Five‐year outcomes of TOOKAD® (WST‐11) vascular‐targeted photodynamic therapy for low‐risk prostate cancer patients: Insights from a tertiary referral centre

PD03-03 DOES PROSTATE CANCER REPRESENT THE MAIN CAUSE OF DEATH IN ALL NODE POSITIVE PROSTATE CANCER PATIENTS? THE IMPACT OF COMPETING CAUSES OF MORTALITY ACCORDING TO TUMOR CHARACTERISTICS AND RECURRENCE STATUS

Glycemic control and outcome of cancer patients.

Exploring Breast and Prostate Cancer Patient Perspectives and Perceptions of Interprofessional Collaboration (IPC) at the Odette Cancer Centre Throughout Their Journey of Cancer Treatment

Distant metastasis, particularly visceral metastasis (VM), represents an important negative prognostic factor for prostate cancer (PCa) patients. However, due to the lower rate of occurrence of VM, studies on these patients are relatively rare. Consequently, studies focusing on prognostic factors associated with PCa patients with VM are highly desirable. To investigate the prognostic factors for overall survival (OS) in PCa patients with lung, brain, and liver metastases, respectively, and evaluate the impact of site-specific and number-specific VM on OS. Data on PCa patients with VM were extracted from the Surveillance, Epidemiology, and End Results database between 2010 and 2015. Univariate and multivariate Cox regression analyses were used to analyze the association between clinicopathological characteristics and survival of patients with different site-specific VM. Kaplan-Meier analyses and Log-rank tests were performed to analyze the differences among the groups. A total of 1358 PCa patients with site-specific VM were identified from 2010 to 2015. Older age (> 70 years) (P < 0.001), higher stage (T3/T4) (P = 0.004), and higher Gleason score (> 8) (P < 0.001) were found to be significant independent prognostic factors associated with poor OS in PCa patients with lung metastases. Higher stage (T3/T4) (P = 0.047) was noted to be the only independent risk factor affecting OS in PCa patients with brain metastases. Older age (> 70 years) (P = 0.010) and higher Gleason score (> 8) (P = 0.001) were associated with shorter OS in PCa patients with liver metastases. PCa patients with isolated lung metastases exhibited significantly better survival outcomes compared with PCa patients with other single sites of VM (P < 0.001). PCa patients with a single site of VM exhibited a superior OS compared with PCa patients with multiple sites of VM (P < 0.001). This is the first Surveillance, Epidemiology, and End Results-based study to determine prognostic factors affecting OS in PCa patients with different site-specific VM. Clinical assessments of these crucial prognostic factors become necessary before establishing a treatment strategy for these patients with metastatic PCa.

Background: Prostate cancer tends to be a slow-growing malignancy, and oftentimes patient mortality is the result of non-cancerous disease processes. Recent studies have identified an increased risk of cardiovascular disease (CVD) in prostate cancer (PCa) patients—this may relate to increased cardiovascular susceptibility compared to the average population. Hypothesis: We hypothesized that prostate cancer patients had a higher propensity for major adverse cardiac events (MACE) than patients with similar cardiovascular risk factors. Aims: Our study aimed to assess CVD susceptibility in PCa patients by evaluating MACE rates in PCa and non-PCa patients within similar baseline cardiovascular risk categories, as determined by coronary artery calcium (CAC) score. Methods: Using data obtained from the CLARIFY registry (Clinicaltrials.gov NCT04075162), a large prospective study of no-charge CAC testing, we identified 1,942 patients with PCa and 50,511 non-PCa patients over 9 years of the program (January 2014-September 2023). Patients were divided by CAC group (CAC = 0, 1-99, 100-399, ≥ 400) and followed for MACE (myocardial infarction, stroke, heart failure admission, revascularization, and death). Cohort analyses compared cumulative MACE probability using Kaplan-Meier and Mantel-Cox test and hazard ratios (HR) from Cox-proportional hazard regression adjusted for race, hypertension, diabetes, hyperlipidemia, and obesity. Results: Median follow-up time was 1.7 years with 289 MACE (15%) in PCa and 2930 MACE (6%) in non-PCa patients. PCa was associated with significantly increased MACE (p &lt; .01) in all CAC groups (Figure). PCa patients had significantly increased hazard for MACE compared to non-PCa patients in CAC = 0 (HR 1.63 [1.14, 2.35], p &lt; .01), CAC = 100-399 (HR 1.53 [1.20, 1.95], p &lt; .01), and CAC ≥ 400 (HR 1.25 [1.04, 1.50], p = 0.02). Conclusion: PCa patients with no prior history of MACE are at a significantly increased risk for MACE in almost all CAC groups after adjustment for multiple factors. These data suggest mechanisms unique to PCa and/or its treatment that confers higher CVD events. Thus, there should be a lower threshold to implement cardiac risk reduction measures, including lifestyle modifications, statins, and other medical therapy, in PCa patients.

