Localized Prostate Cancer Patients Research Articles

Between Pathological Prostate Cancer Lymph Nodes and Sentinel Nodes: Which Information Is the Leader?

On the basis of the concept of sentinel lymph node biopsy (SLNB), SLNs should contain decisive information for clinical outcomes. In localized prostate cancer patients, this study assessed retrospectively clinical outcome after radical laparoscopic prostatectomy associated with SLNB and extensive pelvic lymph node dissection. A total of 231 consecutive patients of intermediate to high risk were analyzed. Recurrence-free survival (RFS) was assessed with Kaplan-Meier curves. Various pathological parameters were analyzed using univariable and multivariable analyses through Cox regression analysis. The study was approved and registered under 2007-R41. The median follow-up was 7.1 years (95% confidence interval, 6.6-7.5). In total, 38/231 (16.5%) patients were pN1. Of these 38 patients, 27 had only SLN involvement (SLNI), 10 patients had both SLN and non-SLNI, and 1 patient had isolated non-SLNI, indicating a false-negative (FN). If the updated Briganti nomogram threshold set at >7% for recommending extensive pelvic lymph node dissection had been applied to these patients, we would have missed 44% (12/27) of patients with SLNI and 50% (5/10) of patients with SLNI and non-SLNI, as well as the FN patient. At the time of final follow-up, 84/231 (36.5%) patients had recurrence. In multivariable analysis, and regarding node status, the most significant prognostic factor was SLN with macrometastases and/or micrometastases, respectively, P = 10-3 and P < 10-3. No more information was obtained with non-SLN status. Probabilities of RFS between negative and positive SLN patients presented a major significant difference (P < 10-15) with a risk of event 8.75 times more frequent if SLN was involved than if it was metastasis-free. SLNB seems to contain decisive information for the clinical outcome of patients with localized intermediate- and high-risk prostate cancer patients. The question raised is thus whether immediate additional postoperative treatment should be offered to patients with metastatic SLN.

Radiogenomics Map-Based Molecular and Imaging Phenotypical Characterization in Localised Prostate Cancer Using Pre-Biopsy Biparametric MR Imaging.

To create a radiogenomics map and evaluate the correlation between molecular and imaging phenotypes in localized prostate cancer (PCa), using radical prostatectomy histopathology as a reference standard. Radiomic features were extracted from T2-weighted (T2WI) and Apparent Diffusion Coefficient (ADC) images of clinically localized PCa patients (n = 15) across different Gleason score-based risk categories. DNA extraction was performed on formalin-fixed, paraffin-embedded (FFPE) samples. Gene expression analysis of androgen receptor expression, apoptosis, and hypoxia was conducted using the Chromosome Analysis Suite (ChAS) application and OSCHIP files. The relationship between gene expression alterations and textural features was assessed using Pearson's correlation analysis. Receiver operating characteristic (ROC) analysis was utilized to evaluate the predictive accuracy of the model. A significant correlation was observed between radiomic texture features and copy number variation (CNV) of genes associated with apoptosis, hypoxia, and androgen receptor (p-value ≤ 0.05). The identified radiomic features, including Sum Entropy ADC, Inverse Difference ADC, Sum Variance T2WI, Entropy T2WI, Difference Variance T2WI, and Angular Secondary Moment T2WI, exhibited potential for predicting cancer grade and biological processes such as apoptosis and hypoxia. Incorporating radiomics and genomics into a prediction model significantly improved the prediction of prostate cancer grade (clinically significant prostate cancer), yielding an AUC of 0.95. Radiomic texture features significantly correlate with genotypes for apoptosis, hypoxia, and androgen receptor expression in localised prostate cancer. Integration of these into the prediction model improved prediction accuracy of clinically significant prostate cancer.

Prostate cancer patients with lymphatic node involvement detected by immunohistochemistry. Is the effort worthwhile?

