Recurrence In Prostate Cancer Patients Research Articles

Impact of delayed pelvic imaging on the staging of biochemical recurrence in prostate cancer patients using [18F]DCFPYL PET/CT: a retrospective evaluation.

The aim of this study was to evaluate the added diagnostic value of additional second stage pelvic scanning as part of the [18F]DCFPYL PET/CT procedure in patients treated for prostate cancer (PCa) who have biochemical recurrence (BR). Consecutive patients with a diagnosis of PCa who underwent a dual-phase PSMA-PET scan between September 2022 and December 2023, were retrospectively included. We analyzed the number and maximum SUV (SUVmax) of lesions only in the pelvic region (prostate, locoregional lymph nodes and bone), based on PSMA-RADS version 2.0 and miTNM criteria. To assess the potential diagnostic benefit of additional delayed pelvic PET/CT imaging as part of the PSMA-PET procedure, the change in molecular TNM classification was evaluated after the procedure. Additional delayed pelvic PET/CT imaging as part of the PSMA-PET procedure resulted in a change in molecular TNM classification in 22 out of 136 patients (16.2%). The highest percentage change was obtained in the miN classification (14/22 patients), followed by the miT classification (7/22) and lastly miM (1/22). Moreover, we found that patients in whom delayed pelvic imaging resulted in a change in molecular TNM classification were significantly older and had a higher PSA level than those in whom delayed imaging did not provide additional information. Pelvic delayed imaging in patients with biochemical recurrence of prostate cancer undergoing PET/CT with [18F]DCFPYL shows a non-negligible influence on patient staging, modifying the miTNM classification in 16.2% of cases, with pelvic lymphatic involvement benefiting the most from the dual study.

Assessing the influence of prostate tissue traits on Gallium-68 prostate-specific membrane-antigen positron-emission tomography/computed tomography: Predictive factors for image positivity and locoregional recurrence in prostate cancer patients treated with radical prostatectomy and without prior or salvage treatment.

BACKGROUNDGallium-68 prostate-specific membrane-antigen positron-emission tomography/computed tomography (68Ga-PSMA-11 PET/CT) has recently emerged as a novel imaging modality, potentially improving oncologic outcomes for prostate cancer patients. This study aimed to assess the potential predictive factors associated with 68Ga-PSMA-11 PET/CT positivity following persistent prostate-specific antigen (PSA) levels and primary biochemical recurrence post-radical prostatectomy (RP), focusing on prostate specimen characteristics. Furthermore, we aim to identify predictive factors for locoregional recurrence. METHODSWe conducted a retrospective analysis of 230 prostate cancer patients treated with RP and without prior salvage or adjuvant radiotherapy or systemic treatments. All patients underwent 68Ga-PSMA-11 PET/CT scans to detect prostate cancer recurrence detection. Pathological findings were carefully examined and correlated with 68Ga-PSMA-11 PET/CT positivity and locoregional recurrence. RESULTSOur analysis showed that 68Ga-PSMA-11 PET/CT positivity was associated with ISUP grade group ≥ 3, presence of positive lymph node invasion at the time of RP, positive extraprostatic extension, involvement of seminal vesicles and post-RP PSA levels ≥ 0.1 ng/ml. Additionally, we identified ISUP grade group 2 and ISUP grade group ≥ 3, whether with or without positive lymph node invasion, along with extraprostatic extension, involvement of seminal vesicles and post-RP PSA ≥ 0.1 ng/ml, were identified as factors associated with pelvic node recurrence. CONCLUSIONSPathological findings emerge as robust predictors of 68Ga-PSMA-11 PET/CT positivity and locoregional recurrences in cases of initial biochemical recurrence or persistence without prior adjuvant or salvage treatment. This diagnostic approach facilitates potential adjustments in management strategies, such as PSMA-guided radiotherapy or PSMA-guided lymphadenectomy.

Comparative analysis of genetic risk scores for predicting biochemical recurrence in prostate cancer patients after radical prostatectomy

BackgroundIn recent years, Genome-Wide Association Studies (GWAS) has identified risk variants related to complex diseases, but most genetic variants have less impact on phenotypes. To solve the above problems, methods that can use variants with low genetic effects, such as genetic risk score (GRS), have been developed to predict disease risk.MethodsAs the GRS model with the most incredible prediction power for complex diseases has not been determined, our study used simulation data and prostate cancer data to explore the disease prediction power of three GRS models, including the simple count genetic risk score (SC-GRS), the direct logistic regression genetic risk score (DL-GRS), and the explained variance weighted GRS based on directed logistic regression (EVDL-GRS).Results and ConclusionsWe used 26 SNPs to establish GRS models to predict the risk of biochemical recurrence (BCR) after radical prostatectomy. Combining clinical variables such as age at diagnosis, body mass index, prostate-specific antigen, Gleason score, pathologic T stage, and surgical margin and GRS models has better predictive power for BCR. The results of simulation data (statistical power = 0.707) and prostate cancer data (area under curve = 0.8462) show that DL-GRS has the best prediction performance. The rs455192 was the most relevant locus for BCR (p = 2.496 × 10–6) in our study.