MP09-16 CONTEMPORARY MAPPING OF POST-PROSTATECTOMY PROSTATE CANCER RELAPSE WITH C-11 CHOLINE PET AND MULTIPARAMETRIC MRI

Male-fertility preservation—sperm cryopreservation is a gold standard for male-fertility preservation—has been paid attention for cancer patients over the past two decades because significant cancer treatment increasing cancer survivors and leading demand for future parenthood.1 Unfortunately, prostate cancer (PC) patients are not adequately informed about treatment-induced infertility before PC treatment although there were certain patients who hope fertility preservation.2 In this study, we report real-world data about sperm cryopreservation before definitive therapy for early-stage PC at our institution. We assessed eight PC patients who visited Reproduction Center of Yokohama City University Medical Center (YCUMC) for purpose of male-fertility preservation before definitive therapy for early-stage PC between 2013 and 2017. It is estimated that about 1.6% (8/500) of PC patients received definitive therapy could hope male-fertility preservation before treatment. We obtained the data of the PC status (prostate-specific antigen [PSA] levels, clinical stage, and Gleason scores), patients' age, type of definitive therapy for PC, sperm concentration, motility, whether to perform sperm cryopreservation, and whether to use of preserved sperm for pregnancy from the electronic medical record. Semen specimens were collected by masturbation after 48–120 h of sexual abstinence. Semen analysis was performed according to WHO guideline.3 Median age of the patients was 57 (range: 45–61). Median PSA levels were 6.1 (range: 4.1–8.6) ng/ml. Of the eight patients analyzed, one, six, and one patient were clinical stage T1c, T2a, and T2c, respectively. Gleason scores distributions were 3 + 3 in two, 3 + 4 in three, 4 + 3 in two, and 4 + 5 in one patient. Planned definitive therapy for PC was radical prostatectomy in one, seed implantation in four, and external beam radiation in three patients. Semen analysis was performed in all eight patients. Four out of eight patients were married and median age of their wife was 44 (range: 37–45). Median sperm concentration and motility were 46.5 × 106/ml (range: 5.3–110.1) and 4.9% (range: 1.3–23.3), respectively. Ejaculatory volume and normal morphology ratio of sperm were not evaluated. Sperm cryopreservation was performed in all patients except one. One patient did not hope cryopreservation because his own will. One patient who received seed implantation used preserved sperm for pregnancy and obtained a healthy baby. Boyd et al. reported that only 8.7% of localized PC patients were informed about the possibility of future male-infertility before PC treatment.2 Most PC patients are relatively aged and most physician tend to avoid about discussing it with their patients. Indeed, Boyd et al. reported that no patients with 55 years or older concerned about future infertility due to PC treatment among localized PC patients. However, patients who concerned about future male-infertility due to PC treatment are existing definitively, especially in young patients.2 Salonia et al. reported that 20% of PC patients hope for preoperative sperm cryopreservation.4 Especially, patients with younger, childless, and intense desire for fatherhood tend to hope for it. In addition, patients with early-stage PC have favorable prognosis. Therefore, physician should inform about possibility of male-infertility due to PC treatment and discuss about sperm cryopreservation before PC treatment with patients who hope male-fertility preservation. For young cancer patients, sperm cryopreservation might play a role not only for male-fertility preservation but also encourage of battle against cancer.5 Although there is no question that the sperm cryopreservation is a gold standard for male-fertility preservation, sperm preservation by testicular sperm extraction (TESE) is also useful. Especially, for the patients with ejaculatory dysfunction, for example, the patients received prostatectomy, radiation therapy for the prostate,6 or androgen ablation therapy,6, 7 TESE might be recommended instead of the sperm cryopreservation. Our study included only small number of patients. Therefore, definitive statement was not established from this study. However, we revealed that PC patients who hope male-fertility preservation before PC treatment were certainly exist. Physician should inform about male-infertility due to PC treatment and discuss about male-fertility preservation with patients. If the patients hope it, semen cryopreservation should be offered. Conceived and designed the study: Takashi Kawahara, Hiroji Uemura, and Yasuhide Miyoshi. Analyzed the data: Shinnosuke Kurodsa, Teppei Takeshima, Yasushi Yumura and Yasuhide Miyoshi. Wrote the paper: Yasuhide Miyoshi. All authors have read and approved the manuscript. None declared. Institutional review board approval of this study was obtained from YCUMC (R20002). Written informed consent was obtained from all patients for this study. N/A. N/A.

