bluuebunny/crossref_metadata_2025 huggingface dataset:
Genomic predictors of response and resistance to 177-Lu-PSMA-617 using circulating tumor DNA.
Authors: Muniz Miguel , Sartor A. Oliver , Bobek Olivia , Orme Jacob , Andrews Jack R. , Quevedo Fernando , Mahmoud Ahmed M. , Kase Adam McLain , Mosalem Osama M , Bryce Alan Haruo , Riaz Irbaz Bin , Thorpe Matthew , Burkett Brian J. , Kendi Ayse T. , Johnson Geoffrey , Ravi Praful , Kwon Eugene D. , Childs Daniel S
Published: January 2024

220

Background: There is a critical need to identify biomarkers of response and resistance to 177Lu-PSMA-617. Post-hoc analyses of VISION have explored the prognostic and predictive value of select clinical parameters. However, we are still in the early stages of deciphering which molecular changes are associated with favorable or adverse treatment outcomes. Methods: We conducted a retrospective analysis of patients with metastatic castration-resistant prostate cancer (mCRPC), who received 177Lu-PSMA-617 at Mayo Clinic in Rochester, Minnesota, in the interval of March 2022 to March 2023. We included patients who provided research authorization, had a baseline PSA of at least 2 ng/mL, received at least 2 cycles of treatment, and had circulating tumor DNA (ctDNA) genomic profiling performed by Guardant (83 gene panel) within 60 days of treatment initiation. Clinical, laboratory, genomic, and radiomic parameters were abstracted by trained research personnel. Two independent analyses of “response” and “resistance” were performed. Response to treatment was defined as 50% or greater decrease in PSA from baseline (PSA50 response: dichotomized yes versus no), and resistance was defined as non-decreasing or rising PSA during treatment (PSA non-response: dichotomized yes versus no). Associations between gene alterations and response and resistance were evaluated via Fisher’s exact tests. Results: Between March 2022 and March 2023, 273 patients received cycle 1 of 177Lu-PSMA-617. A total of 108 patients met the inclusion criteria. The median number of cycles at data cutoff was 6 (IQR: 4,6) with 57 (53%) patients receiving all 6 planned cycles. The median PSA at baseline was 16.65 ng/ml (IQR: 5.20, 66.12). A total of 65 patients (60%) experienced a PSA50 response. No molecular alterations were associated with a higher rate of PSA50 response; however, alterations in ARID1A, AR, and CHEK2 were associated with lack of PSA50 response (Fisher’s exact p < 0.05). Of the 108 evaluable patients, 20 (19%) met criteria for PSA non-response. Alterations in AR, ARID1A, MYC, TP53, CHEK2, ATM, EGFR, and NOTCH1 were significantly associated with PSA non-response (Fisher’s exact p < 0.05); in each case, the presence of the alteration was positively associated with resistance (i.e., more instance of PSA non-response). No biomarkers were found to be inversely associated with PSA non-response. Conclusions: ctDNA assessed by commercially available, targeted sequencing panels prior to treatment may be useful in identifying the patients least likely to benefit from 177Lu-PSMA-617. Further work is ongoing to integrate ctDNA findings with clinical parameters in the hopes of understanding the factors mediating response and resistance to therapy.
Comparative effectiveness of ChatGPT 4.0 and medical oncologists in telemedicine-based management of metastatic prostate carcinoma (mPC).
Authors: Dal Emre , Srivastava Ayana , Chigarira Beverly , Hage Chehade Chadi , Narang Arshit , Gebrael Georges , Ji Richard , Agarwal Neeraj , Swami Umang , Li Haoran
Published: January 2024

226

Background: The advent of telemedicine, accentuated during the COVID-19 pandemic, offers a prospective modality, especially when synergized with artificial intelligence (AI) tools such as ChatGPT 4.0. In this investigation, we sought to investigate the proficiency of ChatGPT vs. medical oncologists in the telemedicine-centric management of mPC. Methods: This IRB-approved retrospective study compared the competencies of ChatGPT and oncologists in conducting telemedicine consultations for patients with mPC. Out of 975 patients screened between April 1, 2022, and March 30, 2023, 102 met the inclusion criteria of having a diagnosis of mPC, attending at least one telemedicine consultation during the specified period, and having documentation available for two consecutive visits to enable the analysis of treatment decisions and outcomes. ChatGPT was asked to pre-chart and determine if a face-to-face consultation is needed. Its clinical competence was assessed using miniCEX, and medical decision-making (MDM). The Cohen's kappa test was used to measure the level of agreement between ChatGPT and oncologists in treatment decisions, and the Mann-Whitney U test was used to compare miniCEX and MDM. Results: The majority of patients were White (97.06%), with a median age of 75 years (range:53 to 99). Nearly all patients were diagnosed with adenocarcinoma (96.08%), with a median Gleason score of 7 (range: 6 to 10). The prevalent metastatic sites were bone (47.4%) and lymph nodes (44.16%). 26.88% had an ECOG score of 0, 54.84% had a score of 1, and 18.28% had a score greater than 1. Common coexisting conditions included diabetes mellitus (11.11%), hypertension (29.82%), hyperlipidemia (24.56%), and depression (7.6%). The primary outcome measured the concordance between ChatGPT and oncologists on whether to continue or cease the current treatment There was a statistical significance in sensitivity and specificity between clinicians and ChatGPT (Chi-squared=5.1, p=0.02). Cohen's Kappa showed a moderate concordance (Kappa = 0.43, p<0.001). There was no difference in the number of diagnoses made by the two parties (p=0.13 and 0.06, respectively). ChatGPT's median miniCEX score was 8 (SD=0.59), and its median MDM length was 41 words (SD=6.06). The average time saved by ChatGPT in pre-charting was 41 minutes (SD=6). Conclusions: ChatGPT showed moderate concordance with oncologists for the management of mPC in telemedicine. Subsequent investigations are needed to explore its potential in healthcare.
The 340B Drug Pricing Program and oral specialty drugs for advanced prostate cancer.
Authors: Faraj Kassem S , Kaufman Samuel , Herrel Lindsey A. , Oerline Mary , Caram Megan Veresh , Shahinian Vahakn B. , Hollenbeck Brent K.
Published: January 2024