Comparison of digital and analog [68Ga]Ga-PSMA-11 PET/CT for detecting post-prostatectomy biochemical recurrence in prostate cancer patients: a prospective study

Digital positron emission tomography/computed tomography (PET/CT) has shown enhanced sensitivity and spatial resolution compared with analog PET/CT. The present study compared the diagnostic performance of digital and analog PET/CT with [68Ga]Ga-PSMA-11 in prostate cancer patients who experienced biochemical recurrence (BCR) after prostatectomy. Forty prostate cancer patients who experienced BCR, defined as serum prostate-specific antigen (PSA) concentrations exceeding 0.2 ng/mL after prostatectomy, were prospectively recruited. These patients were stratified into three groups based on their serum PSA levels. [68Ga]Ga-PSMA-11 was injected into each patient, and images were acquired using both analog and digital PET/CT scanners. Analog and digital PET/CT showed comparable lesion detection rate (71.8% vs. 74.4%), sensitivity (85.0% vs. 90.0%), and positive predictive value (PPV, 100.0% vs. 100.0%). However, digital PET/CT detected more lesions (139 vs. 111) and had higher maximum standardized uptake values (SUVmax, 14.3 vs. 10.3) and higher kappa index (0.657 vs. 0.502) than analog PET/CT, regardless of serum PSA levels. On both analog and digital PET/CT, lesion detection rates and interrater agreement increased with increasing serum PSA levels. Compared with analog PET/CT, digital PET/CT detected more lesions with a higher SUVmax and better interrater agreement in prostate cancer patients who experienced BCR after prostatectomy.

Whole pelvis vs. hemi pelvis elective nodal radiotherapy in patients with PSMA-positive nodal recurrence after radical prostatectomy - a retrospective multi-institutional propensity score analysis

PurposeDespite growing evidence for bilateral pelvic radiotherapy (whole pelvis RT, WPRT) there is almost no data on unilateral RT (hemi pelvis RT, HPRT) in patients with nodal recurrent prostate cancer after prostatectomy. Nevertheless, in clinical practice HPRT is sometimes used with the intention to reduce side effects compared to WPRT. Prostate-specific membrane antigen positron emission tomography / computed tomography (PSMA-PET/CT) is currently the best imaging modality in this clinical situation. This analysis compares PSMA-PET/CT based WPRT and HPRT.MethodsA propensity score matching was performed in a multi-institutional retrospective dataset of 273 patients treated with pelvic RT due to nodal recurrence (214 WPRT, 59 HPRT). In total, 102 patients (51 in each group) were included in the final analysis. Biochemical recurrence-free survival (BRFS) defined as prostate specific antigen (PSA) < post-RT nadir + 0.2ng/ml, metastasis-free survival (MFS) and nodal recurrence-free survival (NRFS) were calculated using the Kaplan-Meier method and compared using the log rank test.ResultsMedian follow-up was 29 months. After propensity matching, both groups were mostly well balanced. However, in the WPRT group there were still significantly more patients with additional local recurrences and biochemical persistence after prostatectomy. There were no significant differences between both groups in BRFS (p = .97), MFS (p = .43) and NRFS (p = .43). After two years, BRFS, MFS and NRFS were 61%, 86% and 88% in the WPRT group and 57%, 90% and 82% in the HPRT group, respectively. Application of a boost to lymph node metastases, a higher RT dose to the lymphatic pathways (> 50 Gy EQD2α/β=1.5 Gy) and concomitant androgen deprivation therapy (ADT) were significantly associated with longer BRFS in uni- and multivariate analysis.ConclusionsOverall, this analysis presents the outcome of HPRT in nodal recurrent prostate cancer patients and shows that it can result in a similar oncologic outcome compared to WPRT. Nevertheless, patients in the WPRT may have been at a higher risk for progression due to some persistent imbalances between the groups. Therefore, further research should prospectively evaluate which subgroups of patients are suitable for HPRT and if HPRT leads to a clinically significant reduction in toxicity.

Interreader and Intrareader Reproducibility of 18F-Flotufolastat Image Interpretation in Patients with Newly Diagnosed or Recurrent Prostate Cancer: Data from Two Phase 3 Prospective Multicenter Studies.

