Metastatic Prostate Cancer Research Articles

SPECT/CT in Early Response Assessment of Patients with Metastatic Castration-Resistant Prostate Cancer Receiving 177Lu-PSMA-617.

177Lu-PSMA-617 (LuPSMA) is a newly established treatment for patients with metastatic castration-resistant prostate cancer (mCRPC), but survival outcomes vary widely, and predictors of treatment responses are needed. This study investigated the role of total tumor volumes (TTVs) and new lesions (NLs) determined by LuPSMA SPECT/CT in early cycles to predict subsequent outcomes in a real-world practice setting. Methods: Between June and December 2022, consecutive patients with mCRPC who received at least 2 administrations of LuPSMA with SPECT/CT 24 h after treatment were retrospectively reviewed. We evaluated associations between TTVs and the appearance of NLs at cycles 2 and 3 with subsequent prostate-specific antigen (PSA) progression-free survival and overall survival (OS) using multivariate Cox regression. All analyses were adjusted for changes in PSA level relative to baseline. Results: Sixty-six mCRPC patients (median age, 74 y) received a median of 4 (interquartile range, 3-5) cycles of LuPSMA. Median follow-up starting at cycle 2 was 42 wk (interquartile range, 33-48 wk), with 24 of 66 patients deceased at the time of the analysis. Changes in TTV measured at the start of cycles 2 and 3 relative to baseline correlated significantly with corresponding changes in PSA level (r = 0.55 and 0.56), but absolute TTVs did not correlate significantly (r = 0.00 and 0.18). Patients with a higher absolute TTV at the start of cycle 2 had worse PSA progression-free survival and OS (hazard ratio [HR], 1.4 [95% CI, 1.1-1.8] and 2.1 [95% CI, 1.5-2.9]), with consistent results at the start of cycle 3 (HR, 2 [95% CI, 1.4-2.9] and 2 [95% CI, 1.2-3.2]). NLs were identified in 13 of 66 and 11 of 51 patients at the start of cycles 2 and 3. NLs at the start of cycle 2 were associated with worse OS (HR, 5.8 [95% CI, 1.9-17.5]), with consistent results at the start of cycle 3 (HR, 4.9 [95% CI, 1.3-18.6]). In multivariate analysis, a higher TTV and the appearance of NLs at the start of cycles 2 and 3 were independently associated with poorer OS. Conclusion: Higher TTVs and NLs on LuPSMA SPECT/CT at the start of cycles 2 and 3 were independently associated with higher risk of death. These measures provided prognostic information independent of changes in PSA. Development of prognostic and predictive models including TTV, NLs, and PSA changes is warranted.

68Ga-MY6349 PET/CT imaging to assess Trop2 expression in multiple types of cancer.

Background Considering trophoblast cell surface antigen 2 (Trop2) is overexpressed in a wide range of human epithelial cancers, it presents an attractive target for the diagnosis and treatment of multiple types of cancer. Herein, we have developed a Trop2-specific radiotracer, 68Ga-MY6349, and present a prospective, investigator-initiated trial to explore the clinical values of 68Ga-MY6349 PET/CT. Methods In this translational study, 90 patients with 15 types of cancer, who underwent 68Ga-MY6349 PET/CT, were enrolled prospectively. Among them, 78 patients underwent paired 68Ga-MY6349 and 18F-FDG PET/CT, and 12 patients with prostate cancer underwent paired 68Ga-MY6349 and 68Ga-PSMA-11 PET/CT. Results Among the 90 patients across 15 types of cancer, 68Ga-MY6349 uptake in tumors was generally high but heterogeneous, varying among lesions, patients, and cancer types. Trop2 expression level determined by immunohistochemistry was highly correlated with 68Ga-MY6349 uptake at primary and metastatic tumor sites. 68Ga-MY6349 PET/CT showed higher tumor uptake (quantified by SUVmax) than 18F-FDG PET/CT in certain types of cancer, including breast (7.2 vs. 5.4, P < 0.001), prostate (9.2 vs. 3.0, P < 0.001), and thyroid cancers (8.5 vs. 3.7, P < 0.001). When compared with 68Ga-PSMA-11, 68Ga-MY6349 PET/CT exhibited comparable lesion uptake (12.2 vs. 12.5, P = 0.223) but a better tumor-to-background contrast (15.8 vs. 12.2, P < 0.001) for primary and metastatic prostate cancer, allowing visualization of more metastatic lesions. Conclusion 68Ga-MY6349 PET/CT is a non-invasive method for comprehensively assessing Trop2 expression in tumors, which can improve the diagnosis and staging for cancer patients, and aid in the decision-making for Trop2-targeted therapies and advancing personalized treatment.

