Low PSA Levels Research Articles

Diagnostic Value of 18F Labelled PSMA PET/CT Imaging in Biochemical Recurrence of Prostate Cancer after Curative Therapy

Abstract Background Prostate cancer is the second most common malignancy and the fifth leading cause of cancer related mortality among men worldwide. Curatively intended treatment is directed for localized disease in form of radical prostatectomy and/or radiation therapy, However biochemical recurrence is encountered in about 15 to 53 % of treated patients within 10 years. Early detection of recurrence is crucial for directing curative salvage therapy. Aim of the Work Aim of the study is to evaluate the diagnostic performance of 18F-PSMA PET/CT imaging in biochemical recurrence of prostate cancer after radical prostatectomy, hormonal therapy and/or external beam. Patients and Methods This study is an exploratory cross-sectional study conducted at radiology department at Ain Shams University Hospitals. Our study included twenty six of previously treated prostate cancer patients referred with rising PSA level. The main source of data was the prospectively conducted 18 F PSMA PET/CT scans and clinical history of the patients referred to the nuclear imaging unit, Ain Shams University Hospitals for evaluation of possibility of disease recurrence. Results Twenty (76.9%) out of twenty six of included patients showed positive scan with at least one lesion suggestive of recurrent prostate carcinoma detected on 18F. PSMA-PET/CT with no positive scans detected at PSA level > 0.2 ng/ml. Participants were divided into three groups based on their PSA level distribution by the 25th and 75th percentiles. The first group included 6 patients representing the first quartile representing the bottom 25% of patients till the 25th percentile with PSA level >0.2). The second group included 14 patients representing the middle 50% with PSA level ranging from 0.2 to 4.5. The third group included 6 patients representing the top 25% from the 75th percentile with PSA level ≥ 4.5. There was a statistically significant very strong positive correlation between PSA level and number of recurrences in local region, regional Lymph nodes, distant Lymph nodes and viscera with p value (<0.001). However, there was no statistically significant correlation between PSA level and recurrence in Osseous regions with p vale (>0.05) Conclusion Our results confirmed the efficiency of 18F-PSMA-1007 PET/CT in detecting biochemical recurrence of prostate cancer at different PSA levels. The likelihood of a pathogenic 18F-PSMA PET/CT appears to be higher in patients with higher PSA levels, however the detection rate is still higher than other methods in patients at low PSA levels.

Isolated spermatic cord metastasis of prostate cancer after radiotherapy detected with 18F-PSMA PET/CT: a case report and literature review.

We report the case of a 65year-old male with prostate cancer previously treated with external beam radiotherapy and 2years of androgen deprivation therapy. His nadir PSA reached undetectable level but gradually increased to 0.89ng/dL. 18F-PSMA PET/CT demonstrated a PSMA-avid lesion at left spermatic cord. Left groin exploration revealed an 8mm left vas deferens mass. Mass excision was performed and pathology result showed prostatic adenocarcinoma. The metastatic route is unknown but the possible routes are intraluminal route via ejaculatory duct, hematogenous route and lymphatic route. This case also highlights the role of 18F-PSMA PET/CT to detect a recurrent lesion at an atypical site in biochemical failure patients even at the low PSA level.

Nutritional Supplement With Fermented Soy in Men With an Elevated Risk of Prostate Cancer and Negative Prostate Biopsies: General and Oncological Results From the Prospective PRAECAP Trial

Introduction & ObjectivesTo investigate the effect of a dietary supplement containing fermented soy on PSA, IPSS, changes in prostate volume and prostate cancer development after a 6-month challenge in men at increased risk of prostate cancer and negative previous biopsies. Materials & MethodsPatients with an elevated risk of PCa, defined by either 1 of the following criteria: PSA > 3 ng/ml, suspect lesion at digital rectal examination (DRE), suspect lesion at transrectal ultrasound (TRUS) / magnetic resonance imaging (MRI) and previous negative prostate biopsies (at least 8 cores) within 12 months before inclusion. Statistical analysis was carried out using a non-parametric one-sided paired Wilcoxon rank sum test, chi-square test and Fisher's exact test. ResultsIn this trial, 94 patients where eligible for analysis. A PSA response was detected in 81% of the cases. In 25.8% (24/93) of patients, a decrease of at least 3 points on the IPSS was observed. The median prostate volume did not statistically change after 6 months (p=0.908). Patients with PSA modulation required fewer investigations and had fewer positive biopsies (p<0.001) and significantly fewer ISUP≥3 lesions (p=0.02). ConclusionsWe observed a significantly lower PSA level after a 6-month challenge with a fermented soy-containing supplement, and an effect on IPSS in a subset of patients. Prescribing a fermented soy supplement in patients with an increased PCa risk could lead to a better selection of patients at real increased risk of having occult PCa.

Clinicopathologic characteristics and outcomes of prostate cancer incidentally discovered at the time of radical cystoprostatectomy: a population-based cohort study.