PurposeTo develop and evaluate a lymph node invasion (LNI) prediction model for men staged with [68Ga]Ga-PSMA-11 PET.MethodsA consecutive sample of intermediate to high-risk prostate cancer (PCa) patients undergoing [68Ga]Ga-PSMA-11 PET, extended pelvic lymph node dissection (ePLND), and radical prostatectomy (RP) at two tertiary referral centers were retrospectively identified. The training cohort comprised 173 patients (treated between 2013 and 2017), the validation cohort 90 patients (treated between 2016 and 2019). Three models for LNI prediction were developed and evaluated using cross-validation. Optimal risk-threshold was determined during model development. The best performing model was evaluated and compared to available conventional and multiparametric magnetic resonance imaging (mpMRI)-based prediction models using area under the receiver operating characteristic curves (AUC), calibration plots, and decision curve analysis (DCA).ResultsA combined model including prostate-specific antigen, biopsy Gleason grade group, [68Ga]Ga Ga-PSMA-11 positive volume of the primary tumor, and the assessment of the [68Ga]Ga-PSMA-11 report N-status yielded an AUC of 0.923 (95% CI 0.863–0.984) in the external validation. Using a cutoff of ≥ 17%, 44 (50%) ePLNDs would be spared and LNI missed in one patient (4.8%). Compared to conventional and MRI-based models, the proposed model showed similar calibration, higher AUC (0.923 (95% CI 0.863–0.984) vs. 0.700 (95% CI 0.548–0.852)—0.824 (95% CI 0.710–0.938)) and higher net benefit at DCA.ConclusionsOur results indicate that information from [68Ga]Ga-PSMA-11 may improve LNI prediction in intermediate to high-risk PCa patients undergoing primary staging especially when combined with clinical parameters. For better LNI prediction, future research should investigate the combination of information from both PSMA PET and mpMRI for LNI prediction in PCa patients before RP.

