Prostate-specific Antigen Changes Research Articles

Radioligand Therapy With 177Lu-PSMA-I&T in Patients With Metastatic Prostate Cancer: Oncological Outcomes and Toxicity Profile.

This study aimed to investigate the oncological outcomes and toxicity profile of 177Lu-PSMA-I&T radioligand therapy (RLT) in patients with metastatic castration-resistant prostate cancer (mCRPC), as well as our initial experience in metastatic hormone-sensitive prostate cancer (mHSPC). A total of 38 consecutive patients with metastatic prostate cancer (33 mCRPC and 5 mHSPC) received 177Lu-PSMA-I&T RLT, with a median of 2 cycles per patient (range, 1-7). Response to RLT was evaluated based on prostate-specific antigen (PSA) changes and imaging response. Clinical progression-free survival and overall survival were used to report oncological outcomes. Toxicity was assessed using the Common Toxicity Criteria for Adverse Events criteria. In mCRPC, 22 (69%), 18 (56%), and 11 (34%) patients achieved any PSA decline, PSA response of ≥30%, and PSA response of ≥50%, respectively. The clinical progression-free survival and overall survival after the first cycle of RLT were 6.3 and 21.4 months, respectively. In mHSPC, 177Lu-PSMA-I&T RLT resulted in excellent PSA response (93.0%-99.9%) in all cases. Clinical progression and cancer-related mortality occurred in only 1 case. Toxicity profile was favorable in both mHSPC and mCRPC. 177Lu-PSMA-I&T RLT demonstrated favorable PSA response (≥30%) in over half of the patients with mCRPC and excellent PSA response in all patients with mHSPC. Toxicity profile was favorable in both mHSPC and mCRPC settings. Further studies are needed to evaluate the role of 177Lu-PSMA-I&T RLT in the management of metastatic prostate cancer.

Study of prostate-specific antigen levels during salvage radiotherapy after prostate cancer surgery

BackgroundAdministration of adjuvant or salvage radiotherapy (RT) after prostate cancer (PCa) surgery is supported by clinical evidence and is a widely adopted strategy. On occasion, we detect changes in prostate-specific antigen (PSA) levels, such as a transient elevation or decline, during RT. Thus, we retrospectively investigated the frequency of changes in PSA levels, their associations with histopathological parameters, PSA doubling time (PSADT), and biochemical recurrence (BR) of PCa.MethodsThis study included 23 consecutive patients who underwent surgery for PCa between 2012 and 2019, received salvage RT without hormone therapy, and exhibited changes in PSA levels during RT. The prostatic bed was irradiated with a total dose of 64 to 66 Gy. BR was defined as consecutive PSA levels exceeding 0.2 ng/mL or having to start hormone therapy because of PSA elevation after salvage RT.ResultsDuring salvage RT after PCa surgery, PSA levels transiently increased in 11 patients (47.8%) and decreased in 12 (52.2%). When factors associated with BR were examined in patients with transient PSA elevation, seminal vesicle invasion and preoperative PSA values were identified as being statistically significant. When factors for BR were examined in patients with a decline in PSA levels, the Gleason score and PSADT were identified as being significant. Among the cases of a decline in PSA levels during salvage RT, those who received a radiation dose of less than 36 Gy did not experience BR. Similarly, patients who exhibited changes in PSA levels during salvage RT and did not have perineural invasion did not experience BR.ConclusionThis is the first study to examine the histopathological factors possibly affecting BR in patients undergoing salvage RT after PCa surgery. The results indicate that in patients with transient PSA elevation, seminal vesicle invasion is a significant risk factor. On the other hand, in patients with a decline in PSA levels during irradiation, the Gleason score and perineural invasion were found to be potential risk factors for BR. These findings suggest that a thorough examination of postoperative histopathological results may be necessary for the optimal management of patients with PCa.