26

Background: Oral specialty drugs like abiraterone and enzalutamide are increasingly used in the management of men with advanced prostate cancer. However, the costs of these drugs can pose barriers to access and continued use, particularly in the socioeconomically disadvantaged population. The 340B program allows participating hospitals to purchase these medications at steep discounts, generating millions of dollars in savings per hospital. These savings afford them the opportunity to invest in programs (e.g., drug discounts) aimed at expanding their safety net. We assessed the effect of 340B participation on the care of men with advanced prostate cancer. Methods: A 20% sample of national Medicare claims data was used to perform a retrospective cohort study of men with advanced prostate cancer from 2012 through 2019 who received their care at a hospital. The primary outcome was the initial use of an oral specialty drug for prostate cancer and secondary outcomes included associated monthly out-of-pocket costs and adherence to treatment. To account for heterogeneity, we evaluated the effects of 1) hospital 340B participation, 2) socioeconomic status, using the social vulnerability index (SVI), and 3) the interaction between hospital 340B participation and SVI on each outcome. Results: Of the men with advanced prostate cancer, 2,237 (67%) and 1,100 (33%) received care at 340B participating and non-participating hospitals. There was no difference in the use of an oral specialty drug in men who received care at a hospital participating and not participating in the 340B program (22% vs 23% p=0.63). Conversely, when assessing variation across SVI, use of an oral specialty drug decreased with increased SVI (i.e., increased vulnerability; OR 0.95, p=0.038). However, the interaction between hospital 340B participation and SVI did not affect oral specialty drug use. Neither 340B participation, SVI, nor their interaction affected patient out-of-pocket costs. Additionally, although neither hospital 340B participation or SVI affected adherence to treatment, the interaction between 340B participation and SVI was significant (OR 1.2, p=0.040). This demonstrated that 340B was associated with better adherence to treatment among more socially vulnerable men. Conclusions: The 340B program did not affect the frequency of men with advanced prostate cancer who were started on an oral specialty drug. However, among those who were already started on therapy, 340B was associated with increased adherence to treatment in more socially vulnerable men. The underlying mechanism by which this occurred was unclear. In light of growing calls from policymakers to reform the 340B program, due to concerns regarding its effectiveness, policymakers could initially shift focus towards providing hospitals with guidance on how to effectively use savings to benefit those most in need.
The effect of dual eligibility on the quality of active surveillance in patients with newly diagnosed prostate cancer.
Authors: Faraj Kassem S , Dunn Rodney , Hollenbeck Brent K. , Shahinian Vahakn B. , Herrel Lindsey A.
Published: January 2024

266

Background: Dual eligible beneficiaries are a particularly vulnerable group of patients who qualify for Medicare due to age and Medicaid due to low income. Fully dual eligible beneficiaries have access to additional support services that may facilitate coordination for their prostate cancer evaluation and treatment, while others (i.e., partial dual eligible beneficiaries) do not have access to these services. The extent to which these additional support services impact the quality of care in men on active surveillance for prostate cancer is unclear. Methods: We performed a cohort study of Medicare beneficiaries diagnosed with prostate cancer between 2015 and 2019. We identified men who were managed with active surveillance and evaluated the quality of care they received in the first year after diagnosis. Ideal surveillance was defined as having both 1-2 PSA tests and a confirmatory test (i.e., multiparametric MRI, genomics, or biopsy) at 1 year. Men who had testing below or above these thresholds were categorized as having “underuse” or “overuse” of active surveillance testing. Differences in active surveillance measures were compared between beneficiaries who were fully dual eligible, partially dual eligible, and those who were not dual eligible. Results: Of 138,785 men with newly diagnosed prostate cancer, 4,611 (3.3%) were fully dual eligible and 2,031 (1.5%) were partially dual eligible. In the year after diagnosis, 1488 (32%) fully dual eligible men, 638 (31%) partially dual eligible men, and 31,133 (31%) non-dual eligible men were managed with active surveillance. Of these men, the use of ideal surveillance was lower in dual eligible beneficiaries (full-11%, partial-9%, non-dual-15%, p<0.001). This corresponded to more underuse (full-70%, partial-74%, non-dual-63%) in dual eligible men and more overuse in non-dual eligible men (full-19%, partial-16%, non-dual-22%). The most common reasons for underuse were 1) both a lack of PSA and confirmatory testing in 26% of all men and 2) adequate PSA testing but no confirmatory test in 23% of all men. Conclusions: Our findings reveal that only a small minority of men with localized prostate cancer who are on active surveillance undergo ideal follow-up testing after diagnosis. Dual eligible men experienced less frequent ideal surveillance, potentially reflecting disparities in the quality of care for these vulnerable men. Partially dual eligible men had the worst rates of ideal surveillance and the highest rates of underuse, which may reflect the lack of support services that fully dual eligible men receive. Policymakers and healthcare providers aiming to improve the quality of active surveillance in the Medicare population should ensure that vulnerable groups have the resources needed to comply with the recommended testing.
Rural-urban disparities in prostate cancer survival: A population-based study.
Authors: Hu Siqi , Chang Chun-Pin , Dodson Mark W. , Deshmukh Vikrant , Newman Michael , Date Ankita , Sanchez Alejandro , Lloyd Shane , ONeil Brock , Hashibe Mia
Published: January 2024

