Biochemical Recurrence Of Prostate Cancer Research Articles

Comparison of clinical performance between late and standard total-body [68Ga]Ga-PSMA-11 in biochemical recurrent prostate cancer.

Enhanced lesion detection in prostate cancer is observed with late [68Ga]Ga-PSMA-11 PET/CT imaging compared to standard [68Ga]Ga-PSMA-11 PET/CT imaging (50-100min p.i.). However, the poor image quality of late imaging using short axial field of view (SAFOV) PET/CT has hindered its sole clinical adoption. Conversely, the image quality of late imaging with a long axial field of view (LAFOV) [68Ga]Ga-PSMA-11 PET/CT fulfills clinical diagnostic requirements. Nonetheless, the diagnostic efficacy of late LAFOV [68Ga]Ga-PSMA-11 PET/CT with forced diuresis and its impact on treatment decisions, compared to standard LAFOV [68Ga]Ga-PSMA-11 PET/CT, remains unclear. This study aims to compare the rate of PET positivity between late and standard LAFOV [68Ga]Ga-PSMA-11 PET/CT and to evaluate the influence of late LAFOV [68Ga]Ga-PSMA-11 PET/CT with forced diuresis on treatment decisions relative to standard scans. From January 2021 to April 2024, 127 patients with biochemical recurrence of prostate cancer post-radical prostatectomy were enrolled to undergo both standard and late LAFOV [68Ga]Ga-PSMA-11 PET/CT scans at Shanghai Renji Hospital. We compared the rate of PET positivity between the two modalities at the patient level and across different anatomical regions. We assessed the added diagnostic value of late LAFOV [68Ga]Ga-PSMA-11 PET/CT and its impact on modifying patient treatment plans. The image quality of late LAFOV [68Ga]Ga-PSMA-11 PET/CT with forced diuresis in all patients met clinical diagnostic requirements. The rate of PET positivity of late LAFOV [68Ga]Ga-PSMA-11 PET/CT with forced diuresis were significantly higher than those of standard LAFOV [68Ga]Ga-PSMA-11 PET/CT (80.31% [102/127] vs. 65.35% [83/127]; P < 0.001). Late LAFOV [68Ga]Ga-PSMA-11 PET/CT demonstrated higher lesion SUVmax (16.69 ± 16.42 vs. 11.91 ± 10.72, P < 0.001) and TBR (6.26 ± 7.21 vs. 3.44 ± 3.57, P < 0.001) compared to standard LAFOV scans. Additionally, 14.17% (18/127) of patients experienced changes in their treatment regimen due to the superior detection capabilities of late LAFOV [68Ga]Ga-PSMA-11 PET/CT with forced diuresis compared to the standard scan. The rate of PET positivity of late LAFOV [68Ga]Ga-PSMA-11 PET/CT with forced diuresis compared to standard LAFOV [68Ga]Ga-PSMA-11 PET/CT highlight its potential as a valuable diagnostic tool for biochemically recurrent prostate cancer. This study paves the way for using late LAFOV [68Ga]Ga-PSMA-11 PET/CT with forced diuresis for prostate cancer imaging in daily clinical practice, facilitating more accurate and timely diagnoses.

A challenging discrimination of an intensely [18F]PSMA-1007-avid solitary lesion at the skull base in a patient with biochemical recurrence of prostate cancer

Abstract Prostate adenocarcinoma metastasis to brain has been reported to occur only up to 0.6% of patients and these are mostly diagnosed in autopsy series. In the setting of biochemical recurrence of prostate cancer, a suspected PSMA-avid (prostate-specific membrane antigen) lesion in the brain is still strongly suggestive of an intracranial metastasis of prostate cancer. This needs, however, a thoroughly recurrency work-up due to other potentially PSMA-avid cranial lesions, as PSMA initially was developed for the imaging of primary CNS tumours. We report of a challenging clinical case of a 71-year-old-patient with a strongly PSMA-avid lesion at the skull base. Given the medical history of a meningioma at the skull base, the further diagnostic work-up with MRI could still not rule out a malignancy, so that the patient needed to undergo a surgical excision of the tumour mass. The histological and immunohistochemical examinations revealed a relapsed CNS WHO grade 1 meningioma. From the aspect of molecular imaging and critical analysis of regular clinical care in a third-level university hospital, we consider this result very intriguing. Hence, we analyse the decision-making process and clinical course of this case in the light of molecular imaging findings.