Cervi Parvum Cornu complex for men with lower urinary tract symptoms: a multicenter, randomized, double-blind, placebo-controlled trial

BackgroundTo evaluate the efficacy and safety of Cervi Parvum Cornu, Angelicae Gigantis Radix and Glycyrrhizae Radix complex (CAG) in men with moderate lower urinary tract symptoms (LUTS). Materials and methodsFrom November 2020 to January 2022, participants with International Prostate Symptom Score (IPSS) of 12–19 in two centers were recruited and randomize into three groups: a CAG 500 mg/day group (CAG 500), a CAG 1000 mg/day group (CAG 1000), and a placebo group (PG). They were treated for 12 weeks. The primary endpoint was change of IPSS at the end of study from baseline. Secondary end points included change of prostate specific antigen (PSA), testosterone, dihydrotestosterone (DHT), maximum urinary flow rate (Q max), post-void residual volume (PVR), International Index of Erectile Function (IIEF), and drug safety. ResultsA total of 103 patients were able to finish the study according to the study protocol. Total IPSS and sub-scores (residual urine sensation, frequency, weak stream, hesistancy, nocturia, and quality of life) in CAG 500 and CAG 1000 were significantly improved at the 12th week compared to those of the PG. Changes of serum PSA, DHT, and testosterone levels at the 12th week from baseline did not show significant differences among the three groups. Q max and PVR changes did not show significant differences among the three groups either. Total IIEF and sub-scores (erectile function, orgasmic function, sexual desire, intercourse satisfaction) in CAG 1000 were significantly improved at 12th week compared to those in PG. No significant adverse events were found. ConclusionsCAG is well tolerated in patients with moderate LUTS. Treatment with CAG for 12 weeks has a therapeutic effect on moderate LUTS.

Prognostic Role of Dynamic Changes in Serological Markers in Metastatic Hormone Naïve Prostate Cancer.

We investigated whether inter-patient variation in the dynamic trajectory of hemoglobin (Hb), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), and prostate-specific antigen (PSA) can prognosticate overall survival (OS) in de novo mHSPC. This is a secondary analysis of the LATITUDE trial in which high-risk de novo mHSPC patients were randomly assigned to receive either androgen deprivation therapy (ADT) plus abiraterone or ADT plus placebo. We used a five-fold cross-validated joint model approach to determine the association of temporal changes in the serological markers with OS. Decision curve analysis was applied to determine the net benefit. When dynamic changes in Hb, LMR, NLR, PLR, and PSA were included in a multivariate joint model, an increase in the log of the current value of PSA (HR: 1.24 [1.20-1.28]) was associated with inferior OS. A multivariate joint model that captured dynamic trajectory of Hb, NLR, PLR, LMR, and PSA up to 24 months, showed a net benefit over the "treat all" strategy at a threshold of probability of approximately ≥30% while no net benefit was seen when dynamic change in PSA was omitted. Our joint model could be used for designing future adaptive trials investigating sequential treatment personalization.

Treatment outcomes of radium-223 in patients with metastatic castration-resistant prostate cancer: An experience before National Health Insurance reimbursement in Taiwan.

Radium-223 (Ra-223), an α-particle-emitting isotope, inhibits bony metastases and prevents patients from skeletal-related events in metastatic castration-resistant prostate cancer (mCRPC). We retrospectively reviewed the treatment response, predictive factors, and adverse events (AEs) of Ra-223 before the National Health Insurance reimbursement in a Taiwanese tertiary institute. Patients treated with Ra-223 before January 2019 were enrolled and categorized into progressive disease (PD) and clinical benefits (CB) groups. Laboratory data before and after the treatment were collected, and spider plots concerning percentage changes of alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and prostate-specific antigen (PSA) were prepared and calculated statistically. CB/PD, baseline ALP, LDH, and PSA levels were also adopted as stratification factors for overall survival (OS). Among 19 patients included, 5 (26.3%) and 14 (73.4%) belonged to the PD and CB groups, respectively, with no significant difference observed in the baseline laboratory data. The percentage changes in ALP, LDH, and PSA levels after Ra-223 treatment were statistically significant among the two groups (ALP: CB 54.3 ± 21.4% vs PD 77.6 ± 11.8%, p = 0.044; LDH: CB 88.2 ± 22.8% vs PD 138.3 ± 49.0%, p = 0.046; PSA: CB 97.8 ± 61.7% vs PD 277.0 ± 101.1%, p = 0.002). The trends of LDH between the two groups in spider plot were separated significantly. There were no differences in the AEs between the two groups. CB had a longer median OS than the PD group (20.50 months vs 9.43 months, p = 0.009). Patients with LDH <250 U/L at baseline tended to have longer OS but without significance. The CB rate of Ra-223 was 73.7%. No predictive factor for treatment response was obtained from pretreatment data. The mean percentage changes in ALP, LDH, and PSA levels compared with baseline significantly differed between the CB and PD groups, especially the LDH levels. The CB and PD groups showed different OS, with LDH levels exhibiting the potential to predict OS.