267

Background: Prostate cancer is the most prevalent malignancy among men in the United States. However, only a limited number of studies have explored the impact of rural-urban disparities in survival among prostate cancer patients with long-term follow-up. In order to investigate disparities in prostate cancer survival, we assess prostate cancer mortality and prognostic factors based on rural-urban residence. Methods: A cohort of 18,134 cancer patients with prostate adenocarcinomas diagnosed between 2004 and 2017 was identified. Residential location information at the time of cancer diagnosis was used to stratify on rural-urban residence. All-cause death and prostate cancer-cause death risks were estimated using Cox proportional hazard regression models. Results: Among prostate cancer patients, 15.1% resided in rural counties in Utah. Patients living in rural counties were different in demographic and clinical characteristics compared to their urban counterparts. An association was observed between rural residence and elevated risks of all-cause mortality (HR=1.19, 99%CI=1.10-1.29) and prostate cancer-specific mortality (HR=1.21, 99%CI=1.03-1.43). Elevated risks of both all-cause and prostate cancer-specific mortality were associated to factors such as unhealthy BMI, comorbidity index ≥1, family history of cancer or prostate cancer, single marital status, low income, low socioeconomic status, government insurance, earlier year of diagnosis, advanced prostate cancer stage, and extensive cancer treatment. Furthermore, the observed disparities in demographic and clinical profiles appeared to contribute to the disparities in all-cause and prostate cancer-specific mortality risks between rural and urban prostate cancer patients. Conclusions: Rural residence exhibited a significant association with the risk of prostate cancer-related and all-cause mortality. Patients residing in rural areas demonstrated distinct factors influencing mortality risks, encompassing both demographic and clinical aspects. These findings underscore the imperative for targeted interventions aimed at mitigating the rural-urban disparities in prostate cancer outcomes.
Identifying racial disparities in adverse dispositions following major surgery for prostate cancer using machine learning.
Authors: Khosla Atulya Aman , Batra Nitya , Ganiyani Mohammad Arfat , Jatwani Karan , Singh Rohit , Chedella Venkata Lakshmi Prajwala , Roy Mukesh , Ramamoorthy Venkataraghavan , Rubens Muni B. , Saxena Anshul , Garje Rohan , Jaiyesimi Ishmael A.
Published: January 2024

269

Background: Machine learning has shown potential in accurately predicting outcomes after urologic surgery, allowing for improved patient selection, risk stratification, and predicting discharge dispositions. Healthcare disparities pose a major public health challenge, leading to unequal health outcomes for different patient groups. Successful measures to mitigate these disparities rely on precise recognition of the demographic groups impacted. In this study, we utilized AI and ML models to predict such adverse outcomes so that early intervention may lead to timely and optimal prostate cancer care. Methods: Using the 2016–2021 ACS National Surgical Quality Improvement Program (NSQIP) data, we identified 84,064 patients who underwent prostatectomy or surgeries related to excision of the prostate. We used Gradient Boosted Trees, Random Forests, and Deep Learning to examine the association between various variables from demographic, clinical, preoperative labs, past medical history domains, and non-home discharge disposition after cancer surgery. Accuracy rates were utilized to compare various models. Results: The median [Q1, Q3] age of the sample was 65.0 [59.0, 69.0] years. The total median [Q1, Q3] hospital length of stay and operation time of the sample was 1.0 [1.0, 2.0] days and 200.0 [153.0, 257.0] minutes, respectively. White non-Hispanic (WNH) patients constituted 62% (n = 52,444) of the sample, and Black non-Hispanic (BNH) were 11% (n = 9547). Smoking prevalence was higher among BNH cases (18.6%) as compared to WNH cases (10.9%). The proportion of cases requiring hypertension medication was 66.6% among BNH compared to 52.6% among WNH. The 30-day readmission rates for WNH, BNH, and White Hispanic (WH) cases were 6.4%, 6%, and 5.6%, respectively. The mortality rates for WNH, BNH, and WH cases were 0.3%, 0.3%, and 0.2%, respectively. The non-home discharge rates for WNH, BNH, and WH cases were 19.8%, 20.6%, and 22.4%, respectively. The machine learning model results showed that the Deep Learning model performed best in predicting discharge disposition after prostatectomy for prostate cancer, with an accuracy of 80.48%. Race was present in the list of important factors, indicating that race had a significant association with the outcome. Conclusions: Our study demonstrated that using a national registry, ML models can accurately identify patient populations affected by healthcare disparities. We found that racial disparities in adverse dispositions persisted after adjusting for covariates. Interventions aimed at reducing these disparities are warranted to improve the quality of life of this subgroup of patients. [Table: see text]
i-Biomarker CaDx: A circulating miRNA-based multi-cancer detection tool with explainable AI for prostate cancer.
Authors: Floares Alexandru George , Zety Adrian Vasile , Floares Carmen , Calin George , Kreutz Carvalho Eduardo , Manolache Florin
Published: January 2024

