tbuckley/cabot-search huggingface dataset:
Can PSMA-PET be a better way to select patients for an intermittent treatment? Results from a prospective cohort.
Authors: Dr. Paulo Sergio Lages, Guilherme Augusto Zulli, Flavio Mavignier Carcano, Michelle Barbosa, Luciana Lages, Paulo Gustavo Bergerot, Diogo Augusto Rodrigues Rosa, Denis L. Jardim, Mariane Fontes Dias, Luiz Flavio Penna Coutinho, Daniel Vargas Pivato de Almeida
Journal: Journal of Clinical Oncology (2024)

e17073 Background: The current strategy for advanced disease is continuous androgen suppression, but new technologies such as PSMA-PET may set a rule for identifying some patients for new strategies. The addition of novel hormone agent (NHA) to systemic treatment of metastatic hormone sensitive prostate cancer (HSPC) has been associated with overall survival benefit and metastasis directed therapy (MDT) has been demonstrated benefit postponing ADT. There is an increasing volume of data on the use of fixed-duration NHA for patients with recurrent HSPC, most of whom are expected to present oligometastatic disease if PSMA PET/CT scans are used. We evaluate clinical outcomes of intermittent androgen deprivation therapy in patients with oligorecurrent or oligometastatic HSPC (or/omHSPC)treated with ADT + NHA + MDT, based on PSMA-PET imaging. Methods: This is a prospective cohort of patients with or/omHSPC treated with fixed-duration ADT + NHA in association with PSMA PET/CT-guided MDT (+ primary tumor irradiation if de novo metastatic) from a single institution in Brazil. Descriptive statistics was used in order to characterize the study population and relapse-free survival (RFS) after systemic therapy discontinuation (defined as PSA &gt; 0.2 ng/mL for previous prostatectomy or &gt; 2+nadir if presence of primary tumor in place) was assessed. Analysis of testosterone recovery and other clinic laboratorial factors were also performed. All patients had an undetectable level of PSA and a PSMA-PET with a complete response to be elegible to the intermittent treatment. Results: Between 2019 and 2023, 20 patients with or/omHSPC were treated with fixed-duration ADT + NHA and PSMA PET/CT-guided MDT. The median age was 64 years-old (range: 47-85), 11 patients presented with de novo omHSPC, and distribution across Gleason grades was: grade 1: 2, grade 2: 3, grade 3: 9, grade 4: 3, and grade 5: 2 patients. Metastasis were diagnosed on bone (7) and/or lymph nodes (19). Median PSA at treatment start for orHSPC population was 3.01 ng/mL (range: 0.15-14.74). The median total testosterone level prior to ADT start was 327 ng/dL (range: 22-494). Distribution across NHA was: abiraterone/prednisone: 13, enzalutamide: 4, apalutamide: 2, abiraterone&gt;enzalutamide: 1 patient. With a median follow-up of 13 months after ADT + NHA discontinuation, no patient has progressed, with 54.5% of patients already presenting testosterone recovery. Conclusions: The results of this single-center prospective cohort incorporating PET-PSMA for inclusion and monitoring patients with oligometastatic and oligorecurrent disease suggests that intermittent androgen blockage is promising in the era of NHA.
Clinician documentation of shared decision making for prostate cancer screening.