Biochemical recurrence after open radical prostatectomy in a single-center cohort with a minimum follow-up of 10 years

Purpose: To investigate the long-term oncological outcomes and report biochemical recurrence (BCR)-free survival for men who underwent open radical prostatectomy at a single center. Materials and methods: A total of 360 patients who underwent open radical prostatectomy at our institution between 2003 and 2011 were included in this study. The BCR-free survival rates were calculated by Kaplan-Meier method and log-rank analysis. Multivariable Cox regression models were used to test the effect of other factors such as age, preoperative prostate-specific antigen (PSA), Gleason score, and surgical margins on BCR. Results: Median patient age was 65.4 years, with a median preoperative PSA level of 6.21 ng/ml. Operating time had a median duration of 155.1 minutes, ranging from 104 to 301 minutes. Nerve-sparing surgery was achievable in 48.1% of patients, including 34.2% undergoing bilateral procedures and 13.9% unilateral. In terms of surgical precision and outcomes, the overall rate of positive surgical margins was 23.6%, which decreased significantly to 11.1% in patients with localized prostate cancer. Lymph node involvement occurred in 3.6% of cases. Postoperative care statistics revealed a median catheterization duration of 9.1 days (range: 4–30 days) and a low rate of significant complications (4.4%). The early continence rate in a standardized pad test was 80.6%. At a median follow-up of 150.5 months, the 5-year and 10-year BCR-free survival rates for the entire cohort were 91.4% and 77.5%, respectively. The 10-year BCR-free survival rates were 84.8%, 81.5%, and 68.5% for low-, intermediate-, and high-risk patients, respectively. Furthermore, the 10-year BCR-free survival rates were 78.8% and 62.8% for localized and locally advanced prostate cancer, respectively. Preoperative PSA &gt;20 ng/ml, postoperative Gleason sum ≥3 + 4, and positive surgical margins were associated with increased risk of BCR on multivariable Cox regression analysis. Conclusion: Our long-term oncological results match or exceed those previously published in similar contemporary cohorts with long follow-up.

Plain language review: the safety of relugolix combination therapy for advanced prostate cancer.

Advanced prostate cancer is a cancer that began in the prostate (a part of the male body) and has spread to other parts of the body. This is a review of two clinical research studies of patients with advanced prostate cancer who were treated with relugolix combination therapy. Relugolix is a medicine taken by mouth that lowers a male sex hormone, called testosterone. Relugolix is sometimes combined with other medicines such as novel hormonal therapies (NHTs) or chemotherapy to treat advanced prostate cancer. In one study, patients were treated with relugolix combined with an NHT (abiraterone or apalutamide). In a second study, patients were treated with relugolix combined with an NHT (enzalutamide) or chemotherapy (docetaxel). Researchers wanted to understand what possible side effects may happen due to taking these medicines together as prescribed. They also wanted to see if relugolix combination therapy worked to lower testosterone in the same way as relugolix taken alone. Researchers found that most of the side effects of relugolix combined with an NHT or chemotherapy were mild or moderate. Side effects of relugolix combination therapy were similar to the side effects of the medicines when taken alone. However, patients who received relugolix with enzalutamide or docetaxel were more likely to have a serious side effect compared with patients who received relugolix taken alone. Testosterone stayed below 50 nanograms per deciliter (known as castration levels) for patients who received relugolix with NHT or chemotherapy. Patients who receive relugolix combination therapy generally experience mild or moderate side effects, rather than serious side effects. No new safety issues were found during these studies. Patients maintained low testosterone levels. Patients and their doctors should discuss the benefits and possible harms of relugolix combination therapy to treat advanced prostate cancer.