This study aimed to comprehensively analyze the clinical characteristics and prognosis of patients with concomitant bladder cancer (BCa) and prostate cancer (PCa) using a large population-based database. Within the Surveillance, Epidemiology, and End Results (SEER) database (2000-2019), we identified patient with concomitant PCa at the time of radical cystoprostatectomy (RCP). Logistic regression and propensity score matching (PSM) analyses were employed to identify risk factors and mitigate confounders, respectively. Kaplan-Meier survival curves were used to estimate cancer-specific survival (CSS). A total of 14,199 BCa patients undergoing RCP were identified, with 28.8% incidentally discovered to have concurrent PCa. Among them, 89.9% exhibited organ-confined (T1-2) PCa. An increased risk of concomitant tumors was observed among older age, white race, and high tumor grade of BCa. Survival analysis revealed no significant difference in CSS between patients with BCa alone and those with concurrent PCa (5-year CSS rate: 71.3% vs. 67.2%, P =0.076). Subgroup analysis and multivariable analysis, however, indicated that concurrent high-risk PCa adversely impacted survival (5-year CSS rate: 71.3% vs. 63.4%, HR 1.27, 95% CI 1.01-1.58, P =0.038) compared to solitary BCa. Notably, the presence of low/intermediate-risk PCa did not affect survival outcomes ( P =0.584). In conclusion, incidentally discovered PCa in RCP specimens is frequent and characterized by organ-confined presentation, lower PSA levels, and Gleason scores. Patients with concurrent high-risk PCa have a worse prognosis compared to those with solitary BCa, while the presence of low/intermediate-risk PCa does not influence oncological prognosis.

Impact of PSMA PET/CT on the therapeutic decision of Prostate Carcinoma Biochemical Recurrence

Background: Prostate Cancer (PCa) is the most common malignant tumor in males and Biochemical Relapse (BCR) consists of a challenging scenario compared to primary staging due to small volume of disease and low PSA levels. Prostate-Specific Membrane Antigen (PSMA), Positron Emission Tomography (PET) presents superior performance and strongly affects therapeutic choice.

Predictors of Early Continence After Single-port Transvesical Robot-assisted Radical Prostatectomy

BackgroundSingle-port (SP) transvesical (TV) robot-assisted radical prostatectomy (RARP) is a feasible approach for patients with clinically localized prostate cancer. Our aim is to identify the factors associated with a short time of return to continence. MethodsWe analyzed the first 110 SP TV RARP consecutive cases performed by one surgeon from 2020 to 2022. Continence was defined as zero to one safety pad. Two statistical analyses were done. First, patients were divided: Group A (n=62) included individuals who achieved continence within the initial week post-catheter removal; Group B (n=48) rest of the patients. Descriptive statistics were compared, followed by logistic regression for independent variables. Second, time to continence was analyzed as a continuous variable employing linear regression. The primary outcomes were the independent variables significantly associated with a short time to continence. ResultsAll cases were completed successfully, without additional ports or conversions. Median urinary catheter duration and time to continence were three and 3.5 days, respectively. Patients achieving continence within one week significantly presented with fewer preoperative urinary tract symptoms, lower PSA levels, and had smaller specimen weights postoperatively. Multivariable logistic regression established low specimen weight as the sole significant factor (p=0.04). Furthermore, linear regression demonstrated that alterations in independent variables accounted for 12.7% of the variance in time to continence (p=0.62). ConclusionsThe regionalization of surgery to the bladder employing a retropubic space-sparing extraperitoneal approach during SP TV RARP contributes to a fast return to continence. According to our model, the factors that significantly predict a shorter time to continence include lower preoperative IPSS, PSA, and postoperative specimen weight.

Mortality Risk for Docetaxel-Treated, High-Grade Prostate Cancer With Low PSA Levels

Patients with high-grade prostate cancer with low levels of prostate-specific antigen (PSA; <4 ng/mL) are at high risk of mortality, necessitating an improved treatment paradigm. To assess for these patients whether adding docetaxel to standard of care (SOC) treatment is associated with decreased prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM). PubMed search from 2000 to 2022. Five prospective randomized clinical trials (RCTs) performed in the US, France, and the United Kingdom evaluating SOC treatment with radiotherapy and androgen deprivation therapy (ADT) or with radical prostatectomy vs SOC plus docetaxel. Individual data were included from patients with nonmetastatic prostate cancer, a PSA level of less than 4 ng/mL, and a Gleason score of 8 to 10. Patients initiated treatment between February 21, 2006, and December 31, 2015 (median follow-up, 7.1 [IQR, 5.4-9.9] years). Data were analyzed on December 16, 2022. Hazard ratio (HR) of ACM and subdistribution HR (sHR) of PCSM adjusted for performance status (1 vs 0 or good health), Gleason score (9 or 10 vs 8), tumor category (T3-T4 vs T1-T2 or TX), and duration of ADT (2 years vs 4-6 months). From a cohort of 2184 patients, 145 patients (6.6%) in 4 RCTs were eligible (median age, 63 [IQR, 46-67] years). Thirty-one patients died, and of these deaths, 22 were due to prostate cancer. Performance status was 0 for 139 patients (95.9%) and 1 for 6 patients (4.1%). A reduced but nonsignificant risk of ACM (HR, 0.51 [95% CI, 0.24-1.09]) and PCSM (sHR, 0.42 [95% CI, 0.17-1.02]) was associated with patients randomized to SOC plus docetaxel compared with SOC. The risk reduction in ACM (HR, 0.46 [95% CI, 0.21-1.02]) was more pronounced among patients with a performance status of 0 and was significant for PCSM (sHR, 0.30 [95% CI, 0.11-0.86]). Adding docetaxel to SOC treatment for patients who are in otherwise good health with a PSA level of less than 4 ng/mL and a Gleason score of 8 to 10 was associated with a significant reduction in PCSM and therefore has the potential to improve prognosis.

PSMA PET Guided Salvage Radiotherapy Among Prostate Cancer Patients in the Post-Prostatectomy Setting: A Single Center Post-Hoc Analysis.

Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) shows improved sensitivity and specificity for detection of locoregional and distant metastatic prostate cancer (PCa) compared to conventional imaging, especially at lower PSA levels as is often the case in the biochemically recurrent (BCR), post radical prostatectomy (RP) setting. Providers are now utilizing PSMA PET findings to guide their salvage radiotherapy (sRT) treatment fields and doses, although it is not well understood how PSMA PET guided sRT impacts patient outcomes. This was a post-hoc analysis of 5 prospective studies of PSMA PET conducted at UCLA from 2016 to 2021 that included patients with recurrent PCa following RP. Patients were included in this retrospective study if they initiated sRT within 3 months of PSMA PET, had at least 12 months of follow up after sRT completion, had available sRT treatment details, and did not have distant metastases (DM) by conventional imaging on upfront staging. Patients treated with palliative RT were excluded. BCR following sRT was defined as an increase in PSA of 0.2 ng/ml above the post sRT nadir. Metastasis directed therapy (MDT) was defined as sRT to all PSMA+ N1 and M1 lesions. Baseline patient demographics, PSMA PET findings, sRT & ADT treatment details, and patient outcome data were collected. A total of 176 patients were included in this study. Median time between RP and PSMA PET was 38 months (range 1-329). Median PSA at the time of the PSMA PET was 0.625 ng/mL (range 0.063-35). PSMA PET was positive in 128 patients (73%): 21 (12%) miT+N0M0, 55 (31%) miTxN1M0 and 52 (30%) miTxNxM1 with 19 (11%) miTxNxM1a, 31 (18%) miTxNxM1b, and 2 (1%) miTxNxM1c. Median number of lesions seen on positive PSMA scans was 1 (range 1-8). 39 (22%) patients were subsequently treated with sRT to the prostate bed (PB) only, 59 (34%) to PB + pelvic lymph nodes (PLNs), 33 (19%) to PLNs only, 7 (4%) to PB + PLNs + DM, 7 (4%) to PLNs + DM, and 31 (18%) to DM only. 59 (34%) patients were treated with concurrent ADT at a median duration of 6 months (range 1-39). At a median follow-up of 32 months (range 12-70) after sRT, 80 patients (45%) did not develop BCR or imaging relapse (IR) following sRT, 24 patients (14%) developed BCR but not IR, 1 patient (<1%) developed IR only, and 70 patients (40%) developed both BCR and IR. The median time to BCR and IR following sRT was 15 months (range 1-48) and 19 months (range 6-61), respectively. 1 year post sRT biochemical recurrence free survival was 77%. Of the 83 patients treated with MDT, 32 (39%) did not develop subsequent disease relapse. This post hoc analysis assessed the outcomes of 176 patients treated with PSMA PET guided salvage RT, proving it to be an effective method for treating both pelvic and extrapelvic recurrent PCa. Further investigation is needed to assess the full extent of patient outcomes in this population.

ADT Use and Nodal Irradiation in Men Receiving Post-Prostatectomy Salvage Radiotherapy within a Statewide Radiation Oncology Quality Consortium.

For men with biochemical recurrence after radical prostatectomy, salvage radiotherapy (SRT) is a standard of care. Outcomes are improved when SRT is delivered at lower PSA levels, and there has been increased emphasis on more timely treatment. With early SRT, however, there remains uncertainty as to the optimal use and duration of androgen deprivation therapy (ADT) and pelvic lymph node radiation (PLNRT). Moreover, PET imaging and genomic classifiers have emerged as tools to guide treatment decisions, but their uptake in routine practice is unknown. To address these questions, we analyzed a contemporary cohort treated with SRT within the Michigan Radiation Oncology Quality Consortium (MROQC). We hypothesized that ADT and PLNRT practices would reflect recent trial results in this setting. Eligible patients receiving SRT at an MROQC center were enrolled from 06/09/20 to 11/04/22. Data was prospectively collected via patient-, physician-, and physicist-completed forms. Patients were matched to the Michigan Urological Surgery Improvement Collaborative (MUSIC) database for additional treatment- and patient-related data. Univariable (UVA) and multivariable analyses (MVA) were performed to test associations between patient/tumor factors and ADT or PLNRT use. A total of 191 patients across 26 centers were enrolled in the MROQC database. Of these, 116 were matched to the MUSIC database. Median time from RP to SRT was 17 months (IQR 8 - 33 months). The median post-RP PSA prior to SRT was 0.25 (IQR 0.16 - 0.60). Early SRT was defined as pre-SRT PSA ≤0.5, and 27% (n = 31/116) had a pre-SRT PSA >0.5. Twenty-eight were pT3b/T4, 97% were pN0/NX, and 51% had positive surgical margins. Fractionation was conventional (>28 fractions) in 58% and moderate hypofractionation (20-28 fractions) in 38%. Table 1 describes the patients receiving ADT and/or PLNRT. Median ADT duration was 6 mo (IQR 6 - 7 mo). MVA revealed pre-SRT PSA >0.5 (OR 5.05 [1.89 - 15.33]) and pT3b/T4 disease (OR 4.23 [1.40 - 14.56]) were significantly associated with ADT use (p <0.05), but not grade group (GG) or margin status. PLNRT was significantly associated with pre-SRT PSA >0.5 (OR 3.04 [1.21 - 8.42], p <0.05) but not pT stage, margin status, or GG. PET imaging was performed in 37% of men (52% negative, 21% prostate bed alone uptake, and 26% lymph node positivity) and genomic classifiers were performed in 24%. Nearly 75% of biochemically recurrent prostate cancer patients within MROQC received early SRT, and about half received ADT. A pre-SRT PSA >0.5 was strongly associated with ADT and PLNRT. With prostate bed SRT alone, very few received ADT. Given the considerable heterogeneity in treatment, additional studies may help identify patients who most benefit from ADT + PLNRT, and who may be spared potential added toxicity.