Authors: Phuong Nhi Le, Nicholas Shungu
Journal: Journal of Clinical Oncology (2024)

e17109 Background: Prostate cancer is the second leading cause of cancer death among US men and disproportionally impacts Black men. Black men are 2.2 times more likely to die from prostate cancer than non-Hispanic white men. Guidelines recommend that men make an informed decision about prostate cancer screening following a conversation with their clinician about risks and benefits. Despite known racial prostate cancer disparities, Black men receive PSA screening at lower rates than Non-Hispanic White men. Black men also report inadequate education to make informed decisions about prostate cancer screening. Little is known contemporarily about how often shared decision-making (SDM) conversations occur and how they affect rates of PSA tests. The purpose of this project was to determine the extent to which clinicians are documenting prostate cancer shared decision making conversations in men aged 45 to 69, to investigate whether this documentation differs based on patient race, and to examine the relationship between SDM conversations and completion of prostate cancer screening. Methods: This retrospective chart review included 300 Black men and 300 age-matched White men between the ages of 45 and 69 who had an outpatient visit at a Medical University of South Carolina (MUSC) outpatient family medicine clinic from 2019-2020. Frequency of documented SDM conversations by patient race and frequency of PSA ordering by patient race were analyzed using Pearson chi-squares. Multivariable logistic regression was run with documented shared decision-making conversation and screening PSA ordered as dependent variables and patient demographic and clinical data as independent variables. Results: 28.1% of Black men and 29.1% of White men completed PSA screening (p=0.68). 12.1% of Black men and 6.5% of White men had SDM conversations documented (p=0.13). Among 300 Black men, SDM was associated with increased likelihood of screening PSA (p&lt;0.01). SDM was not associated with family history of cancer, colon cancer screening, or insurance. Screening PSA was associated with insurance type among Black men (p = 0.03). Among 300 non-Black men, there was no association between SDM and screening PSA. There was also no association between insurance type and screening PSA. Conclusions: Rates of PSA screening and documented SDM conversations were strikingly low regardless of race at this large academic medical center. It is imperative that primary care clinicians engage in and appropriately document prostate cancer screening SDM conversations in order to uphold the current standard of care and reduce prostate cancer mortality. The increased likelihood of prostate cancer screening in Black men who had SDM conversations stresses the importance of these conversations in the fight to eliminate racial prostate cancer disparities.
Post-progression survival of patients with metastatic hormone-sensitive prostate cancer (mHSPC) who received darolutamide or placebo: Post hoc analysis of ARASENS.
Authors: Marc-Oliver Grimm, Matthew Raymond Smith, Maha H. A. Hussain, Fred Saad, Karim Fizazi, Natasha Littleton, Noman Paracha, Shankar Srinivasan, Frank Verholen, Bertrand F. Tombal
Journal: Journal of Clinical Oncology (2024)

5083 Background: Darolutamide (DARO) is a structurally distinct and highly potent androgen receptor pathway inhibitor (ARPI). In ARASENS (NCT02799602), the addition of DARO to androgen-deprivation therapy (ADT) and docetaxel (DOC) significantly reduced the risk of death by 32.5% in patients (pts) with mHSPC, despite most placebo (PBO) pts (75.6%) receiving subsequent therapy. DARO also delayed time to progression to metastatic castration-resistant prostate cancer (mCRPC; median, not reached vs 19.1 months for PBO), resulting in a longer time in mHSPC, which is associated with improved quality of life vs mCRPC. We report post-progression subsequent anticancer therapies and related survival from ARASENS. Methods: Pts with mHSPC were randomized 1:1 to DARO 600 mg twice daily or PBO in addition to ADT + DOC. After treatment discontinuation, pts entered active and long-term survival follow-up periods during which assessments included subsequent therapies and survival outcomes. Post-progression survival was defined as time from first subsequent therapy to death using Kaplan-Meier estimates. Results: Of 1305 treated pts (DARO n=651; PBO n=654), 315 receiving DARO and 495 receiving PBO entered follow-up. Of these, 57% (n=179) and 76% (n=374), respectively, received subsequent therapy; abiraterone and enzalutamide were the most frequent first subsequent therapy (Table). In the DARO arm, 90% of first subsequent therapies were ARPI or chemotherapy. Minimal difference was observed in post-progression survival between subsequent therapies, suggesting subsequent therapy with another ARPI does not provide further survival benefit vs non-ARPI options (mainly chemotherapy). In contrast, in the PBO arm where the majority (78%) received first subsequent therapy with an ARPI, a survival benefit was observed vs non-ARPI subsequent therapies (median, 23.0 vs 13.5 months). Conclusions: DARO+ADT+DOC increased overall survival vs PBO+ADT+DOC and also delayed time to progression to mCRPC. DARO pts had similar survival with all post-progression therapies. Pts receiving PBO+ADT+DOC quickly progressed to mCRPC and treatment with an ARPI in ARPI-naïve pts improved survival. Clinical trial information: NCT02799602 . [Table: see text]
Matching-adjusted indirect comparisons (MAICs) of talazoparib plus enzalutamide (TALA+ENZA) versus olaparib plus abiraterone and prednisone/prednisolone (OLAP+AAP) for first-line (1L) therapy in patients with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair mutations (HRRm)/BRCAm.
