanced squamous cell carcinoma of the penis (aPeCa) have a poor prognosis (21% 2-year overall survival from moment of diagnosis) and high morbidity, due to progressive locoregional disease. Pre-clinical studies show high rates of infiltrating immune cells and high PD-L1 expression, suggesting that immunotherapy may be beneficial for these patients. In the PERICLES study, we assess the activity of atezolizumab (atezo) in aPeCa pts, with or without radiotherapy (RT) to control locoregional lymph node disease. Methods: A single-centre phase 2 study with two treatment arms (non-randomized) was conducted in 32 histologically confirmed aPeCa pts with a WHO performance status of 0-1 (NCT03686332). Any previous treatment except for immunotherapy was allowed. Study treatment consisted of atezo 1200 mg every 3 weeks (all pts). Pts expected to benefit from RT for locoregional disease control (cohort A) additionally received 33 fractions of 1.5 Gy (locoregional affected lymph node regions and penile region) and 1.8 Gy (macroscopic tumor + margin) irradiation. Response was evaluated with 12-weekly CT scans of the abdomen and thorax using RECIST1.1. Toxicity was scored by NCI-CTCAE V4. The primary endpoint was 1-year progression free survival (PFS) for the full cohort. Results: From Oct 2018 to Aug 2021, 20 pts were included in cohort A (RT + atezo) and 12 pts in cohort B (only atezo). Median follow-up was 22 months (interquartile range (IQR) 4.3-14). Median age was 67 years (IQR 60-72) and all patients had stage IV aPeCa. Pts received no prior treatment (25%), or prior RT (34%), chemoradiation (22%), chemotherapy (6%) or surgery (69%). An immunotherapy or radiotherapy-related grade 3-4 AE was observed in 3/32 (9.4%) and 1/20 (5.0%) patients, respectively. There were no grade 5 treatment-related AEs. One-year PFS was 12% (95% confidence interval (CI) 4.0-33), which did not meet the primary objective. The response rate of RECIST1.1 evaluable pts was 30% (see table). In two patients with pulmonary metastases, a complete response was observed. Initial responses with early progression were seen in 5 pts. Median overall survival (OS) was 12 months (95% CI 5.4-19). Conclusions: Anti-tumor activity of atezo was observed in aPeCa, including complete and durable responses. The trial failed to meet its primary objective (PFS). Our results suggest that a subset of aPeCa pts has incomplete immunological activity and/or early resistance to atezo. Analysis of tumor tissue collected in this trial (including on-treatment biopsies) could suggest new therapeutic strategies to overcome resistance and improve clinical outcome to immunotherapy in aPeCa. Clinical trial information: NCT03686332. [Table: see text]
Identifying patient profiles and mapping the patient journey across three countries in a large-scale, fully digital survey of patients with prostate cancer.
Authors: Morgans Alicia K. , Lehmann Reiner , Heidenreich Axel , Allen Stephen , Carl Ernst-Günther , Wolinsky Howard , Poschenrieder Andreas , Mirante Osvaldo , O'Sullivan Joe M.
Published: February 2022

16

Background: A survey of patients with prostate cancer (PCa) was conducted to map their experiences, expectations and attitudes, and to identify challenges and unmet needs in diagnosis, therapy patterns, care teams, quality of life (QoL), patient organizations and resources. Here, we describe the initial survey results and explore differences in diagnosis and therapy patterns between 3 countries. Methods: Don’tBePatient Intelligence conducted a large survey in patients with non-metastatic (M−) and metastatic (M+) PCa in Germany (DE), the UK and the US from Feb 9–Apr 10, 2021 in collaboration with patient organizations and medical experts. Recruitment was through social media advertising and patient organizations. Data were evaluated using descriptive and advanced statistics. Results: Of 33,882 survey starters, 15,824 completed, split 50.1%/49.9% in rural/urban areas. In DE/US, diagnosis through healthcare screening was more frequent than in the UK (M−/M+: DE 77%/58%; UK 42%/21%; US 77%/63%) where a higher percentage of symptomatic diagnosis was recorded (M−/M+: DE 18%/39%; UK 49%/75%; US 12%/31%). Prostatectomy was the predominant therapy in M− PCa in DE/US (71%/57%). In the UK, radiotherapy was slightly more frequent than prostatectomy (48% vs. 41%) and active surveillance was more common than in DE/US (14% vs. 6%/9%). Hormone therapy was the most common therapy in M+ PCa in all countries (DE 65%; UK 77%; US 73%). Chemotherapy was received by < 2% of patients with M− PCa in all countries but was more frequent in M+ PCa in the UK than DE/US (38% vs. 21%/27%; table). Satisfaction levels were generally high (> 80%) for all therapies in all countries. Conclusions: To our knowledge this is the largest digital survey conducted in patients with PCa, allowing identification of unmet needs in the patient journey. Preliminary data suggest that rates of screening are lower in the UK than DE/US; this may correlate with the higher rate of symptomatic and potentially later-stage diagnosis, highlighting the role of routine screening. Relatively low active surveillance rates in DE/US may reflect a lower likelihood of men with M− versus M+ PCa to respond to the survey. Further analyses will include impact of differences in patient journey, trust in healthcare professionals, access to information, involvement with patient advocacy groups and QoL. [Table: see text]
Financial toxicity and its effect on screening for prostate and colon cancer.
Authors: Herriges Michael Joseph , Shenhav-Goldberg Rachel , Peck Juliet Irene , Shapiro Oleg , Jacob Joseph M , Basnet Alina , Bratslavsky Gennady , Goldberg Hanan
Published: February 2022