O06 Prostate-specific membrane antigen positron emission tomography before meeting the Phoenix criteria for biochemical recurrent prostate cancer after radiotherapy: Earlier detection of recurrences

O06 Prostate-specific membrane antigen positron emission tomography before meeting the Phoenix criteria for biochemical recurrent prostate cancer after radiotherapy: Earlier detection of recurrences

Late erosion of an Adjustable Transobturator Male System (ATOMS®) device

IntroductionThis report describes late erosion of an Adjustable Transobturator Male System device which was inserted for post‐prostatectomy incontinence. The Adjustable Transobturator Male System device eroded the bulbar urethra 5 years post insertion, despite initial improvement of symptoms.Case presentationFollowing an open radical retropubic prostatectomy, a 64 year‐old male patient developed post‐prostatectomy incontinence. He had a known urethral stricture and had also undergone salvage radiotherapy for biochemical recurrence of prostate cancer. His incontinence was initially successfully treated with an Adjustable Transobturator Male System device, yet this eroded his bulbar urethra 5 years post insertion, which was deemed to be a late erosion.ConclusionUrologists should be aware that late erosion of the Adjustable Transobturator Male System device can occur, and risk stratification of patients undergoing Adjustable Transobturator Male System device insertion may help to minimize erosion rates.

Long-Term Outcomes of Prostate-Specific Membrane Antigen–PET Imaging of Recurrent Prostate Cancer

Although prostate-specific membrane antigen positron emission tomography (PSMA-PET) has shown improved sensitivity and specificity compared with conventional imaging for the detection of biochemical recurrent (BCR) prostate cancer, the long-term outcomes of a widespread shift in imaging are unknown. To estimate long-term outcomes of integrating PSMA-PET into the staging pathway for recurrent prostate cancer. This decision analytic modeling study simulated outcomes for patients with BCR following initial definitive local therapy. Inputs used were from the literature and a retrospective cohort study conducted at 2 institutions. The base case analysis assumed modest benefits of earlier detection and treatment, and scenario analyses considered prostate-specific antigen (PSA) level at imaging and different outcomes of earlier vs delayed treatment. The analysis was performed between April 1, 2023, and May 1, 2024. (1) Immediate PSMA-PET imaging, (2) conventional imaging (computed tomography and bone scan [CTBS]) followed by PSMA-PET if CTBS findings were negative or equivocal, and (3) CTBS alone. The main outcomes were detection of metastases, deaths from prostate cancer, and life-years and quality-adjusted life-years (QALYs) gained. The model estimated that per 1000 simulated patients with BCR (assumed median age, 66 years), PSMA-PET is expected to diagnose 611 (95% uncertainty interval [UI], 565-656) patients with metastasis compared with 630 (95% UI, 586-675) patients diagnosed using CTBS followed by PSMA-PET and 297 (95% UI, 202-410) patients diagnosed using CTBS alone. Moreover, the estimated number of prostate cancer deaths was 512 (95% UI, 472-552 deaths) with PSMA-PET, 520 (95% UI, 480-559 deaths) with CTBS followed by PSMA-PET, and 587 (95% UI, 538-632 deaths) with CTBS alone. Imaging with PSMA-PET yielded the highest number of QALYs, which were 824 (95% UI, 698-885) higher than CTBS. These results differed by PSA level at the time of testing, with the highest incremental life-years and QALYs and lowest number of deaths from prostate cancer among patients with PSA levels of at least 5.0 ng/mL. Finally, the estimates were sensitive to the expected benefit of initiating therapy for recurrent prostate cancer earlier in the disease course. The results of this decision-analytic model suggest that upfront PSMA-PET imaging for the evaluation of BCR is expected to be associated with reduced cancer mortality and gains in life-years and QALYs compared with the conventional imaging strategy, assuming modest benefits of earlier detection and treatment.

89Zr]Zr-PSMA-617 PET/CT in a Patient with Biochemical Recurrence of Prostate Cancer and Prior Indetermined Findings on [18F]PSMA-1007 Imaging.