RWD55 Predicting Metastatic Disease Progression in Prostate Cancer Patients Using Machine Learning of PSA Kinetics

Although only 5% of patients with prostate cancer (PCA) have metastases at diagnosis, approximately 20% of those with early stage disease have recurrence with metastases, often years later. Changes in prostate specific antigen (PSA) levels can predict recurrence. A machine learning approach to serum PSA lab kinetics, after diagnosis of localized PCA, was used to forecast progression with metastases.

Trends in diagnosis of de novo metastatic hormone sensitive prostate cancer in US Veterans, 2002-2021.

10527 Background: The incidence of non-localized prostate cancer in the US has been increasing since 2011. While the etiology of this increase is unknown, improved detection of metastatic disease and changes in prostate-specific antigen (PSA) screening may be contributing factors. In this retrospective study, we report the frequency and characteristics of veterans with de novo metastatic prostate cancer to understand changes in the diagnosis over time. Methods: The study population consisted of veterans diagnosed with de novo metastatic Hormone Sensitive Prostate Cancer (mHSPC) with a biopsy between 2002 and 2021 in the Veterans Health Affairs Prostate Cancer Data Core were included. All patients had no prior diagnosis of prostate cancer and were classified as SEER stage ‘distant’. We collected the highest PSA within 3 months of diagnosis, age, race, and calculated the Charlson Comorbidity Index. Year of diagnosis was categorized into 5-year periods and differences over tine were assessed by chi-square linear by linear ANOVA test for linearity as appropriate. Results: 15,485 patients were diagnosed with de novo mHSPC between 2002 and 2021. The mean age was 72.9 years and the median PSA was 88.0 ng/mL. There was a 39% increase of the number of patients diagnosed with mHSPC (from 3,274 between 2002-2006 to 4,560 between 2017-2021). Mean age increased from 71.6 years between 2002-2006 to 74.4 between 2017-2021 (p &lt; 0.001). Median PSA decreased from 96.6 ng/mL in 2002-2006 to 80.3 ng/mL in 2006-2021 (p &lt; 0.001). The percentage of patients who were identified as black decreased from 29.8% between 2002-2006 to 25.4% between 2017 and 2021 (p &lt; 0.001). Mean comorbidity index increased from 3.2 between 2002-2006 to 4.5 between 2017-2021 (p &lt; 0.001). BMI increased from 26.2 between 2002-2006 to 27.2 between 2017-2021 (p &lt; 0.001). Median overall survival improved from 26.7 months in 2002-2006 to 31.7 months in 2016-2021 (p &lt; 0.001). Conclusions: Over a 20-year period, the Veterans diagnosed with prostate cancer were older, with higher comorbidities and with decreased PSA at diagnosis. Additionally, overall survival improved from 26.7 to 31.7 months. The findings of this study are consistent with a reduction in screening and more sensitive imaging modalities to detect metastatic disease combined with changes in the veteran population and improvements in treatment of mHSPC. Further study is warranted to understand these trends over the same time period. [Table: see text]

Prognostic role of early prostate specific antigen changes after [177 Lu]Lu-PSMA radioligand therapy of metastasized prostate cancer: A meta-analysis.

Approximately 10%-20% of prostate cancers progress to metastatic and castration-resistant forms (mCRPC). Radioligand (RLT) therapy with [177 Lu]Lu-prostate-specific membrane antigen (PSMA) is an emerging treatment for metastasized mCRPC and its efficacy is assessed not only but also by prostate specific antigen (PSA) measurement after 12 weeks or more after treatment. Our aim was to evaluate the role of early PSA measurement after RLT in predicting overall survival (OS) of mCRPC patients. A systematic search on PubMed, Web Of Science and Scopus was performed from January to December 2022. PRISMA guidelines for prognostic studies was adopted. Risk of bias was assessed using quality of prognostic studies (QUIPS). Twelve studies at low-intermediate risk of bias, were included in the meta-analysis (1646 patients, mean age 70 years). About 50% of patients showed a PSA decline after 1-2 of [177 Lu]Lu-PSMA, and more than 30% reported a PSA decline ≥50%. The median OS range for patients with any PSA decline was 13-20 months, while for patients with stable or increased PSA, the median OS fell to 6-12 months. The OS rate for a PSA decline after the one-two [177 Lu]Lu-PSMA cycles was 0.39 (95% CI: 0.31-0.50), while OS for a PSA decline ≥50% was 0.69 (95% CI: 0.57-0.83). A PSA decline is observed in almost 50% of mCRPC patients after 1-2 [177 Lu]Lu-PSMA cycles, with a significantly longer OS compared to stable or increased PSA levels, respectively. Accordingly, any PSA decline after 1-2 cycles of therapy should be regarded as a favourable prognostic factor for OS.