21

Background: The term ‘financial toxicity’ or ‘hardship’ is used to describe the financial problems patients experience due to high out-of-pocket costs for their healthcare. Financial toxicity in the context of cancer treatment is an area of recent study due to the significant costs associated with these treatments, but little is known about the effect of financial toxicity on cancer prevention. We examined the effects of financial toxicity on the utilization of screening tests for prevalent cancers, including prostate and colon cancer, using a US nationally representative survey-based data source. We hypothesized that patients with more financial hardship would show an association with decreased prevalence of prostate and colon cancer screening. Methods: This cross-sectional survey-based US study included men and women aged 18+ from the National Health Interview Survey (NHIS) database from January – December 2018. A financial hardship score between 0 and 1 was formulated by summarizing the responses from ten financial toxicity questions including if in the past 12 months one was unable to afford prescription medication or healthcare; or if one had to skip or take less medicine to save money. A higher score was associated with a worse financial hardship score. The primary outcomes of the study were self-reported occurrence of PSA blood testing for prostate cancer screening, and occurrence of colonoscopy for colon cancer screening. Results: As shown in table, a higher financial hardship score was associated with a decreased odds ratio for having a PSA test of 0.916 (95% CI 0.867-0.967, p=0.002) and colonoscopy of 0.969 (95% CI 0.941-0.998, p=0.039). Conclusions: Worse financial hardship is associated with a decreased probability of having PSA or colonoscopy screening tests. Awareness of this specific toxicity needs to be raised, examining the association of financial toxicity and screening of prostate, colon, and other additional cancers. [Table: see text]
Racial disparity in survival of African-American (AA) patients diagnosed with metastatic prostate cancer: Analysis of surveillance epidemiology and end results program.
Authors: Farooq Muhammad Zain , Shrivastava Trilok , Sarfraz Humaira , Ba Aqeel Sheeba Habeeb , Fu Pingfu , Mangla Ankit
Published: February 2022