We report a case of a 79-year-old male patient with a history of radical prostatectomy for prostate cancer. The patient presented with biochemical reoccurrence; however, previous conventional PSMA PET/CT using [18F]PSMA-1007 showed two indetermined findings with low uptake in the right iliac lymph nodes. Further MRI evaluation provided no additional information. A recently introduced PSMA tracer, [89Zr]Zr-PSMA-617 (half-life: 3.3 days), was administered in an attempt to confirm the diagnosis and aid in potential radiation planning. [89Zr]Zr-PSMA-617 PET/CT clearly revealed the previously indetermined right iliac lymph nodes as definitely metastatic and also identified additional lymph node metastases that were undetected in prior scans. This case highlights the potential superior sensitivity of [89Zr]Zr-PSMA-617 PET/CT in detecting recurrent disease, especially in unclear settings of [18F]PSMA-1007 PET/CT and demonstrates its potential for guiding targeted radiation therapy with curative intent.

Outstanding increase in tumor-to-background ratio over time allows tumor localization by [89Zr]Zr-PSMA-617 PET/CT in early biochemical recurrence of prostate cancer

BackgroundPositron emission tomography/computed tomography (PET/CT) using prostate-specific membrane antigen (PSMA)-targeted radiotracers labeled with zirconium-89 (89Zr; half-life ~ 78.41 h) showed promise in localizing biochemical recurrence of prostate cancer (BCR) in pilot studies.MethodsRetrospective analysis of 38 consecutive men with BCR (median [minimum–maximum] prostate-specific antigen 0.52 (0.12–2.50 ng/mL) undergoing [89Zr]Zr-PSMA-617 PET/CT post-negative [68Ga]Ga-PSMA-11 PET/CT. PET/CT acquisition 1-h, 24-h, and 48-h post-injection of a median (minimum–maximum) [89Zr]Zr-PSMA-617 tracer activity of 123 (84–166) MBq.Results[89Zr]Zr-PSMA-617 PET/CT detected altogether 57 lesions: 18 local recurrences, 33 lymph node metastases, 6 bone metastases in 30/38 men with BCR (78%) and prior negative conventional PSMA PET/CT. Lesion uptake significantly increased from 1-h to 24-h and, in a majority of cases, from 24-h to 48-h. Tumor-to-background ratios significantly increased over time, with absolute increases of 100 or more. No side effects were noted. After [89Zr]Zr-PSMA-617 PET/CT-based treatment, prostate-specific antigen concentration decreased in all patients, becoming undetectable in a third of patients. Limitations: retrospective, single center design; infrequent histopathological and imaging verification.ConclusionThis large series provides further evidence that [89Zr]Zr-PSMA-617 PET/CT is a beneficial imaging modality to localize early BCR. A remarkable increase in tumor-to-background ratio over time allows localization of tumor unidentified on conventional PSMA PET/CT.

Hypoxia-associated gene signatures are not prognostic in high-risk localised prostate cancers undergoing androgen deprivation therapy with radiotherapy

PurposeMen with high-risk prostate cancer (PCa) are treated with androgen deprivation therapy (ADT) and radiotherapy, but the disease reoccurs in 30% of patients. Biochemical recurrence of PCa after treatment is influenced by tumour hypoxia. Tumours with high levels of hypoxia are aggressive, resistant to treatment, and have increased metastatic capacity. Gene expression signatures derived from diagnostic biopsies can predict tumour hypoxia and radiosensitivity, but none are in routine clinical use, due to concerns about the applicability of these biomarkers to new patient cohorts. There has been no or limited testing in cohorts of high-risk PCa. Methods and materialsWe generated transcriptomic data for cohorts of high-risk PCa patients. Patients were treated with ADT followed by external beam radiotherapy with or without a brachytherapy boost. Biomarkers curated from the literature were calculated from pre-treatment biopsy gene expression data. The primary endpoint for survival analyses was biochemical recurrence-free survival (bRFS) and the secondary endpoints were distant metastasis-free survival (DMFS) and overall survival. ResultsThe performance of the selected biomarkers was poor, with none achieving prognostic significance for bRFS or DMFS in any cohort. The brachytherapy boost cohort received shorter durations of ADT than the conventionally fractionated or hypofractionated cohorts (Wilcoxon rank sum test, p=2.1 × 10-18 and 2.3 × 10-10 respectively) and had increased risk of distant metastasis (log-rank test, p=8 × 10-4). There were no consistent relationships between biomarker score and outcome for any of the endpoints. ConclusionsHypoxia and radiosensitivity biomarkers were not prognostic in high-risk PCa patients treated with ADT plus radiotherapy. We speculate that the lack of prognostic capability could be caused by the variable hypoxia-modifying effects of the ADT that these high-risk patients received before and during definitive treatment with radiotherapy. A deeper understanding of biomarker construction, performance and inter-cohort transferability in relation to patient characteristics, sample handling and treatment modalities is required before hypoxia biomarkers can be recommended for routine clinical use in the pre-treatment setting.