Repeatability of quantitative MR fingerprinting for T1 and T2 measurements of metastatic bone in prostate cancer patients.

MR fingerprinting (MRF) has the potential to quantify treatment response. This study evaluated the repeatability of MRF-derived T1 and T2 relaxation times in bone metastasis, bone, and muscle in patients with metastatic prostate cancer. This prospective single-centre study included same-day repeated MRF acquisitions from 20 patients (August 2019-October 2020). Phantom and human data were acquired on a 1.5-T MR scanner using a research MRF sequence outputting T1 and T2 maps. Regions of interest (ROIs) across three tissue types (bone metastasis, bone, muscle) were drawn on two separate acquisitions. Repeatability of T1 and T2 was assessed using Bland-Altman plots, together with repeatability (r) and intraclass correlation (ICC) coefficients. Mean T1 and T2 were reported per tissue type. Twenty patients with metastatic prostate cancer (mean age, 70 years ± 8 (standard deviation)) were evaluated and bone metastasis (n = 44), normal-appearing bone (n = 14), and muscle (n = 20) ROIs were delineated. Relative repeatability of T1 measurements was 6.9% (bone metastasis), 32.6% (bone), 5.8% (muscle) and 21.8%, 32.2%, 16.1% for T2 measurements. The ICC of T1 was 0.97 (bone metastasis), 0.94 (bone), 0.96 (muscle); ICC of T2 was 0.94 (bone metastasis), 0.94 (bone), 0.91 (muscle). T1 values in bone metastasis were higher than in bone (p < 0.001). T2 values showed no difference between bone metastasis and bone (p = 0.5), but could separate active versus treated metastasis (p < 0.001). MRF allows repeatable T1 and T2 measurements in bone metastasis, bone, and muscle in patients with primary prostate cancer. Such measurements may help quantify the treatment response of bone metastasis. Question MR fingerprinting has the potential to characterise bone metastasis and its response to treatment. Findings Repeatability of MRF-based T1 measurements in bone metastasis and muscle was better than for T2. Clinical relevance MR fingerprinting allows repeatable T1 and T2 quantitative measurements in bone metastasis, bone, and muscle in patients with primary prostate cancer, which makes it potentially applicable for disease characterisation and assessment of treatment response.

The impact of progression-directed therapy on survival in metastatic castration-refractory prostate cancer: MEDCARE phase 3 trial.

Metastatic castration-refractory prostate cancer (mCRPC) presents a therapeutic challenge despite advancements in treatment. Once mCRPC is attained, patients face limited survival prospects. Next-line systemic treatment (NEST) is the standard of care for progressive mCRPC, encompassing various therapeutic options with associated toxicity and costs. In patients with oligoprogressive mCRPC, data suggest that progression-directed therapy (PDT), such as metastasectomy or stereotactic body radiotherapy, delays the initiation of NEST. The MEDCARE phase III trial aims to assess the impact of PDT on overall survival (OS) in oligoprogressive mCRPC. In this multicentric, randomised, prospective trial, we aim to randomise 246 patients in 1:1 allocation ratio between the standard-of-care therapy (surveillance or NEST) or PDT while continuing the current systemic treatment. Patients will be stratified based on number of progressive lesions (one vs ≥one), location of progressive lesions (local recurrence, N or M1a vs M1b or M1c) and previous systemic therapy (palliative androgen-deprivation therapy [pADT] vs pADT + androgen receptor-targeted agent or patients who received docetaxel in the past). The primary endpoint is OS, and the secondary endpoints include quality of life, radiographic progression-free survival (PFS), modified PFS, prostate cancer-specific survival and PDT-induced toxicity. This is the first randomised phase 3 trial in the setting of PDT in patients with oligoprogressive mCRPC with OS as the primary endpoint.