Authors: Elena Castro, Di Wang, Anja Haltner, Stefanie Paganelli, Alexander Niyazov, Melissa Kirker, Allison Thompson, Imtiaz Samjoo
Journal: Journal of Clinical Oncology (2024)

5063 Background: Poly-ADP ribose polymerase inhibitors (PARPi) in combination with a novel hormonal therapy (NHT) have shown benefit for the 1L treatment of mCRPC in an all-comers population as well as HRRm and BRCAm subpopulations (TALA+ENZA [TALAPRO-2; NCT03395197] and OLAP+AAP [PROpel; NCT03732820]). In the absence of head-to-head studies, their comparative efficacy is unknown. The relative efficacy of TALA+ENZA (n=200 HRRm; n=71 BRCAm) vs OLAP+AAP (n=111 HRRm; n=47 BRCAm) in these subpopulations were estimated using MAICs for radiographic progression-free survival (rPFS) based on blinded independent central review and overall survival (OS). Methods: Unanchored MAICs were conducted using individual patient data from TALAPRO-2 Cohort 2 (data cutoff [DCO]: 03/10/22 [rPFS/OS]) and published summary level data from PROpel (DCO: 30/07/21 [rPFS]; 12/10/22 [OS]). To align across the two trials, patients from TALAPRO-2 with specific HRRm/BRCAm (co-occurring or standalone) that were not assessed in PROpel were removed from the dataset for each analysis. TALAPRO-2 patients were also matched based on PROpel’s eligibility criteria and characteristics were adjusted for key prognostic factors identified in the literature and clinical expertise including prior taxane chemotherapy in castration sensitive prostate cancer (CSPC), visceral metastasis, bone only metastasis, Eastern Cooperative Oncology Group score, prostate-specific antigen levels, Gleason score, BRCA1 and BRCA2. Results: After the removal of patients with specific gene mutations not assessed in PROpel and those who received prior NHT in CSPC, 157 and 64 patients remained in the TALA+ENZA arm for HRRm and BRCAm, respectively. The comparative effect estimates for rPFS and OS are presented in the Table. None of the results were statistically significant. Conclusions: These analyses demonstrate numerically favorable results for TALA+ENZA compared to OLAP+AAP highlighting its therapeutic potential in 1L mCRPC for patients with HRRm and BRCAm. Limitations include inability to adjust for all characteristics and biases due to unobserved trial differences. [Table: see text]
Abiraterone with discontinuation of gonadotropin-releasing hormone (GnRH) analogues in patients (pts) with metastatic prostate cancer (PC): A single arm, phase II study.
