PSA Increase Research Articles

COVID-19’s effects on symptoms associated with benign prostatic hyperplasia

PurposeThe objective of this study was to identify the relationship between COVID-19 and lower urinary tract symptoms in patients with benign prostatic hyperplasia.Materials and methodsData from forty outpatients who had recovered from COVID-19 and had previously been diagnosed with and treated medically for benign prostatic hyperplasia were assessed. Pre- and post-COVID-19 assessments were also conducted for prostate volume, total serum PSA concentration, and lower urinary tract symptoms. Hospitalizations related to COVID-19, the time interval between COVID-19 recovery and urologist referrals, and comorbidities were considered. Independent Student’s t-tests or chi-square tests were used to compare changes in all variables. For the Spearman rank correlation analysis, only variables with a univariate analysis of p < 0.10 were included in the multiple regression models, with the significance threshold set at two-tailed p < 0.05.ResultsAfter COVID-19, there was an increase in IPSS (12.87 ± 3.76), total serum PSA (1.56 ± 0.87), and prostate volume (10.68 ± 11.73). Multiple linear regression analysis of the independent predictors of IPSS increase revealed pre-COVID-19 IPSS with intermittency and straining as leading symptoms and bladder catheterization during COVID-19. Pre-COVID-19 frequency and nocturia status were found to be independent predictors of increased blood volume, hospital treatment for COVID-19, and bladder catheterization. A weak stream, UTI, and hypertension were found to be independent predictors of a PSA increase. The time from COVID-19 recovery to urologist referral was shorter in patients with post-COVID-19 IPSS increase (p < 0.05).ConclusionDetermining the predictors of the effects of COVID-19 on worsening BPH symptoms is essential for continued monitoring and treatment.

Natural history of PIRADS-2 lesions on serial multiparametric magnetic resonance imaging: Real-life data from an Academic Center

Introduction/BackgroundThe natural history of prostate imaging reporting and data system (PIRADS) score 2 lesions on serial mpMRIs is largely unknown. Herein, we aimed to evaluate the patients with PIRADS-2 index lesions by using serial mpMRI scans to reveal the rates of mpMRI upgrade in PIRADS score and prostate cancer (PCa) detection. Methods/MaterialsAll mpMRI scans with a PIRADS-2 index lesion from our mpMRI database were evaluated retrospectively. Data from 214 biopsy-naïve patients with a PIRADS-2 index lesion on the initial mpMRI who then underwent at least 1 follow-up mpMRI were reevaluated by an experienced uroradiologist and only those (n = 172) who had a PIRADS-2 index lesion on the initial mpMRI according to PIRADS v2.1 were included in the study. mpMRI progression was defined as the detection of any PIRADS ≥3 lesion at follow-up mpMRI. Histopathological results were evaluated in patients undergoing biopsy upon mpMRI progression. ResultsA total of 172 patients with a mean age of 60.1 ± 8.6 years were evaluated. The median PSA at baseline mpMRI was 4.7 (IQR; 3.3–6.7) ng/dl. Overall mpMRI progression was detected in 54 patients (31.4%), 37 were upgraded to PIRADS-3, 16 to PIRADS-4, and one to PIRADS-5. Multivariate logistic regression analysis revealed that a PSA increase of ≥25% during follow-up was the only predictor of mpMRI upgrade (P = 0.019, OR: 2.384). 30 out of 54 patients underwent a prostate biopsy and PCa was detected in 15 patients; 5 with ISUP grade 1, 10 with ISUP grade 2. ConclusionsAlmost half of the patients with a PIRADS-2 index lesion were upgraded to PIRADS ≥3 when evaluated with serial mpMRI when a PSA increase of ≥25% was observed during follow-up. PCa was detected in half of the patients who underwent a biopsy. Serial mpMRI can be recommended when monitoring patients with elevating PSA ≥25%, a prostate biopsy can be considered upon a mpMRI progression.

Prostate Risk and Monitoring During Testosterone Replacement Therapy.

Men with hypogonadism have reduced risk of prostate cancer mortality; whether testosterone treatment increases the risk of prostate safety events in men with hypogonadism remains controversial. Several studies including 4 larger randomized trials-the Testosterone Trials, TEstosterone and Atherosclerosis Progression in Aging Men (TEAAM) trial, Testosterone for Diabetes Mellitus trial, and Testosterone Replacement therapy for Assessment of long-term Vascular Events and efficacy ResponSE in hypogonadal men (TRAVERSE) trial-treated men with testosterone or placebo for 1 year or longer and reported prospectively ascertained prostate safety data. The TRAVERSE Trial, because of its large size, longer duration, and adjudication of prostate events, has provided comprehensive data on the risk of adverse prostate events during testosterone replacement therapy (TRT). Among men with hypogonadism, carefully screened to exclude those at high risk of prostate cancer, the incidences of high-grade or any prostate cancer, acute urinary retention, surgical procedure for benign prostatic hyperplasia, prostate biopsy, or new pharmacologic therapy for lower urinary tract symptoms were low and did not differ between the testosterone and placebo groups. Testosterone did not worsen lower urinary tract symptoms. TRT was associated with a greater increase in prostate-specific antigen than placebo in the first year of treatment. Testosterone treatment of men with hypogonadism, screened to exclude those at high risk of prostate cancer, is associated with low risk of adverse prostate events. Baseline evaluation of prostate cancer risk and a standardized monitoring plan can minimize the risk of unnecessary prostate biopsy while enabling the detection of high-grade prostate cancers in men receiving TRT.