28

Background: Amongst all cancers in men, prostate cancer (PCa) is the most common cancer, and the second leading cause of death. Racial disparities in PCa care in the United States (US) are known to exist. However, it is not clear if this disparity is also noted specifically in patients diagnosed with metastatic PCa (metaPCa). We analyzed the Surveillance Epidemiology and End results Program (SEER) 18 registry, to determine the racial disparity in survival of AA patients diagnosed with metaPCa compared to other races recorded in this registry. Methods: Cancer incidence data was obtained from the SEER 18 registry (2000-2018). The data was analyzed using StataMP 16 (StataCorp) software. Demographic and clinical outcomes were recorded from the registry. We performed univariate Cox regression using proportional hazard model and obtained Kaplan Meier curves to look at the difference in survival based on different age groups and race. Results: A total of 51,979 cases were identified with metaPCa, out of whom 75.8% were Whites. 40,579 deaths were recorded. Mean age group of patients with metaPCa were 70-74 years. Grade 3 poorly differentiated adenocarcinoma was noted in 54.6% patients. There was no statistically significant difference in survival of AA patients with metaPCa compared to Non-Hispanic Whites (NHW) (Hazard Ratio (HR): 0.99; 95%CI 0.96,1.03 p = 0.71) or Alaskan and American Natives (AIAN) with metaPCa (HR:1.048; 95%CI 0.91,1.21 p = 0.539). AA with metaPCa had a statistically better outcome compared to Asian and Pacific Islanders with metaPCa (HR:0.775; 95%CI 0.731,0.821 p = 0.00). Amongst patients with less than 65 years of age with metaPCa, AA patients had statistically better survival than NHW (HR: 0.94; 95% CI 0.89-0.98 p = 0.05). No statistically supported racial disparity in survival was observed in patients above 65 years with metaPCa (AA to NHW patients- HR: 0.99; 95% CI 0.96,1.03 p = 0.71). Conclusions: Although racial disparities exist in survival of all patients diagnosed with prostate cancer, when it comes to those with metaPCA, there is no statistically supported racial disparity amongst AA patients compared to NHW, except for those who are younger than 65 years where white patients have a worse outcome compared to AA diagnosed with metaPCa.
Dual-tracer PET/CT-targeted, mpMRI-targeted, systematic biopsy, and combined biopsy for the diagnosis of prostate cancer.
Authors: Qiu Dongxu , Li Jian , Zhang Jinwei , Chen Minfeng , Gao Xiaomei , Tang Yongxiang , Zhang Ye , Yi Xiaoping , Yin Hongling , Gan Yu , Wang Guilin , Zu Xiongbing , Hu Shuo , Cai Yi
Published: February 2022

34

Background: Growing evidence proved the efficacy of multiparametric MRI (mpMRI) and prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT)-guided targeted biopsy (TB) in prostate cancer (PCa) diagnosis, but there is no direct comparison between mpMRI-TB and PSMA PET/CT-TB. Gastrin-releasing peptide receptor (GRPR) highly expressed in PCa, which can compensate for the unstable expression of PSMA in PCa. Therefore, we designed a study to compare the efficiency of mpMRI-TB, dual-Tracer (GRPR and PSMA) PET/CT-TB, systematic biopsy, and combined biopsy for the diagnosis of prostate cancer. Methods: 112 suspicious PCa patients were enrolled from September 2020 and June 2021 in this prospective and comparative effectiveness study. Patients with positive dual-tracer PET/CT or mpMRI results underwent TB and all enrolled patients underwent SB after TB. The primary outcome was the detection rates of PCa in different biopsy strategies. Secondary outcomes were the performance of three imaging methods, omission diagnostic rates, and upgrading and downgrading of biopsy samples relative to those of prostatectomy specimens in different biopsy strategies. Results: In 112 men, clinically significant PCa (grade group≥2) accounted for 34.82% (39/112) and nonclinically significant PCa (grade group = 1) accounted for 4.46% (5/112). 68Ga-PSMA PET/CT-TB achieved higher PCa detection rate (69.77%) and positive ratio of biopsy cores (0.44) compared with SB (39.29% and 0.12) and mpMRI-TB (36.14% and 0.23), respectively (P < 0.005). Dual-tracer PET/CT as a triage test avoided 52.67% (59/112) unnecessary biopsy, whereas dual-tracer PET/CT-TB plus SB achieved high detection rate (77.36%) without misdiagnosis of csPCa. Conclusions: Dual-tracer PET/CT could screen patients for avoiding unnecessary biopsy. Dual-tracer PET/CT-TB plus SB might be a more effective and promising strategy for definite diagnosis of clinically significant PCa than mpMRI-TB.
Piflufolastat F 18-PET/CT in prostate cancer patients: An analysis of OSPREY (Cohorts A and B) standardized uptake value (SUV) results stratified by PSA and gleason score.
Authors: Gorin Michael A. , Rowe Steven P. , Pienta Kenneth J. , Carroll Peter R. , Pouliot Frederic , Probst Stephan , Saperstein Lawrence , Preston Mark , Alva Ajjai Shivaram , Patnaik Akash , Stambler Nancy , Siegel Barry A. , Morris Michael J.
Published: February 2022