Authors: Dimitrios Makrakis, Sanjay Goel, Darciann O'Sullivan, Monique White, Benjamin Adam Gartrell
Journal: Journal of Clinical Oncology (2024)

5086 Background: Abiraterone acetate (AA) is approved in metastatic PC. AA inhibits CYP17, required for androgen biosynthesis. A first in human trial suggested that AA monotherapy was inadequate to maintain castrate testosterone (T) in non-castrate men and AA development required continued GnRH analogues. However, T recovery is often delayed post GnRH analogue cessation; the need for their ongoing use to maintain castrate T with AA use is unclear and studies are limited. We present a single arm, phase II trial of pts with metastatic PC treated with AA+Prednisone (AAP) after GnRH discontinuation. Methods: We conducted a single arm, phase II study for pts with metastatic PC treated with AAP with GnRH analogue discontinuation. Entry criteria required metastatic PC treated with AAP and GnRH analogue &amp; baseline T of &lt;50 ng/dl without previous orchiectomy. After enrollment AAP was continued with GnRH analogue discontinuation. Primary endpoint was the pt proportion with castrate T (&lt;50 ng/dl) at 6 months. Secondary endpoints included time to LH normalization, PSA response, radiographic progression-free survival (rPFS) and overall survival (OS). T, PSA &amp; LH levels were monitored at 12-week intervals. We used descriptive statistics to assess the time to non-castrate testosterone levels, LH normalization time &amp; mean T, LH &amp; PSA levels at each monitoring timepoint. Results: We enrolled 31 pts; 27 were evaluable at 6 months. Median age was 69 years. Race/Ethnicity included 21 (68%) non-Hispanic black (68%) and 10 (32%) Hispanic pts. Sixteen (52%) had castration-resistant disease as AAP indication. Mean duration of ADT and AAP prior to enrollment were 29.1 (3-204) and 9.2 (1-38) months, respectively. Median follow up was 28 months. At 6 months, 25/27 (92%) patients had castrate T as did 22/26 (85%) at 12 months, 18/23 (78%) at 18 months, 16/22 (73%) at 24 months and 11/17 (65%) at 30 months. There were no treatment discontinuations due to toxicity Mean T, LH and PSA values at timepoints are reported. rPFS and OS will be reported later. Conclusions: Pts with metastatic PC treated with AAP after GnRH analogue discontinuation often remain castrate with AAP monotherapy even 30 months after GnRH analogue cessation. Phase III trials showing benefit of AAP required continued GnRH analogue; this small phase II study does not change standard of care but does suggest that further evaluation of AAP monotherapy may be warranted; AAP without use of GnRH inhibitors successfully suppressed T levels. Further randomized clinical trials are needed to assess the role of AAP monotherapy without GnRH analogues in metastatic PC. Clinical trial information: NCT03565835 . [Table: see text]
Nanoliposomal Irinotecan With Fluorouracil and Leucovorin or Gemcitabine Plus Cisplatin in Advanced Cholangiocarcinoma: A Phase II Study of the AIO Hepatobiliary-YMO Cancer Groups (NIFE-AIO-YMO HEP-0315)
Authors: Thomas J. Ettrich, Dominik P. Modest, Marianne Sinn, Jana K. Striefler, Bernhard Opitz, Thorsten Goetze, Eike Gallmeier, Stefan Angermeier, Ludwig Fischer von Weikersthal, Lutz Jacobasch, Dirk Waldschmidt, Michael Niedermeier, Michael Sohm, Andreas W. Berger, Giulia Manzini, Uli Fehrenbach, Timo Alexander Auer, Clarissa Hosse, Daniel Vogele, Disorn Sookthai, Marina Schaaf, Rainer Muche, Axel Hinke, Thomas Seufferlein, Lukas Perkhofer
Journal: Journal of Clinical Oncology (2024)

First-line therapy options in advanced cholangiocarcinoma (CCA) are based on the ABC-02 trial regimen (gemcitabine/cisplatin [G/C]). The NIFE trial examined nanoliposomal irinotecan/fluorouracil/leucovorin (nal-IRI/FU/LV) as alternative first-line therapy in advanced CCA.
Maximal androgen blockade therapy (MAB) for prostate cancer (PC) and risk of bone fractures: A systematic literature review and meta-analysis.