Interreader and intrareader reproducibility of 18F-flotufolastat PET/CT scans in newly diagnosed and recurrent prostate cancer patients was assessed from masked image evaluations from two phase 3 studies. Methods: 18F-flotufolastat PET/CT images of newly diagnosed (n = 352) or recurrent (n = 389) patients were evaluated by 3 masked readers. Cohen κ was used to assess pairwise patient- and region-level interreader agreement. Agreement among all readers was assessed using Fleiss κ. Intrareader agreement between the first and repeat read (20% of images, ≥4 wk later) was assessed using Cohen κ. Results: Pairwise interreader agreement was 95% or better (newly diagnosed) and 75% or better (recurrent). The κ coefficients were impacted by the high-agreement-low-κ paradox: Cohen κ ranged from not estimable to 0.55, whereas Fleiss κ was 0.50 (newly diagnosed) and 0.41 (recurrent). Agreement was highest in the prostate of newly diagnosed patients (≥95%) and in the pelvic lymph nodes in recurrent patients (≥87%). Intrareader agreement was 86% or better across both populations. Conclusion: 18F-flotufolastat PET/CT images can be reliably interpreted, with a high degree of inter- and intrareader agreement.

Testosterone replacement therapy (TRT) in patients with locoregional prostate cancer (LPC) treated with prior androgen deprivation therapy (ADT): A single center review.

e24045 Background: In LPC, ADT may be combined with radiation therapy (RT) for 4-24 months. Post-ADT, a significant proportion of men experience prolonged hypogonadism. TRT can alleviate symptoms and improve metabolic outcomes. Contrary to longstanding concerns, there is no substantial evidence of increased prostate cancer recurrence in patients (pts) treated with single modalities (surgery or RT). However, sparse data ( &lt; 100 cases published to our knowledge) exist regarding recurrence risk of LPC with TRT after prior ADT, where baseline T levels may fall below the androgen receptor saturation point. Methods: We retrospectively abstracted clinical data from hospital records of men with stage I – IVA PC, treated with prior concurrent ADT and RT and subsequently received TRT between January 2014 and September 2023. Extracted data included demographics, cancer diagnosis/staging, ADT/TRT treatment details and PSA and clinical outcomes. The co-primary endpoints were change in PSA and incidence of PC recurrence. Results: 21 pts met criteria. Median age was 77. ISUP Grade Groups (GG) included: GG1: 2, GG2: 2, GG3: 8, GG4: 2, and GG5: 7. AJCC 8th ed. stages were: I: 2, II: 7, III: 7, IV-A: 5. The median duration of prior ADT was 8 months (IQR 5 – 17) and the median interval from RT to TRT was 19 months (IQR: 12 – 44). Prior to TRT, the median testosterone level was 30.5 ng/dL (IQR: 17-76). TRT formulations included: injection: 6, oral: 4, topical: 13. The median follow-up period from the start of TRT was 13 months, and the median duration on TRT was 10 months (IQR: 5-22). TRT was ongoing in 15 (71.4%) pts and discontinued in 6 (28.6%). Reasons for discontinuation included testosterone recovery (1), hospice (not PC related) (2), no perceived benefit (2), MD concern for PSA rise (1). After TRT, the median testosterone level was 336 ng/dL (IQR: 207-462). Median PSA pre- and post-TRT were undetectable and 0.08 ng/dL, respectively. None of the subjects experienced PC recurrence or PC-specific mortality. One pt showed PSA bounce without recurrence. Median BMI was unchanged before (28.3 kg/m2) and after (27.7 kg/m2) TRT (p = 0.48). Due to the nature of the study, quality of life measures and metabolic parameters could not be systematically abstracted. Conclusions: In men with LPC who remained hypogonadal long-term after prior ADT and RT, we found that TRT was not associated with a significant rise in median PSA and no cases of PC recurrence were documented. This included many with a history of very high-risk cancers (eg. GG ≥ 4, Stage ≥ III). This study adds to the sparse existing literature in this clinical setting and together they support the case for a prospective trial utilizing TRT in patients who remain hypogonadal after ADT and radiation.

1769: Intraprostatic recurrence in prostate cancer patients in the FLAME trial

1769: Intraprostatic recurrence in prostate cancer patients in the FLAME trial

P11 Joint modelling to assess the relationship between time to curative treatment and treatment recurrence in Prostate Cancer patients

P11 Joint modelling to assess the relationship between time to curative treatment and treatment recurrence in Prostate Cancer patients

Abstract CT108: Phase I data from TENDU101, a first-in-human trial of a novel synthetic peptide conjugate cancer vaccine platform assessed in recurrent prostate cancer patients before salvage treatment