IntroductionLymph node (LN) status is one of the main prognostic factors in localized prostate cancer (CaP) patients after surgery. Examining palpable lymph nodes with hematoxylin and eosin (HE) is the most common approach in clinical practice; however, immunohistochemistry (IHC) has been reported to increase the LN detection rate. We reviewed the oncological results of patients with LN metastasis detected by IHC. MethodsRetrospective study of CaP patients who underwent lymphadenectomy at the time of the prostatectomy. Extended lymphadenectomy was performed with complementary indocyanine green (ICG) guidance. Three groups were considered according to LN status. Definition of the pN+ group was made if LNs were detected by HE, occulted lymph node-positive (OLN+) was considered when ≥ 1 LN was identified with IHC and occulted lymph node-negative (OLN-) if no metastatic nodes were found. Oncological outcomes were reported regarding PSA kinetics, biochemical recurrence (BCR), need for secondary treatments and metastasis-free survival (MFS). ResultsA total of 283 patients with a median follow-up of 69 months were included in the study. Immunohistochemical assessment revealed metastatic LNs in 8.9% of patients. The rate of locally advanced disease and positive surgical margins was higher in the OLN + and pN + groups vs the OLN – group (P < 0.05). At the end of follow-up, 19%, 44% and 52% of patients from the OLN -, OLN + and pN + groups experienced BCR (P < 0.001), respectively. Additionally, 2.6%, 17% and 22% of patients developed metastatic progression from the OLN -, OLN + and pN+ group (P < 0.001), respectively. In the multivariate analysis, the OLN + group had a higher risk HR: 12 (95% CI, 2.4-56; P = 0.002) of metastatic progression in comparison with OLN – patients. This difference was not observed in the risk of biochemical recurrence HR 1.8 (95% CI, 0.9-3.8; P = 0.09). ConclusionConventional HE histological analysis underdiagnosed nearly 10% of patients. IHC-detected patients were at higher risk of metastasis development than OLN - patients. This report highlights the importance of optimizing the anatomopathological analysis properly.

Differences in real-world outcomes by risk classification for localized prostate cancer patients after radiation therapy.

Limited real-world evidence exists on the long-term clinical outcomes of patients with localized prostate cancer (LPC) who received external beam radiation therapy (EBRT) as the initial treatment. This study evaluated clinical outcomes of US patients with high-risk LPC (HR-LPC) and low/intermediate-risk LPC (LIR-LPC) who received EBRT. This retrospective study using Surveillance, Epidemiology, and End Results-Medicare linked data from 2012 to 2019 included patients ≥ 65 years old who received EBRT as initial therapy. Baseline patient characteristics were summarized, metastasis-free survival (MFS), overall survival, and time to initiation of advanced prostate cancer treatment were compared using Kaplan-Meier (KM) and adjusted Cox proportional hazard (PH) models. 5-year survival probabilities stratified by race/ethnicity (non-Hispanic [NH] White, NH Black, NH Asian, and Hispanic) were assessed. Of 11,313 eligible patients, 41% (n = 4600) had HR-LPC and 59% (n = 6713) had LIR-LPC. Patient characteristics for both groups were comparable, with mean age at EBRT initiation > 70 years, 86% white, and mean follow-up time >40 months. More patients in the HR-LPC than LIR-LPC groups (78% vs 34%) had concurrent androgen deprivation therapy use and for a longer duration (median 10.4 months vs. 7.4 months). A higher proportion of HR-LPC patients developed metastasis, died, or received advanced prostate cancer treatment. Adjusted Cox PH survival analyses showed significantly (p < 0.0001) higher risk of mortality (hazard ratios[HR], 1.57 [1.38, 2.34]), metastasis or death (HR, 1.97 [1.78, 2.17]), and advanced prostate cancer therapy use (HR, 2.57 [2.11, 3.14]) for HR-LPC than LIR-LPC patients. Within 5 years after the initial EBRT treatment, 18%-26% of patients with HR-LPC are expected to have died or developed metastasis. The 5-year MFS rate in the HR-LPC group was lower than the LIR-LPC group across all racial/ethnic subgroups. NH Black patients with HR-LPC had the highest all-cause mortality rate and lowest rate of receiving advanced prostate cancer treatment, compared to other racial/ethnic subgroups. This real-world study of clinical outcomes in patients with LPC treated with EBRT suggests substantial disease burden in patients with HR-LPC and highlights the need for additional treatment strategies to improve clinical outcomes in patients with HR-LPC.

Clinical VMAT machine parameter optimization for localized prostate cancer using deep reinforcement learning.

Volumetric modulated arc therapy (VMAT) machine parameter optimization (MPO) remains computationally expensive and sensitive to input dose objectives creating challenges for manual and automatic planning. Reinforcement learning (RL) involves machine learning through extensive trial-and-error, demonstrating performance exceeding humans, and existing algorithms in several domains. To develop and evaluate an RL approach for VMAT MPO for localized prostate cancer to rapidly and automatically generate deliverable VMAT plans for a clinical linear accelerator (linac) and compare resultant dosimetry to clinical plans. We extended our previous RL approach to enable VMAT MPO of a 3D beam model for a clinical linac through a policy network. It accepts an input state describing the current control point and predicts continuous machine parameters for the next control point, which are used to update the input state, repeating until plan termination. RL training was conducted to minimize a dose-based cost function for prescription of 60Gy in 20 fractions using CT scans and contours from 136 retrospective localized prostate cancer patients, 20 of which had existing plans used to initialize training. Data augmentation was employed to mitigate over-fitting, and parameter exploration was achieved using Gaussian perturbations. Following training, RL VMAT was applied to an independent cohort of 15 patients, and the resultant dosimetry was compared to clinical plans. We also combined the RL approach with our clinical treatment planning system (TPS) to automate final plan refinement, and creating the potential for manual review and edits as required for clinical use. RL training was conducted for 5000 iterations, producing 40 000 plans during exploration. Mean±SD execution time to produce deliverable VMAT plans in the test cohort was 3.3±0.5 s which were automatically refined in the TPS taking an additional 77.4±5.8 s. When normalized to provide equivalent target coverage, the RL+TPS plans provided a similar mean±SD overall maximum dose of 63.2±0.6Gy and a lower mean rectum dose of 17.4±7.4 compared to 63.9±1.5Gy (p=0.061) and 21.0±6.0 (p=0.024) for the clinical plans. An approach for VMAT MPO using RL for a clinical linac model was developed and applied to automatically generate deliverable plans for localized prostate cancer patients, and when combined with the clinical TPS shows potential to rapidly generate high-quality plans. The RL VMAT approach shows promise to discover advanced linac control policies through trial-and-error, and algorithm limitations and future directions are identified and discussed.