Assessing Therapeutic Response to Radium-223 with an Automated Bone Scan Index among Metastatic Castration-Resistant Prostate Cancer Patients: Data from Patients in the J-RAP-BSI Trial.

To evaluate the usefulness of change in the automated bone scan index (aBSI) value derived from bone scintigraphy findings as an imaging biomarker for the assessment of treatment response and survival prediction in metastatic castration-resistant prostate cancer (mCRPC) patients treated with Ra-223. This study was a retrospective investigation of a Japanese cohort of 205 mCRPC patients who received Ra-223 in 14 hospitals between July 2016 and August 2020 and for whom bone scintigraphy before and after radium-223 treatment was available. Correlations of aBSI change, with changes in the serum markers alkaline phosphatase (ALP) and prostate-specific antigen (PSA) were evaluated. Additionally, the association of those changes with overall survival (OS) was assessed using the Cox proportional-hazards model and Kaplan-Meier curve results. Of the 205 patients enrolled, 165 (80.5%) completed six cycles of Ra-223. Following treatment, ALP decline (%ALP < 0%) was noted in 72.2% (148/205), aBSI decline (%aBSI < 0%) in 52.7% (108/205), and PSA decline (%PSA < 0%) in 27.8% (57/205). Furthermore, a reduction in both aBSI and ALP was seen in 87 (42.4%), a reduction in only ALP was seen in 61 (29.8%), a reduction in only aBSI was seen in 21 (10.2%), and in both aBSI and ALP increasing/stable (≥0%) was seen in 36 (17.6%) patients. Multiparametric analysis showed changes in PSA [hazard ratio (HR) 4.30, 95% confidence interval (CI) 2.32-8.77, p < 0.0001], aBSI (HR 2.22, 95%CI 1.43-3.59, p = 0.0003), and ALP (HR 2.06, 95%CI 1.35-3.14, p = 0.0008) as significant prognostic factors for OS. For mCRPC patients treated with Ra-223, aBSI change is useful as an imaging biomarker for treatment response assessment and survival prediction.

The Efficacy of Cyclooxygenase-2 Inhibitors for the Male Treatment of Lower Urinary Tract Symptoms: A Systematic Review and Meta-Analysis.

To investigate the potential use of cyclooxygenase-2 (COX-2) inhibitors in the treatment of lower urinary tract symptoms (LUTS) in male patients, we conducted a comprehensive meta-analysis. Our study involved the identification and collection of randomized controlled trials (RCTs) from leading databases including PubMed, MEDLINE, EMBASE, and Cochrane Library. The primary objective of this analysis was to evaluate the effectiveness of COX-2 inhibitors for the treatment of LUTS. Our analysis involved six short-term (within 3 months) RCTs involving 707 patients. We found that COX-2 inhibitor treatment significantly improved the International Prostate Symptom Score (IPSS) of patients (mean difference [MD] = -2.99, 95% confidence interval (CI): -3.65 to -2.33, p < .00001), nocturia frequency (MD = -1.90; 95% CI: -3.18 to -0.61, p = .004), and maximum flow rate (Qmax) (MD = 1.02; 95% CI: 0.06 to 1.98, p = .04). However, no significant differences were found between patients in terms of changes in prostate-specific antigen (PSA) (MD = 0.02; 95% CI: -0.39 to 0.43, p = .92) and total prostate volume (TPV) (MD = -2.93; 95% CI: -6.45 to 0.59, p = .10). Therefore COX-2 inhibitors are an effective treatment for LUTS.

A Phase I Dose Escalation and Expansion Study of Epidiolex (Cannabidiol) in Patients with Biochemically Recurrent Prostate Cancer.