Patterns of Recurrence Following Radiation and ADT for Pathologic Lymph Node Positive Prostate Cancer: A Multi-Institutional Study

Retrospective studies have suggested that post-operative radiation therapy (RT) can reduce the risk of cause-specific mortality in men with pathologic nodal involvement (pN1) after radical prostatectomy (RP). We evaluated prognostic factors and patterns of recurrence in patients who received post-operative RT +/- androgen deprivation therapy (ADT) for pN1 disease in a multicentric cohort of 4 academic centers. Data from patients with pN1 prostate cancer after RP who subsequently received RT with short term (< = 6 mo) or long term (>6 mo) ADT were obtained from 4 academic institutions. Patterns of recurrence, biochemical progression free survival (bPFS) and distant metastasis free survival (DMFS) were evaluated. A total of 270 patients with a median follow-up of 48 months were included. Gleason grade group (GG) 2 was present in 20 patients (7.5%), GG 3 in 81 (30%), GG4 in 36 (13.5%), GG5 in 130 (49%) patients. 256 (95%) patients had extracapsular extension, 70% had seminal vesicle invasion, 59% had positive surgical margins, and 66% had a detectable post-operative PSA. The number of positive nodes at surgery were 1 in 59%, 2 in 19% and >2 in 22% of patients. Of the 83 patients that had pre-RT imaging, 46 (55%) had a PET scan (PSMA, or fluciclovine); 25 (30%) of those had lymph nodes detected on imaging prior to RT. Median time from RP to RT was 6 mo (IQR 4.5-9.1 mo). 96% received radiation to both the prostate bed (median dose 68.4Gy) and pelvic lymph nodes (median dose 46Gy). ADT was prescribed short-term (20%) or long-term (68%), while 26 (10%) received no ADT, and 7 (3%) had an unknown duration. Biochemical failure (bF) was observed in 29% of men, with 5% having pelvic nodal failure and 11.5% having distant metastases (majority in bones, followed by paraaortic nodes) at last follow up. Of 59 patients who had normal baseline testosterone levels, 37% recovered their testosterone by last follow-up. The 4-year bRFS was 72% for all patients and was 83% for those with a pre-RT PSA of <0.1 ng/mL, 76% for PSA 0.1-<0.5 ng/mL, 60% for PSA 0.5-2 ng/mL, and 35% for PSA >2 ng/mL. On multivariable analysis, maximum pre-RT PSA ≥0.5 (0.5 to 2.0 vs <0.1 HR = 3.19; >2.0 vs <0.1 HR = 9.00), use of LTADT (HR = 0.47), and percent pN1 (HR = 1.03) were significantly associated with bF. Pre-RT PSA >2 (HR = 4.10), use of LT ADT (HR = 0.33) and percent pN1 (HR = 1.03) were also significantly associated with DM. In pN1 patients, pelvic RT and ADT at low PSA levels is associated with improved oncologic outcomes compared to treatment at higher levels, suggesting that PSA may have prognostic value for pN1 prostate cancer.

Detection Rate of 18F-rhPSMA-7.3 PET in Patients with Suspected Prostate Cancer Recurrence at PSA Levels

Novel molecular imaging agents yield potential for localization of disease in patients with biochemical recurrence of prostate cancer when PSA levels are still low, and may facilitate early intervention with selective therapy to optimize outcomes. Radiohybrid (rh) positron emission tomography (PET) radiopharmaceutical, 18F-rhPSMA-7.3, is a novel high affinity prostate-specific membrane antigen (PSMA)-targeting ligand with potential for low bladder activity. The SPOTLIGHT study (NCT04186845) evaluated the diagnostic performance of 18F-rhPSMA-7.3 in men with suspected prostate cancer recurrence. Here, we report findings from a post-hoc analysis of SPOTLIGHT data, which determined the 18F-rhPSMA-7.3 detection rates (DR) at low-very low PSA levels. Patients enrolled in SPOTLIGHT underwent PET 50-70 min after IV administration of 296 MBq 18F-rhPSMA-7.3. Scans were evaluated by 3 blinded central readers, with the majority read representing agreement between ≥2 independent readers. For the present analysis, all patients with an evaluable 18F-rhPSMA-7.3 PET and who had a baseline PSA <1 ng/mL were selected. Overall (patient-level) and regional DR by majority read were determined, stratifying DR according to the patients' baseline PSA level (<0.2, ≥0.2 - <0.3, ≥0.3 - <0.5, and ≥0.5 - <1 ng/mL). In total, 389 patients (median [range] PSA, 1.10 [0.03-135] ng/mL, 84 with intact prostate) had an evaluable 18F-rhPSMA-7.3 scan. The overall DR was 83% (322/389) by majority read. Of the 389 patients with an evaluable 18F-rhPSMA-7.3 scan, 188 had a baseline PSA <1 ng/mL and were eligible for the present analysis. Despite low patient numbers in some PSA categories, moderate to high DR were observed, with the patient-level DR shown to increase with increasing baseline PSA (see table). Overall, 68% (128/188) of patients with a PSA <1 ng/mL and 64% (77/121) of patients with a PSA <0.5 ng/mL had a positive 18F-rhPSMA-7.3 scan by majority read. Regional DR were broadly consistent across all PSA categories. Of note, extrapelvic lesions were observed in 21% (25/121) of patients with a PSA <0.5 ng/mL and 27% (51/188) of all patients with a PSA <1 ng/mL. Among this cohort of patients with low-very low PSA levels, more than two-thirds were found to have positive 18F-rhPSMA-7.3 scans. Of clinical significance, over a quarter of patients had extrapelvic findings. 18F-rhPSMA-7.3 PET may be a useful tool for treatment planning in patients with early biochemical recurrence of prostate cancer where curative salvage therapy is of prime consideration.