Phase II trial of multi-tyrosine kinase inhibitor ESK981 in combination with PD-1 inhibitor nivolumab in patients with metastatic castration-resistant prostate cancer.

Increasing the response rates of immune checkpoint inhibitors in patients with metastatic castration-resistant prostate cancer (mCRPC) presents a significant challenge. ESK981 is a multi-tyrosine kinase and PIKfyve lipid kinase inhibitor that augments immunotherapeutic responses. In this phase II study, ESK981 was combined with the PD-1 blocking monoclonal antibody nivolumab to test for potentially improved response rates in patients with mCRPC who have progressed on androgen receptor (AR)-targeted agents and chemotherapy. Eligible patients received ESK981 orally once daily for five consecutive days, followed by a two-day break. Patients were also treated with nivolumab intravenously on Day 1 of each 28-day cycle. The primary endpoints were a 50% reduction in prostate-specific antigen (PSA50), and safety. Secondary endpoints included radiographic progression free survival (rPFS) and overall survival (OS). Additional investigations included whole exome sequencing in patients. Ten patients were enrolled. The maximum PSA decline from baseline of 14% was achieved in only one patient. Grade 3 treatment-related adverse events (AEs) included fatigue, anemia, and lymphopenia. There were no Grade 4 events. The median rPFS was 3.7 months (95% CI, 1.6-8.4). The median OS was 9.6 months (95% CI, 1.8-22.4). The study was terminated due to futility after 10 patients. Whole exome sequencing identified AR amplification in 63% of patients (5/8). ESK981 + nivolumab showed no antitumor activity in patients with AR-positive (AR+) mCRPC. Further evaluation of ESK981 combined with the PD-1 inhibitor nivolumab in AR + mCRPC patients is not warranted. (Trial registration: ClinicalTrials.gov NCT04159896. Registration date: November 12, 2019.).

Combined Nabpaclitaxel pressurized intraPeritoneal aerosol chemotherapy with systemic Nabpaclitaxel-Gemcitabine chemotherapy for pancreatic cancer peritoneal metastases: protocol of single-arm, open-label, phase II trial (Nab-PIPAC trial).

Current therapies show limited efficacy against peritoneal metastases (PM) from pancreatic cancer. Pressurized intra-peritoneal aerosol chemotherapy (PIPAC) has emerged as a novel intraperitoneal drug delivery method. Recently, a dose-escalation study identified the safe dose of Nabpaclitaxel for PIPAC administration, an ideal intraperitoneal chemotherapy agent against pancreatic cancer. Combining systemic NabPaclitaxel-Gemcitabine with NabPaclitaxel-PIPAC may enhance disease control in pancreatic cancer patients with PM. The Nab-PIPAC trial is a single-center, prospective, open-label, phase II study (ClinicalTrials.gov identifier: NCT05371223). Its primary goal is to evaluate the antitumor activity of the combined treatment based on Disease Control Rate (DCR) using RECISTv.1.1 criteria. Secondary objectives include feasibility, safety, pathological response, progression-free and overall survival, nutritional status, quality of life, pharmacokinetics of NabPaclitaxel-PIPAC, and PM molecular evolution via translational research. The treatment protocol consists of three courses, each with two cycles of intravenous NabPaclitaxel-Gemcitabine and one cycle of NabPaclitaxel-PIPAC, with standard metastatic pancreatic cancer doses for the former and 112.5 mg/m2 for the latter. Sample size follows Simon's two-stage design: 12 patients in stage one and 26 in stage two (80 % power, 0.1 alpha). Partial results will be available after first stage enrollment. This trial aims to determine the antitumor efficacy and safety of combining NabPaclitaxel-PIPAC with systemic NabPaclitaxel-Gemcitabine in pancreatic cancer patients with PM.