Abstract Synthetic peptides are explored in the clinic in cancer vaccine development for the purpose of inducing tumor-directed T cell responses. Their immunogenicity is dependent on the chosen adjuvant and target organ exposure (lymphoid organs). To improve peptide immunogenicity, we have developed a technology enabling cross-linking of endogenous, pre-existing circulating antibodies (Abs) by employing a three-dimensional chemistry design. Multiple identical tetanus toxin-derived B cell epitopes (MTTEs) are conjugated to synthetically made antigenic tumor peptides intended to induce T cell responses. Here we report the first clinical safety assessment of the vaccine platform in the trial TENDU101 (NCT04701021). The cancer vaccine candidate (TENDU) was designed to include longer synthetic peptides harboring prostate cancer derived epitopes (CD4 and CD8) from PAP and PSMA. The study was a 3+3 design and doses were 40, 400 and 960 microgram in patients with documented recurrent disease after radical prostatectomy. A tetanus toxoid (TTd) containing vaccine boost was followed by TENDU vaccination via subcutaneous injection in the abdomen (4 doses in total with a 2 week interval) in n=9 patients (gr 1, 2, 3.1). For group 3.2 (n=3) TENDU vaccination was administrated in the same arm as the TTd vaccination. Primary objective was safety and secondary objective assessment of immune responses and preliminary anti-tumor responses. A total of 52 adverse events (AEs) were reported, most mild and deemed unrelated to vaccination. Six treatment-related AEs were reported of which 50% were mild transient injection site reactions in a single patient (gr 3.1), and three events of increases in lipase levels in two patients (gr 2). No serious AEs was reported. T cell responses pre/post TENDU were assessed in a total of six patients of which five patients displayed increased response against vaccine-related CD8 and CD4 epitopes (ELISpot). The three patients with the greatest increase in T cell responses were found to display the highest anti-MTTE IgG responses. A trend towards decrease in circulating tumor cells from screening to the end of treatment visit was observed in the patients with the highest levels of anti-MTTE IgGs post TENDU vaccination. There were no trends for decrease in PSA and/or PAP at the end of treatment and follow-up measurements were affected by initiation of radiation and short-term androgen deprivation. The administration of TTd and TENDU to the same anatomical location although spaced in time appeared to negatively influence immune responses to TTd and TENDU. In conclusion, the novel synthetic peptide conjugate vaccine conjugate was found safe with no serious AEs reported and a positive correlation between anti-MTTE and T cell responses was noted in patients when TENDU was administrated in the abdomen. Citation Format: Wolfgang Lilleby, Anna Bergqvist, Aikaterini Nasi, Wenche Rasch, Sara Mangsbo. Phase I data from TENDU101, a first-in-human trial of a novel synthetic peptide conjugate cancer vaccine platform assessed in recurrent prostate cancer patients before salvage treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT108.

Abstract 1725: Role of PRMT5 in neuroendocrine prostate cancer development

Abstract Background: Neuroendocrine prostate cancer (NEPC) is a lethal subtype of prostate cancer responsible for an estimated 20-30% of castration resistant prostate cancer (CRPC) deaths. While NEPC can arise de novo, the majority of these cases emerge as treatment-induced NEPC (tNEPC). Our data establish PRMT5:MEP50 as a key epigenetic regulator in NEPC and provide a potential predictive biomarker for tNEPC. Methods: Here we generated an in vitro cell culture model and mouse model to mimic the clinical conditions in androgen signaling inhibitor (ASI) or androgen deprivation treatment (ADT) We developed an in vitro cell culture and in vivo model to mimic the clinical conditions in enzalutamide-resistant prostate cancer. Regulation and role of protein arginine methyltransferase 5 (PRMT5) and its cofactor methylosome protein 50 (MEP50) were determined by treating cells and mice tumors with doxycycline inducible-shRNAs and catalytic inhibitors followed by analysis of cell viability, neurite growth, and effects on neuroendocrine related gene transcription. Pro-NEPC development effects were analyzed by immunofluorescence, immunohistochemical analysis, and western blot. PRMT5:MEP50-dependent methyltransferase activity was further validated by observing histone deposition levels via western blot and ChIP-qPCR. For clinical correlation, PRMT5 and MEP50 expression levels were comprehensively analyzed in both CRPC and NEPC patient prostate tissue samples. Results: Our clinical and computational analyses have identified increased expression of PRMT5:MEP50 in NEPC. Overexpression of PRMT5 and MEP50 in prostate cancer cells is sufficient to induce neuroendocrine differentiation (NED) in prostate cancer cells. Gene depletion of PRMT5 and MEP50 prevented the NE phenotype induced by androgen receptor inhibition and resensitized the prostate cancer cells to ASI/ADT. PRMT5 and MEP50 facilitate chromatin modulation through the dimethylation of H4R3, which is highly correlated with the NED phenotype. Moreover, overexpression of PRMT5 and MEP50 in mouse prostate induces NEPC development, and gene downregulation can prevent NED in a xenograft mouse model. Elevated PRMT5 and MEP50 correlated with increased recurrence in prostate cancer patients receiving ADT and their recurrence probability after the treatment. Conclusion: Our data establish PRMT5:MEP50 as a key epigenetic regulator in NEPC and provide a potential predictive biomarker for tNEPC. Citation Format: Hye Seung Nam, Xuehong Deng, Chang-Deng Hu. Role of PRMT5 in neuroendocrine prostate cancer development [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 1725.