Recurrence of mucinous prostate cancer in rectal wall due to needle-track seeding from previous transrectal prostate biopsy.

Needle-track seeding of prostate cancer into the rectal wall following transrectal prostate biopsy is exceedingly rare. We report a case of mucinous prostate cancer recurrence in the rectal wall due to biopsy needle seeding, discovered after robot-assisted radical prostatectomy. A 67-year-old man underwent robot-assisted radical prostatectomy for mucinous prostate cancer (clinical stage T2cN0M0, Gleason score of 4 + 4, and initial prostate-specific antigen level of 8.8 ng/mL). Five years postoperatively, endoscopy revealed a rectal tumor, which was diagnosed as needle-track seeding from the previous transrectal prostate biopsy. Following resection of this rectal tumor, the patient's prostate-specific antigen level fell to <0.008 ng/mL. No signs of recurrence or metastasis were observed 3 months postoperatively. While rare, transrectal prostate biopsies can pose a small risk of needle-track seeding into the rectal wall. Endorectal examination should be considered if biochemical recurrence of prostate cancer occurs following radical prostatectomy.

Pattern of Failure in Patients with Biochemical Recurrence After PSMA Radioguided Surgery.

Prostate-specific membrane antigen (PSMA)-targeted radioguided surgery (RGS) is evolving as a new treatment modality for patients with early biochemical recurrence of prostate cancer and disease limited to locoregional lymph nodes on PSMA-ligand PET/CT. Nevertheless, the pattern of failure (locoregional vs. systemic) after PSMA RGS remains unknown. Therefore, the aim of this retrospective analysis was to evaluate the pattern of disease using PSMA-ligand PET in patients experiencing relapse after PSMA RGS. Methods: We evaluated 100 patients with biochemical recurrence after previous PET-guided PSMA RGS who underwent PSMA-ligand PET (median prostate-specific antigen [PSA], 0.9 ng/mL; range, 0.2-14.2 ng/mL). All suspicious lesions for recurrent prostate cancer were grouped according to the molecular imaging TNM classification system. Detection rates and lesion localization were determined and stratified by PSA values and the International Society of Urological Pathology grade group. Further, lesion localization was compared before and after PSMA RGS. Results: The median time between PSMA RGS and PSMA-ligand PET for relapse was 11.4 mo (range, 5.5-25.6 mo). In total, 91 of 100 (91%) patients showed PSMA-ligand-positive findings. PSMA PET detection rates were 82.6%, 92.6%, 91.3%, and 96.3% for PSA levels of 0.2-0.49, 0.5-0.99, 1-1.99, and at least 2 ng/mL, respectively. More than half of the patients (53%; 48/91) showed local recurrence or pelvic lymph node metastases only. Extrapelvic lymph node metastases, bone metastases, and visceral metastases were present in 22% (20/91), 16% (15/91), and 9% (8/91) of the patients, respectively. With increasing International Society of Urological Pathology grade group, the percentage of patients with bone and visceral metastases increased, whereas the number of patients with only locoregional disease decreased. Conclusion: PSMA-ligand PET is a useful method to detect and localize recurrent disease in patients with biochemical failure after PSMA RGS, with more than half of the patients presenting with locoregional recurrence, offering the potential for a second local therapy (e.g., radiation therapy or repeated surgery).

Construction of a cuproptosis‑related lncRNA signature to predict biochemical recurrence of prostate cancer.