Frequent consumption of edible mushrooms, such as white button mushrooms (WBM), has been associated with a lower risk of prostate cancer [1]. Our laboratory at City of Hope has over 20 years of collective experience in defining the anticancer mechanisms of WBM [2, 3]. Previous studies have indicated that WBM consumption has anti-androgenic activities in prostate cancers in both preclinical models [4] and clinical trials [5]. In our first-in-human phase 1 trial on prostate cancer patients, we ensured the safety of consuming WBM in humans. In addition to observing a therapeutic-responsive decline in prostate-specific antigen (PSA), the levels of myeloid-derived suppressor cells (MDSCs) reduced in responders to WBM treatments [5]. These observations led us to hypothesize that WBM may mitigate the progression of prostate cancer in part by modulating the immune response. In the current study, we conducted translational research in syngeneic murine models and in prostate cancer patients from an ongoing phase 2 trial, aiming to define the immunomodulatory activity and mechanisms of WBM. We confirmed that WBM consumption in mouse models altered the number and function of immunosuppressive cells (MDSCs) and anti-tumor immune cells (T &amp; NK cells), ultimately enhancing the intratumor and systemic immune responses. At a bulk-transcriptional level, we observed the elevated expression of programmed cell death protein 1 (PD-1) in xenograft tumors. In our single immune cell profiling of patients’ blood specimens following 3 months of WBM consumption in freeze-dried tablets form, we investigated the transcriptional landscape of circulating immune cells in response to WBM interventions. The level of circulating neutrophil-associated PMN-MDSCs decreased, and the remaining cells showed transcriptional profiles associated with "neutrophil chemotaxis", "leukocyte aggregation", and "regulation of inflammatory response", as functions associated with enhanced anti-tumor activity. Lastly, we also showed in a mouse model that WBM consumption synergistically enhances the anticancer activity of anti-PD1 drugs, indicating that WBM may be used as adjuvant therapy with immune checkpoint inhibitors. In summary, our results from prostate cancer patients and murine models show the immunomodulatory effects of WBM consumption and provide a scientific foundation for the application of WBM in alleviating prostate cancer progression. References 1, Zhang S., et al. Int. J. Cancer. 2019; 146:2712-2720. 2, Chen S., et al. Cancer Res. 2006; 66:12026-12034. 3, Adams L.S., et al. Nutr. Cancer. 2008; 60:744-756. 4, Wang X., et al. J. Nutr. Biochem. 2021; 89:108580.5, Twardowski P., et al. Cancer. 2015; 121:2942-2950. Citation Format: Xiaoqiang Wang, Shoubao Ma, Przemyslaw Twardowski, Clayton Lau, Yin Chan, Kelly Wong, Jinhui Wang, Xiwei Wu, Paul Frankel, Timothy G. Wilson, Timothy W. Synold, Cary Presant, Jianhua Yu, Shiuan Chen. Reduction of PMN-MDSC level/activity following the consumption of white button mushroom in prostate cancer murine models and patients: A translational study to mitigate cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1831.

In this study mitochondrial D-Loop variations in Iranian prostate cancer and benign prostatic hyperplasia (BPH) patients were investigated. Tumour samples and corresponding non-cancerous prostate tissue from 40 prostate cancer patients and 40 age-matched BPH patients were collected. The entire mtD-loop region (16024-576) was amplified using the PCR method and products were gel-purified and subjected to direct nucleotide sequencing. A total of 129 variations were found, the most frequent being 263A-G and 310T-C among both BPH and prostate cancer patients. Variation of 309 C-T was significantly more frequent in prostate cancer patients (P value<0.05). Four novel variations were observed on comparison with the MITOMAP database. Novel variations were np16154delT, np366G-A, np389G-A and 56insT. There was no correspondence between the different variations and the age of subjects. Considering that D-loop variations were frequent in both BPH and prostate cancer patients in our study, the fact that both groups had high average age can be a possible contributing factor. D-loop polymorphisms and microsatellite instability can influence cell physiology and result in a benign or malignant phenotype. Significantly higher frequency of 309 C-T variation in cancer patients is a notable finding and must be a focus of attention in future studies.