Prostate-specific membrane antigen PET/CT-guided, metastasis-directed radiotherapy for oligometastatic castration-resistant prostate cancer.

e17057 Background: Systemic treatments for metastatic castration-resistant prostate cancer (mCRPC) include androgen deprivation therapy (ADT), androgen receptor pathway inhibitors (ARPIs), chemotherapy, and radiopharmaceutical therapy, all of which have associated toxicity. We hypothesized that prostate-specific membrane antigen (PSMA) PET/CT-guided, metastasis-directed radiotherapy may offer durable disease control with low toxicity rates in patients with mCRPC who have a limited number of metastatic sites. Methods: We retrospectively screened 7 prospective databases of PSMA PET/CT scans conducted between 1/2016-2/2023 for patients with mCRPC who had ≤5 sites of oligorecurrent or oligoprogressive disease and received metastasis-directed radiotherapy to all sites of disease. Castration resistance was defined as either radiographic progression or biochemical progression (two consecutive prostate-specific antigen [PSA] increases ≥3 weeks apart) while on ADT with serum testosterone &lt;50 ng/dL. Progression-free survival (PFS), freedom from new lines of systemic therapy, and overall survival (OS) were calculated from the start of metastasis-directed radiotherapy using Kaplan-Meier analysis. Progression was defined as the first instance of biochemical progression (PSA increase of 25% and 2 ng/mL above nadir, confirmed by repeat measurement ≥3 weeks later), radiographic progression, biopsy-proven recurrence, new systemic or local therapy, or death. Toxicity was graded according to Common Terminology Criteria for Adverse Events (CTCAE), Version 5. Results: Twenty-six patients met inclusion criteria with a median follow-up of 34.6 months (interquartile range, 28.1-47.2 months). All patients previously received ADT, 20 (77%) received ARPIs, and 3 (12%) had prior chemotherapy. Median PSA was 1.2 ng/mL, median time from initial diagnosis was 6.2 years, and median time from castration resistance was 1.8 years. Between 10/2017-4/2023, 12 patients (46.2%) had one treated metastatic site, 11 patients (42.3%) had two, and 3 patients (11.5%) had three. Twenty-four patients (92.3%) received concurrent systemic therapy. Median PFS was 16.4 months (95% confidence interval [CI], 11.4-21.4 months). Four-year PFS was 26.7% (95% CI, 8.9-44.5%). Median time to initiation of a new line of systemic therapy was 18.0 months (95% CI, 0-36.2 months). Four-year freedom from new lines of systemic therapy was 36.1% (95% CI, 15.5-56.7%). Median OS was not reached. Four-year OS was 72.5% (95% CI, 51.1-93.9%). Grade 2 and ≥3 toxicity rates were 3.8% and 0%, respectively. Conclusions: For patients with oligometastatic CRPC, PSMA PET/CT-guided metastasis-directed radiotherapy appears to offer durable disease control with low toxicity. Further prospective studies are needed to compare PSMA PET/CT-guided versus conventional imaging-guided radiotherapy.

THE ROLE OF DOCETAXEL AS FIRST-LINE CHEMOTHERAPY ON PSA LEVEL AND QOL IN CRPC PATIENTS

Objective: Prostate cancer is the second most common cancer in men and the fifth leading cause of death worldwide. 10-20% of cases can progress to a more aggressive stage called castration-resistant prostate cancer (CRPC) with a higher death rate. Clinical guidelines recommend docetaxel as first-line chemotherapy and evaluated using the PSA test. This study aims to investigate the effect of docetaxel chemotherapy on PSA levels in CRPC. Material &amp; Methods: A retrospective study was conducted from January 2016 until August 2022 according to the medical records database Saiful Anwar Hospital. There were 16 patients who met the inclusion criteria, including male patients with a diagnosis of CRPC who received castration therapy and found an increase in PSA 3 times of nadir or found 2 or more bone metastatic lesions or soft tissue lesions &gt; 2 cm, received 6 series of docetaxel chemotherapy, and have a PSA data was performed before and after chemotherapy. Statistical analysis was performed using a differential T-test. Results: The results, obtained were significantly different (p&lt;0.05) on the average PSA (log) pre-post chemotherapy, visual analog scale (VAS), and quality of life, and not significantly different on BMI pre-post chemotherapy. Conclusion: 6 cycles of docetaxel chemotherapy resulted in a decrease in PSA levels of CRPC significantly. It showed an excellent response to docetaxel chemotherapy in managing CRPC patients. Limitations of this study were specifically the retrospective cohort study model and the ability to reduce PSA levels in assessing the prognosis of CRPC. Keywords: Castration-resistant prostate cancer, chemotherapy, docetaxel, prostate-specific antigen.