Biochemical recurrence (BCR) is common in prostate cancer (PCa), and patients with BCR usually have a poor prognosis. Cuproptosis is a unique type of cell death, and copper homeostasis is crucial to the occurrence and development of malignancies. The present study aimed to explore the prognostic value of cuproptosis-related long non-coding RNAs (lncRNAs; CRLs) in PCa and to develop a predictive signature for forecasting BCR in patients with PCa. Using The Cancer Genome Atlas database, transcriptomic, mutation and clinical data were collected from patients with PCa. A total of 121 CRLs were identified using Pearson's correlation coefficient. Subsequently, a 6-CRL signature consisting of AC087276.2, CNNM3-DT, AC090198.1, AC138207.5, METTL14-DT and LINC01515 was created to predict the BCR of patients with PCa through Cox and least absolute shrinkage and selection operator regression analyses. Kaplan-Meier curve analysis demonstrated that high-risk patients had a low BCR-free survival rate. In addition, there was a substantial difference between the high- and low-risk groups in the immune microenvironment, immune therapy, drug sensitivity and tumor mutational burden. A nomogram integrating the Gleason score, 6-CRL signature and clinical T-stage was established and evaluated. Finally, the expression of signature lncRNAs in PCa cells was verified through reverse transcription-quantitative PCR. In conclusion, the 6-CRL signature may be a potential tool for making predictions regarding BCR in patients with PCa, and the prognostic nomogram may be considered a practical tool for clinical decision-making.

Body composition in recurrent prostate cancer and the role of steroidogenic genotype.

Hormone therapy (HT) to treat prostate cancer is reported to cause adverse changes in body composition. Clinically, interpatient body composition changes are heterogeneous, but the biologic and clinical determinants of body composition toxicity are unknown. Herein, we test the hypothesis that inherited polymorphisms in steroidogenic genes are associated with differential change in body composition after HT. Men with biochemically recurrent prostate cancer (BCR) who received 8 months of LHRH analog (LHRHa) +/- abiraterone acetate (AAP) were eligible if they had: 1) CT imaging of L3 prior to and after treatment, and 2) nucleated cells collected. Cardiometabolic co-morbidities were retrospectively extracted. Body composition was measured using an AI-based segmentation tool. Germline DNA whole exome or genome sequencing was performed. In 162 men treated with 8 months of HT, median skeletal muscle mass (SMMi) loss was 6.6% and subcutaneous adipose gain was 12.3%. Men with type 2 diabetes had higher loss of SMMi after treatment (-11.1% vs. -6.3%, p = 0.003). For the 150 men with germline NGS, SRD5A2 rs523349 genotype was associated with differential loss in skeletal muscle density after HT, (-1.3% vs. -7.1%, p=0.04). In addition, HSD3B1 rs104703 genotype was associated with decreased baseline visceral adipose tissue (63.0 cm2/m2 vs. 77.9, p=0.05). In men with BCR, HT induced notable loss of skeletal muscle and increased subcutaneous adipose tissue. An inherited polymorphism in SRD5A2 and T2DM were associated with differential skeletal muscle toxicity. These findings suggest that inherited polymorphisms may contribute to the body composition toxicity observed with HT.

1614P PSA responses and PSMA scan changes after immunotherapy for biochemically recurrent prostate cancer (BCR) without androgen deprivation therapy (ADT)

1614P PSA responses and PSMA scan changes after immunotherapy for biochemically recurrent prostate cancer (BCR) without androgen deprivation therapy (ADT)

Prognostic significance of a negative PSMA PET/CT in biochemical recurrence of prostate cancer