2023 expert consensus on decision pathway of metastatic hormone-sensitive prostate cancer management in Taiwan

This short communication presents a consensus-based expert opinion from a multidisciplinary team of Taiwanese experts in urology, medical oncology, and radiation oncology regarding the management of metastatic hormone-sensitive prostate cancer (mHSPC). Through a comprehensive review of recent clinical trials examining the efficacy of novel hormonal agents (NHAs) and docetaxel, alongside updated guidelines for mHSPC management, the experts have deliberated on the practical implications from currently available literatures. The discussion focused on the combination of androgen deprivation therapy, NHAs, and docetaxel, as reported in the leading studies including ARASENS (ODM-201 in Addition to Standard ADT and Docetaxel in Metastatic Castration Sensitive Prostate Cancer), ENZAMET (Enzalutamide in First Line Androgen Deprivation Therapy for Metastatic Prostate Cancer), and PEACE-1 (A Phase III Study for Patients with Metastatic Hormone naive Prostate Cancer) trial. The risk-benefit ratio between prolonged overall survival and the incidence of major adverse events was thoroughly evaluated. This consensus underscores the recommendation that early initiation of intensified triplet therapy with docetaxel, NHA, and androgen deprivation therapy is beneficial for fit mHSPC patients with highly aggressive disease characteristics, effectively prolonging overall survival with manageable risk of adverse events.

Possibilities of radiological methods of diagnosis of metastatic castration-resistant prostate cancer (Review Article).

Abstract Metastatic castration-resistant prostate cancer (mCRPC) is characterized by the progression of the tumor process when it becomes unresponsive to androgen-deprivation therapy. The incidence of bone metastases in these patients reaches up to 90%. Imaging modalities play a pivotal role in the diagnosis of this oncological condition. Computed tomography (CT) and magnetic resonance imaging (MRI) offer advantages in anatomical visualization; however, they face limitations in assessing the efficacy of prostate cancer treatment. Scintigraphy is applicable in screening for skeletal bone metastatic involvement but has limitations in assessing disease progression. Positron emission tomography combined with computed tomography (PET/CT) and single-photon emission computed tomography (SPECT/CT) are utilized for early detection of local or systemic spread of prostate cancer. The assessment of quantitative data on radiopharmaceutical uptake using PSMA PET imaging is used for predicting the efficacy of antitumor therapy. With the introduction of the radiopharmaceutical 177Lu-PSMA into clinical practice, the perspective of conducting radionuclide therapy with simultaneous efficacy evaluation through hybrid imaging methods has emerged. The capabilities of imaging modalities in assessing bone metastases present a particular interest for research and systematization of the data obtained to develop optimal parameters for conducting radioligand therapy and evaluating its efficacy. Aims: To explore the capabilities of imaging modalities in diagnosing metastatic castration-resistant prostate cancer. Conclusions: The analyzed literature data indicate that imaging methods for diagnosing mCRPC vary in sensitivity and specificity, have their advantages and disadvantages, which underscores the necessity for a comprehensive approach in their utilization. The development and advancement of methods for quantitative assessment of treatment efficacy, identification of prognostic markers can influence a more informed choice of treatment tactics and radiopharmaceutical selection, potentially leading to an increase in overall survival.

TPX2 serves as a novel target for expanding the utility of PARPi in pancreatic cancer through conferring synthetic lethality

BackgroundPARP inhibitors (PARPi) have been licensed for the maintenance therapy of patients with metastatic pancreatic cancer carrying pathogenic germline BRCA1/2 mutations. However, mutations in BRCA1/2 are notably rare in pancreatic...