35

Background: The OSPREY clinical trial was a phase 2/3 prospective study of prostate specific membrane antigen (PSMA) PET/CT using piflufolastat F 18. Piflufolastat F 18 (aka 18F-DCFPyL or PyL) is a novel PSMA-targeting radiopharmaceutical approved for imaging of PCa pts both at initial staging and for disease recurrence. Here we describe SUV results by biopsy status, baseline PSA levels, and Gleason score (GS). Methods: Piflufolastat F 18 -PET/CT was evaluated in men with NCCN high-risk PCa scheduled to undergo radical prostatectomy with pelvic lymphadenectomy (RP-PLND) (Cohort A) and men with radiologically suspected recurrent/metastatic PCa (Cohort B). A single IV dose of 9 mCi (333 MBq) of piflufolastat F 18 was administered followed by PET/CT acquisition 1-2 hours later. Piflufolastat F 18 uptake in various lesion locations as defined by maximum and peak SUV (SUVmax, SUVpeak) were determined by three blinded, independent central readers for each tissue (e.g., bone, lymph nodes (LN), soft tissue). To measure SUVs, the reader placed a volume of interest (VOI) on each identified lesion. SUVmax was defined as the maximum single-voxel SUV within the VOI. SUVpeak within the VOI was defined as the average SUV within a fixed-sized VOI (1 cm diameter sphere), representing the cluster with the highest average SUV. Results: 345 men underwent piflufolastat F 18-PET/CT. Cohort B (n = 93 evaluable) SUVmax and SUVpeak were significantly higher for biopsy positive (+) (one biopsy lesion/pt) when compared to biopsy negative (-) lesions from bone and LN. SUVpeak for biopsied bone and LN (Cohort B) appeared to increase with rising baseline PSA. In high-risk PCa pts, SUVpeak for prostate (Cohort A; n = 252 evaluable) increased with baseline PSA and were highest for GS 9-10 (Table). Conclusions: Piflufolastat F 18-PET/CT uptake was significantly higher in biopsy + lesions and increased with baseline PSA. Prostate SUVpeak was highest for GS 9-10. Clinical trial information: NCT02981368. [Table: see text]
68 Ga-PSMA PET/CT for preoperative lymph nosde staging of high-risk prostate cancer.
Authors: Heidenreich Axel , Schmautz Maximilian , Pfister David A. , Hartmann Florian
Published: February 2022

38

Background: The present study evaluates the potential role of 68Ga-PSMA PET/CT to detect pelvic lymph node metastases in newly diagnosed, treatment-naïve high risk prostate cancer (PCa) patients prior to radical prostatectomy and extended pelvic lymphadenectomy. Methods: A total of 165 men with newly diagnosed high risk PCa (ISUP grade 4/5, PSA > 20 ng/ml or ≥cT3a) were included in this retrospective analysis. All men had undergone a transperineal MR fusion biopsy and all men underwent RPE with epLND. Patients with neoadjuvant ADT, TRUS guided biopsies, previous radiation or surgeries in the small pelvis were excluded. Imaging findings and pathohistological findings were correlated and sensitivity, specificity, positive and negative predictive values were calculated. The correlation of clinical and biopsy characteristics with PSMA PET/CT. Results: The median PSA was 24.5 (6.7-185) ng/ml, the median number of dissected lymph nodes was 21-5 (14-45). A total of 68/165 (41,2%) patients had lymph node metastases (LNM) of which 43 (63.2%) were positive on PSMA-PET/CT whereas 25 (36.8%) LNM were negative on PSMA PET/CT. 97/165 (58.8%) pts had pN0 disease of whom 93 (95.9%) and 3 (4.1%) demonstrated negative and positive PSMA PE/CT findings, resp. n = 47 had positive PSMA PET/CT and 40 (85.1%) demonstrated LNM, 7 (14.9%) had pN0 disease. N = 118 had negative PSMA PET/CT of which 93 (78.8%) and 25 (21.2%) were true and false negative, resp. Sensitivity was 63.2%, specificity was 97.0%, and positive and negative predictive values were 93.5% and 78,8%, respectively. 3564 lymph nodes were resected, 149 (4.2%) had LNM. 88/149 (59.1%) were detected on PSMA PET/CT and 61 (40.9%) were undetected. On a per lymph node base, sensitivity and specificity were 40.4% and 94.5%, resp; positive and negative predictive values were 59.1% and 97.3%. Conclusions: PSMA-PET/CT has a high reliability to identify patients with high risk PCA and LNM. If a positive lesion is detected, epLND is mandatory due to high frequency of undetected small LNM. PSMA-PET/CT, is superior to standard imaging and it might replace CT/MRI of the small pelvis.
Do prostate MRI reports consider focal therapy when describing diagnostic findings? A descriptive review and analysis of concordance among prostate MRI reports and radical prostatectomy pathology reports.
Authors: Benidir Tarik , Hofmann Martin , Weight Christopher , Klein Eric A. , Purysko Andrei
Published: February 2022