Circadian Rhythm Effects on the Extraction and Identification of Semen on Semen-Stained Fabrics Using Seminal Fluid Biochemistry

The rate of rape and other sexually induced crimes is rapidly on the increase worldwide with weak empirical confirmational tools, and expensive financial implications This is further compounded by poor proof of the time of the committal of the crime and its attendant effect on the parameter of interest. This called for a cheap and accurate approach involving the use of biochemical parameters indicative of seminal fluids on fabrics and other ancillary materials found in a crime scene. This study was therefore designed to validate a suitable seminal fluid biochemical approach to detecting seminal stained fabrics and the attendant circadian rhythm effects. Seminal fluid biochemical parameters used for the study include prostate-specific antigen, gamma-glutamyl transferase, acid phosphatase, magnesium, zinc, and inorganic phosphorus. These parameters were analyzed using WHO-approved methods after the extraction phase from dried stained fabrics. Forty (40) participants were recruited for the study divided into two groups; nocturnal and diurnal. The mathematical and empirical analysis data were analyzed using One-way ANOVA (Post Hoc) on an SPSS 25 version platform. The result showed a significant increase (p&lt; 0.05) in seminal PSA, GGT, and ACP in the semen-stained fabrics when compared to distilled water-stained fabrics. In a similar vein, there was a significant increase in seminal ACP and PSA concentrations in the nocturnal group when compared to the diurnal, whereas seminal GGT decreased. In conclusion, this study has shown that semen-stained fabric can be detected for the presence of seminal fluids using seminal PSA, ACP, and GGT. Also, the effect of circadian rhythm should be considered during result interpretation.

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.

Final Analysis of a Phase III Controlled Randomized Study of Stereotactic Body Proton Therapy or Conventionally Fractionated Proton Therapy for Early Prostate Cancer: PCG GU002

To determine if stereotactic body proton therapy (SBPT) is non-inferior to conventionally fractionated proton therapy (CFPT) in patients with early prostate cancer. Multicenter, randomized, controlled, open-label, non-inferiority phase 3 trial that included patients with histologically confirmed low-risk prostate adenocarcinoma defined by Gleason score ≤6, PSA <10 ng/mL, and clinical stage T1-2a N0 M0 by AJCC 7th Ed. Eligible participants were randomly assigned (initially 1:1 and later 2:1 ratio) to CFPT (79.2 Gy in 44 fractions for 9 weeks) or SBPT (38 Gy in 5 fractions for 1 week). Concurrent or adjuvant androgen deprivation therapy was not allowed. The primary endpoint was freedom from failure (FFF) at 2 years, defined as the first occurrence of local, regional, or distant recurrence, biochemical failure by the Phoenix definition (increase of PSA ≥2 ng/mL over the nadir PSA), or the start of salvage therapy including ADT. Secondary endpoints included GI and GU grade ≥2 toxicity according to CTCAE v4 criteria, as well as health-related quality of life (HRQoL) metrics assessed by AUASI and EPIC scores. Non-inferiority would be declared if the 1-sided 95% confidence interval limit for the difference in 2-year FFF rate was below 4.2% between both groups by Clopper-Pearson exact method. Between November 2010 and September 2020, 133 patients were enrolled and randomly assigned to CFPT (n = 45) or SBPT (n = 88). Median follow-up was 5 years (IQ 3.9-5.2), with the last patient enrolled followed for at least 2 years. The 2-year FFF was 100% for both groups, fulfilling the pre-specified criteria for non-inferiority of SBPT compared to CFPT. By KM estimates, 5-year FFF was 97.4% and 100% (P = 0.1), and the 5-year OS was 97.1% and 95.5% (P = 0.46) for patients treated with CFPT and SBPT, respectively. The cumulative incidence of any grade ≥3 toxicities at 5 years was 0% and 5.7% (P = 0.14) for patients treated with CFPT and SBPT, respectively. The frequency of GI grade ≥2 toxicity at 6 months was of 0% and 2.3% (P = 0.55), and at 2 years was of 6.7% and 3.4% (P = 0.69) for patients treated with CFPT and SBPT, respectively. The frequency of GU grade ≥2 toxicity at 6 months was of 2.2% and 5.7% (P = 0.42), and at 2 years was of 8.9% and 5.7% (P = 0.54) for patients treated with CFPT and SBPT, respectively. Changes in HRQoL scores at 2 years were similar between groups (Table). SBPT is non-inferior to CFPT regarding FFF and associated with similar long-term toxicity rates and HRQoL metric scores.