Unveiling the chasm of economic burden from metastatic prostate cancer through a nationwide retrospective cohort study

Objective To analyze the clinical and economic consequences of the progression to castration-resistant status for patients with metastatic hormone-sensitive prostate cancer (mHSPC) and metastatic castration-resistant prostate cancer (mCRPC) in South Korea. Methods This retrospective cohort study was conducted using National Health Insurance claims data from 2013 to 2021. Patients defined as newly diagnosed with mHSPC had an index date of first claim for metastatic PC between 2015 and 2016 and no exposure to CRPC medicines during the washout period. All-cause monthly medical and end-of-life costs were described for mHSPC and mCRPC. Descriptive statistics were used to analyze medical costs, and generalized estimating equations were used to evaluate the correlation between medical costs and significant variables, including disease progression, death, and clinical characteristics. Results Of the 3,739 patients with mHSPC included (mean 72.9 years), 779 progressed to mCRPC. The overall study population underwent a median 60.48-months follow-up period. The average monthly medical cost depending on CRPC progression was 1.5 times in the mCRPC than in the mHSPC group ($1,734.2 vs. $1,185.4). Monthly medical costs for those who progressed to mCRPC were 2.4 times one year after progression than one year before. In all groups, the average total medical costs gradually increased near mortality. Disease progression and death had a significant correlation with medical costs, by 1.7 times and 2.46 times, respectively. Conclusion This study highlights the economic and health benefits of preventing progression to castration resistance in patients with mHSPC based on real-world data.

Prognostic role of prostate specific antigen kinetics in primary high volume metastatic hormonal sensitive prostate cancer treated with novel hormonal therapy agents

The prognostic value of prostate-specific antigen (PSA) kinetics in primary high-volume metastatic hormone-sensitive prostate cancer (mHSPC) patients treated with novel hormonal therapy agents is still unclear. Here, we retrospectively reviewed the data of 102 patients with primary high-volume mHSPC who received novel hormonal therapy agents. The median follow-up was 32.25 ± 14.51 months and the median nadir PSA (nPSA) was 0.20 (0.06, 11.71) ng/mL after treatment. The mean time to nPSA was 10.82 ± 7.27 months and 55 patients (53.9%) had a PSA-density (PSA-D) ≤ 0.08 at 3-months. Univariate and multivariate Cox regression analyses showed that the absence of visceral metastases, nPSA ≤ 0.2 and PSA-D ≤ 0.08 were independent prognostic factors for better PFS and OS (all P < 0.05). Moreover, patients with nPSA ≤ 0.2 and PSA-D ≤ 0.08 had the best PFS and OS, and the combination of the nPSA and PSA-D had a better predictive accuracy for PFS and OS than nPSA and PSA-D alone. Thus, Visceral metastases, nPSA and PSA-D were independent prognostic factors for primary high-volume mHSPC patients treated with novel hormonal therapy agents. Patients with lower nPSA and PSA-D had a best survival outcome, and the combination of nPSA and PSA-D had a better effect on prognosis predicting.

Unearthing a prostate cancer cfDNA signature that "stems" from AR alterations.

Androgen receptor (AR) alterations portend a poor prognosis in patients with advanced prostate cancer. A recent study identified a stemness signature enriched in cell-free DNA from AR-altered patients, associated with worse outcomes. These findings highlight the potential of epigenomic liquid biopsy tools to discover novel clinically relevant tumor molecular subtypes.

Role of non-coding RNA in lineage plasticity of prostate cancer.

The treatment of prostate cancer (PCa) has made great progress in recent years, but treatment resistance always develops and can even lead to fatal disease. Exploring the mechanism of drug resistance is of great significance for improving treatment outcomes and developing biomarkers with predictive value. It is increasingly recognized that mechanism of drug resistance in advanced PCa is related to lineage plasticity and tissue differentiation. Specifically, one of the mechanisms by which castration-resistant prostate cancer (CRPC) cells acquire drug resistance and transform into neuroendocrine prostate cancer (NEPC) cells is lineage plasticity. NEPC is a subtype of PCa that is highly aggressive and lethal, with a median survival of only 7 months. With the development of high-throughput RNA sequencing technology, more and more non-coding RNAs have been identified, which play important roles in different diseases through different mechanisms. Several ncRNAs have shown great potential in PCa lineage plasticity and as biomarkers. In the review, the role of ncRNA in PCa lineage plasticity and its use as biomarkers were reviewed.

Experience of rescue therapy with [177Lu]Lu-rhPSMA-10.1 in patients with primary or acquired resistance to [177Lu]Lu-PSMA-I&T.