Application of 18F-PSMA-1007 PET/MR Imaging in Early Biochemical Recurrence of Prostate Cancer: Results of a Prospective Study of 60 Patients with Very Low PSA Levels ≤ 0.5 ng/mL.

Sixty patients with BCR after radical prostatectomy (RP) with PSA ranged 0.1-0.5 ng/mL were enrolled in a prospective study. All patients underwent simultaneous whole-body and pelvic 18F-PSMA-1007 PET/MR. The obtained results were verified by 12-month follow-up. Fifty-three lesions were detected in 45 patients with 75% detection rate. The mean PSA value was 0.31 ng/mL. Of all PSMA-positive foci, 91% were localized in the pelvis, and only 9% of lesions were located in the extrapelvic region. Local recurrences were detected in 29%, PSMA-positive lymph nodes were detected in 64% of patients and bone metastases lesions were detected in 7% of patients. 18F-PSMA-1007 PET/MR seems to be an excellent diagnostic tool in patients with early BCR with very low PSA levels, especially with dt PSA < 6 months. The synergistic effect of combining 18F-PSMA-1007 and whole-body PET/MR with precise multiparametric assessment of pelvic lesions is of particular benefit in early BCR.

Node Oligorecurrence in Prostate Cancer: A Challenge.

Within the oligometastatic state, oligorecurrent lymph node disease in prostate cancer represents an interesting clinical entity characterized by a relatively indolent biology that makes it unique: it can be treated radically, and its treatment is usually associated with a long period of control and excellent survival. Additionally, it is an emergent situation that we are facing more frequently mainly due to (a) the incorporation into clinical practice of the PSMA-PET that provides strikingly increased superior images in comparison to conventional imaging, with higher sensitivity and specificity; (b) the higher detection rates of bone and node disease with extremely low levels of PSA; and (c) the availability of high-precision technology in radiotherapy treatments with the incorporation of stereotaxic body radiotherapy (SBRT) or stereotaxic ablative radiotherapy (SABR) technology that allows the safe administration of high doses of radiation in a very limited number of fractions with low toxicity and excellent tolerance. This approach of new image-guided patient management is compelling for doctors and patients since it can potentially contribute to improving the clinical outcome. In this work, we discuss the available evidence, areas of debate, and potential future directions concerning the utilization of new imaging-guided SBRT for the treatment of nodal recurrence in prostate cancer.

Predictive factors associated with differential pathologic response to neoadjuvant chemohormonal therapy in high-risk localized prostate cancer

To explore the clinical parameters and molecular biomarkers that can predict differential pathologic response to neoadjuvant chemohormonal therapy (NCHT) in prostate cancer (CaP).A total of 128 patients with primary high-risk localized CaP who had received NCHT followed by radical prostatectomy (RP) were included. Androgen receptor (AR), AR splice variant-7 (AR-V7) and Ki-67 staining were evaluated in prostate biopsy specimens by immunohistochemistry. The pathologic response to NCHT in whole mount RP specimens was measured based on the reduction degree of tumor volume and cellularity compared to the paired pretreatment needle biopsy, and divided into 5 tier grades (Grades 0-4). Patients with Grades 2 to 4 (the reduction degree more than 30%) were defined as having a favorable response. Logistic regression was performed to explore the predictive factors associated with a favorable pathologic response. The predictive accuracy was evaluated by receiver operating characteristic (ROC) curve and area under the ROC curve (AUC).Ninety-seven patients (75.78%) had a favorable response to NCHT. Logistic regression showed that the preoperative PSA level, low AR expression and high Ki-67 expression in biopsy specimens were associated with a favorable pathologic response (P < 0.05). Furthermore, the AUC of the preoperative PSA level, AR and Ki-67 were 0.625, 0.624 and 0.723, respectively. Subgroup analysis revealed that the rate of favorable pathologic response to NCHT was 88.5% in patients with ARlowKi-67high, which was higher than patients with ARlowKi-67low, ARhighKi-67low, and ARhighKi-67high (88.5% vs. 73.9%, 72.9%, and 70.9%, all P < 0.05).A lower preoperative PSA level was an independent predictive factor for a favorable pathologic response. Moreover, the expression status of AR and Ki-67 in biopsy specimens were associated with differential pathologic response to NCHT, and AR low/Ki-67 high was also associated with favorable response but warrants further evaluation in this patient subgroup and future trial clinical trial design.

PSMA PET guided salvage radiotherapy among patients with prostate cancer in the post-prostatectomy setting: A single center post-hoc analysis.