The superior detection rate of total-body [68Ga]Ga-PSMA-11 PET/CT compared to short axial field-of-view [68Ga]Ga-PSMA-11 PET/CT for early recurrent prostate cancer patients with PSA < 0.2ng/mL after radical prostatectomy.

[68Ga]Ga-PSMA PET imaging has been extensively utilized for the detection of biochemical recurrence (BCR) in prostate cancer. However, the detection rate declines to merely 10-40% when PSA levels are < 0.2ng/mL employing short axial field-of-view (SAFOV) PET. Prior studies exhibited superior detection rates with total-body [68Ga]Ga-PSMA-11 PET compared to SAFOV [68Ga]Ga-PSMA-11 PET in BCR patients with PSA > 0.2ng/mL. Nevertheless, the diagnostic utility of total-body [68Ga]Ga-PSMA-11 PET for BCR patients when PSA is < 0.2ng/mL remains unclear. This study aimed to assess whether total-body [68Ga]Ga-PSMA-11 PET/CT could improve the detection rate compared to SAFOV [68Ga]Ga-PSMA-11 PET/CT in BCR patients with PSA < 0.2ng/mL. Eighty BCR patients with PSA < 0.2ng/mL underwent total-body [68Ga]Ga-PSMA-11 PET/CT. These patients were matched by baseline qualities to another 80 patients who received SAFOV [68Ga]Ga-PSMA-11 PET/CT. The detection rates of total-body [68Ga]Ga-PSMA-11 PET/CT and SAFOV [68Ga]Ga-PSMA-11 PET/CT were compared utilizing a chi-square test and stratified analysis. Image quality of total-body [68Ga]Ga-PSMA PET/CT and SAFOV [68Ga]Ga-PSMA-11 PET/CT was assessed based on subjective scoring and objective parameters. The objective parameters measured were SUVmax, SUVmean, standard deviation (SD) of SUV, and signal-to-noise ratio (SNR) of liver and gluteus maximus. The image quality of total-body [68Ga]Ga-PSMA PET/CT was superior to that of SAFOV [68Ga]Ga-PSMA-11 PET/CT in both early and delayed scans. The detection rate of total-body [68Ga]Ga-PSMA PET/CT for BCR patients with PSA < 0.2ng/mL was significantly higher than that of SAFOV [68Ga]Ga-PSMA-11 PET/CT (73.75% vs. 43.75%, P < 0.001). Total-body [68Ga]Ga-PSMA PET/CT resulted in noteworthy modifications to the treatment regimen when contrasted with SAFOV [68Ga]Ga-PSMA-11 PET/CT. In BCR patients with PSA < 0.2ng/mL, total-body [68Ga]Ga-PSMA-11 PET/CT not only demonstrated a significantly higher detection rate compared to SAFOV [68Ga]Ga-PSMA-11 PET/CT but also led to significant alterations in treatment regimens.

Quantitative and Qualitative Assessment of Urinary Activity of 18F-Flotufolastat-PET/CT in Patients with Prostate Cancer: a Post Hoc Analysis of the LIGHTHOUSE and SPOTLIGHT Studies

PurposeTo evaluate the impact of urinary activity on interpretation of 18F-flotufolastat (18F-rhPSMA-7.3) PET/CT, we conducted a post hoc qualitative and quantitative analysis of scans acquired in two phase 3 studies of 18F-flotufolastat.ProceduresNewly diagnosed or recurrent prostate cancer patients enrolled in LIGHTHOUSE (NCT04186819) or SPOTLIGHT (NCT04186845), respectively, underwent PET/CT 50–70 min after intravenous administration of 296 MBq 18F-flotufolastat. For the present analysis, 718 18F-flotufolastat scans (352 from LIGHTHOUSE and 366 from SPOTLIGHT) were re-evaluated by three board-certified nuclear medicine physicians. Reader 1 performed a quantitative assessment (SUVmax and SUVmean) of bladder activity in a circular region-of-interest over the maximum diameter of bladder activity in the transverse plane. All three readers qualitatively assessed the impact of any urinary activity in the bladder on image interpretation using a three-point scale (0 = no/minimal visible urinary activity, 1 = urinary activity visible but distinction between urine and disease possible and 2 = assessment inhibited by urinary activity) and the presence/absence of ureteric activity and halo artifacts.ResultsIn total, 712/718 scans were evaluable. Reasons for exclusion were cystectomy, renal failure, or urinary catheter in situ (n = 2 each). The median bladder SUVmax and SUVmean were 17.1 and 12.5, respectively. By majority read, 682/712 (96%) patients had either no urinary activity (score = 0) or visible activity that could be distinguished from disease uptake (score = 1). In the minority of patients (24, 3.4%) where urinary activity did impact assessment (score = 2), the median bladder SUVmean was higher (20.5) than those scored 0 (3.8) or 1 (14.0). Ureteric activity was absent in 401 (56%) patients. Halo artifacts were observed in only two (0.3%) patients (majority read).Conclusions18F-Flotufolastat urinary activity did not influence disease assessment for the majority of patients. While this study was not designed as a head-to-head comparison, the median bladder SUVs are lower than previously reported values for other renally cleared PSMA-PET radiopharmaceuticals.