Radioligand therapy is an increasingly important option for the treatment of metastatic castrate-resistant prostate cancer (mCRPC). Radiohybrid ligands targeting prostate-specific membrane antigen (PSMA) are a novel group of theranostic radioligand therapy agents for which higher tumour absorbed radiation doses have been demonstrated compared to established PSMA ligands. Here, we report data from ten patients who were treated within a compassionate use program with the radiohybrid PSMA-ligand [177Lu]Lu-rhPSMA-10.1 after experiencing disease progression under treatment with [177Lu]Lu-PSMA-I&T. Ten patients with advanced PSMA-positive prostate cancer who showed progression under treatment with [177Lu]Lu-PSMA-I&T received up to three cycles of rescue therapy with [177Lu]Lu-rhPSMA-10.1 (7.4-8.1 GBq per cycle). Efficacy (PSA response according to PCWG3 and RECIP) and overall survival were evaluated. Adverse events were recorded from first application. Despite progression with [177Lu]Lu-PSMA-I&T, after the first cycle of [177Lu]Lu-rhPSMA-10.1 rescue therapy, five patients (50%) showed a decrease in serum PSA level. In imaging, three of the ten patients (30%) showed a partial radiologic response. Four of the five patients with a decrease of serum PSA under [177Lu]Lu-rhPSMA-10.1 had initially responded to treatment with [177Lu]Lu-PSMA-I&T but had become resistant. However, the remaining patient had shown continuous disease progression during [177Lu]Lu-PSMA-I&T therapy but showed an immediate response to [177Lu]Lu-rhPSMA-10.1. The additional treatment with [177Lu]Lu-rhPSMA-10.1 was generally well tolerated by all patients. Patients showing tumour progression while receiving [177Lu]Lu-PSMA-I&T radioligand therapy may benefit from rescue therapy with the novel radiohybrid PSMA ligand, [177Lu]Lu-rhPSMA-10.1. Higher tumour absorbed radiation doses with [177Lu]Lu-rhPSMA-10.1 may overcome primary and acquired radiation resistance.

Influence of metastatic sites and burden on oncological outcomes in patients progressing to metastatic castration resistant prostate cancer

PurposeMetastatic castration-resistant prostate cancer (mCRPC) patients harbor reduced life expectancy after first-line treatment progression. Currently, no information is available regarding the influence of metastatic sites and osseous burden on progression-free (PFS) and overall survival (OS) of mCRPC patients.MethodsWe relied on the Frankfurt Metastatic Cancer Database of the Prostate (FRAMCAP) database to select patients progressing to mCRPC and stratified them according to lymph node vs. osseous vs. visceral metastatic sites. Moreover, we stratified osseous mCRPC patients regarding the number of metastatic lesions. Endpoints were PFS and OS in uni- and multivariable Cox regression models.ResultsOf 363 patients, 9.4% harbored M1a vs. 78% M1b vs. 12% M1c mCRPC with significantly higher PSA in M1b (9 vs. 22 vs. 8ng/ml). Rates of DeNovo (15% vs. 60% vs. 56%) were significantly lower in the M1a mCRPC group, compared to M1b and M1c (p < 0.001). In PFS analyses, a median of 12.7 vs. 10.1 vs. 15.9 months for M1a vs. M1b vs. M1c mCRPC was observed (p > 0.05). In multivariable Cox regression models, M1c mCRPC was independently at higher risk for progression (hazard ratio [HR]: 5.93, p = 0.048), relative to M1a. Regarding OS, significant differences were observed (p = 0.002), with median OS of 58 vs. 42 vs. 25 months for M1a vs. M1b vs. M1c mCRPC and corresponding HRs of 1.54 (p = 0.11) and 2.76 (p < 0.01). In multivariable models M1c mCRPC was associated with higher risk of death (HR: 3.56, p = 0.049), relative to M1a. No differences were observed after stratification according to number of bone lesions (all p ≥ 0.05).ConclusionM1c mCRPC patients are independently at higher risk for progression and death, while M1a patients harbor best cancer-control outcomes.