5009 Background: Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) shows improved sensitivity and specificity for detection of locoregional and distant metastatic prostate cancer (PCa) compared to conventional imaging, especially at lower PSA levels as is often the case in the biochemically recurrent (BCR), post radical prostatectomy (RP) setting. Providers are now utilizing PSMA PET findings to guide their salvage radiotherapy (sRT) treatment fields and doses, although it is not well understood how PSMA PET guided sRT impacts patient outcomes. Methods: This was a post-hoc analysis of 5 prospective studies of PSMA PET conducted at UCLA from 2016 to 2021 that included patients with recurrent PCa following RP. Patients were included in this retrospective study if they initiated sRT within 3 months of PSMA PET, had at least 12 months of follow up after sRT completion, had available sRT treatment details, and did not have distant metastases (DM) by conventional imaging on upfront staging. Patients treated with palliative RT were excluded. BCR following sRT was defined as an increase in PSA of 0.2 ng/ml above the post sRT nadir. Metastasis directed therapy (MDT) was defined as sRT to all PSMA+ N1 and M1 lesions. Baseline patient demographics, PSMA PET findings, sRT &amp; ADT treatment details, and patient outcome data were collected. Results: 176 patients were included in this study. Median time between RP and PSMA PET was 38 months (range 1-329). Median PSA at the time of the PSMA PET was 0.625 ng/mL (range 0.063-35). PSMA PET was positive in 128 patients (73%): 21 (12%) miT+N0M0, 55 (31%) miTxN1M0 and 52 (30%) miTxNxM1 with 19 (11%) miTxNxM1a, 31 (18%) miTxNxM1b, and 2 (1%) miTxNxM1c. Median number of lesions seen on positive PSMA scans was 1 (range 1-8). 39 (22%) patients were subsequently treated with sRT to the prostate bed (PB) only, 59 (34%) to PB + pelvic lymph nodes (PLNs), 33 (19%) to PLNs only, 7 (4%) to PB + PLNs + DM, 7 (4%) to PLNs + DM, and 31 (18%) to DM only. 59 (34%) patients were treated with concurrent ADT at a median duration of 6 months (range 1-39). At a median follow-up of 32 months (range 12-70) after sRT, 80 patients (45%) did not develop BCR or imaging relapse (IR) following sRT, 24 patients (14%) developed BCR but not IR, 1 patient (&lt;1%) developed IR only, and 70 patients (40%) developed both BCR and IR. The median time to BCR and IR following sRT was 15 months (range 1-48) and 19 months (range 6-61), respectively. 1 year post sRT biochemical recurrence free survival was 77%. Of the 83 patients treated with MDT, 32 (39%) did not develop subsequent disease relapse. Conclusions: This post-hoc analysis assessed the outcomes of 176 patients treated with PSMA PET guided salvage RT, proving it to be an effective method for treating both pelvic and extrapelvic recurrent PCa. Further investigation is needed to assess the full extent of patient outcomes in this population.

Abstract 3064: Exosome-based therapeutic strategy for neuroendocrine prostate cancer

Abstract Background: Therapy-induced neuroendocrine prostate cancer (NEPC) is an aggressive variant of castration-resistant prostate cancer (CRPC) that is increasing in incidence with the widespread use of second generation of androgen receptor (AR)-pathway inhibitors (APIs) such as Enzalutamide (ENZ). NEPC arises from CRPC-Adenocarcinomas (CRPC-Adeno) via a reversible trans-differentiation process, referred to as neuroendocrine differentiation (NED) wherein prostate cancer cells (PCa) undergo a lineage switch. As a result of this lineage switching, PCa cells exhibit neuroendocrine (NE) features, characterized by expression of neuronal markers such as enolase 2 (ENO2), chromogranin A (CHGA) and synaptophysin (SYP). Due to lack of AR signaling, these PCa variants are impervious to anti-androgen therapy and constitute an aggressive variant of advanced CRPC with survival times &amp;lt; 1 year. Clinically, NEPC manifests as the presence of visceral metastatic disease including metastasis to liver, lung, central nervous system or bone despite low serum PSA levels. Current therapeutic options for NEPC are limited to highly toxic platinum drugs. The primary objective of our study is to evaluate novel, exosome-based therapies for NEPC. Methods: Exosomes were isolated from HEK-293T cells by ultracentrifugation. Isolated exosomes were characterized by Nanoparticle Tracking Analyses and electron microscopy. These exosomes were engineered to express biotinylated CEACAM-5 antibody on their cell surface. Exosomes were packaged with a combination of drugs (EZH2 inhibitor and AR inhibitor) by sonication. Engineered exosomes were tested in vitro using NEPC cell line NCI-H660 and in vivo using LuCaP 145.1 patient-derived xenograft model. Results: Engineered exosomes reduced the viability of NEPC cells. CEACAM5-labelled exosomes trafficked to tumor cells as CECAM5 is a surface protein expressed by NEPC cells. Conclusions: Engineered-exosome based therapy may provide a new avenue as a targeted therapy for NEPC. Citation Format: Amritha Sreekumar, Sharanjot Saini. Exosome-based therapeutic strategy for neuroendocrine prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3064.

PSMA-11 PET/CT for Detection of Recurrent Prostate Cancer in Patients With Negative Choline PET/CT.

Prostate adenocarcinoma (CaP) is the leading cancer in men. After curative treatment, from 27% to 53% of patients will experience biochemical recurrence (BR). With the development of focal therapies, precise early identification of recurrence's sites is of utmost importance in order to deliver individualized treatment on positive lesions. The aim of this study was to assess the detection rate (DR) of 68Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) in selected patients with prostate cancer BR and recent negative 18F-choline PET/CT. We performed a retrospective analysis including all patients with CaP referred for BR with a negative 18F-choline PET/CT, and who underwent 68Ga-PSMA-11 PET/CT between October, 2018 and December, 2019. The overall DR of 68Ga-PSMA-11 PET/CT was calculated, and described according to BR characteristics especially PSA levels and velocity. Patients were followed up for at least 1 year. Patient management following 68Ga-PSMA-11 PET/CT and PSA levels evolution after treatment were also recorded. One hundred fifty-nine patients comprising 164 examinations were analyzed. The overall DR of 68Ga-PSMA-11 PET/CT for BR was 65.9% (95CI, 58.6-73.1). The DR was 52.5% (95CI, 39.9-65.0), 70.6% (95CI, 55.3-85.9), 70.4% (95CI, 53.1-87.6), and 78.6% (95CI, 66.2-91.0) for PSA levels between 0.2 and 0.49 ng/mL, 0.5 to 0.99 ng/mL, 1 to 1.99 ng/mL and PSA ≥ 2 ng/mL, respectively. The DR was 70.7% (95CI, 59.0-82.4) with a PSA doubling time (PSA-DT) ≤6 months and 65.2% (95CI, 55.5-74.9) with a PSA-DT >6 months. Around 3/4 of patients (75.9%) with a positive 68Ga-PSMA-11 PET/CT initiated treatment, including surgery (2.4%), stereotactic radiotherapy ± androgen deprivation therapy (ADT) (22%) or external conformational radiotherapy ± ADT (46.3%). Patient management changed in 43 cases (39.8%). Our study confirmed the ability of 68Ga-PSMA-11 PET/CT to detect occult biochemical recurrence, even in a selected population of CaP patients with negative 18F-choline PET/CT, even at low PSA levels.