272

Background: Prostate cancer is a pressing concern, demanding early and accurate detection for effective intervention. Conventional methods, like digital rectal exams and prostate-specific antigen (PSA) tests, often lack the required specificity. Circulating microRNAs (miRNAs) have emerged as promising non-invasive biomarkers for various cancers, including prostate cancer. The i-Biomarker CaDx is a cutting-edge, technology-neutral platform designed for multi-cancer early detection, boasting an impressive accuracy rate of 99-100%. This study aims to assess the effectiveness of i-Biomarker CaDx specifically for prostate cancer using publicly endorsed datasets while leveraging explainable artificial intelligence (XAI) to gain deeper insights. Methods: The utilized dataset (GSE112264) contains 809 prostate cancer patients matched with an equal number of age-matched healthy controls from multiple datasets. Microarray technology was employed to profile circulating miRNAs. A diverse range of classification paradigms, including decision trees, neural networks, and support vector machines, were utilized for attribute identification, classification, and seamless integration of XAI. Rigorous hyperparameter optimization was conducted, and the best-performing classifiers were amalgamated into the final model, weighted by their respective efficacies. We assessed i-Biomarker CaDx's performance through rigorous cross-validation and independent test datasets. The XAI component provided detailed insights into miRNA variations associated with diagnostic outcomes. Results: Our findings reveal that i-Biomarker CaDx exhibits exceptional diagnostic accuracy, achieving a remarkable 100% accuracy rate when evaluated on the designated dataset. Diagnostic metrics, including sensitivity, specificity, and predictive values, surpass conventional prostate cancer diagnostic methods like digital rectal exams and PSA tests. The designed models, incorporating decision trees, neural networks, and support vector machines, effectively decipher intricate miRNA relationships relevant to prostate cancer using XAI. Thus, our analyses shed light on miRNA patterns and their associations with prostate cancer, enhancing the understanding of the underlying molecular complexities of the disease. Conclusions: i-Biomarker CaDx, a pioneering technology-agnostic multi-cancer early diagnostic platform, demonstrates outstanding performance in detecting prostate cancer, surpassing traditional diagnostic methods. The integration of XAI allows for in-depth exploration of miRNA alterations and their impact on prostate cancer, enriching our interpretations at both the population and individual levels. These findings underscore the substantial potential of i-Biomarker CaDx as a transformative, non-invasive diagnostic tool for prostate cancer.
Contemporary diagnosis of very low risk prostate cancer in a multi-centered hospital system.
Authors: Bennett Richard , Li Eric , Ho Austin Y. , Aguiar Jonathan , Mahenthiran Ashorne Krithiesh , Kumar Sai , Suk-ouichai Chalairat , Neill Clayton , Patel Hiten Dilip , Schaeffer Edward M. , Jawahar Anugayathri , Ross Ashley
Published: January 2024

274

Background: NCCN very low risk (VLR) prostate cancer is frequently clinically insignificant and thus over-diagnosed. Use of MRI prior to patient selection for prostate biopsy and to inform biopsy targeting can reduce the diagnosis of VLR disease. Indeed, a recent publication has reported no VLR diagnoses since 2018. We sought to better understand the incidence of VLR disease in our multi-hospital institutional cohort. Methods: We retrospectively identified 3197 patients who were newly diagnosed with prostate cancer at our eleven-hospital system from January 2018 – June 2023. Within this cohort, we identified patients who met VLR criteria. Patient clinical, pathological, and imaging characteristics were collected for analysis. Biopsies were considered MRI-informed if MRI was performed within two years prior to prostate biopsy. Biopsies were considered targeted if at least one region of interest was designated on pathology. Patients who had incomplete clinical records (n=2) were excluded from analysis. Active surveillance as initial disease management was defined as no treatment within one year of diagnosis. Welch’s two-sample t-test, Pearson’s chi-squared test, and Fisher’s exact tests were performed to compare clinical characteristics. PSA was log transformed for analysis. Results: In the study period, 11% (351/3195) of men diagnosed with prostate cancer were classified as NCCN very low risk. The incidence of VLR diagnoses was steady from 2018-2023 (p=0.8) despite increased usage of MRI-informed biopsies (p<0.001). Use of MRI-informed biopsy was similar for detection of VLR and higher risk disease (68% vs 72%, p=0.07). Of VLR patients who received a targeted biopsy, 69% (127/184) of disease was found in systematic regions only, 21% (39/184) was found in targeted regions only, and 10% (18/184) was found both systematically and in targeted regions. On multivariable analysis, black race, logPSA, and PIRADS 4 and 5 regions were negatively associated with VLR disease (Table). 86% (304/351) of VLR patients chose active surveillance as their initial disease management. Conclusions: VLR disease comprises a significant minority of prostate cancer diagnoses. The incidence of VLR has remained unchanged despite increased utilization of MRI-informed biopsies in our hospital system. In the majority of cases the diagnosis of VLR is made from the template biopsy (whether MRI-informed or not). Patients should, and frequently do, choose active surveillance to manage their disease. Use of nomograms and limiting biopsy of PI-RADS 3 lesions may decrease the incidence of VLR prostate cancer.[Table: see text]
What criteria do clinicians use to classify men as “high risk” among patients with biochemically recurrent nonmetastatic castration-sensitive prostate cancer?
Authors: Freedland Stephen J. , Ribbands Amanda , Butcher Jake , Walley Maria , Barlow Sophie , Russell David , Bland Christopher S , Touya Maelys , Ivanova Jasmina I.
Published: January 2024