41

Background: Focal therapy (FT) for prostate cancer (PCa) is becoming an attractive option for men seeking treatments that minimize the morbidity of whole gland therapy. Prostate MRI reports should include lesion location, presence of bilateral extension and presence of multifocality as these radiographic features are essential in selecting appropriate candidacy. We aim to evaluate concordance of disease between MRI and final pathology reports. Methods: We conducted a retrospective review of pathology reports from radical prostatectomies (RP) performed at our institution between 2016-2019, in patients whom also underwent pre-operative prostate MRI’s. The number and locations of PI-RADS ≥ 3 lesions described in MRI reports were compared against the RP findings and assessed for disease concordance in terms of lesion location, extent (unilateral vs. bilateral extent) and/or the presence of tumor multifocality. Fischer’s exact test was used for statistical analysis. Results: A total of 1593 patients underwent RP, among which 416 (26.1%) had preoperative prostate MRI’s. A majority (65.3%) (n = 273/416) of MRI’s reported a single PI-RADS > 3 lesion, 51/416 (12.3%) had negative MRI’s and 22.1% (92/416) described >2 PI-RADS ≥ 3 lesions. A total of n = 388/416 (93.2%) had detailed descriptions of their MRI and path reports for comparative analysis. MRI and final path tumor concordance with respect to unifocal extent or multifocality was low at 37.2%. When a single PI-RADS > 3 lesion was described, concordance with final path was 37.6% as compared to 55.6% when >2 lesions were described (p = 0.006). Discordant findings at final path included the presence of tumor multifocality (80.7%) or the extent of a unifocal lesion (19.3%). Lesions crossing the midline were uncommonly reported on MRI (16%). When prostate midline assessment was included in the evaluation of lesion extent, the degree of concordance with final pathology improved from 33.3% to 64.2% (p = 0.038). Conclusions: Prostate MRI reports have a large discordance with RP reports. Tumor multifocality and/or unifocal disease crossing the midline may not hold significant meaning if the disease is ultimately organ confined and the treatment is aimed at the whole gland. However, in the context of focal therapy, these findings are of germane importance. Radiologists are encouraged to consider focal therapy as a treatment strategy when describing MRI findings and acknowledge the importance of tumor multifocality/bilaterality in this context.
Attainment of early, deep prostate-specific antigen response in metastatic castration-sensitive prostate cancer: A comparison of patients initiated on apalutamide or enzalutamide.
Authors: Lowentritt Benjamin , Pilon Dominic , Khilfeh Ibrahim , Rossi Carmine , Muser Erik , Kinkead Frederic , Waters Dexter , Ellis Lorie , Lefebvre Patrick
Published: February 2022

43

Background: Deep prostate-specific antigen (PSA) response, defined as a ≥90% decline in PSA (PSA90), is an important early prognostic factor for achieving radiographic progression free survival and overall survival in patients with metastatic castration-sensitive prostate cancer (mCSPC) treated with a next generation androgen receptor inhibitor (ARI) or androgen biosynthesis inhibitor. This study compared PSA90 responses among patients with mCSPC at first use of a next generation ARI. Methods: Clinical data from 69 community urology practices in the United States were evaluated. Patients with mCSPC were classified into treatment cohorts based on their first filled prescription (index date) for apalutamide (APA) or enzalutamide (ENZ) after 12/16/2019. Patients were followed from index date until the earliest of index regimen discontinuation, treatment switch, end of clinical activity or end of data availability (03/05/2021). Included patients had ≥12 months of clinical activity to assess baseline characteristics. Inverse probability of treatment weighting (IPTW) was used to reduce baseline confounding by controlling for age, race, index year, androgen deprivation therapy (ADT) use ≥6 months, first-generation antiandrogen use, most recent PSA level, most recent testosterone level, Gleason score, and time between metastasis and the index date. PSA90 was defined as the earliest attainment of ≥90% decline in PSA relative to baseline PSA (most recent value within 13 weeks pre-index). The proportion of patients achieving a PSA90 and the time to PSA90 was compared using a weighted Kaplan-Meier (KM) analysis and weighted Cox proportional hazards models. Results: A total of 186 APA patients and 165 ENZ patients met the study criteria. Patients’ characteristics were generally well balanced after IPTW (Table). By 6 months, 73.6% of APA and 69.5% of ENZ patients had a post index PSA measurement. At 6 months, significantly more mCSPC patients initiated on APA attained PSA90 response than patients initiated on ENZ (p=0.014; Table). This result continued to remain significant at 9 months and at the end of the follow-up (Table). The median time to PSA90 was 3.1 months for APA patients and 5.2 months for ENZ patients. Conclusions: This real-world study of mCSPC cohorts demonstrates that initiation of APA leads to significantly more patients achieving a deep PSA response more rapidly than patients initiating ENZ. [Table: see text]
Practice patterns in the management of metastatic castration-sensitive prostate cancer: A single-center survey-based study.
Authors: Lu Eric , Wang Xiaoyan , Shen John
Published: February 2022