High clonal diversity and spatial genetic admixture in early prostate cancer and surrounding normal tissue

Somatic copy number alterations (SCNAs) are pervasive in advanced human cancers, but their prevalence and spatial distribution in early-stage, localized tumors and their surrounding normal tissues are poorly characterized. Here, we perform multi-region, single-cell DNA sequencing to characterize the SCNA landscape across tumor-rich and normal tissue in two male patients with localized prostate cancer. We identify two distinct karyotypes: ‘pseudo-diploid’ cells harboring few SCNAs and highly aneuploid cells. Pseudo-diploid cells form numerous small-sized subclones ranging from highly spatially localized to broadly spread subclones. In contrast, aneuploid cells do not form subclones and are detected throughout the prostate, including normal tissue regions. Highly localized pseudo-diploid subclones are confined within tumor-rich regions and carry deletions in multiple tumor-suppressor genes. Our study reveals that SCNAs are widespread in normal and tumor regions across the prostate in localized prostate cancer patients and suggests that a subset of pseudo-diploid cells drive tumorigenesis in the aging prostate.

Proteomic Identification of Small Extracellular Vesicle Proteins LAMB1 and Histone H4 for Prostate Cancer Diagnosis and Risk Stratification.

Diagnosis and stratification of prostate cancer (PCa) patients using the prostate-specific antigen (PSA) test is challenging. Extracellular vesicles (EVs), as a new star of liquid biopsy, has attracted interest to complement inaccurate PSA screening and invasiveness of tissue biopsy. In this study, a panel of potential small EV (sEV) protein biomarkers is identified from PCa cell lines using label-free LC-MS/MS proteomics. These biomarkers underwent further validation with plasma and urine samples from different PCa stages through parallel reaction monitoring-based targeted proteomics, western blotting, and ELISA. Additionally, a tissue microarray containing cancerous and noncancerous tissues is screened to provide additional evidence of selected sEV proteins associated with cancer origin. Results indicate that sEV protein LAMB1 is highly expressed in human plasma of metastatic PCa patients compared with localised PCa patients and control subjects, while sEV protein Histone H4 is highly expressed in human urine of high-risk PCa patients compared to low-risk PCa patients and control subjects. These two sEV proteins demonstrate higher specificity and sensitivity than the PSA test and show promise for metastatic PCa diagnosis, progression monitoring, and risk stratification.

DNA methylation markers for risk of metastasis in a cohort of men with localized prostate cancer

ABSTRACT Accurately identifying life-threatening prostate cancer (PCa) at time of diagnosis remains an unsolved problem. We evaluated whether DNA methylation status of selected candidate genes can predict the risk of metastasis beyond clinical risk factors in men with untreated PCa. A nested case-control study was conducted among men diagnosed with localized PCa at Kaiser Permanente California between 01/01/1997–12/31/2006 who did not receive curative treatments. Cases were those who developed metastasis within 10 years from diagnosis. Controls were selected using density sampling. Ninety-eight candidate genes were selected from functional categories of cell cycle control, metastasis/tumour suppressors, cell signalling, cell adhesion/motility/invasion, angiogenesis, and immune function, and 41 from pluripotency genes. Cancer DNA from diagnostic biopsy blocks were extracted and analysed. Associations of methylation status were assessed using CpG site level and principal components-based analysis in conditional logistic regressions. In 215 cases and 404 controls, 27 candidate genes were found to be statistically significant in at least one of the two analytical approaches. The agreement between the methods was 25.9% (7 candidate genes, including 2 pluripotency markers). The DNA methylation status of several candidate genes was significantly associated with risk of metastasis in untreated localized PCa patients. These findings may inform future risk prediction models for PCa metastasis beyond clinical characteristics.

Bothersome Hot Flashes Following Neoadjuvant Androgen Deprivation Therapy and Stereotactic Body Radiotherapy for Localized Prostate Cancer.