Cannabinoids (CBD) have anti-tumor activity against prostate cancer (PCa). Preclinical studies have demonstrated a significant decrease in prostate specific antigen (PSA) protein expression and reduced tumor growth in xenografts of LNCaP and DU-145 cells in athymic mice when treated with CBD. Over-the-counter CBD products may vary in activity without clear standardization, and Epidiolex is a standardized FDA-approved oral CBD solution for treatment of certain types of seizures. We aimed to assess the safety and preliminary anti-tumor activity of Epidiolex in patients with biochemically recurrent (BCR) PCa. This was an open-label, single center, phase I dose escalation study followed by a dose expansion in BCR patients after primary definitive local therapy (prostatectomy +/- salvage radiotherapy or primary definitive radiotherapy). Eligible patients were screened for urine tetrahydrocannabinol prior to enrollment. The starting dose level of Epidiolex was 600 mg by mouth once daily and escalated to 800 mg daily with the use of a Bayesian optimal interval design. All patients were treated for 90 days followed by a 10-day taper. The primary endpoints were safety and tolerability. Changes in PSA, testosterone levels, and patient-reported health-related quality of life were studied as secondary endpoints. Seven patients were enrolled into the dose escalation cohort. There were no dose-limiting toxicities at the first two dose levels (600 mg and 800 mg). An additional 14 patients were enrolled at the 800 mg dose level into the dose expansion cohort. The most common adverse events were 55% diarrhea (grade 1-2), 25% nausea (grade 1-2), and 20% fatigue (grade 1-2). The mean PSA at baseline was 2.9 ng/mL. At the 12-week landmark time-point, 16 out of 18 (88%) had stable biochemical disease, one (5%) had partial biochemical response with the greatest measurable decline being 41%, and one (5%) had PSA progression. No statistically significant changes were observed in patient-reported outcomes (PROs), but PROs changed in the direction of supporting the tolerability of Epidiolex (e.g., emotional functioning improved). Epidiolex at a dose of 800 mg daily appears to be safe and tolerable in patients with BCR prostate cancer supporting a safe dose for future studies.

The impact of the apparent diffusion coefficient for the early prediction of the treatment response after definitive radiotherapy in prostate cancer patients

PurposeWe assessed early changes in apparent diffusion coefficient (ADC) and serum prostate specific antigen (PSA) values after definitive radiotherapy (RT) without androgen deprivation treatment in low- and intermediate-risk prostate cancer (PC) patients. Materials and MethodsThe clinical data and ADC parameters of 229 PC patients were retrospectively evaluated. Pre-treatment and post-treatment serum PSA and primary tumor ADC values were calculated. Post-treatment DW-MRI was performed median 4.1 months after completion of definitive RT. The prognostic factors predicting freedom from biochemical failure (FFBF) and progression-free survival (PFS) were analyzed using univariable and multivariable analyses. ResultsWith a median follow-up time of 80.8 months, the 5-year FFBF and PFS rates were 95.9% and 89.3%, respectively. Eleven patients (4.8%) had PSA relapse, with a median of 34.4 months after the completion of RT. A statistically significant difference in post-treatment ADC values was noted between patients with and without recurrence (0.94 ± 0.07 vs. 1.10 ± 0.20 × 10-3 mm2/sec; p< 0.001). Patients with a Gleason score (GS) of 6 and low-risk disease had significantly higher post-treatment tumor ADC and PSA levels than patients with a GS of 7 and intermediate-risk disease. The 5-year FFBF rate in patients with tumor ADC ≤ 0.96 × 10-3 mm2/sec was significantly lower than patients with tumor ADC > 0.96 × 10-3 mm2/sec (85.5% vs. 100; p< 0.001). In the multivariable analysis, a lower ADC value, GS 4 + 3 and intermediate-risk disease were independent predictors of worse FFBF. In the multivariate analysis, a lower post-treatment ADC value and a GS of 4 + 3 were significant prognostic factors for a lower PFS. ConclusionThese findings suggest that the post-treatment tumor ADC value could be used for early treatment response evaluation after definitive RT in PC patients.

Quantitative assessment of PSMA PET response to therapy in castration-sensitive prostate cancer using an automated imaging platform for disease identification and measurement

RationaleProstate cancer treatment response may be automatically quantified using a molecular imaging analysis platform targeting prostate-specific membrane antigen (PSMA).MethodsA retrospective analysis of patients with castration-sensitive prostate cancer who underwent PSMA-targeted molecular imaging prior to and 3 months or more after treatment was conducted. Disease burden was analyzed with aPROMISE, an artificial intelligence imaging platform that automatically quantifies PSMA-positive lesions. The calculated PSMA scores for prostate/bed, nodal, and osseous disease sites were compared with prostate-specific antigen (PSA) values.ResultsOf 30 eligible patients, the median decline in prostate/bed, nodal, and osseous disease PSMA scores were 100% (range 52–100%), 100% (range − 87–100%), and 100% (range − 21–100%), respectively. PSMA score decline was significantly associated with PSA decline.ConclusionChanges in aPROMISE PSMA scores are associated with changes in PSA and may quantify treatment response.