BackgroundProstate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) is becoming standard of care for men with biochemical recurrence (BCR) of prostate cancer. The implications of a negative PSMA PET/CT scan in this population remain unclear. This study aims to assess the outcome of patients with BCR post radical prostatectomy (RP) who have negative [18F]DCFPyL PET/CT scan at relapse.MethodsThis is a post-hoc subgroup analysis of a prospective non randomized clinical trial. One hundred and one patients (median age, 75 years) with BCR after RP, who tested negative on [18F]DCFPyL PET/CT and subsequently either underwent salvage radiotherapy (sRT) with or without androgen deprivation therapy (ADT) or were followed without active treatment, were included. Freedom from progression (FFP) after negative PSMA PET/CT was determined based on follow-up imaging selected as per clinical practice. Uni- and multivariate Cox regression analyses were performed to examine the association of patients' characteristics, tumor-specific variables, and treatment with clinical progression at the last follow-up. FFP at 1-, 2-, and 3-year were reported using Kaplan Meier analysis.ResultsThe median PSA level at PET/CT was 0.56 ng/mL (range, 0.4–11.3). Sixty five (64%) patients were followed without receiving further treatment, and 36 (36%) received sRT (18% to the prostate bed only and 18% to the prostate bed and pelvic lymph nodes) within 3 months of the PSMA PET. Seventeen of the sRT patients (17 of 36, 47%) received concomitant androgen deprivation therapy (ADT). Median follow-up was 39 months. Subsequent clinical progression was detected in 21 patients (21%), with 52% in pelvic lymph nodes, 52% in the prostatic fossa, 19% in distant lymph nodes, 14% in lungs, and 10% in bones. The FFP was 95% (95% CI: 91%-99%) at 12 months, 87% (95% CI: 81%-94%) at 24 months, and 79% (95% CI: 71%-88%) at 36 months. Multivariate Cox regression analysis revealed that an initial International Society of Urological Pathology (ISUP) grade 5 was significantly associated with clinical progression at the last follow-up (hazard ratio, 5.1, P value, 0.04). Furthermore, the receipt of sRT correlated significantly with lower clinical progression at the last follow-up (hazard ratio, 0.2, P value, 0.03), whereas other clinical and tumor-specific parameters did not. Following surveillance-only and sRT, 29% (19 of 65) and 6% (2 of 36) of patients, respectively, showed clinical progression. In the sRT group, no significant difference was observed in FFP between patients who underwent sRT to the prostatic fossa versus those who received sRT to the prostatic fossa and pelvic lymph nodes, although the numbers in these groups were small.ConclusionsThis study suggests that salvage radiotherapy is associated with a decreased or delayed clinical progression in patients with biochemical recurrence following radical prostatectomy who have negative PSMA PET/CT scan results. The analysis also underscores the prognostic significance of the initial ISUP grade, with ISUP grade 5 being associated with worse outcomes.Trial registrationRegistered September 14, 2016; NCT02899312.

Impact of Cryopreserved Placental Allografts on Biochemical Recurrence in Prostate Cancer.

Human placental allografts are widely used to promote wound healing. Placental (or amniotic membrane/umbilical cord) allografts are placed along the neurovascular bundles during radical prostatectomy to improve continence and erectile function recovery. It is unknown whether placental allografts impact biochemical recurrence (BCR). This was a single-surgeon retrospective study of 566 robotic radical prostatectomies performed from April 2015 to March 2021. The patients were divided into three groups: the negative control, Brand A, and Brand B. Brand A and Brand B were both cryopreserved amniotic membrane (CAM) allografts. A total of 324 cases were included for BCR Kaplan-Meier and risk-adjusted multivariate analyses (362 for continence analysis). In vitro analyses were performed to determine the effect of CAM allografts on prostate cancer (PCa) cell line growth. For propensity score-matched analysis (adjusting for pre-operative PSA, tumor stage, Gleason Grade, and margin status), (1) the allograft groups did not show differences in time to BCR vs. the negative control group (p = 0.7), and (2) combined allograft treatment groups showed better continence recovery vs. the negative controls (p = 0.01). In vitro, placental allografts reduced PCa cell line growth in co-culture assays. cryopreserved AM allografts (combined or individual brands) did not show a significant effect on BCR but improved continence recovery for PCa patients.

Olaparib Without Androgen Deprivation for High-Risk Biochemically Recurrent Prostate Cancer Following Prostatectomy