Androgen deprivation therapy (ADT) improves local cancer control in unfavorable localized prostate cancer treated with radiotherapy. ADT is known to cause hormonally related symptoms that resolve with testosterone recovery. Hot flashes are particularly burdensome. This study sought to evaluate the timeline of hot flashes following short-course ADT and stereotactic body radiotherapy (SBRT) as well as its relationship with testosterone recovery. Institutional IRB approval was obtained for this retrospective review of prospectively collected data (IRB#: 2009-510). ADT was initiated three months prior to the start of SBRT. Hot flashes were self-reported via question 13a of the Expanded Prostate Index Composite (EPIC)-26 prior to ADT initiation, the first day of robotic SBRT, and at each follow-up (one, three, six, nine, 12, 18, 24, and 36 months). The responses were grouped into three relevant categories (no problem, very small-small problem, and moderate-big problem). Scores were transformed to a 0-100 scale with higher scores reflecting less bother. Testosterone levels were measured at each follow-up. From 2007 to 2010, 122 localized prostate cancer patients (nine low-, 64 intermediate-, and 49 high-risk according to the D'Amico classification) at a median age of 72 years (range 54.5-88.3) were treated with short course ADT (three to six months) and SBRT (35-36.25 Gy) at Georgetown University Hospital. Thirty-two percent were Black and 27% were obese. Seventy-seven percent of patients received three months of ADT. At baseline, 2% of men experienced hot flashes that were a "moderate to big problem" and that proportion peaked at the start of SBRT (45%) before returning to baseline (2%) nine months post-SBRT with a cumulative incidence of 52.4%. The median baseline EPIC-26 hot flash score of 94 declined to 50 at the start of SBRT but this returned to baseline (92) by six months post SBRT. These changes were both statistically and clinically significant (MID = 9.5083, p<0.01). Testosterone recovery (> 230 ng/dL) occurred in approximately 70% of patients by 12 months post SBRT. Resolution of hot flashes correlated with testosterone recovery. Bothersome hot flashes occur in greater than 50% of men treated with neoadjuvant ADT. Resolution of hot flashes occurs in the majority of patients within one year after treatment. Reassurance of the temporary nature of hot flashes may assist in reducing patient anxiety. Measuring testosterone levels at follow-up visits may allow for anticipatory counseling that may limit the associated bother.

(032) Prevalence of Testosterone Deficiency and Risk Factors in Patients with Localized Prostate Cancer After Radical Prostatectomy

Abstract Introduction Testosterone therapy (TTh) is contra-indicated in patients with prostate cancer (PCa), however according to the recent AUA guideline, TTh can be offer for localized PCa with no evidence of active disease. However, it is not known how much localized PCa patients suffer from testosterone (T) deficiency after treatment in real clinical practice, and further clinical characteristics on those potential candidates for TTh is insufficient. Objective This study analyzed T profile of patients with localized PCa who underwent radical prostatectomy (RP) to determined the prevalence of testosterone deficiency and its risk factors. Methods We reviewed patients who underwent RP for localized PCa between 2016 and 2021. Patients with less than 1 year of follow-up and patients with biochemical recurrence or distant metastasis during follow-up were excluded. In addition, we exclude the patient who had no T profile preoperatively and postoperative 1 year. The serum T level threshold for T deficiency was defined as 3.0 ng/mL. The primary outcome was the prevalence of TDS, and the secondary outcome was the predicting factors of TDS. Results A total of 192 patients underwent RP with localized PCa during the study period. Among them, 120 patients were analyzed, excluding patients without baseline T and follow-up T level at postoperative 1 year (n=67) and patients with BCR during the follow-up (n=5). Eighteen of 120 patients (15.0%) had T deficiency before RP. Excluding preoperative T deficiency, 33 (32.4%) of 102 patients had their T level reduced to less than 3.0 ng/ml after RP. Among them, 16 patients (15.7%) had persistent decreased T level. Table 1. Summarized the baseline characteristics of patients with and without T deficiency after RP. BMI (OR: 1.586, p&amp;lt; 0.001) was statistically significant in multivariate logistic regression to identify the predicting factor for T deficiency after RP. Conclusions In the patients with localized prostate cancer, there were a significant number of TTh candidates. In particular, obese patients had a higher risk of T deficiency. Disclosure No.

Exploring Information Seeking Anxiety Among Localized Prostate Cancer Patients.