MP40-20 CAN WE PREDICT FOR MISSED CLINICALLY SIGNIFICANT PROSTATE CANCERS ON MRI-TARGETED BIOPSY ALONE?

You have accessJournal of UrologyCME1 Apr 2023MP40-20 CAN WE PREDICT FOR MISSED CLINICALLY SIGNIFICANT PROSTATE CANCERS ON MRI-TARGETED BIOPSY ALONE? Woon Chau Tsang, Kaiying Wang, Abner Quek, Ziting Wang, Edmund Chiong, and Qinghui Wu Woon Chau TsangWoon Chau Tsang More articles by this author , Kaiying WangKaiying Wang More articles by this author , Abner QuekAbner Quek More articles by this author , Ziting WangZiting Wang More articles by this author , Edmund ChiongEdmund Chiong More articles by this author , and Qinghui WuQinghui Wu More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003278.20AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: MRI-Targeted prostate biopsy (TBx) strategy has been shown to diagnose more clinically significant prostate cancer (csPCa) and less clinically insignificant prostate cancer (ciPCa). Currently, the yield of systematic or saturation biopsy in addition to TBx remains remain unclear. This study aims to evaluate for factors that may predict for csPCa that are missed on TBx alone. METHODS: From 2015 to 2022, we collected prospective single-centre data of consecutive patients who underwent prostate biopsy. We included patients who were biopsy-naïve, had prior negative biopsies, or were on active surveillance for low risk prostate cancer. mpMRI-ultrasound fusion-guided robotic-assisted TBx was performed for every lesion of Prostate Imaging Reporting and Data System (PIRADS) 3 and above, and every patient additionally received saturation biopsy (SBx). Patient data, MRI lesion characteristics, PIRADS score and biopsy results were evaluated. csPCa was defined as ISUP grade group 2 and above. RESULTS: 499 men underwent combined TBx and SBx. The median serum PSA was 7.31ug/L. The overall cancer detection rate was 65.7%, where csPCa rate was 45.1%. The overall cancer and csPCa rates for TBx only vs TBx plus SBx, was 52.9% vs 65.7% (p<0.01), and 39.9% vs 45.1% (p=0.10) respectively. If only TBx was performed, 19.5% of all cancers and 11.5% of csPCa would have been missed. Patients with missed csPCa on TBx only had lower PSA (7.75 vs 10.6, p<0.01), higher prostate volume (59.5 vs 42.9cc, p=0.04), and lower PSA density (0.164 vs 0.271, p<0.01). They also had lower prostate health index (PHI) score (50.6 vs 61.9, p=0.04), although PHI density was similar (1.22 vs 1.56, p=0.09). A smaller index lesion diameter was also predictive of missed csPCa on TBx (8.70 vs 12.2 mm, p<0.01). Patients with PIRADS 3 index lesions were more likely to have missed csPCa on TBx than PIRADS 4 and 5, with a missed csPCa rate of 25.8% vs 11.8% vs 3.45% (p<0.01) respectively. Age, number of lesions on mpMRI, and indication for biopsy were not predictive of missed csPCa. CONCLUSIONS: In our series, TBx alone strategy can miss 11.5% of csPCa. Factors predictive of missed csPCa include initial low PSA level, larger prostate volume, low PSA density, low PHI, small index lesion diameter and lower PIRADS score of the index lesion. A nomogram is created to aid decision making on patient selection to omit systematic biopsy when performing TBx. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e553 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Woon Chau Tsang More articles by this author Kaiying Wang More articles by this author Abner Quek More articles by this author Ziting Wang More articles by this author Edmund Chiong More articles by this author Qinghui Wu More articles by this author Expand All Advertisement PDF downloadLoading ...

MP17-12 IMMUNE SCORE OF TUMOR-INFILTRATING CD8+ AND FOXP3+ LYMPHOCYTES AS A NOVEL PROGNOSTIC BIOMARKER IN HIGH-RISK LOCALIZED PROSTATE CANCER WHO UNDERWENT RADICAL PROSTATECTOMY