Utility of PSMA PET Guided Metastasis-Directed Radiotherapy

Metastasis-directed radiotherapy (MDT) is becoming a mainstay in the management of oligometastatic prostate cancer (PCa), and PSMA-PET is currently the most sensitive imaging modality for PCa metastasis screening. The efficacy of MDT guided by PSMA-PET imaging has not yet been well characterized. Moreover, the optimal role of androgen deprivation therapy (ADT) in the context of MDT is not known. We sought to assess the efficacy of PSMA PET-guided MDT in patients with metastatic PCa treated with and without ADT. This is a single institutional retrospective study of patients diagnosed with metastatic prostate cancer by PSMA-PET imaging who were treated with MDT. Biochemical progression was defined as a PSA increase of ≥ 25% and ≥ 2 ng/mL if PSA was ≥ 2 ng/mL at time of initiating salvage treatment, or a PSA increase of ≥ 25% if PSA was < 2 ng/mL at time of salvage treatment. Survival analyses were performed using the Kaplan-Meier method with log-rank testing for significance. Cumulative incidence analyses were performed with Gray's testing for significance. Adverse event data were assessed per CTCAE v5 guidelines. A total of 196 PSMA PET-avid lesions from 101 patients were irradiated with stereotactic body radiotherapy (SBRT). Median time from prior definitive locoregional therapy to MDT was 6.2 years. 79 patients had hormone-sensitive PCa (HSPC) and 22 patients had castration-resistant PCa (CRPC) at time of MDT. 47 of 79 (59%) patients with HSPC received ADT along with MDT, and 20 of the 47 patients received augmented ADT. 25 of the 32 (78%) HSPC patients receiving MDT without ADT had undergone at least one prior course of ADT, and none had castrate levels of testosterone at time of MDT with a median testosterone level of 341 ng/dl. With a median follow-up of 22.4 months, 5 of 196 lesions (2.6%) demonstrated radiographic progression. 2-year cumulative incidence of progression from HSPC to CRPC was 11% in patients who received ADT at time of MDT and 35% in those who did not (P = 0.027). Median biochemical progression free survival of patients with CRPC, HSPC treated without ADT, and HSPC treated with ADT following MDT was 5.4, 7.6, and 43.9 months respectively (P<0.0001). 2-year overall survival of the abovementioned groups was 72.2%, 100%, and 97.5% respectively (P<0.001). No Grade 3-5 adverse effects were observed. MDT guided by PSMA-PET imaging is well-tolerated and delays biochemical progression in patients with CRPC and HSPC, with a greater effect observed in patients also receiving ADT.

Survival and Economic Impact of Rapid Prostate-Specific Antigen Doubling Time in Patients With Nonmetastatic Castration-Resistant Prostate Cancer.

In patients with nonmetastatic castration-resistant prostate cancer (nmCRPC), prostate-specific antigen doubling time (PSADT) is associated with risk of metastasis and survival. This study evaluated the association of PSADT with clinical and economic outcomes in a real-world setting among patients with nmCRPC not receiving novel hormonal therapy (NHT), using 2-month PSADT thresholds. We retrospectively identified Veterans Health Administration patients with nonmetastatic prostate cancer and ≥2 PSA increases after medical/surgical castration (2012-2016). The third measurement was the index (CRPC) date. Patients with ≥3 postindex PSA measurements, including index, were followed until death or ≥12 months until disenrollment, study end, or death, and grouped into 2-month cohorts based on postindex PSADT. Cox regression models assessed association between PSADT, time to metastasis, and death. Healthcare resource utilization and costs were evaluated. Among 2800 evaluable patients, median follow-up was 30 months and median PSADT was 17 months. Relative to the reference cohort (PSADT >12 months), all cohorts had significantly higher metastasis risk. PSADT ≤10-month cohorts had significantly greater mortality risk than the reference; hazard ratios (95% confidence intervals) ranged from 12.3 (9.2, 16.4) in the PSADT ≤2-month cohort to 1.3 (0.9, 2.0) in the >10 to ≤12-month cohort. Total costs were significantly higher for cohorts up to and including the PSADT >8 to ≤10-month cohort, than for the reference cohort. Mean per patient per month all-cause medical plus pharmacy costs were $6623, $4768, and $4049 in the PSADT ≤2-month, >2 to ≤4-month cohort, and >4 to ≤6-month cohorts, respectively, versus $1911 in the PSADT >12-month cohort (P <0.05). Most patients with nmCRPC have PSADT >12 months and a long natural history. For those with shorter PSADT, the risk of metastasis, death, and costs increased. These data can help select patients for NHT and conversely those who can safely delay NHT for nmCRPC.

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.

Personalized precision combination therapies based on potential actionability and coalterations and therapeutic opportunities for CDK12-mutated prostate cancer.

e17068 Background: Translational studies have reported that CDK12 aberrations in metastatic castration-resistant prostate cancer (mCRPC) are related to homologous recombination (HR) deficiency and focal tandem duplications(FTDs), characterized by gene fusions and fusion-induced neoantigens (FINAs). In prostate cancer,CDK12 aberrations as a biomarker have been reported associated with poor prognosis, whether hormonal and taxane therapies as well as to PARP inhibitors. Herein, we aimed to molecularly, pathologically, and clinically characterize CDK12-aberrant mCRPC. Methods: Clinical data and molecular analyses are collected from the mCRPC patients treated in our center. Thirty-two patients with prostate cancer underwent soft tissue biopsy or sufficient ctDNA(Circulating Tumor DNA) for NGS and confirmed the CDK12 aberrations. Twenty-eight patients had advanced to the stage of mCRPC, and twenty-seven of them had exhausted standard treatment.All of the twenty-seven patients consented to the individualized therapiees based on NGS.PSA50 response rate and progression-free survival(PFS) are used to describe clinical features and outcomes to various individualized therapies, including sensitivity to poly (ADP-ribose) polymerase (PARP) inhibitors (PARPis) and PD-1/PD-L1 inhibitors monotherapy or combined with other off-label drugs. Results: Of the 32 patients with CDK12-aberrant prostate cancer, 19(59.4%) had detected biallelic CDK12 alterations. At diagnosis,17 (68%) patients' PSA≥100ng (only 26 patients retained the PSA data), 27 (93.1%) had Gleason grade group 4-5(only 29 patients retained the pathology),16(51.6%) had lymph node metastasis, 16(51.6%) had bone metastasis.13 patients received PARPi combine NHT(Novel hormone therapy) or not after NHT therapy resistance,only 1 patient PSA response reached PSA50.9 patients received PARPi combine temozolomide,2 reached PSA50,1 patient's liver metastases were significantly reduced ang reached PR.In that five patients,4 of 5 were monotherapied by PARPi.21 patients accepted PD-1/PD-L1 combined with PARPi or other off-label drugs based on the NGS or not.Four patients accepted immune monotherapy,only 1 reached PSA50. In the remaining 17 combined treatment patients, PSA50 responses were noted in 23.5%. What is noteworthy is that,4 of 16 happened HPD(hyperprogressive disease) with clinical manifestations such as rapid increase of PSA and significant decrease of ECOG score. Conclusions: CDK12-aberrant mCRPC is an aggressive subtype and have worse prognosis to PARPi. PARPi combine with temozolomide may be a effective therapeutic schedule. Along with NGS development,more therapeutic drugs are available to us to benefits for patients.But immunotherapy is questionable to CDK12-aberrant mCRPC because of the lower response rate and higher risk of HPD.