Information seeking anxiety is a multidimensional construct that is operationalized as having elements of worry, confusion, and disorganization. Much remains unknown about the ways information seeking anxiety operates among cancer patients in the United States. This study investigated the application of the information seeking anxiety concept among prostate cancer patients by documenting their assessment experiences and examining relationships between information seeking anxiety and treatment information search behaviors. A purposive sample of African American and Caucasian men (N = 63) within 5 years of being diagnosed with localized disease (stage T1 or T2) were recruited to participate through cancer registries, advertisements, and word-of-mouth. Participants completed a self-administered survey with items that collected demographic information, treatment information-seeking behaviors, and information seeking anxiety evaluations. All surveys were completed in one sitting and a majority of men (82.5%, N = 52) completed the information seeking anxiety assessment with no assistance. During their first interactions with available sources of information (e.g., doctors, internet, peers), most survivors (95.2%, N = 60) reported some level of information seeking anxiety. Specifically, 55.5% (N = 35) were confused about what to look for, 60.3% (N = 38) were worried they would not find the right information, 55.5% (N = 35) were uncomfortable with the search process, and 49.2% (N = 31) reported being disorganized. The composite information seeking anxiety measure was moderately correlated with men's self-reported time to start searching for treatment information (p = .02; r = .306). Information seeking anxiety appears to delay the treatment information gathering activities of prostate cancer survivors with localized disease. This previously undocumented barrier to the delivery of prostate cancer care services should be investigated in other studies with larger and more diverse samples.

Image-guided moderately hypofractionated radiotherapy for localized prostate cancer: a multicentric retrospective study (IPOPROMISE)

BackgroundModerate hypofractionated radiotherapy is a treatment option for the cure of localized prostate cancer (PCa) patients based on the results of randomized prospective trials, but there is a clinical concern about the relatively short length of follow-up, and real-world results on outcome and toxicity based on cutting-edge techniques are lacking. The objective of this study is to present the long-term results of a large multicentric series.Materials and methodsWe retrospectively evaluated 1325 PCa patients treated with daily volumetric image-guided hypofractionated radiotherapy between 2007 and 2020 in 16 Centers. For survival endpoints, we used Kaplan–Meier survival curves and fitted univariate and multivariable Cox’s proportional hazards regression models to study the association between the clinical variables and each survival type.ResultsAt the end of the follow-up, 11 patients died from PCa. The 15-year values of cancer-specific survival (CSS) and biochemical relapse-free survival (b-RFS) were 98.5% (95%CI 97.3–99.6%) and 85.5% (95%CI 81.9–89.4%), respectively. The multivariate analysis showed that baseline PSA, Gleason score, and the use of androgen deprivation therapy were significant variables for all the outcomes. Acute gastrointestinal (GI) and genitourinary (GU) toxicities of grade ≥ 2 were 7.0% and 16.98%, respectively. The 15-year late grade ≥ 2 GI and GU toxicities were 5% (95%CI 4–6%) and 6% (95%CI 4–8%), respectively.ConclusionReal-world long-term results of this multicentric study on cutting-edge techniques for the cure of localized PCa demonstrated an excellent biochemical-free survival rate of 85.5% at 15 years, and very low rates of ≥ G3 late GU and GI toxicity (1.6% and 0.9% respectively), strengthening the results of the available published trials.

Comparison of serum uric acid levels between localised prostate cancer patients and a control group.

The aim of this study is to find out whether serum uric acid levels in patients with localised prostate cancer differ from patients with lower urinary tract symptoms without carcinoma prostate. We performed a prospective observational study of 60 patients having age ⩾ 50 years with c/o lower urinary tract symptoms( LUTS) evaluated by digital rectal examination (DRE), prostate-specific antigen (PSA) level and ultrasonography kidney, ureter, bladder (USG KUB) prostate and patients who were suspicious for carcinoma prostate underwent trans rectal ultrasonography (TRUS) biopsy of prostate. Patients with biopsy s/o prostate cancer were evaluated for metastasis and localised cancer patients were considered as CASE group. Patients with negative biopsy and other patients having LUTS were considered as CONTROL group. The age, serum uric acid level, PSA value, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and white blood cell (WBC) count were measured. Serum uric acid level was compared in both the groups. The mean serum uric acid level was lower in prostate cancer group (4.77 mg/dl) than control group (6.22 mg/dl) that was statistically significant (p < 0.001). The mean PSA value was 7.43 ng/dl in cancer group and 2.72 ng/dl in control group. (p < 0.001). The mean C-reactive protein (CRP) values were 1.32 and 0.45 respectively (p < 0.001), erythrocyte sedimentation rate (ESR) were found 21 and 10.5 respectively (p < 0.001)and total leucocyte counts (TLC) were found 6.450 and 5.120 respectively (p < 0.001). All were statistically significant (p < 0.05). The serum uric acid levels measured in localised prostate cancer patients were found to be reduced compared to the control group and inflammatory markers were found to be increased. Decreased levels of serum uric acid and increased levels of inflammatory markers were determined as risk factors for prostate cancer.

Nonsurgical salvage options for locally recurrent prostate cancer after primary definitive radiotherapy: a systematic review and meta-analysis.