You have accessJournal of UrologyCME1 Apr 2023MP17-12 IMMUNE SCORE OF TUMOR-INFILTRATING CD8+ AND FOXP3+ LYMPHOCYTES AS A NOVEL PROGNOSTIC BIOMARKER IN HIGH-RISK LOCALIZED PROSTATE CANCER WHO UNDERWENT RADICAL PROSTATECTOMY Hiromi Sato, Shintaro Narita, Yoshiko Takahashi, Masanori Ishida, Mizuki Kobayashi, Soki Kasima, Ryohei Yamamoto, Taketoshi Nara, Mingguo Huang, Kazuyuki Numakura, Mitsuru Saito, Hiroshi Nanjo, and Tomonori Habuchi Hiromi SatoHiromi Sato More articles by this author , Shintaro NaritaShintaro Narita More articles by this author , Yoshiko TakahashiYoshiko Takahashi More articles by this author , Masanori IshidaMasanori Ishida More articles by this author , Mizuki KobayashiMizuki Kobayashi More articles by this author , Soki KasimaSoki Kasima More articles by this author , Ryohei YamamotoRyohei Yamamoto More articles by this author , Taketoshi NaraTaketoshi Nara More articles by this author , Mingguo HuangMingguo Huang More articles by this author , Kazuyuki NumakuraKazuyuki Numakura More articles by this author , Mitsuru SaitoMitsuru Saito More articles by this author , Hiroshi NanjoHiroshi Nanjo More articles by this author , and Tomonori HabuchiTomonori Habuchi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003237.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: For several cancer patients, immunotherapy has resulted in better outcomes, and tumor-infiltrating lymphocytes (TILs) have promising potential to be associated with prognosis of cancer. However, the clinical significance of TILs in high-risk localized prostate cancer (HRLPCa) is largely unknown. Here we investigate the effect of tissue-resident T cells on clinical outcomes in patients with HRLPCa who had a radical prostatectomy (RP). METHODS: Tumor microarrays were built using prostatectomy specimens from 240 cores of 80 HRLPCa treated with RP. Each specimen was scored individually using immunohistochemistry for the mean numbers of the CD3+, CD4+, CD8+, and FoxP3+ TILs (IHC). After being classified into high- and low-infiltration groups for each TILs, the association between the immune scores, clinicopathological characteristics, and biochemical recurrence-free survival (bRFS) was statistically evaluated. RESULTS: Patients in the higher infiltrate groups for CD3+, CD4+, CD8+, and FoxP3+ TILs had significantly lower PSA levels than those in the lower infiltrate groups, and the rate of pathological T3–4 disease was significantly higher in the low CD4+ group than in the CD4+ high group (p=0.015). No significant difference in bRFS was observed between the low and high groups of each TILs. The FoxP3 high+CD8 low group had significantly worse bRFS than the other groups (2-year bRFS: 88.5% vs. 60.0%, p=0.004) after the groups were divided into four groups, including FoxP3 low +CD8 low, FoxP3 low+CD8 high, FoxP3 high+CD8 low, and FoxP3 high+CD8 high. In contrast, the combination of CD4 and FoxP3 scores was not statistically related to bPFS (p=0.228). FoxP3 high+CD8 low was found to be an independent predictor of bRFS outcome in the multivariate analysis (hazard ratio: 3.431; 95% CI: 1.048–11.240; p=0.049); as well as pathological T3–4 diseases (hazard ratio: 3.546; 95% CI: 1.250–10.060; p=0.017). CONCLUSIONS: The combined IHC scores with CD8 and FoxP3 in RP specimens may be a potential biomarker for biochemical recurrence in patients with HRLPCa. Source of Funding: GlaxoSmithKline plc © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e217 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hiromi Sato More articles by this author Shintaro Narita More articles by this author Yoshiko Takahashi More articles by this author Masanori Ishida More articles by this author Mizuki Kobayashi More articles by this author Soki Kasima More articles by this author Ryohei Yamamoto More articles by this author Taketoshi Nara More articles by this author Mingguo Huang More articles by this author Kazuyuki Numakura More articles by this author Mitsuru Saito More articles by this author Hiroshi Nanjo More articles by this author Tomonori Habuchi More articles by this author Expand All Advertisement PDF downloadLoading ...

PSMA-PET/CT-guided salvage radiotherapy in recurrent or persistent prostate cancer and PSA < 0.2 ng/ml

PurposeThe purpose of this retrospective, multicenter study was to assess efficacy of PSMA-PET/CT-guided salvage radiotherapy (sRT) in patients with recurrent or persistent PSA after primary surgery and PSA levels < 0.2 ng/ml.MethodsThe study included patients from a pooled cohort (n = 1223) of 11 centers from 6 countries. Patients with PSA levels > 0.2 ng/ml prior to sRT or without sRT to the prostatic fossa were excluded. The primary study endpoint was biochemical recurrence-free survival (BRFS) and BR was defined as PSA nadir after sRT + 0.2 ng/ml. Cox regression analysis was performed to assess the impact of clinical parameters on BRFS. Recurrence patterns after sRT were analyzed.ResultsThe final cohort consisted of 273 patients; 78/273 (28.6%) and 48/273 (17.6%) patients had local or nodal recurrence on PET/CT. The most frequently applied sRT dose to the prostatic fossa was 66–70 Gy (n = 143/273, 52.4%). SRT to pelvic lymphatics was delivered in 87/273 (31.9%) patients and androgen deprivation therapy was given to 36/273 (13.2%) patients. After a median follow-up time of 31.1 months (IQR: 20–44), 60/273 (22%) patients had biochemical recurrence. The 2- and 3-year BRFS was 90.1% and 79.2%, respectively. The presence of seminal vesicle invasion in surgery (p = 0.019) and local recurrences in PET/CT (p = 0.039) had a significant impact on BR in multivariate analysis. In 16 patients, information on recurrence patterns on PSMA-PET/CT after sRT was available and one had recurrent disease inside the RT field.ConclusionThis multicenter analysis suggests that implementation of PSMA-PET/CT imaging for sRT guidance might be of benefit for patients with very low PSA levels after surgery due to promising BRFS rates and a low number of relapses within the sRT field.