(077) Testosterone Therapy in Men on Active Surveillance for Prostate Cancer

Abstract Introduction The role of testosterone therapy (TTH) in men with prostate cancer (PC) is debated, especially in men on active surveillance (AS). Objective This study aimed to review our data on TTH in this population. Methods The study population consisted of (i) men with PC on active surveillance (ii) with two total T (TT) levels &amp;lt;300 ng/dL (iii) associated with symptoms (iii) performed using LCMS (v) conducted in an early morning fashion who (vi) pursued T therapy (TTH). TTH included exogenous (transdermal, intramuscular) and clomiphene citrate (CC) in the setting of low/low-normal LH levels. T lab work including PSA levels, were checked within 4 weeks of TTH initiation, every three months in the first year and every six months after that. Target TT level was the middle tertile of the normal reference range at our institution. We report on T and PSA levels in this group. Results 82 patients are included. Mean age = 64 ± 9 years. Median pre-TTH PSA levels were 4.6 [3.4, 6.7] ng/mL. Mean baseline TT levels were 305 ± 145 ng/dL. 19% of these men had a TT level &amp;lt;200 ng/dL. Median Gleason score (GS) was 6 with 90% 3+3, 9% 3+4 and 1% 4+3. Median duration on AS before TTH was 14 [1, 43] months. 45% received transdermal T, 19% intramuscular T and 36% CC. Post-TTH TT = 553 ± 268 ng/dL, PSA = 4.9 [3.2, 9.2] Median duration of TTH at last follow-up was 14 [1, 39] months. Median PSA change per patient was 0.3 [-0.9, 2.6] ng/mL, representing a median of 14 (-24, 70) % change in PSA per patient (p= 0.045). 42% had a decrease in PSA, 58% an increase. In 88% of men who experienced a rise in PSA, the PSA rose ≥10%. 50% of men on TTH who had a PSA level below 4 ng/dL rose above 4. 28% of men experienced a PSA level increase ≥1 ng/mL per year. In 18% of these men, TTH was stopped and definitive PC treatment was instituted. In men with ≤1 ng/mL per year increase in PSA, another 18% opted for definitive PC treatment. The most common reason for this was PSA anxiety. Conclusions In men with PC on AS treated with TTH, minimal changes in PSA were seen, with equal numbers of men experiencing a rise and a drop in PSA. About fifth of men ceased AS and proceeded to definitive therapy for their PC. Disclosure No

Clinical and molecular determinants of PSA response to bipolar androgen therapy in prostate cancer.

Bipolar androgen therapy (BAT) is a novel therapy known to be effective in a subset of men with metastatic castrate resistant prostate cancer (mCRPC). A better understanding of responders and nonresponders to BAT would be useful to clinicians considering BAT therapy for patients. Herein we analyze clinical and genetic factors in responders/nonresponders to better refine our understanding regarding which patients benefit from this innovative therapy. mCRPC patients were assessed for response or no response to BAT. Patients with PSA declines of greater than 50% from baseline after 2 or more doses of testosterone were considered to be responders. Whereas, nonresponders had no PSA decline after 2 doses of testosterone and subsequently manifest a PSA increase of >50%. Differences between these two groups of patients were analyzed using clinical and laboratory parameters. All patients underwent genomic testing using circulating tumor DNA (ctDNA) and germline testing pre-BAT. Twenty five patients were nonresponders and 16 were responders. Baseline characteristics between nonresponders and responders varied. Responders were more likely to have had a radical prostatectomy as definitive therapy and were more likely to have been treated with an androgen receptor (AR) antagonist (enzalutamide or apalutamide) immediately before BAT (compared to abiraterone). Duration of prior enzalutamide therapy was longer in responders. Nonresponders were more likely to have bone-only metastases and responders were more likely to have nodal metastases. Assays detected ctDNA AR amplifications more often in responding patients. Responders trended toward having the presence of more TP53 mutations at baseline. BAT responders are distinct from nonresponders in several ways however each of these distinctions are imperfect. Patterns of metastatic disease, prior therapies, duration of prior therapies, and genomics each contribute to an understanding of patients that will or will not respond. Additional studies are needed to refine the parameters that clinicians can utilize before choosing among the numerous treatment alternatives available for CRPC patients.