Authors: Fabio Turco, Isabella Saporita, Mariangela Calabrese, Federica Maria Carfi, Andrea Mogavero, Giorgio Treglia, Silke Gillessen, Massimo Di Maio, Marcello Tucci, Consuelo ButtIgliero, Ursula Vogl
Journal: Journal of Clinical Oncology (2024)

e17111 Background: Androgen deprivation therapy (ADT) increases the risk of fractures. The addition of an androgen receptor pathway inhibitor (ARPI) to ADT (MAB) has shown to improve outcomes compared to ADT monotherapy in patients (pts) with metastatic castration-resistant PC (mCRPC), non-mCRPC (nmCRPC), metastatic hormone-sensitive PC (mHSPC), high-risk localized disease and high-risk biochemical relapse. There is no definitive evidence whether MAB increases the risk of fractures compared to ADT alone. Methods: We conducted a systematic review of all clinical trials assessing treatment with an ARPI plus ADT for pts with PC having placebo plus ADT as control arm, using the PubMed/Medline and Cochrane library databases. We also performed a meta-analysis to compare the risk of fractures of each ARPI versus placebo. Further we assessed the number of pts receiving bone protecting agents (BPA) in the studies selected. The comparison between ARPI and placebo in terms of risk of fractures was performed using odds ratio (OR) as meta-analytic outcome. Results: We identified 15 studies comprising 15183 pts (8638 treated with an ARPI and 6545 with placebo), of which 3 studies evaluated abiraterone, 3 apalutamide, 3 darolutamide and 6 enzalutamide. Each ARPI resulted in a statistically significant increase in the risk of fractures compared to placebo (see table), but without statistical differences among the different ARPIs since there is an overlap between the confidence intervals (CI) of the pooled outcome measure of different ARPIs compared to placebo. Only 7/15 studies reported the number (n°) of pts treated with a BPA of which 4 were in mCRPC, 2 in nmCRPC and one in the mHSPC setting. The highest percentage was found in studies including mCRPC pts, of which 35-50% received a BPA. In the studies in the nmCRPC setting, 10-11% of pts received a BPA while in the only mHSPC study reporting data on the use of BPA only two pts (0.4%) in the ARPI group received BPA and no patient in the placebo group. Conclusions: In our meta-analysis MAB resulted in a statistically significant increase in fracture risk compared to ADT regardless of the ARPI used. Data on the use of BPA should be properly reported in future clinical trials. Since long term MAB represents the standard of care in various settings of PC, the use of a BPA should be generally recommended. Dosing and frequency of BPA needs to be adapted according to the specific PC setting. [Table: see text]
Hematologic toxicity in <sup>177</sup>lu-PSMA-617 treatment for mCRPC: Unraveling the impact of PSMA PET bone tumor volume (PSMA-bTTV).
Authors: Alireza Ghodsi, Ridvan Arda Demirci, Roman Gulati, Ruben Raychaudhuri, Heather H. Cheng, Jessica E. Hawley, Todd Yezefski, Michael C. Haffner, Robert Bruce Montgomery, Peter Nelson, Michael Thomas Schweizer, Evan Y. Yu, Delphine L. Chen, Amir Iravani
Journal: Journal of Clinical Oncology (2024)

5075 Background: Lutetium-177 prostate-specific membrane antigen ( 177 Lu-PSMA-617) is a life-prolonging treatment approved by the FDA in metastatic castration-resistant prostate cancer (mCRPC), at a very late stage when there frequently reduced bone marrow reserve. We aim to report the incidence of hematologic toxicity during treatment and potential risk factors in a single-center study. Methods: This retrospective single-institution case series included mCRPC patients who underwent at least one cycle of 177 Lu-PSMA-617 treatment between June 2022 and January 2024. Hematological parameters were documented at baseline, 3 weeks after each treatment, and before each subsequent treatment administration. Then, we captured the nadir values for each parameter during treatment. Hematologic toxicities were assessed using the Common Terminology Criteria for Adverse Events v5.0, with Grades 3 and 4 considered significant. Multivariable logistic regression analyses were conducted to investigate the association between hematological adverse events and baseline characteristics including PSMA-bTTV, measured by semi-automatic contouring of the PSMA-expressing whole-body bone metastases on pre-treatment PSMA PET. Results: Our study included 138 mCRPC patients (median age: 73y, prior chemotherapy: 92%, prior radiation: 43.5%, bone involvement: 89.1%), who underwent a median of 3 cycles (IQR: 2-5) of 177 Lu-PSMA-617 treatment. At baseline, 8 (5.8%) patients had grade 3 anemia, 2 (1.4%) patients had grade 3 leukopenia, and 1 (0.7%) patient had grade 3 thrombocytopenia. Nadir values during treatment indicated that 23 (16.7%) had grade 3 anemia, 5 (3.6%) had grade 3 leukopenia, and 11 (8%) had grade 3 and 4 thrombocytopenia. Multivariable analysis of predisposing factors for hematologic adverse events showed that the PSMA-bTTV was significantly associated with occurrence of any grade ≥3 hematologic toxicity, anemia, and thrombocytopenia after adjusting for other baseline clinical variables (Table). Conclusions: Over 1 in 5 patients with mCRPC experienced significant hematologic adverse events during treatment with 177 Lu-PSMA-617. Bone tumor volume is a possible risk factor for developing significant hematologic toxicity. [Table: see text]
Avoiding unnecessary biopsy: Development of a predictive calculator to identify non-prostate cancer in patients with Prostate Imaging Reporting and Data System category ≥ 4 lesions.