45

Background: Advanced hormonal therapies (abiraterone, enzalutamide, apalutamide) and docetaxel have demonstrated an overall survival benefit when added to androgen deprivation therapy (ADT) for metastatic castration-sensitive prostate cancer (mCSPC). There are no randomized controlled trials comparing these agents, resulting in heterogeneity in first-line therapy and sequencing of therapies. Methods: We surveyed practice patterns and underlying rationale behind first-line therapy selection for mCSPC among medical and urologic oncologists at a single center (academic and community-based practices). Responses were anonymous. We evaluated associations between responses using Friedman’s test with posthoc pair-wise comparison and Fisher exact test where appropriate. Results: From 6/2021-8/2021, we received 72/77 (94%) of distributed surveys. Of the 72 providers, 39 (31 med/onc, 8 uro/onc) reported treating mCSPC. For high-volume disease, most selected ADT plus docetaxel (41%) as first-line therapy. For low-volume disease, most selected ADT plus abiraterone (31%). There continues to be the use of bicalutamide in the treatment of low-volume mCSPC (18%). When asked to rank the most important factors when considering first-line therapy, clinical symptoms (skeletal event, bone pain, anorexia, weight loss, fatigue, visceral metastases) and disease volume were ranked higher than cost for both oncologists (p<0.01) and urologists (p = 0.03 for symptoms vs. cost and p<0.01 for disease volume vs. cost). When considering perceived barriers to selecting first-line therapy, 64% of providers identified out-of-pocket costs. Although uro/onc was less comfortable managing side effects of docetaxel compared to med/onc (0% vs. 100% comfortable, p<0.01), comfort levels with managing toxicities of hormonal therapies were comparable (100% vs. 97% comfortable, p=0.54). Conclusions: Given limitations of cross-trial comparison of efficacy from registration trials, the selection of front-line therapy for mCSPC often depends on shared decision-making. By this survey-based study, we observed docetaxel being favored for high-volume disease and abiraterone being favored for low-volume disease. Although cost did not factor into the selection of therapy, it was cited as the most common barrier faced by providers. [Table: see text]
Treatment (tx) patterns among men with metastatic castration resistant prostate cancer (mCRPC) in the United States (US).
Authors: Barata Pedro C. , Leith Andrea , Ribbands Amanda , Montgomery Rachel , Last Matthew , Arondekar Bhakti , Niyazov Alexander , Ivanova Jasmina
Published: February 2022