MP67-05 IMPACTS ON FUNCTIONAL AND ONCOLOGICAL OUTCOMES OF ROBOTIC-ASSISTED RADICAL PROSTATECTOMY 10 YEARS AFTER THE TASKFORCE RECOMMENDATIONS AGAINST PSA SCREENING

You have accessJournal of UrologyCME1 Apr 2023MP67-05 IMPACTS ON FUNCTIONAL AND ONCOLOGICAL OUTCOMES OF ROBOTIC-ASSISTED RADICAL PROSTATECTOMY 10 YEARS AFTER THE TASKFORCE RECOMMENDATIONS AGAINST PSA SCREENING Marcio Covas Moschovas, Jaber Abdel, Shady Saikali, Seetharam Bhat, Marco Sandri, Travis Rogers, David Loy, and Vipul Patel Marcio Covas MoschovasMarcio Covas Moschovas More articles by this author , Jaber AbdelJaber Abdel More articles by this author , Shady SaikaliShady Saikali More articles by this author , Seetharam BhatSeetharam Bhat More articles by this author , Marco SandriMarco Sandri More articles by this author , Travis RogersTravis Rogers More articles by this author , David LoyDavid Loy More articles by this author , and Vipul PatelVipul Patel More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003330.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: For experienced surgeons, prostate cancer outcomes are ultimately affected by the pathology of the disease they treat. Over the last decade, we have experienced a dramatic alteration in the pathology we are addressing. During this time, the most significant shift in prostate cancer management was the 2012 USPSTF (United States Preventive Service Task Force) decision to recommend against PSA screening. This has affected the types of prostate cancers we are treating and potentially influenced treatment outcomes. We aimed to analyze the functional and oncologic trends in prostate cancer outcomes in the largest single surgeon series. METHODS: We retrospectively reviewed our prospective IRB-approved prostate cancer registry for 11396 patients that underwent RALP between 2008 and 2021. Each patient had at least a 12-month follow-up. The cohort was divided into two groups before and 6 months after the USPSTF recommendation. Group 1: 1/2008- 12/2012, Group 2: 1/ 2013-12-2021. Group 1 had 4760 patients, and Group 2 had 6636 patients, with a median follow-up of 109 and 38 months, respectively. We assessed the functional and oncologic outcomes of the two groups. RESULTS: We detected time-trend changes after 2012. There was a migration to younger ages, less than 60, and an increase in the median preoperative PSA (5 to 6 ng/ml). There was 18% increase in the higher grade and stage of the disease, Gleason ≥3+4 (19% increase), and ≥ pT3 (18% increase). This translated into a 6% increase in positive surgical margins with an initial rapid increase that was tempered with a surgical adjustment in the amount of (NS) nerve sparing. There was a 24% reduction in full nerve sparing in response to the worsening pathology. Outcomes were also affected by the modification in NS. Comparing groups 1 and 2, there was a significant decline in post-operative outcomes: 12-month continence reduction by 9%, reduction in potency by 27%, and trifecta by 22%. CONCLUSIONS: We have witnessed a significant change in the types of patients we are seeing and the outcomes we are able to deliver. We are seeing younger patients with higher-grade diseases, and the increasing number of high-risk patients has led to worse functional and oncologic outcomes. The initial rapid rise in PSM was leveled by the move towards more partial nerve sparing. The USPSTF recommendation has affected the oncology and outcomes of prostate cancer in an increasingly younger patient population. Source of Funding: none © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e944 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Marcio Covas Moschovas More articles by this author Jaber Abdel More articles by this author Shady Saikali More articles by this author Seetharam Bhat More articles by this author Marco Sandri More articles by this author Travis Rogers More articles by this author David Loy More articles by this author Vipul Patel More articles by this author Expand All Advertisement PDF downloadLoading ...