300

Background: In patients with biochemically recurrent (BCR) nonmetastatic castration-sensitive prostate cancer (nmCSPC), guidelines support the use of clinical factors such as prostate-specific antigen doubling time (PSADT) and Gleason score to identify high-risk patients who are more likely to develop metastases and could benefit from earlier intervention. The current study aimed to understand criteria used by physicians in the real-world to categorize patients with BCR nmCSPC as high-risk. Methods: This analysis used data from the Adelphi Real World nmCSPC retrospective survey, completed by urologists and radiation oncologists in the US. Physicians extracted data from medical charts for their last 6–8 patients diagnosed with high-risk BCR nmCSPC since January 2021 (until July 2023). A physician attitudinal survey was also completed. Data were analyzed descriptively. Results: Overall, 84 physicians provided data (68 urologists; 16 radiation oncologists). When asked in general (not patient specific) to name clinical factors used to determine level of risk, physicians cited using multiple factors, most frequently PSADT (93%), Gleason score (88%), absolute PSA rise following definitive therapy (86%), and clinical stage (85%). PSADT was cited as the single most important clinical factor by nearly 50%, followed by Gleason score, clinical stage, and absolute PSA rise following definitive therapy (Table). For physicians who used PSADT to risk stratify, the median (IQR) threshold for high-risk was 6 (6–9) months. Aggregated patient-level data were analyzed for 352 patients with high-risk BCR nmCSPC, as defined by the physicians. Clinical factors used to classify patients as having high-risk BCR in this study included PSADT (58%), Gleason score (44%), absolute PSA rise after definitive therapy (42%), clinical stage (21%), and pathological findings at radical prostatectomy (15%). Overall, 65% of patients had a PSADT ≤9 months after BCR, and 68% had a PSADT < 12 months (high-risk per the AUA guidelines). Conclusions: Physicians reported using multiple clinical factors to classify patients as having high-risk BCR nmCSPC, with PSADT considered the most important for risk stratification. Appropriate and timely identification of patients as high-risk may help to identify patients for whom earlier intervention could be beneficial.[Table: see text]
Patients with prostate cancer consider clinical trial options significantly earlier in their journey compared to patients with other solid tumors.
Authors: Edry-Botzer Liat , Lapidot Yelena , Katz Hanna , Bader Tzvia , Gaziel Avital
Published: January 2024

305

Background: A common misconception is that oncology clinical trials (CT) are a last resort for those who have exhausted treatments or are in advanced stages. This is reflected in the patient (pt) population seeking CT and the greater focus on CT tailored to progressive, refractory, or recurrent diseases. Due to effective screening and its natural progression, prostate cancer (PC) is discovered relatively early, compared to other cancers. Effective, sophisticated non-systemic approaches for treatment are also available in the clinical and also within CT for this cancer. In this study, using real-world pt data, we explored whether those differences impact the way PC pts digitally search for CT. Methods: Leal Health, an AI-based platform, matches cancer pts to CT using pt-reported questionnaires to create individual clinical profiles. These profiles include disease status, stage, biomarkers, treatment history, diversity, and demographics. We analyzed a cohort of 35,671 pt profiles, comparing different clinical and non-clinical parameters between PC pts and those with other solid tumors (bladder, CRC, lung, breast). Results: Leal's data revealed a significantly greater proportion of newly diagnosed PC pts who actively pursued CT, in comparison to individuals diagnosed with other solid tumors (49% vs. 32%, p<0.0001). Additionally, there were significantly fewer available PC trials for newly diagnosed pts compared to relapsed/refractory cases (p<0.0001). The increase in matched trials was 1.61-fold for relapsed/refractory PC pts (p<0.0001) and 2.08-fold for pts with other solid tumors (p<0.0001). A stratified analysis showed that male gender is not a dominant driver for the difference. PC pts were often diagnosed at earlier stages with better performance status compared to other cancer types (p<0.001 for both comparisons). 51% of newly diagnosed PC pts were at stage 1, compared to only 35% of other solid tumors cancer types were. Furthermore, 12% of newly diagnosed PC cases had metastatic disease compared to 26% for other solid tumors. Conclusions: Our research highlights a shift in the traditional pt decision-making, with PC pts showing proactive interest in CT much earlier in their journey compared to other cancers. Male gender alone does not account for this significant difference, which is primarily linked to PC type. While more research is needed, immediate implications and opportunities arise. For example, the significant representation of newly diagnosed PC pts in the digital space represents an opportunity to introduce CT options to pts through this channel and invest in research and trial designs for those pt populations who are not adhering to the traditional standard of care approach before exploring CTs.
Prognostic value of FDG, PSMA, and DOTATATE uptake on PET imaging in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Pouliot Frederic , Saad Fred , Rousseau Étienne , Richard Patrick O. , Zamanian Atefeh , Probst Stephan , Levesque Eric , Castonguay Vincent , Marcoux Nicolas , Juneau Daniel , Lodde Michele , Lattouf Jean-Baptiste , Buteau François-Alexandre , Hamilou Zineb , Pavic Michel , Castilloux Jean-François , Bouvet Guillaume , Tetu Amélie , Guérin Brigitte , Beauregard Jean-Mathieu
Published: January 2024