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Background: Novel hormonal therapies (NHTs) and docetaxel were initially approved for the tx of men with mCRPC. Over time, these agents moved earlier in the disease continuum and are now also used in metastatic castration sensitive prostate cancer (mCSPC). Little is known about first-line (1L) mCRPC tx patterns for men with prior taxane-based chemotherapy (CT) or NHT exposure. This study evaluated the impact of taxane CT or NHT use in mCSPC on recent 1L tx patterns among men with mCRPC in the US. Methods: Participating physicians collected information from medical charts for the next consecutive 4 adult men with mCRPC during January-August 2020. A subset of men had prior mCSPC tx information available. 1L mCRPC txs were described overall and stratified by previous tx with taxane CT or NHT during mCSPC. No statistical comparisons were performed. Results: 116 adult men with mCRPC and known mCSPC tx history were included. Mean age was 70 years; 15% had known family history of prostate cancer; 70% had bone metastases and 33% had visceral metastases at data collection. Overall, 10% (12/116) of men had been previously treated with taxane CT and 28% (32/116) were treated with NHT during mCSPC. 1L mCRPC tx was initiated on average 35 days after mCRPC diagnosis. NHT was the most common 1L mCRPC tx regardless of prior taxane CT or NHT use. Men pre-treated with taxane CT were more likely to initiate mCRPC tx with NHT than taxane naïve men. NHT pre-treated men were less likely to initiate 1L mCRPC tx with NHT and more likely to initiate tx with docetaxel than NHT naïve men. 53% of men with prior NHT tx were rechallenged with NHTs in 1L mCRPC. (Table). Conclusions: Findings from this US real-world study among men with mCRPC suggest physicians most commonly initiate 1L mCRPC life-prolonging tx with NHT regardless of prior taxane CT or NHT exposure. Additional studies with larger sample sizes are needed to confirm these findings and better understand optimal tx sequencing, especially as new tx options become available.[Table: see text]
Use of bone modifying agents for metastatic castrate-resistant prostate cancer.
Authors: Mitchell Aaron Philip , Meza Akriti Mishra , Farooki Azeez , Panageas Katherine , Bach Peter B. , Lipitz-Snyderman Allison , Morris Michael J.
Published: February 2022

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Background: Bone modifying agents (BMAs) prevent skeletal related events (SREs) among patients with metastatic, castrate-resistant prostate cancer (mCRPC) involving the bone. The utilization of BMAs among patients with mCRPC and bone metastasis has not been well defined, and the number of patients who may benefit but are undertreated is not known. We conducted this study to measure patterns of BMA among mCRPC patients. Methods: We used linked SEER cancer registry and Medicare claims data. Our cohort included men newly diagnosed with de-novo stage IV prostate adenocarcinoma during 2007-2015, with followup through 2016. We included those age > = 66 at diagnosis, had continuous enrollment in Medicare Parts A and B from 180 days prior to diagnosis through the outcome period and Part D from diagnosis through outcome period, and who received androgen deprivation therapy. We further limited the cohort to those who subsequently received a CRPC-defining therapy (eg., abiraterone, sipuleucel-T, docetaxel if occurring prior to CHAARTED trial results). We grouped the cohort according to those who did vs. did not have evidence of bone metastasis in claims. Our primary outcome was receipt of a BMA (zoledronic acid or denosumab) within 180 days of initiating a CRPC-defining therapy. Among patients who received BMAs after initiating CRPC therapy, we further characterized the time at which they first initiated a BMA. Results: Our sample included 1,303 patients, of which 85% had evidence of bone metastasis. Overall, 58% received a BMA within 180 days of initiating a CRPC-defining therapy. 66% of patients with evidence of bone metastasis received BMAs, compared to 16% of those without evidence. Of patients who received BMAs, 38% first received BMAs between 90 days prior to starting CRPC therapy and 180 days after; the remaining 62% were previously receiving BMAs during the castrate-sensitive phase of disease. Among patients with evidence of bone metastasis who initiated CRPC-defining therapy in 2007-2009, 65% received BMAs; this proportion was 69% and 64% for those began CRPC therapy during 2010-2013 and 2014-2016, respectively. Conclusions: Approximately two-thirds of patients with mCRPC and bone metastases received BMAs within 180 days of initiating a CRPC-defining therapy. In most cases BMA therapy was initiated while patients still had castrate-sensitive disease, for which BMAs are indicated only at lower doses for the prevention of osteoporotic fractures. Further work is needed to understand whether real-world dosing is in line with clinical indications, and whether the one-third of patients who did not receive BMA therapy appropriately reflects the proportion of patients with contraindications. Further work is also needed to characterize patient and provider factors associated with appropriate BMA use.
Preliminary results of the "DUO" observational study: Quality of life assessment and cross-sectional follow-up of prostate cancer patients treated with degarelix.
Authors: Roupret Morgan , Rozet Francois , Delattre Diane Dalila , Lacour Hugo , Ghassan Fallouh , Durand Matthieu , Mongiat Artus Pierre
Published: February 2022