MP59-18 THE INCIDENCE OF CLINICALLY SIGNIFICANT PROSTATE CANCER AFTER HoLEP

You have accessJournal of UrologyCME1 Apr 2023MP59-18 THE INCIDENCE OF CLINICALLY SIGNIFICANT PROSTATE CANCER AFTER HoLEP Ali S Antar, Tudor Borza, Ethan Richmond, Glenn O Allen, Jordan R Krieger, Margaret A Knoedler, Christopher M Manakas, Wei Huang, Dan R Gralnek, and Matthew D Grimes Ali S AntarAli S Antar More articles by this author , Tudor BorzaTudor Borza More articles by this author , Ethan RichmondEthan Richmond More articles by this author , Glenn O AllenGlenn O Allen More articles by this author , Jordan R KriegerJordan R Krieger More articles by this author , Margaret A KnoedlerMargaret A Knoedler More articles by this author , Christopher M ManakasChristopher M Manakas More articles by this author , Wei HuangWei Huang More articles by this author , Dan R GralnekDan R Gralnek More articles by this author , and Matthew D GrimesMatthew D Grimes More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003312.18AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Rates of incidental prostate cancer (iPCa) after Holmium Laser Enucleation of the Prostate (HoLEP) are higher than in other bladder outlet surgeries. Management presents a challenge considering the effects of HoLEP on anatomy and other causes of mortality in the older population. We examined cancer characteristics and initial management of patients with iPCa after HoLEP to understand the significance of these incidentally discovered cancers. METHODS: Patients with iPCa were identified over a 4 year period from a prospectively maintained institutional database. Clinical data collected included preoperative PSA levels, cancer stage, grade, initial management, post operative PSA, staging imaging or biopsy. We defined clinically significant cancers as those where treatment other than watchful waiting was recommended by NCCN guidelines based on predicted life expectancy, which was estimated using the Social Security Life Expectancy Calculator. RESULTS: 183/913 (20%) patients were diagnosed iPCa after HoLEP. 133 patients (73%) had clinically significant and 50 patients (27%) had clinically insignificant iPCa. Of clinically significant cancers, 7 patients with high risk PCa were managed with upfront local treatment and the rest underwent PSA surveillance (Figure 1). 11 experienced a PSA increase and underwent local treatment after confirmatory biopsy: 3 underwent RALP, 7 underwent XRT and one underwent ADT, all with appropriate PSA response to treatment. The clinically insignificant population underwent PSA observation. 9 were lost to follow up and 5 experienced a PSA increase triggering intervention: 4 underwent XRT and 1 underwent ADT with appropriate PSA response. At a mean follow-up of 16.3 months (IQR 7.9–13.4 months), there were 6 deaths, all from non-cancer related causes. CONCLUSIONS: Despite the low risk nature of many post-HoLEP iPCA, the majority were classified as clinically significant cancers based on NCCN guidelines. Data driven guidelines for pre-operative screening evaluation and post-operative management of iPCa after HoLEP are critical given the frequency and clinical implications these cancer diagnoses. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e815 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ali S Antar More articles by this author Tudor Borza More articles by this author Ethan Richmond More articles by this author Glenn O Allen More articles by this author Jordan R Krieger More articles by this author Margaret A Knoedler More articles by this author Christopher M Manakas More articles by this author Wei Huang More articles by this author Dan R Gralnek More articles by this author Matthew D Grimes More articles by this author Expand All Advertisement PDF downloadLoading ...

Comparison of Hormone-Sensitive Oligorecurrent Prostate Cancer Patients Based on Routine Use of Choline and/or PSMA PET/CT to Guide Metastasis-Directed Therapy

In hormone-sensitive oligorecurrent prostate cancer (PC), the literature showed [68Ga]Ga-PSMA (PSMA) and [18F]F-choline (FCH) PET/CT can successfully guide metastasis-directed therapies (MDT). This observational retrospective study aimed to explore, in routine use, the impact of FCH or PSMA PET/CT in guiding MDT for hormone-sensitive oligometastatic PC at different recurrences. In 2017-2020, patients initially treated with radical prostatectomy but, in biochemical recurrence (with PSA ≤ 2 ng/mL), diagnosed as oligometastatic based on FCH or PSMA PET/CT, were identified. MDT was stereotactic body radiotherapy (SBRT), elective nodal or prostate bed radiotherapy ± boost and ± androgen deprivation therapy (ADT). The primary endpoint was biochemical relapse-free survival (BR-FS), defined as a PSA increase ≥ 0.2 ng/mL above the nadir and increasing over two successive samples and the secondaries were ADT-free survival (ADT-FS). 123 patients (70 PSMA and 53 FCH) were included. The median follow-up was 42.2 months. The median BR-FS was 24.7 months in the PSMA group versus 13.0 months in the FCH group (p = 0.008). Similarly, ADT-FS (p = 0.001) was longer in patients in the PSMA group. In multivariate analysis, a short PSA doubling time before imaging (p = 0.005) and MDT with SBRT (p = 0.001) were poor prognostic factors for BR-FS. Routine use of FCH or PSMA PET/CT in hormone-sensitive PC showed an advantage for using PSMA PET/CT to guide MDT in terms of BR-FS and ADT-FS in patients with low PSA value. Prospective studies are needed to confirm these hypotheses.

Dynamic assessment of serum chromogranin A and treatment response with abiraterone acetate in metastatic castration-resistant prostate cancer.

Elevated serum chromogranin A (CGA) is associated with intrinsic or treatment-related neuroendocrine differentiation (NED) in men with metastatic castration-resistant prostate cancer (mCRPC). Fluctuations in serum CGA during treatment of mCRPC have had conflicting results. We analyzed the impact of (i) rising serum CGA and (ii) baseline CGA/PSA ratio during treatment to identify associations with abiraterone acetate (AA) therapy. Between June 2013 and August 2015, 92 men with mCRPC were enrolled in a prospective trial with uniform serum CGA processing performed before initiating abiraterone acetate/prednisone (AA/P) and serially after 12 weeks of AA/P treatments. Serum CGA was measured using a homogenous automated immunofluorescent assay. Patients receiving proton pump inhibitors or with abnormal renal function were excluded due to possible false elevations of serum CGA (n = 21 excluded), therefore 71 patients were analyzed. All patients underwent a composite response assessment at 12-weeks. Kaplan-Meier estimates and Cox Regression models were used to calculate the association with time-to-treatment failure analyses and overall survival. An increase in chromogranin was associated with a lower risk of treatment failure (hazard ratio [HR]: 0.52, p = 0.0181). The median CGA/PSA ratio was 7.8 (2.6-16.0) and an elevated pretreatment CGA/PSA ratio above the median was associated with a lower risk of treatment failure (HR: 0.54 p value = 0.0185). An increase in CGA was not found to be associated with OS (HR: 0.71, 95% CI: 0.42-1.21, p = 0.207). An elevated baseline CGA/PSA ratio was not associated with OS (HR: 0.62, 95% CI: 0.37-1.03, p = 0.062). An increase in PSA after 12 weeks of treatment was associated with an increased risk of treatment failure (HR: 4.14, CI: 2.21-7.73, p = < 0.0001) and worse OS (HR: 2.93, CI: 1.57-4.45, p = < 0.0001). We show that an increasing chromogranin on AA/P and an elevated baseline CGA/PSA in patients with mCRPC were associated with a favorable response to AA/P with no changes in survival. There may be limited clinical utility in serum CGA testing to evaluate for lethal NED as AA/P did not induce lethal NED in this cohort. This highlights that not all patients with an increasing CGA have a worse OS.