Prognostic value of Controlling Nutritional Status score for postoperative complications and biochemical recurrence in prostate cancer patients undergoing laparoscopic radical prostatectomy.

Controlling Nutritional Status (CONUT) score was used for screening the preoperative nutritional status. The correlation between the CONUT score and the prognosis of patients with prostate cancer (PCa) has yet to be elucidated. Herein, we analyzed the prognostic value of CONUT scores in patients with PCa who underwent laparoscopic radical prostatectomy. Data of 244 patients were retrospectively evaluated. Perioperative variables and follow-up data were analyzed. The patients were categorized into 2 groups according to their preoperative CONUT scores. Postoperative complication and incontinence rates were also compared. The Kaplan-Meier method was used to estimate the median biochemical recurrence-free survival (BCRFS) between the 2 groups. Univariate and multivariate Cox regression analyses were performed to identify the potential prognostic factors for BCRFS. Patients were categorized into the low-CONUT group (CONUT score <3, n = 207) and high-CONUT group (CONUT score ≥3, n = 37). The high-CONUT group had a higher overall complication rate (40.5% vs.19.3%, p = 0.004), a higher major complication rate (10.8% vs. 3.9%, p = 0.013), and longer postoperative length of stay (8 days vs. 7 days, p = 0.017). More fever, urinary infection, abdominal infection, scrotal edema, rash, and hemorrhagic events (all p values < 0.05) were observed in the high-CONUT group. A higher rate of urinary incontinence was observed in the high-CONUT group at 1 (34.4% vs. 13.2%, p = 0.030) and 3 months (24.1% vs. 8.2%, p = 0.023) postoperatively. The high-CONUT group had shorter medium BCRFS (23.8 months vs. 54.6 months, p = 0.029), and a CONUT score ≥3 was an independent risk factor for a shorter BCRFS (hazards ratio, 1.842; p = 0.026). The CONUT score is a useful predictive tool for higher postoperative complication rates and shorter BCRFS in patients with PCa who undergo laparoscopic radical prostatectomy.

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.

DCE-MRI-Based Atlas for Prostate Bed Recurrence after Radical Prostatectomy: Consistency of CTV Delineation with the Available Contouring Guidelines

To create a magnetic resonance image (MRI)-based atlas of prostate bed recurrence for prostate cancer patients undergoing salvage radiotherapy (sRT) after radical prostatectomy and to evaluate the consistency of contouring guidelines for the prostatic fossa clinical target volume (PF-CTV) delineation. Patients with biochemical recurrence and prostate bed lesions at MRI before sRT were included. A reference patient was identified and the lesion(s) of each patient was mapped by a deformable co-registration among T2 weighted (T2w) images. The structure sets were combined to create a 3D recurrence incidence map, overlapped on T2w reference set, then transferred to the planning CT. The volume and the location of the lesions were extracted. On the reference CT, 5 PF-CTV contouring strategies were implemented: Radiation Therapy Oncology Group (RTOG); European Organization for Research and Treatment of Cancer (EORTC); Francophone Group of Urological Radiotherapy (GFRU); Faculty of Radiation Oncology Genito-urinary Group (FROGG) and Princess Margaret Hospital (PMH). Coverage was assessed after identifying the centroid of each lesion: if the centroid was included in the PF-CTV, the coverage was considered complete (fully covered-FC), otherwise uncovered (UC). The coverage was evaluated for each contouring strategy and compared with the chi-squared test; the strength of the correlation was assessed with the phi coefficient. A total of 112 patients with 124 recurrences were identified. The lesions were located at the vesicourethral anastomosis (VUA), around the bladder neck (BN) and beyond the bladder (RV) in 63, 36 and 25 cases. Regardless the contouring strategy, 89.1% of the lesions were FC. Coverage was higher (p<0.001) for BN (95.6%) over RV (83.2%) and VUA (73.7%) lesions. FC/UC rates were 66.1%/33.9%, 83.9%/16.1%, 89.5%/10.5%, 83.1%/16.9%, 87.1%/12.9% for EORTC, FROGG, GFRU, RTOG and PMH, respectively. At pair-wise comparison, the EORTC definition had lower coverage (p<0.001) and was poorly correlated to the other strategies (phi values ranging 0.385-0.540, p <0.001). Conversely, the correlations between the other definitions were >0.700, the highest between PMH-FROG (0.812, p<0.001). After selecting VUA lesions only (N = 63), the probability of FC was 60.3%, 74.6%, 82.5%, 71.4% and 79.4% for EORTC, FROGG, GFRU, RTOG and PMH, respectively. The EORTC definition performed poorly than GFRU (p = 0.006) and PMH (p = 0.020). When considering lesions above the VUA (N = 61), the performance improved (FC: 72.1%, 93.4%, 96.7%, 95.1% and 95.1% for EORTC, FROGG, GFRU, RTOG and PMH, respectively) but the EORTC was significantly less covering and its correlation with the others was ≤ 0.1. According to the criterium of coverage our data do not support the use of the EORTC definition. Here we provide an MRI-based atlas of prostatic bed recurrence that can optimize sRT contours.