Background and Objectives: To describe the predictors of cribriform variant status and perineural invasion (PNI) in robot-assisted radical prostatectomy (RARP) histology. To define the rates of upgrading between biopsy specimens and final histology and their possible predictive factors in prostate cancer (PCa) patients undergoing RARP. Material and Methods: Within our institutional database, 265 PCa patients who underwent prostate biopsies and consecutive RARP at our center were enrolled (2018-2022). In the overall population, two independent multivariable logistic regression models (LRMs) predicting the presence of PNI or cribriform variant status at RARP were performed. In low- and intermediate-risk PCa patients according to D'Amico risk classification, three independent multivariable LRMs were fitted to predict upgrading. Results: Of all, 30.9% were low-risk, 18.9% were intermediate-risk and 50.2% were high-risk PCa patients. In the overall population, the rates of the cribriform variant and PNI at RARP were 55.8% and 71.1%, respectively. After multivariable LRMs predicting PNI, total tumor length in biopsy cores (>24 mm [OR: 2.37, p-value = 0.03], relative to <24 mm) was an independent predictor. After multivariable LRMs predicting cribriform variant status, PIRADS (3 [OR:15.37], 4 [OR: 13.57] or 5 [OR: 16.51] relative to PIRADS 2, all p = 0.01) and total tumor length in biopsy cores (>24 mm [OR: 2.47, p = 0.01], relative to <24 mm) were independent predicting factors. In low- and intermediate-risk PCa patients, the rate of upgrading was 74.4% and 78.0%, respectively. After multivariable LRMs predicting upgrading, PIRADS (PIRADS 3 [OR: 7.01], 4 [OR: 16.98] or 5 [OR: 20.96] relative to PIRADS 2, all p = 0.01) was an independent predicting factor. Conclusions: RARP represents a tailored and risk-adapted treatment strategy for PCa patients. The indication of RP progressively migrates to high-risk PCa after a pre-operative assessment. Specifically, the PIRADS score at mpMRI should guide the decision-making process of urologists for PCa patients.

Few small-scaled studies performed systematic analysis of the benefits of extending prostate specific membrane antigen positron-emission tomography/ computed tomography (68Ga-PSMA I&T PET/CT) to the lower extremities in prostate cancer (PCa) patients. We hypothesized that 68Ga-PSMA I&T PET/CT positive lesions are rare in lower extremities of prostate cancer (PCa) patients, the clinical implication is negligible and may therefore be omitted. We retrospectively analyzed 1,068 PCa patients who received 68Ga-PSMA I&T PET/CT in a single institution (2016-2018). Of those, 285 (26.7%) were newly diagnosed, 529 (49.5%) had biochemical recurrence (BCR) and 254 (23.8%) were castration-resistant prostate cancer (CRPC) patients. Of 1,068 68Ga-PSMA I&T PET/CTs, positive lesions in the lower extremities were identified in 6.9% patients (n=74). Positive lesions in the lower extremities were most common in CRPC patients (19.7%; n=50), followed by newly diagnosed (3.2%; n=9) and BCR (2.8%; n=15) PCa patients. Only 3 patients presented with exclusive lesions in the lower extremities, respectively 0.8% (n=2) in CRPC and 0.4% (n=1) in newly diagnosed PCa. Both CRPC (94.1%, n=47) and BCR (80.0%, n=12) patients with PSMA-positive lesions predominantly received systemic therapy. Identification of lower extremities lesions with PSMA PET/CT is uncommon and exclusive lesions are rare. PSMA PET/CT findings of the lower extremities did not change therapy management. Thus, scanning of the lower extremities can be omitted in standard protocols.

e19615 Background: Recent papers by Stopeck et al (J Clin Oncol, 2010), and by Fizazi et al (Lancet, 2011) evaluated rates of pathologic fractures (PF) in breast cancer (BC) and prostate cancer (PC) patients with bone metastases, and concluded that 23% and 15% of the patients on zoledronic acid (ZOL) respectively had a PF. Since these results were obtained within a randomized controlled trial environment, it is very important to compare these rates to those observed in actual practice. The objective of this study was therefore to determine the rate of PF among both BC and PC patients with bone metastases treated with ZOL in clinical practice. Methods: A patient chart review was conducted in two institutions, Florida Cancer Specialists (FCS) and Georgia Cancer Specialists (GCS) to determine the rate of PF in BC and PC patients with bone metastases initiating ZOL. BC and PC patients with confirmed diagnoses who initiated ZOL treatment from 2005 thru 2007 were included in the study. The patients were required to have been on ZOL for a minimum of 18 months following initiation of treatment. Demographic information, baseline clinical characteristics, and outcomes related to the treatment of bone metastases were assessed. Results: A total of 207 BC patients and 178 PC patients were included in the sample. Median age in the BC group was 65, and in the PC group was 74. In the BC cohort, of the 207 patients, only 17 (8.2%) patients had a PF. In the PC cohort, of the 178 patients, only 8 (4.5%) patients had a pathological fracture. When evaluated by institution, only 5 (4.7%) BC patients, and 4 (4%) PC patients from FCS had a pathological fracture; and only 12 (12%) BC and 4 (5.2%) PC patients from GCS had a pathological fracture. Conclusions: The findings from this study indicate that the rate of pathological fractures associated with ZOL treatment in clinical practice is very different from that observed in a randomized controlled trial setting. Physicians, payers and policy makers should carefully consider these findings in both clinical pathway decisions and formulary inclusion.