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Background: The use of androgen deprivation therapy (ADT), has increased over time in the treatment of prostate cancer (PCa). ATD is accompanied by side effects, some of which may increase the cardiovascular (CV) risk. The aim of this study was to evaluate the prevalence of cardiovascular risks and quality of life at the initiation of degarelix, a GnRH antagonist, and 6 months later, in patients with advanced hormone-sensitive PCa. Methods: The DUO study is a PASS, pharmaco-epidemiologic, longitudinal, multicenter observational study. It prospectively enrolled PCa patients during the first 6 months of treatment with degarelix. cohort to describe the prevalence of real-life cardiovascular co-morbidities in. The study was carried out in 46 French urology centers. At D0 and M6, the prevalence of CV, osteoporotic, metabolic, mood disorder, geriatric and sexual morbidity and risk factors were recorded using validated tools and questionnaires. EQ-5D questionnaire measured quality of life. The evolution of the disease (PSA levels) and the tolerance of the treatments were also reported. Results: A total of 124 patients with advanced hormone-dependent PCa (of whom 26.6% were metastatic) were included. At D0 57.7% of patients had a CV morbidity and CV risk factors. Metabolic co-morbidities were also present in 60.6% of patients, osteoporotic risk factors in 34%, sexual disorders in 58%, and mood disorders in 36%. ONCO-G8 score ≤ 14 was observed in 45.6% of patients aged ≥ 70 years. The percentage of patients with CV co-morbidities remained stable (56.7%). The rates of osteoporotic, metabolic, sexual, and mood-related morbidity and risk factors also remained unaltered. Likewise, quality of life remained stable between D0 and M6 (Scores: 0.765 and 0.813 respectively). At the same time, the median PSA rate decreased by -98.4% from D0 (p < 0.001). 42 adverse events (AEs) were reported in 22 patients: degarelix-related AEs were reported in 4.4% of patients. Conclusions: The results of the DUO study showed high prevalence of CV co-morbidity and risk factors in patients with advanced PCa. It also showed no significant increase in CV co-morbidities and risk-factors during the first 6 months of treatment with degarelix as it was observed for osteoporotic, metabolic, sexual, and mood-related disorders. The GnRH antagonist was well tolerated without major impact on quality of life. Assessment of multiple co-morbidities at the initiation and during ADT is mandatory for the optimal management of patients.
Correlation of the rate of metastasis-free survival with the presence of pathogenic germline genetic mutations in patients with prostate cancer at a community practice.
Authors: Ramanathan Siddharth , Ramanathan Sadhna , Martinez Alvaro , Korman Andrew , Ghilezan Michael , Levin Michael , Gerndt Zachary Alan , Shen Nathan , Wojno Kirk , Korman Howard , Balaraman Savitha
Published: February 2022

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Background: Loeb et al. recently highlighted that academic physicians were statistically more likely to recommend genetic testing to prostate cancer patients per NCCN guidelines compared to physicians at community practices. Several articles have outlined the rate of pathogenic mutations and metastasis free survival (MFS) for prostate cancer patients treated at academic institutions. However, there is a relative paucity of equivalent data regarding patients treated at community urology clinics. We felt it was important to retrospectively review data from our large community based uro-oncology practice and present our findings in an effort to clarify this topic. Methods: We collected data on 562 prostate cancer patients treated at our multidisciplinary uro-oncology clinic between 2016 and 2018. We found 363 patients that satisfied the inclusion criteria of having germline genetic mutation testing and at least 1 year of follow-up. Patients were stratified into three categories based on the results of their germline genetic test: negative for germline mutations, positive for germline pathogenic mutations, or positive for VUS (variant of uncertain significance) mutations. Analysis of variances (ANOVA) was conducted to assess for any differences in age, Gleason score, metastasis rate, and MFS across the groups. A significance level of.05 was used. Results: All patients were treated according to guideline recommendations as was standard for the practice. There was no statistically significant difference in average age or Gleason score between the groups. There was also no statistically significant difference between the MFS across the three groups. Although the metastasis rate and MFS in the group without any mutations (9.8%, 18.3 months) was clinically significant compared to the groups with pathogenic mutations (7.5%, 16.5 months) and VUS mutations (7%, 16.6 months), the differences were not statistically significant (p=.754 and.127 respectively). Conclusions: In our community based uro-oncology practice, we found no statistically significant difference in MFS between patients with pathogenic germline mutations, patients without germline mutations, and patients with VUS mutations at 1 year of follow-up. This does not exclude the possibility of an impact of germline mutations on MFS as the data matures to reach 5 or more years of follow-up.[Table: see text]