Clinical Usefulness of PSMA PET/CT Imaging in Patients with Suspected Recurrence of Prostate Cancer after Primary RT with PSA below the Phoenix Criteria Threshold: Systematic Review and Meta-Analysis

To assess the detection rate and the patterns of PSMA PET/CT uptake in patients with suspected prostate cancer recurrence after primary radiotherapy with serum PSA levels below the accepted Phoenix definition criteria for biochemical recurrence. The meta-analysis was performed according to the PRISMA statement. Studies providing data on patients with suspected prostate cancer recurrence after primary radiotherapy with serum PSA levels below the accepted Phoenix definition criteria were included. Atotal of 5 studies included a total of 1334 patients, of which 489 patients with suspected BCR and serum PSA levels below the Phoenix criteria were included. The PSMA PET/CT detection rate (DR) was 60% for PSA <0.5 ng/mL, 76% for PSA 0.5-1 ng/mL, 81.03% for PSA 1-2 ng/mL, and 89.5% for PSA>2. No significant differences were found in the locations of PSMA-PET/CT uptake among those with PSA ≤2 ng/mL, compared with those meeting the Phoenix criteria. The PSMA-PET/CT uptake of local-only recurrence was more likely in patients with PSA <2 ng/mL (local-only recurrence PSA >2 ng/mL [40.07%] vs PSA <2 ng/mL [58.10%]), RR: 0.718 (95% CI: 0.579-0.892). Lymph node, bone, and visceral metastasis detection rates could be extracted from 3 studies (432 patients). For lymph nodes, the DR was 46% (95% CI: 38-54) in patients outside the Phoenix criteria threshold, and 50% (95% CI: 39-62) in patients with PSA>2 ng/mL. The DR for bone metastases was 19% (95% CI: 12-28) in patients outside the Phoenix criteria threshold, and 25% (95% CI: 19-31) in patients with PSA>2 ng/mL. The DR for visceral metastases was 3% (95% CI: 0-7) in patients outside the Phoenix criteria threshold, and 2% (95% CI: 0-4) in patients with PSA>2 ng/mL. The potentially salvageable disease was considered when all evidence of avid disease could be safely treated with local therapy. This data could be extracted from two studies (343 patients). A higher proportion of disease potentially amenable to salvage therapy was reported in patients outside the Phoenix criteria threshold [salvageable disease: PSA ≤2 ng/mL: 69% (95% CI: 57-80), and PSA >2 ng/mL: 61% (95% CI: 55-66). The pooled risk ratio meta-analysis showed no statistically significant differences between the two previous groups RR: 0.91 (95% CI: 0.75-1.10). PSMAPET/CT can detect prostate cancer recurrence in patients with PSA levels below the Phoenix criteria threshold (reaching up to 80%). Local-only recurrence detection by PSMA PET/CT was more likely in patients with PSA <2 ng/mL. The data from the present meta-analysis shows that a critical review of the Phoenix criteria in the era of PSMA PET/CT might be warranted. Nevertheless, the lack of anatomopathological validation and the retrospective nature of the studies are some of our limitations.

Concurrent Radiation and Deep Hyperthermia Therapy for the Treatment of Recurrent Prostate Cancer