Prostate-Specific Antigen Stratification for Predicting Advanced Prostate Cancer Events in Men Approaching Age Limits for Recommended Screening.

Our goal was to quantify the ability of various PSA values in predicting the likelihood of developing metastatic or fatal prostate cancer in older men. We used a random sample of patients in the US Veterans Health Administration to identify 80,706 men who had received PSA testing between ages 70 to 75. Our primary end point was time to development of either metastatic prostate cancer or death from prostate cancer. We used cumulative/dynamic modeling to account for competing events (death from non-prostate cancer causes) in studying both the discriminative ability of PSA as well as for positive predictive value and negative predictive value at 3 time points. PSA demonstrated time-dependent predictive discrimination, with receiver operating characteristic area under the curve at 5, 10, and 14 years decreasing from 0.83 to 0.77 to 0.73, respectively, but without statistically significant difference when stratified by race. At PSA thresholds between 1 and 8 ng/mL, the positive predictive value of developing advanced prostate cancer was significantly greater in Black than White patients. For instance, at a PSA > 3, at 5, 10, and 14 years, White patients had 2.4%, 2.9%, and 3.7% risk of an event, whereas Black patients had 4.3%, 6.5%, and 8.3% risk. In men aged 70 to 75 deciding whether to cease PSA testing with borderline-elevated PSA values, the risk of developing metastatic or fatal prostate cancer is quantifiable and relatively low. Risk assessment in this setting must account for the higher incidence of prostate cancer in Black men.

P049 Real-world outcomes on biochemical recurrence and overall survival following hypofractionated radiotherapy for patients with non- metastatic prostate cancer – a single centre experience

P049 Real-world outcomes on biochemical recurrence and overall survival following hypofractionated radiotherapy for patients with non- metastatic prostate cancer – a single centre experience

Patient preferences for metastatic prostate cancer treatment: a discrete choice experiment

BackgroundTo examine the preference weightings for risk/benefit attributes of therapy in metastatic prostate cancer(mPC) patients, encompassing hormone-sensitive(mHSPC) and castration-resistant(mCRPC) settings. Patients and MethodsA non-interventional cross-sectional survey employing a discrete choice experiment was conducted, recruiting 200 mHSPC and 100 mCRPC patients within 5 years of diagnosis from the urology and oncology specialty clinics between Feb 2023 and Jul 2023. Patients were randomized into 2 blocks of 9 questions, choosing 1 out of 2 medication profiles consisting five attributes, each with 3 levels, determined from a group interview of 5 patients. A mixed logit model estimated attribute-level preference weightings, with tradeoff points calculated. ResultsMedian age was 75(IQR:71-81), 170(56.7%) had no income, 245(81.7%) cared for themselves, mean maximum out-of-pocket treatment cost was US$20,456(SD:43,568), and 160(53.3%) claimed not to consider further treatment when cost exceeding their affordability. Patients favoured self-care ability(4.37,P<.001) and life expectancy extension(2.83,P<.001), disfavoured adverse effects (-6.97,P<.001) and treatment cost(in HK$million or USD$128,205)(-3.14,P<.001). mCPRC patients was more sensitive to treatment cost(-3.61vs-2.97), life expectancy extension(3.47vs2.55) and adverse effects(-7.55vs-6.80) compared to mHSPC patients. Higher financial affordability patients exhibited higher sensitivity to self-care ability(4.89vs4.02) and adverse effects(-7.57vs-6.70). ConclusionThe chance of adverse effects was pivotal in treatment decisions, followed by self-care ability, with cost remaining a major access barrier. Micro AbstractExamining the preference weightings for risk/benefit attributes of therapy in metastatic prostate cancer patients, we recruited 200 hormone-sensitive and 100 castration-resistant patients for a cross-sectional discrete choice experiment survey. A mixed logit model estimated attribute-level preference weightings, calculating tradeoff points. The chance of adverse effects and self-care ability were pivotal in treatment decisions, with cost remaining a major access barrier.