31

Background: In mCRPC, fluorodeoxyglucose (FDG) and prostate-specific membrane antigen (PSMA) PET/CT are often used in combination for selecting patients for PSMA-radioligand therapy (PSMA-RLT). Few studies have specifically assessed the prognostic value of FDG+/PSMA- lesions, which exclude patients from PSMA-RLT. Also, little is known about the significance of somatostatin receptor expression, a potential biomarker of neuroendocrine differentiation of mCRPC, which can be assessed with DOTATATE-PET/CT. 3TMPO is a prospective study in progressing mCRPC patients who were imaged with up to 3 PET tracers. Here, we report on patient’s overall survival (OS), with respect to the presence of FDG+/PSMA- and DOTATATE+ lesions. Methods: In 3TMPO (NCT04000776, protocol in PMID 34674367), all patients had 68Ga-PSMA-617 and 18F-FDG PET/CT scans. A 68Ga-DOTATATE scan was ordered if an FDG+/PSMA- lesion was found. For all tracers, positivity was defined as lesion SUVpeak being 1.5x higher than liver SUVmean. Kaplan-Meier with log-rank test was used to assess the difference in OS between groups. Cox regression model was used to quantify the effect of factors predictive of OS. Results: The median [95% CI] OS of the 98 enrolled patients was 10.2 [8.5-11.8] mo. At least one FDG+/PSMA- lesion was found in 45 (45.9%) patients and their OS was shorter than that of the others: 5.6 [4.3-6.9] vs. not reached (p=0.0001). Six (16.2%) of 37 patients who underwent 68Ga-DOTATATE-PET had ≥1 DOTATATE+ lesion and their OS was shorter than that of patients without a DOTATATE+ lesion: 3.0 [2.2-3.7] vs. 6.4 [1.6-11.1] mo. (p=0.0004). Characteristics significantly associated with worse OS were ECOG, ISUP grade, number of metastases, number of lines of therapy, presence of visceral metastases, FDG and PSMA molecular tumor volumes (MTV) (p<0.05). In a multivariate analysis adjusted for the number of metastases and of treatment lines, the presence of an FDG+/PSMA- lesion increased the risk of death (HR [95% CI]=2.4 [1.4-4.3], p=0.002), and this was also significant after adjusting for both PSMA and FDG-MTV (HR [95% CI]=2.9 [1.4-5.8], p=0.003). Conclusions: mCRPC patients harboring FDG+/PSMA- lesion(s) had a shorter OS than those who did not, and their prognosis was even poorer if they also had DOTATATE+ lesion(s). Upfront FDG/PSMA-PET followed by DOTATATE-PET might help clinicians to guide patient towards palliative care vs. further systemic therapy, including PSMA-RLT. Clinical trial information: NCT04000776 .
Hierarchical clustering analysis for predicting 30-day readmissions after major surgery for prostate cancer.
Authors: Khosla Atulya Aman , Batra Nitya , Ganiyani Mohammad Arfat , Singh Rohit , Jatwani Karan , Chedella Venkata Lakshmi Prajwala , Roy Mukesh , Ramamoorthy Venkataraghavan , Rubens Muni B. , Saxena Anshul , Jaiyesimi Ishmael A. , Garje Rohan
Published: January 2024

311

Background: Effective risk assessment techniques and follow-up strategies are scarce for patients with prostate cancer because of the heterogeneity of the population. We aimed to conduct a study for better risk stratification, applying machine learning–based classification to patients with prostate cancer who underwent major surgery. Methods: We identified eligible patients who underwent prostatectomy or surgeries related to excision of the prostate using data from the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) for the years 2016–2021. Hierarchical clustering was conducted with variables such as age, BMI, smoking status, taking HTN medication, past medical history (diabetes, COPD, and CHF), preoperative labs (Na, BUN, creatinine, WBC count, HCT, and platelet count), operation time in minutes, and major complications. A multivariate logistic regression analysis was also conducted with a 30-day readmission as an outcome. The model accounted for cluster groups (high risk vs. low risk), among other variables. Results: The median [Q1, Q3] age of the sample ( n = 83,776) was 65.0 [59.0, 69.0] years. The participants were divided into two clusters (low-risk cluster, n = 72891; high-risk cluster, n = 10885) by hierarchical clustering, using 31 clinical variables. Patients in the high-risk cluster showed higher median levels of BUN (21 vs. 16 mg/dL), WBC count (7 vs. 6.5 /uL), platelet count (225 vs. 221/μL), and operation time (231 vs. 197 minutes). 30-day readmission rates were higher among the high-risk cluster (12.1% vs. 5.4%; p < 0.001). Similar trends were observed for minor complications (10.7% vs. 5.2%), major complications (8% vs. 2.5%), and reoperation (3.4% vs. 1.3%). Results from logistic regression showed that cases in the high-risk cluster were 1.10 (95% CI: 1.03, 1.17; p < 0.0015) times as likely to return to the hospital within 30 days of discharge as compared to the cases in the low-risk cluster (AUROC: 78.6%). Conclusions: In our study, hierarchical clustering divided prostate cancer cases into subgroups with a higher 30-day readmission risk. Applying machine learning–derived classification to prostate cancer patients undergoing major surgery may contribute to better risk stratification, leading to better prognosis and follow-up strategies.[Table: see text]
EMBARK post hoc analysis of sexual activity (SA) patient-reported outcome (PRO) measures.
Authors: Freedland Stephen J. , Mulhall John , Gleave Martin , De Giorgi Ugo , Saad Fred , Rannikko Antti , Ivanova Jasmina I. , Nasr Anchen , Reisman Arlene , Ganguli Arijit , Kral Pavol , Shore Neal D.
Published: January 2024