BackgroundTo shed light on the survival outcomes of prostate cancer (PCa) patients diagnosed after a prior cancer and identify prognostic factors for overall survival (OS) and cancer-specific survival (CSS) in PCa patients.MethodsIn the primary group, a total of 1,778 PCa patients with a prior cancer were identified in the Surveillance, Epidemiology, and End Results (SEER) database from 2005 to 2015, retrospectively. Baseline characteristics and causes of death (COD) of these patients were collected and compared. In the second group, a total of 10,296 PCa patients [5,148 patients with PCa as the only malignancy and 5,148 patients with PCa as their second primary malignancy (SPM)] diagnosed between 2010 and 2011 were extracted to investigate the impact of prior cancers on survival outcomes.ResultsIn PCa patients with a prior cancer, the most common type of prior cancer was from gastrointestinal system (29.92%), followed by urinary system (21.37%). Patients were more likely to die of the prior caner, and those with prior cancer from respiratory system had the worst survival outcomes. Moreover, the overall ratios in patients with stage (PCa) I–II and III–IV diseases were 0.21 and 1.65, indicating that patients with higher stage diseases were more likely to die of PCa. In the second group, patients with PCa as the SPM had worse OS than those with PCa as the first primary cancer. Lastly, prognostic factors for OS and CSS in PCa patients were explored.ConclusionsPCa remains to be an important COD for patients with a prior malignancy, especially for those with high-stage diseases. PCa patients with a prior cancer had worse survival outcomes than those without.

To explore the correlation between plasma level of lncRNA TUG1 with PSA level, Gleason grading and tumor node metastasis (TNM) stage of prostate cancer (PCa) patients. This study aims to evaluate the potential diagnostic and prognostic values of TUG1 in PCa. Plasma level of TUG1 in 70 PCa patients and 70 healthy controls was determined using the quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Correlation between plasma level of TUG1 with PSA level, Gleason grading and TNM stage of PCa patients was analyzed. The potential diagnostic value of TUG1 in PCa was explored by introducing the receiver operating characteristic (ROC) curve. The survival analysis of PCa patients undergoing radical prostatectomy was conducted using the Kaplan-Meier method and the log-rank test. Finally, the regulatory effects of TUG1 on in vitro proliferative and migratory abilities of PCa cells were examined by the cell counting kit-8 (CCK-8) and the transwell assay, respectively. QRT-PCR data revealed a higher plasma level of TUG1 in PCa patients than in those of healthy controls. In particular, PCa patients with stage III+IV had a higher level of TUG1 relative to those with stage I+II. Moreover, the TUG1 level was higher in PCa patients with a higher PSA level (≥ 10 ng/mL), Gleason grading (≥ 7) or TNM stage (N1, M1). There was no significant correlation between the plasma level of TUG1 and the age of PCa patients. The ROC and Kaplan-Meier curves indicated the diagnostic and prognostic values of TUG1 in PCa. The overexpression of TUG1 markedly accelerated PCa cells to proliferate and migrate. The plasma level of TUG1 is upregulated in PCa patients and is correlated to PSA level, Gleason grading and TNM stage of PCa. TUG1 exerts certain diagnostic and prognostic values in PCa. The overexpression of TUG1 markedly accelerates PCa cells to proliferate and migrate.