To conduct a meta-analysis to provide the latest evidence of nonsurgical local salvage options in the first-line radiotherapy (RT) failure setting for localized prostate cancer patients. Recurrence of localized prostate cancer after primary RT remains a clinical challenge. There is no consensus on optimal nonsurgical local salvage therapies, which mainly consist of cryotherapy (CRYO), high-intensity focused ultrasound (HIFU), high/low-dose-rate brachytherapy (HDR/LDR), and stereotactic body radiotherapy (SBRT). Our study was performed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The authors systematically searched PubMed, Web of Science, Cochrane Library, and ClinicalTrials.gov up to September 2023 to identify potentially relevant studies. The risk of bias was assessed using the European Association of Urology (EAU) items. Biochemical recurrence-free survival (bRFS) and genitourinary/gastrointestinal toxicities were the outcomes of interest. Pooled rates with 95% CIs were evaluated. A total of 99 studies comprising 8440 patients were included. The pooled rate of 1-year biochemical control (BC) was highest for LDR (0.88, 95% CI: 0.72-0.95) and lowest for SBRT (0.68, 95% CI: 0.49-0.83). The pooled rate of 5-year BC was highest for CRYO (0.52, 95% CI: 0.33-0.69) and lowest for HDR (0.23, 95% CI: 0.08-0.51). HIFU presented the worst outcome of grade ≥3 genitourinary toxicities (GU3), with a rate of 0.22 (95% CI: 0.12-0.3). Conversely, CRYO (0.09, 95% CI: 0.04-0.14), HDR (0.05, 95% CI: 0.02-0.07), LDR (0.10, 95% CI: 0.06-0.14), and SBRT (0.06, 95% CI: 0.03-0.09) presented low rates of GU3. All subgroups induced a quite low incidence of grade ≥3 gastrointestinal toxicities (GI3). Nonsurgical salvage therapies are promising modalities for prostate cancer in the local radiorecurrence setting. Based on the preliminary evidence from this study, CRYO and SBRT might present a relatively steady efficacy of BC with acceptable treatment-related toxicities.

Pretreatment Interstitial Lung Abnormalities Detected on Abdominal Computed Tomography Scans in Prostate Cancer Patients.

Prostate cancer and interstitial lung abnormality (ILA) share similar risk factor, which is men and older age. The purpose of this study was to investigate the prevalence of pretreatment ILA among prostate cancer patients who underwent abdominal computed tomography (CT) within 1 year at their first visit to the urology department. In addition, we aimed to assess the association between pretreatment ILA and long-term survival in prostate cancer patients. This study was conducted in patients who had a first visit for prostate cancer at urology department between 2005 and 2016 and underwent an abdominal CT within 1 year. A thoracic radiologist evaluated the presence of ILA through inspecting the lung base scanned on an abdominal CT. The association between pretreatment ILA and survival was assessed using Kaplan-Meier analysis with log-rank test. Specific survival rates at 12, 36, and 60 months according to the presence of ILA were evaluated using z -test. Cox regression analysis was used to assess the risk factors of mortality. A total of 173 patients were included (mean age, 70.23 ± 7.98 years). Pretreatment ILA was observed in 10.4% of patients. Patients with ILA were more likely to be older and current smokers. Pretreatment ILA was associated with poor survival ( P < 0.001). Age ≥70 years (hazards ratio [HR], 1.98; 95% confidence interval [CI], 1.24-3.16; P = 0.004), metastatic stage (HR, 2.26; 95% CI, 1.36-3.74; P = 0.002), and ILA (HR, 1.96; 95% CI, 1.06-3.60; P = 0.031) were the independent risk factors of mortality. An ILA (HR, 3.94; 95% CI, 1.78-8.72; P = 0.001) was the only independent risk factor of mortality in localized stage prostate cancer patients. This study provides important insights into the unexplored effect of pretreatment ILA in prostate cancer patients. Pretreatment ILAs were observed considerably in the lung bases scanned on the abdominal CT scans among prostate cancer patients. Furthermore, pretreatment ILAs were the risk factor of mortality. Therefore, lung bases should be routinely inspected in the abdominal CT scans of prostate cancer patients. This result may help clinicians in establishing personalized management strategy of prostate cancer patients.