313

Background: In the phase 3 EMBARK trial (NCT02319837), enzalutamide (ENZ) + leuprolide (L) and ENZ monotherapy (mono) delayed metastasis-free survival (MFS) vs placebo (P) + L without impairing global health-related quality of life (HRQoL) in high-risk biochemically recurrent (BCR) nonmetastatic hormone-sensitive prostate cancer (nmHSPC) (PSA doubling time ≤9 months). A prespecified PRO analysis showed that SA (measured as a composite score using European Organization for Research and Treatment of Cancer QoL Questionnaire-Prostate 25 [QLQ-PR25]) was better preserved with ENZ mono vs P + L and no significant difference between ENZ + L vs P + L. A post hoc analysis at the HRQoL item level was conducted to understand the effect on SA in each comparison and enable shared decision-making between physicians and patients. Methods: Men with high-risk BCR nmHSPC were randomized (1:1:1) to ENZ + L (double blind), ENZ mono (open label), and P + L (double blind). HRQoL was assessed at baseline and every 12 weeks until metastasis/death. This post hoc analysis assessed effects on time to confirmed (two consecutive visits) deterioration (TTCD) using predefined thresholds of one category decline from baseline in sexual interest, activity, satisfaction, erectile function, and feeling like a man using QLQ-PR25 item 50; QLQ-PR25 item 51; FACT-P item GS7; FACT-P item BL5; and FACT-P item P5 measures, respectively (Table). Intent-to-treat principle was applied. Results: At baseline, 327–332 men per arm completed the PRO surveys; overall completion rates were ≥85%, except for GS7 (≤36% due to voluntary response). ENZ mono vs P + L : TTCD in items 50 (interest) and 51 (activity), GS7 (satisfaction), and BL5 (erectile function) was delayed with ENZ mono. ENZ + L vs P + L: no significant differences in TTCD were observed, except a shorter TTCD by a median 0.06 months in BL5 (erectile function) with ENZ + L (Table). Conclusions: This post hoc item-level analysis of the EMBARK trial confirmed that SA was better preserved with ENZ mono vs P + L in terms of interest, activity, satisfaction, and maintaining erection. Further, the SA PROs were similar between ENZ + L and P + L, implying there is no further SA burden when adding ENZ to androgen-deprivation therapy. Clinical trial information: NCT02319837 . [Table: see text]
Baseline disease characteristics of participants enrolled on ENZARAD (ANZUP1303) and DASL-HiCaP (ANZUP1801) trials of highly effective androgen receptor antagonists in high-risk localized or locally advanced prostate cancer (PCa).
Authors: Niazi Tamim , Nguyen Paul L. , Williams Scott , Stockler Martin R. , Martin Andrew James , Horvath Lisa , Thomas Hayley , Zebic Danka Sinikovic , Roncolato Felicia , Lim Tee , Jose Chakiath , Martin Jarad , Chung Hans T. , Ebacher Annie , Morgan Scott C. , Hughes Simon , McBride Sean Matthew , Kelly Paul J. , Davis Ian D. , Sweeney Christopher ,   The Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP)
Published: January 2024

328

Background: ENZARAD investigates the addition of enzalutamide or conventional nonsteroidal anti-androgens (NSAA) to radiation therapy (RT) and ADT for high-risk localized PCa. DASL-HiCaP investigates the addition of darolutamide or placebo to RT and androgen deprivation therapy (ADT) using Luteinizing hormone releasing hormone analog (LHRHA) for very-high-risk localized PCa as either primary definitive therapy, or as early salvage treatment after prostatectomy where PSA has persisted or become detectable within 12 months. Methods: The eligibility of DASL-HiCaP differed from ENZARAD by excluding patients solely based on PSA > 20ng/mL and also allowing a very-high risk patient population suitable for salvage radiation post prostatectomy. Participants in DASL-HiCaP were randomized 1:1 to darolutamide 600mg twice daily or placebo plus LHRHA for 96 weeks; all received external beam radiotherapy including mandated pelvic radiation. Participants in ENZARAD were randomized 1:1 to enzalutamide 160mg daily for 24 months or conventional NSAA for 6 months, plus LHRHA for 24 months, and EBRT. Brachytherapy boost was allowed in both trials and pelvic nodal radiation was at investigator’s discretion in ENZARAD. The primary end point for both trials is metastasis-free survival (MFS) (time from randomization to first evidence of metastasis or death from any cause). MFS events are based on conventional imaging with 99mTc bone scan and CT, and/or MRI. Lesions evident only on PSMA PET are not counted as MFS events. Results: The median age for both trials was 71-years. Complete baseline characteristics are summarised in the Table. ENZARAD randomized 802 participants across 8 countries. Half had Gleason score 9 (52%), 45% had cT3 PCa, 42% had cT2, and 11% were cN1. Gleason score 7 was present in up to 11% of ENZARAD population. DASL-HiCaP randomized 1,107 participants across 6 countries. Most had Gleason score 9 (69%), 41% had cT3 PCa, 32% had cT2, and 28% were cN1. Gleason score 7 was present in <5% of the DASL-HiCaP population. Conclusions: ENZARAD and DASL-HiCaP will define the efficacy of more potent hormonal therapy in the adjuvant setting of patients with both high- and very-high-risk disease and in both primary and salvage radiation settings. Clinical trial information: NCT02446444 and NCT04136353 . [Table: see text]
Utilization of genetic counseling and testing for patients with prostate cancer following integration of a genetic counselor into a genitourinary cancer clinic.
Authors: Byrne Lindsey , Lewis Mckenna , Wang Shihua , Clinton Steven K.
Published: January 2024