Olaparib is a poly(adenosine diphosphate-ribose) polymerase inhibitor that provides benefit in combination with hormonal therapies in patients with metastatic prostate cancer who harbor homologous recombination repair (HRR) alterations. Its efficacy in the absence of androgen deprivation therapy has not been tested. To determine the activity of olaparib monotherapy among patients with high-risk biochemically recurrent (BCR) prostate cancer after radical prostatectomy. This phase 2, single-arm nonrandomized controlled trial enrolled genetically unselected patients across 4 sites in the US from May 2017 to November 2022. Eligible patients had BCR disease following radical prostatectomy, a prostate-specific antigen (PSA) doubling time of 6 months or shorter, an absolute PSA value of 1.0 ng/mL or higher, and a testosterone level of 150 ng/dL or higher. Treatment was with olaparib, 300 mg, by mouth twice daily until doubling of the baseline PSA, clinical or radiographic progression, or unacceptable toxic effects. The primary end point was a confirmed 50% or higher decline in PSA from baseline (PSA50). Key secondary end points were outcomes by HRR alteration status, as well as safety and tolerability. Of the 51 male patients enrolled (mean [SD] age, 63.8 [6.8] years), 13 participants (26%) had a PSA50 response, all within the HRR-positive group (13 of 27 participants [48%]). All 11 participants with BRCA2 alterations experienced a PSA50 response. Common adverse events were fatigue in 32 participants (63%), nausea in 28 (55%), and leukopenia in 22 (43%), and were consistent with known adverse effects of olaparib. In this nonrandomized controlled trial, olaparib monotherapy led to high and durable PSA50 response rates in patients with BRCA2 alterations. Olaparib warrants further study as a treatment strategy for some patients with BCR prostate cancer but does not have sufficient activity in those without HRR alterations and should not be considered for those patients. ClinicalTrials.gov Identifier: NCT03047135.

Usefulness of Tissue Biomarkers versus Prostate-Specific Membrane Antigen-Positron Emission Tomography for Prostate Cancer Biochemical Recurrence after Radical Prostatectomy.

Despite curative-intent local therapy, approximately 27% to 53% of prostate cancer (PCa) patients experience prostate-specific antigen (PSA) recurrence, known as biochemical recurrence (BCR). BCR significantly raises the risk of PCa-related morbidity and mortality, yet there is no consensus on optimal management. Prostate-specific membrane antigen-positron emission tomography (PSMA PET) has emerged as highly sensitive imaging, distinguishing local recurrences from distant metastases, crucially influencing treatment decisions. Genomic biomarkers such as Decipher, Prolaris, and Oncotype DX contribute to refining recurrence risk profiles, guiding decisions on intensifying adjuvant therapies, like radiotherapy and androgen deprivation therapy (ADT). This review assesses PSMA PET and biomarker utility in post-radical prostatectomy BCR scenarios, highlighting their impact on clinical decision-making. Despite their promising roles, the routine integration of biomarkers is limited by availability and cost, requiring further evidence. PSMA PET remains indispensable for restaging and treatment evaluation in these patients. Integrating biomarkers and PSMA PET promises to optimize personalized management strategies for BCR, though more comprehensive consensus-building studies are needed to define their standardized utility in clinical practice.

Combination of Blood Adiponectin and Leptin Levels Is a Predictor of Biochemical Recurrence in Prostate Cancer Invading the Surrounding Adipose Tissue.

Biochemical recurrence is a process that progresses to castration-resistant prostate cancer (CRPC) and prediction of biochemical recurrence is useful in determining early therapeutic intervention and disease treatment. Prostate cancer is surrounded by adipose tissue, which secretes adipokines, affecting cancer progression. This study aimed to investigate the correlation between blood adipokines and CRPC biochemical recurrence. We retrospectively analyzed the clinical data, including preoperative serum adipokine levels, of 99 patients with pT3a pN0 prostate cancer who underwent proctectomy between 2011 and 2019. The primary outcome was biochemical recurrence (prostate-specific antigen: PSA > 0.2). We identified 65 non-recurrences and 34 biochemical recurrences (one progressed to CRPC). The initial PSA level was significantly higher (p = 0.006), but serum adiponectin (p = 0.328) and leptin (p = 0.647) levels and their ratio (p = 0.323) were not significantly different in the biochemical recurrence group compared with the non-recurrence group. In contrast, significantly more biochemical recurrences were observed in the group with adiponectin < 6 μg/mL and Leptin < 4 ng/mL (p = 0.046), initial PSA > 15 ng/mL, clinical Gleason pattern ≥ 4, and positive resection margin. A significant difference was also observed in the multivariate analysis (hazard ratio: 4.04, 95% confidence interval: 1.21-13.5, p = 0.0232). Thus, low preoperative serum adiponectin and high leptin levels were significantly associated with biochemical recurrence in adipose tissue-invasive prostate cancer, suggesting that they may be useful predictors of biochemical recurrence. Further studies with larger cases are needed to increase the validity of this study.