Abstract A021: Pre and post treatment transcriptomic analysis provide new insights on the mechanisms underlying the efficacy of PARPi and Androgen blockage in prostate cancer

Abstract Aim: Recent phase 3 trials (PROPEL, TALAPRO2) have demonstrated survival benefits when combining PARP inhibitors (PARPi) with androgen pathway inhibitors (API) in prostate cancer (PC) treatment. Importantly, this benefit is observed regardless of homologous repair deficiency (HRD) status, suggesting alternative underlying mechanisms beyond synthetic lethality. However, the complete identification of all the PC patients who can benefit from this combination therapy remains an unmet need. Therefore, further investigation into the distinct molecular pathways involved and identification of biomarkers of response is critical and is the aim of this study. Methods: We have performed an exploratory transcriptomic analysis including RNA-seq, differential expression analysis and gene set enrichment analyses (GSEA) of pre and post treatment biopsies of localized PC patients (pts) with higher risk of relapse and that were included in a window of opportunity (WoO) study. We have included pts recruited to the CANCAP-3 study that were exposed to either two weeks of olaparib alone or in combination with degarelix (1:1 randomization). A corresponding transcriptomic analysis of pre and post enzalutamide biopsies of patients recruited to the WoO study DARANA was also included. Results: GSEA results have shown p53 hallmark upregulation more pronounced in the combination cohort. In the combination cohort the androgen response genes were downregulated. Additionally, canonical cell cycle progression hallmarks (E2F and G2M checkpoint) were suppressed with a significant downregulation of the Prolaris signature. In the olaparib monotherapy cohort pts with the greatest PSA decline demonstrated large reductions in the Prolaris score. Furthermore, in the olaparib monotherapy cohort the two patients that relapsed within 4 years of follow up demonstrated greater Prolaris scores. Interestingly, a significant positive correlation between HR deficiency signatures and reduced prostate cancer proliferation index was observed across the study cohorts, although there was only minimal overlap in the genes constituting these two signatures. This correlation was maintained excluding HRD pts (n=2). Finally, this relationship was also observed following analysis of the DARANA trial. Conclusions: Tissue transcriptomic data analysis of PC pts can provide further insights on the possible biological mechanisms that underlie the effect of this drug combination. In this study the expression of HRD signature appeared to be in direct proportion to the reduction in cellular proliferation (Prolaris). This was seen in the combination treatment cohort, as well as in a separate API monotherapy study (DARANA). This suggests that androgen inhibition is the main driver for the reduction in HR signature. However, this phenomenon may represent a consequence of cell cycle arrest occurring more readily in cells with the greatest HR defect. Further studies are needed to further explain the unique upstream processes that contribute to an AR-supported DNA damage response, in the context of PARP inhibition. Citation Format: Ana Filipa Palma dos Reis, Toby Milne-Clark, Amit Dipak Amin, Liliya Nazlamova, Simon Pacey, Harveer Dev. Pre and post treatment transcriptomic analysis provide new insights on the mechanisms underlying the efficacy of PARPi and Androgen blockage in prostate cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Damage Repair: From Basic Science to Future Clinical Application; 2024 Jan 9-11; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2024;84(1 Suppl):Abstract nr A021.

Timing of High-Dose-Rate Brachytherapy With External Beam Radiation Therapy in Patients With Intermediate- and High-Risk Localized Prostate Cancer and Its Effects on Toxicity and Quality of Life: A Randomized Controlled Trial (THEPCA)

BackgroundHDR brachytherapy(HDR-BT) and external beam radiotherapy(EBRT) are effective treatments for prostate cancer(PC) but cause genitourinary(GU) and gastrointestinal(GI) toxicities. There is no consensus on the timing of HDR-BT in relation to EBRT and the effect of sequencing on patients. ObjectiveThe primary objective was to assess differences, if any, in the incidence of Grade 3 or higher GU toxicities from treatment. We also aimed to explore the incidence of G1-4 GI toxicities, quality of life and patient satisfaction. Suppression of PSA and signals for survival differences were also analysed. MethodologyA single-centre randomised trial in intermediate and high-risk localised PC patients to receive HDR-BT before (Arm A) or after (Arm B) EBRT. Toxicities were graded using CTCAE. IIEF and FACT-P were used to assess erectile dysfunction and QOL at 0, 3, 9 and 12 months. Results50 patients were recruited to each arm, with 48 and 46 patients completing treatment and follow up in each arm. 81.5% had high-risk disease. There were no G3 or G4 GU or GI toxicities. G1 urinary frequency was the most common adverse event experienced in both arms, peaking in incidence 3 months after commencing treatment (45.7 and 42.2% in Arm A and B, respectively). Up to 11 % of patients reported G1 urinary frequency at 12 months. Other G1 GU toxicities experienced by >10% of patients were urinary tract obstruction, tract pain and urgency. These symptoms also peaked in incidence at 3 months. G2 GU toxicities were uncommon and experienced in a maximum of 2 patients within each arm at any time point.Over 30% of patients had G1 flatulence at baseline and this remained the most frequently occurring G1 GI toxicity throughout the study, peaking at 12months (21.4% and 25.6% in Arm A and Arm B, respectively). Other GI toxicities experienced by more than 10% of patients were GI pain, proctitis and rectal mucositis, most of which demonstrated a peak incidence at 3 or 9 months. G2 GI toxicities were uncommon, except G2 flatulence.No significant difference was found in CTCAE, IPSS, IIEF, FACT-P and QOL scores between the arms.Median PSA follow-up was 5 years. 7 patients had treatment failure in each arm. DFRS was 93.3% and 90.7% at 5 years in Arm A and B respectively, with median failure time of 60 and 48 months in Arm A and B respectively. There were no statistically significant difference between arms. ConclusionsThe sequencing of HDR-BT and EBRT did not impact the incidence of G3 or G4 toxicities and no significant differences were seen in other patient reported outcomes. Treatment was well tolerated with maintained QOL scores. Treatment failure was low in both arms in a high-risk cohort, however a larger study with longer follow up is underway to establish whether the difference in median time to failure between the two arms is a signal of superiority.