343

Background: Individuals with prostate cancer may have a 10-20% chance of harboring genetic markers for inherited risk. It is critical that germline genetic testing (GGT) is integrated into prostate cancer care to improve therapy and promote prevention and early detection for individuals and their families. We hypothesized that embedding a genetic counselor (GC) into a multidisciplinary genitourinary (GU) Cancer Clinic would enhance referrals and subsequent GGT. We created a retrospective and prospective study to evaluate the impact on genetic counseling referrals, genetic risk assessments provided, and GGT frequencies before (2016-2018) and after (2019-2022) GC integration into the GU clinic at The James Cancer Hospital at The Ohio State University. Methods: A chart review of 2,593 individuals with prostate cancer seen in the GU program from 2016 to 2022 was performed. Data was analyzed by the Chi Square test. Results: Only 39 referrals to the cancer genetics program were documented in 2016-2019 with an increase to 367 during 2019-2022, despite the COVID pandemic. During the 2016-2019 period GGT was offered to 28% and completed in 26% of referred individuals, whereas GGT was offered to 77% (P<0.0001) and completed in 64% (P<0.0001) in the subsequent period. Individuals proceeding with genetic counseling and GGT were younger in the initial period and became more broadly based in subsequent years. Black patients represented only 8% of referrals in 2016-2019 but increased to 16% in the subsequent period. Individuals with a family history of prostate cancer (P<0.0001) as well as higher Gleason grade (P<0.0001), stage (P<0.0001), metastatic disease (P<0.0001), and PSA (P=0.0507) were more likely to choose genetic counseling. Conclusions: The integration of a GU focused GC into a multidisciplinary GU Cancer Clinic at an academic program dramatically increased genetic counseling referrals, and a greater proportion of individuals with prostate cancer proceeded with GGT. Future studies will analyze barriers and factors promoting referrals to a GC so that we may continue to offer individuals and their families' evidence-based treatment and prevention options.
Subgroup analyses of efficacy outcomes by baseline tumor size in the phase 3, open-label CLEAR trial.
Authors: Grünwald Viktor , Motzer Robert J. , Haanen John B. A. G. , Schmidinger Manuela , Staehler Michael D. , Goh Jeffrey C. , Voog Eric , Climent Miguel Ángel , George Saby , Burgents Joseph E. , Xie Ran , McKenzie Jodi , Porta Camillo
Published: January 2024

364

Background: In the primary analysis of the phase 3 open-label CLEAR trial, lenvatinib + pembrolizumab (L+P) showed statistically significant and clinically meaningful improvements in progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) compared with sunitinib (S) in patients (pts) with advanced renal cell carcinoma (aRCC) (Motzer NEJM 2021). Outcomes were further corroborated by results of the final prespecified analysis of CLEAR (Motzer ASCO 2023). We report efficacy outcomes per baseline tumor size in the L+P arm of CLEAR. Methods: 1069 treatment-naïve pts with aRCC and a clear-cell component were randomized (1:1:1) to: L 20 mg PO QD + P 200 mg IV Q3W; or L 18 mg + everolimus 5 mg PO QD; or S 50 mg PO QD (4 wks on/2 wks off). Stratification factors included geographic region and MSKCC prognostic risk group. IMDC risk groups (derived programmatically) are presented in this analysis. Efficacy outcomes were evaluated by quartiles of baseline sums of diameters of target lesions. Tumor assessments were performed by independent imaging review per RECIST v1.1. Results: Pts were grouped into 4 categories: ≤Q1 (34.72 mm), >Q1 - ≤Q2 (60.06 mm), >Q2 - ≤Q3 (108.56 mm) and >Q3 per baseline tumor sizes (Table). For pts with ≤Q1 baseline tumor sizes, 40.7% and 58.0% were in the favorable and intermediate + poor IMDC risk subgroups, respectively. For pts with >Q3 baseline tumor sizes, 6.3% and 93.8% were in the favorable and intermediate + poor IMDC risk groups, respectively. Median OS, PFS, ORR, complete response (CR), partial response (PR), and near-CR (PR with maximum tumor shrinkage ≥75%) by baseline tumor size categories are in the Table. Conclusions: In CLEAR, clinically meaningful efficacy with L+P was observed across pts with aRCC irrespective of their baseline tumor sizes. These results support the use of L+P for the 1L treatment of aRCC across pts with both low and high baseline tumor size. Clinical trial information: NCT02811861 . [Table: see text]