Authors: Hong Zeng, Yuntian Chen, Yandong Xie, Jindong Dai, Minghao Wang, Qian Wang, Nanwei Xu, Junru Chen, Guangxi Sun, Jinge Zhao, Hao Zeng, Pengfei Shen
Journal: Journal of Clinical Oncology (2024)

e17094 Background: The application of the Prostate Imaging Reporting and Data System (PI-RADS) has accelerated the use and promotion of multi-parameter magnetic resonance imaging (mpMRI) in prostate cancer (PCa) detection. Despite the high PCa detection rate, a considerable proportion of PI-RADS category 4 and 5 lesions are benign. The primary goal of this study is to develop and validate a prediction model for non-prostate cancer (non-PCa) in biopsy-naive patients with PI-RADS category ≥ 4 lesions. Methods: We retrospectively collected patients with PI-RADS category 4 or 5 lesions who underwent transperineal biopsies at West China Hospital from January 2018 to December 2022. Cases with prostate-specific antigen (PSA) &gt; 20 ng/ml, PCa away from the area of the index lesion, and &gt; 3 months from mpMRI to prostate biopsy were excluded. The included patients were randomly divided into a training cohort (70%) and a validation cohort (30%) for building and validating the prediction model, respectively. Logistic regression was used to screen independent predictors of non-PCa, and a nomogram was drawn based on the regression coefficients of the prediction model. The discrimination and calibration were assessed by the C-index and the calibration plots, respectively, the latter being quantified by the Brier score. Decision curve analysis (DCA) and clinical impact curve (CIC) were applied to measure the clinical net benefit. Results: A total of 1580 patients were included and the prevalence of non-PCa was 40.1%. Five independent predictors of non-PCa were incorporated into the optimal model, including age, prostate volume (PV), prostate-specific antigen density (PSAD), apparent diffusion coefficient (ADC) values, and lesion zone. The C-index was 0.925 (95%CI, 0.910-0.939) and 0.931 (95%CI, 0.910-0.953) in the training cohort and validation cohort, respectively. Favorable agreement was exhibited from the calibration curve, with a Brier score of 0.104. The DCA demonstrated an increased net benefit of the nomogram over a wide range of threshold probabilities compared to biopsy-free-all or biopsy-free-none strategy. At biopsy-free thresholds of 60%, 70%, and 80%, the nomogram was able to avoid 74.0%, 65.8%, and 55.6% unnecessary biopsies against 9.0%, 5.0%, and 3.6% of missed PCa (or 35.9%, 30.2%, and 25.1% men forewent biopsies, respectively). Conclusions: We developed the first five-item predictive model based on quantitative ADC and PSAD in patients with PI-RADS category ≥ 4 lesions. In a risk-averse scenario, the strategy may safely identify non-PCa to support clinical decision-making and reduce unnecessary prostate biopsies. [Table: see text]