Salvage Radiotherapy in Localised Prostate Cancer Patients over a 4-year Follow-up Period: Single Centre Analysis

Salvage Radiotherapy in Localised Prostate Cancer Patients over a 4-year Follow-up Period: Single Centre Analysis

Computed Tomography-Based Radiomics for Long-Term Prognostication of High-Risk Localized Prostate Cancer Patients Received Whole Pelvic Radiotherapy.

Given the high death rate caused by high-risk prostate cancer (PCa) (>40%) and the reliability issues associated with traditional prognostic markers, the purpose of this study is to investigate planning computed tomography (pCT)-based radiomics for the long-term prognostication of high-risk localized PCa patients who received whole pelvic radiotherapy (WPRT). This is a retrospective study with methods based on best practice procedures for radiomics research. Sixty-four patients were selected and randomly assigned to training (n = 45) and testing (n = 19) cohorts for radiomics model development with five major steps: pCT image acquisition using a Philips Big Bore CT simulator; multiple manual segmentations of clinical target volume for the prostate (CTVprostate) on the pCT images; feature extraction from the CTVprostate using PyRadiomics; feature selection for overfitting avoidance; and model development with three-fold cross-validation. The radiomics model and signature performances were evaluated based on the area under the receiver operating characteristic curve (AUC) as well as accuracy, sensitivity and specificity. This study's results show that our pCT-based radiomics model was able to predict the six-year progression-free survival of the high-risk localized PCa patients who received the WPRT with highly consistent performances (mean AUC: 0.76 (training) and 0.71 (testing)). These are comparable to findings of other similar studies including those using magnetic resonance imaging (MRI)-based radiomics. The accuracy, sensitivity and specificity of our radiomics signature that consisted of two texture features were 0.778, 0.833 and 0.556 (training) and 0.842, 0.867 and 0.750 (testing), respectively. Since CT is more readily available than MRI and is the standard-of-care modality for PCa WPRT planning, pCT-based radiomics could be used as a routine non-invasive approach to the prognostic prediction of WPRT treatment outcomes in high-risk localized PCa.

Prediction of biochemical recurrence after laparoscopic radical prostatectomy

BackgroundRadical prostatectomy (RP) has been considered primary treatment for localized prostate cancer. Biochemical recurrence (BCR) occur approximately 20–30% in five year after RP. We aim to develop a novel nomogram to predict BCR-free survival (BCRFS) and performed external validation using a validation cohort that may help clinicians to make better decision for tailoring adjuvant treatment to specific group of patients.Materials and methodsThis retrospective cohort study included 370 localized and regional prostate cancer patients who underwent laparoscopic radical prostatectomy (LRP) in Songklanagarind hospital between January 2010 and December 2019, the patients were divided into two groups (primary cohort and validation cohort). BCR-free survival was created using Kaplan-Meier curve. Predictive factors for BCR were identified with univariable and multivariable analysis using Cox proportional hazards model. Predictive nomogram was created using these identified factors and developed for the prediction of biochemical recurrence free survival (BCRFS) at 1 and 5 years after LRP.ResultsFor primary Songklanagarind cohort, BCR was found in 105 patients (44.7%). Overall 1-year BCR-free survival was 52.8%, and 5-year BCR-free survival was 45.7% with median time to BCR of 18.1 months. Multivariable analysis identified unfavorable factor to BCRRF which are high initial serum PSA (> 20) (p < 0.001; HR 3.2), ISUP Gleason grade group > = 3 (p 0.033; HR 2.2), positive surgical margins (p 0.046; HR 1.5), and seminal vesicle involvement (p < 0.001; HR 5.2) and using for develop a novel nomogram to predict BCR. Concordance index 0.78.ConclusionProstate cancer patients with unfavorable factors, including high initial PSA (> 20), ISUP Gleason grade group > = 3, positive margin and extra-prostatic tumor extension are considered high risks and independent predictors of biochemical recurrence. This predictive models could potentially improve the 1 and 5-year BCR prediction after RP, according to the study’s findings and will aid medical professionals in achieving the goal of clinical prediction and creating a proper management for the localized treatment of prostate cancer underwent laparoscopic radical prostatectomy.