Primary tumor heterogeneity on pre-treatment [68Ga]Ga-PSMA PET/CT for the prediction of biochemical recurrence in prostate cancer

PurposeThe aim of this study is to research the value of the texture analysis of primary tumors in pre-treatment [68Ga]Ga-PSMA PET in the prediction of the development of biochemical recurrence (BCR) in prostate cancer patients who underwent definitive therapies. Methods51 patients with prostate adenocarcinoma who had a pre-treatment [68Ga]Ga-PSMA-11 PET/CT and underwent definitive radiotherapy (RT) or radical prostatectomy (RP) were included in the study. Demographics, clinicopathologic features, the presence of BCR, and the last follow-up date of patients were recorded. Textural and conventional PET parameters (maximum standardized uptake value (SUVmax), total lesion-PSMA (TL-PSMA), and PSMA-tumor volume (PSMA-TV)) were obtained from PET/CT images using LifeX program. Parameters were grouped using the Youden index in ROC analysis. Factors predicting the BCR were determined using Cox regression analyses. Results29 (56.9%) patients have received primary curative RT, while the remaining 22 (43.1%) patients have undergone RP. 5 (22.7%) patients with RP and 3 (10.3%) patients with curative RT have developed BCR during the follow-up. INTENSITY-BASED-minimum grey level (P=.050), GLCM-sum variance (P=.019), and GLCM-cluster prominence (P=.050) were associated with BCR in univariate analysis. INTENSITY-BASED-minimum grey level (P=.009) and GLCM-sum variance (P=.004) were found as independent predictors of BCR in the multivariate analysis. ConclusionTumor heterogeneity on pre-treatment [68Ga]Ga-PSMA PET is associated with a high risk of BCR in PCa patients who underwent definitive therapies.

Final Results of the ANDROCAN Study: Histopathological Characteristics and Biochemical Recurrence at 5 Years of Localized Prostate Cancer According to Preoperative Gonadal Status

Background and objectiveFailure rates after first-line treatment of localized prostate cancer (PCa) treatment remain high; therefore, it is essential to improve the selection and identification of at-risk patients to reduce mortality. The aim of the ANDROCAN study was to evaluate the biochemical recurrence (BCR) in patients with localized PCa treated by total prostatectomy at 5 yr after surgery, according to their presurgery gonadal status. MethodsA prospective cohort study was conducted including 1318 patients undergoing total prostatectomy for localized PCa with a 5-yr postoperative follow-up. Clinical and hormonal data (assays of total testosterone [TT], bioavailable testosterone [BT], dihydrotestosterone, estrone, and estradiol were performed by gas chromatography/mass spectrometry) as well as metabolic syndrome parameters were collected at baseline before surgery. Pathological data (predominant Gleason grade 4 and stage) were collected and cross-referenced centrally. Factors associated with BCR were assessed by a multivariate analysis, and BCR-free survival was assessed by a Kaplan-Meier analysis. Key findings and limitationsAmong the 1318 patients, 237 had BCR of PCa. Considering demographic characteristics, populations with and without BCR were similar. However, patients with BCR had cancers with a higher Gleason score (p = 0.0001) and higher prostate-specific antigen (PSA) values (p = 0.0005) at baseline. Gleason score, pT >3a, and PSA level at baseline were positively correlated with BCR (p < 0.0001, p < 0.0001, and p = 0.0048, respectively), while BT and TT levels were not associated with BCR. This study includes patients with varying clinical characteristics, such as cancer history and metabolic syndrome, introducing variability that makes it challenging to isolate the specific effects of gonadal status on BCR. Another limitation is the lack of evaluation of long-term BCR beyond 5 yr, potentially overlooking recurrences that occur between 5 and 15 yr after surgery. This could lead to an underestimation of the actual long-term recurrence rates. Conclusions and clinical implicationsOverall, PSA levels, high Gleason score, and pT >3a are associated with a greater likelihood of disease recurrence following initial treatment and could serve as important prognostic indicators for predicting the risk of BCR. In this prospective study, biochemical hypogonadism was not associated with a higher occurrence of BCR within 5 yr of prostatectomy. The biological gonadal status of preoperative patients could potentially be useful for therapeutic decisions but does not provide an indication for the oncological follow-up. Patient summaryFive-year follow up of patients after surgery showed that there is no association between hypogonadism (low levels of total testosterone and bioavailable testosterone) and cancer recurrence. However, cancer recurrence seems to be more associated with aggressiveness of cancer at the time of detection.