68GaPSMA-11 PET/CT to monitor treatment response in patients with metastatic prostate cancer: The concordance between biochemical response and PSMA response.

49 Background: The aim of this study was to assess whether PSMA PET is associated with flares, with discordant results in regard to biochemical response, and with positivity rates at low PSA values while monitoring metastatic prostate cancer (mPCa) receiving systemic treatment. Methods: A total of 96 patients with PSMA PET-detected mPCa who underwent at least one follow-up scan after receiving systemic treatment were included in the study. PSA levels at baseline PSMA PET-CT (bPSMA) and follow-up PSMA PET scans (fPSMA) were recorded. Any significant PSMA uptake at prostate and/or metastatic lesions were considered PSMA positivity. PSMA response were decided according to PSMA PET Progression (PPP) criteria . Biochemical progression was defined as ≥25% increase in PSA (1 ng/dL was the minimal starting value). PSMA PET and PSA response were dichotomized into progressive disease (PD) vs non-PD. Discordant responses among different metastases and prostate were defined as the condition when some metastatic lesions (or prostate) are responding (CR or PR) to systemic treatment while others had progressed. Results: A total of 346 serial PSMA PET/CT (96 bPSMA and 249 fPSMA) scans were evaluated. The median time between consecutive PSMA PET scans was 6.3 months (IQR: 4.7 – 10.6) Overall PSMA PET positivity rate of fPSMA scans was 88.4% (220/249). PSMA positivity rates according PSA levels were summarized. PPP was detected in 93 cases (37.8%) and biochemical progression was observed in 73 cases (30.2%). PSA and PSMA responses were highly concordant (Cohen’s K=0.623, p&lt;0.001). PSA-PSMA discordant responses were detected in 39 scans (17%). The possible causes could be identified in 34 of 39 scans (87%) while no obvious reason for discordance could be shown in the remaining 5. Conclusions: PSMA PET/CT showed very high detection rates of malignant lesions even in very low PSA values when monitoring treatment response in patients receiving systemic treatment for mPCa. PSA and PSMA responses were highly concordant. In cases with discordance, the reason seems to be the discordant behaviour of intraprostatic and metastatic lesions and not necessarily PSMA flares. PSMA PET is a promising biomarker to assess treatment response in patients with mPCa. [Table: see text]

Extended therapy with [177Lu]Lu-PSMA-617 in responding patients with high-volume metastatic castration-resistant prostate cancer

PurposeThe currently used scheme for radioligand therapy (RLT) of patients with metastatic castration-resistant prostate cancer (mCRPC) consists of 4–6 cycles of 6.0–7.4 GBq [177Lu]Lu-PSMA-617 each. This standard treatment scheme has proved safe and effective resulting in objective response in most patients with no significant toxicity. Many patients, however, show high-volume residual tumor burden after the sixth cycle and may benefit from treatment continuation. Extended treatment with additional cycles has been withheld due to concerns on potential increased toxicity.MethodsTwenty-six patients with high-volume residual tumor burden (according to CHAARTED) after standard RLT with [177Lu]Lu-PSMA-617 and no alternative treatment option received additional RLT cycles reaching a median of 10 (range 7–16) cycles with a mean activity of 7.4 ± 0.9 GBq per cycle. Response assessment with [68Ga]Ga-PSMA-11 PET/CT was done every 2–3 cycles or if disease progression was clinically suspected or based on change in PSA value (according to the PCWG3 criteria). Toxicity was measured using routine blood work up including blood counts, liver and renal function, and was graded according to CTCAE v5.0 criteria. Survival outcome was calculated based on the Kaplan-Meier method.ResultsFurther PSA decline of 33 ± 28% during the extended treatment was observed in 21/26 (81%) patients, whereas 5/26 (19%) patients showed a PSA increase; correspondingly in 11/21 patients with an initial response (PR or SD) to extended cycles, treatment was discontinued due to progressive disease, whereas six (23%) patients achieved low-volume residual disease. Two (8%) patients died without showing progression, and two (8%) patients are still under therapy. The median progression-free survival was 19 (95% CI: 15–23) months, and the overall survival was 29 (95% CI: 18–40) months. Grade ≥ 3 hematological toxicities occurred in 4/26 (15%) patients during treatment extension, and nephrotoxicity (grade ≥ 3) was observed in 1/26 (4%) patient during the follow-up.ConclusionExtended radioligand therapy is a feasible treatment option in patients with high-volume residual tumor after the completion of standard treatment with six cycles of [177Lu]Lu-PSMA-617. Improved survival and the acceptable safety profile warrant further investigation of the concept of additional cycles in selected patients.