Robustpreclinical and clinical data have established hyperthermia as an effective radiosensitizer which can be used in the setting of recurrent disease to enhance the therapeutic window. We present a single institution experience examining outcomes in recurrent prostate cancer (RPCA) patients treated with concurrent deep hyperthermia (DHT) and radiation (RT). We hypothesized that concurrent DHT and RT would be well tolerated and would provide durable local control without unexpected toxicity. Consecutive RPCA patients treated with concurrent DHT and pelvic RT were retrospectively analyzed. Patients received twice weekly DHT treatments in addition to daily or twice daily (BID) RT. DHT was delivered using a concentric ring radiofrequency phased array system to a target temperature of 40-43°C. Acute and late treatment associated toxicities, graded per Common Terminology Criteria for Adverse Events (CTCAE) v5.0, were evaluated. Survival and control outcomes were evaluated using the Kaplan-Meier method. Eighteen patients were included for analysis. Median patient age was 69 yrs (64-82 yrs). Fifteen (83%) patients had received prior RT and 12 (67%) patients had undergone radical prostatectomy. At time of treatment, two patients had RPCA which had dedifferentiated to a small cell phenotype. Eight (44%) patients had extra-pelvic disease at time of treatment. Seventeen (94%) patients received proton RT, while 1 (6%) received photon RT. Median RT dose was 49 Gy (range 30-73.8 Gy). Five (28%) patients received BID RT. Fifteen (83%) patients also received sequential or concurrent systemic therapy including androgen deprivation therapy or chemotherapy. A total of 142 DHT treatments were administered (median of 7.5 treatments). Fourteen (78%) patients completed ≥ 75% of planned DHT treatments. Reasons for inability to complete treatment included discomfort and abnormal vital signs during DHT. Only one patient reported Grade 2 pain and pruritus attributed to concurrent RT and DHT. One acute Grade 3 RT toxicity (diarrhea) was reported. No late Grade 3+ toxicities occurred. Of ten patients (56%) treated with curative intent, 8 (44%) had no reported failures at 2-year follow up while two had distant failure and biochemical failure respectively. Three (17%) patients were treated with palliative intent for disease related pain; two reported partial relief and one reported complete pain relief. With a median follow-up of 27 months (1-46 months), 2-year failure free survival was 41.4% (95% CI: 27.8-55%), local control was 76.5% (95% CI 66.2-86.8%) and overall survival was 70.9% (95% CI 58.4-83.3%). Our results suggest that concurrent RT and DHT is well tolerated and allows for safe escalation of local therapy for RPCA, providing patients with durable local control and palliation with an acceptable toxicity profile. Prospective validation is warranted.

Conditional Prostate Cancer-Specific Survival Probabilities in Recurrent Prostate Cancer Patients Receiving Radiation ± Antiandrogen Therapy: Secondary Analysis of a Randomized Clinical Trial

Salvage radiation therapy (SRT) and androgen-deprivation therapy (ADT) are routinely used in patients with elevated prostate-specific antigen (PSA) levels after radical prostatectomy (RP) for prostate cancer (PCa). Although prostate cancer-specific survival (PCSS) following SRT is useful when counseling patients at the time of treatment, the utility of this data from time of diagnosis diminishes over time. Conditional survival (CS) can provide more relevant estimates, especially given long-term PCa survivorship. The primary aim of this study was to analyze CS estimates for recurrent PCa patients undergoing SRT ± ADT. The secondary objective was to determine if factors prognostic of PCSS at diagnosis remain relevant in survivorship. We analyzed data from 760 post-RP patients enrolled in NRG/RTOG 9601 (1998-2003). Eligible patients included men who had undergone prior RP and had pT2/T3 disease without nodal involvement and detectable PSA levels of 0.2-4.0 ng/mL. Patients were randomly assigned to undergo SRT and receive either 24 mo of ADT or placebo. OS was calculated (Kaplan-Meier), cumulative incidence was used to estimate PCSS rates, and prognostic factors associated with PCSS were analyzed by multivariable Cox proportional hazards modeling (MVA). Patients were followed for a median of 13 y. The 5- and 10-y PCSS estimates from diagnosis were 98.52% and 92.7%, respectively. At 1- (n = 755), 3- (n = 727), 5- (n = 680), and 8-y (n = 602) survivorship, chances of PCSS at an additional 5-y were 97.41%, 95.29%, 93.76%, and 91.04%, respectively. On MVA at diagnosis, omission of ADT (HR 2.156, P = 0.0003), increasing age (HR 1.833, P = 0.03), Gleason score (GS) 7 (HR 2.356, P = 0.0057), and GS 8-10 (HR 4.841, P < 0.0001) were associated with PCa-specific mortality. For those who achieved survivorship at 1-, 3-, 5-, and 8-y, all variables remained prognostic of PCa-specific mortality on MVA. Conditional risk of death from PCa for patients treated with SRT increases over time. The initial risk of dying from PCa over a given period, however, is higher than if already having survived a portion of that period. ADT, younger age, and lower GS continue to confer a reduced risk of PCa-specific mortality for long-term survivors. This data can be used to inform survivorship care planning, giving patients more relevant prognostic information during continued surveillance after completion of treatment.

148 Impact of Statin Use on Biochemical Recurrence in Prostate Cancer Patients Treated with Radiation Therapy

148 Impact of Statin Use on Biochemical Recurrence in Prostate Cancer Patients Treated with Radiation Therapy