MP79-03 COMPARISON OF HEMATOCRIT CHANGE IN TESTOSTERONE-DEFICIENT MEN TREATED WITH INTRANASAL TESTOSTERONE GEL VERSUS INTRAMUSCULAR TESTOSTERONE CYPIONATE: A SINGLE-CENTER RANDOMIZED CLINICAL TRIAL

You have accessJournal of UrologyCME1 Apr 2023MP79-03 COMPARISON OF HEMATOCRIT CHANGE IN TESTOSTERONE-DEFICIENT MEN TREATED WITH INTRANASAL TESTOSTERONE GEL VERSUS INTRAMUSCULAR TESTOSTERONE CYPIONATE: A SINGLE-CENTER RANDOMIZED CLINICAL TRIAL Marco-Jose Rivero, Jesse Ory, Halifax Canada, Parris Diaz, Raul Clavijo, Nannan Thirumavalavan, Ruben Blachman-Braun, Justin Loloi, Ari Bernstein, and Ranjith Ramasamy Marco-Jose RiveroMarco-Jose Rivero More articles by this author , Jesse OryJesse Ory More articles by this author , Halifax CanadaHalifax Canada More articles by this author , Parris DiazParris Diaz More articles by this author , Raul ClavijoRaul Clavijo More articles by this author , Nannan ThirumavalavanNannan Thirumavalavan More articles by this author , Ruben Blachman-BraunRuben Blachman-Braun More articles by this author , Justin LoloiJustin Loloi More articles by this author , Ari BernsteinAri Bernstein More articles by this author , and Ranjith RamasamyRanjith Ramasamy More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003356.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Testosterone therapy is associated with rise in hematocrit (HCT) and subsequent risk of polycythemia and thrombotic events. Incidence of these side effects may vary depending on the route of administration of testosterone therapy formulation. In this study, we compared the effects of intranasal testosterone gel (NT) and intramuscular testosterone cypionate (TC) on HCT and serum total testosterone (T) levels in testosterone-deficient men over 4 months. METHODS: Patients between 18 and 75 years of age with a diagnosis of testosterone deficiency were recruited. Testosterone deficiency (TD) was defined as two measurements of serum total testosterone below 300 ng/dL combined with one or more characteristic clinical symptoms. Men were randomized (1:1) to receive either NT (5.5 mg per nostril) three times a day or TC (200 mg intramuscularly) once every two weeks. The primary outcomes were changes in HCT and serum T before and after 4 months of treatment. Secondary outcomes were changes in estradiol, prostate-specific antigen, and 17-hydroxyprogesterone. RESULTS: 49 men were randomized to receive either NT (n=20) or TC (n=29). The median participant age was 47 years with a mean serum T of 236.6 ng/dL and mean HCT of 43.3%. The prevalence of participants who screened positive for obstructive sleep apnea on STOP-BANG questionnaire was 70% for the NT group and 72% for the TC group. Men in both groups experienced significantly increased serum T levels throughout the study period (p<0.001), although a larger increase was seen in the TC group. There was an increase in the mean HCT of the TC group from 42.6% to 46.0% at 4-month follow-up (p=0.006), while the NT group experienced no significant changes in mean HCT (p=0.903). The TC group experienced significant increases in estradiol (p<0.001) and decreases in 17-hydroxyprogesterone (p<0.001) at 4-month follow-up, while the NT group experienced no such changes. CONCLUSIONS: Although both NT and TC regimens are effective in treating men with TD, NT does not appear to significantly affect HCT levels. Patients who are at increased risk of developing polycythemia or those who wish to avoid changes in estradiol or 17-hydroxyprogesterone levels may benefit from short-acting testosterone therapy formulations such as NT. Source of Funding: This project was funded by an investigator-initiated grant provided by Acerus Pharmaceuticals © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1142 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Marco-Jose Rivero More articles by this author Jesse Ory More articles by this author Halifax Canada More articles by this author Parris Diaz More articles by this author Raul Clavijo More articles by this author Nannan Thirumavalavan More articles by this author Ruben Blachman-Braun More articles by this author Justin Loloi More articles by this author Ari Bernstein More articles by this author Ranjith Ramasamy More articles by this author Expand All Advertisement PDF downloadLoading ...

MP11-07 RADIOLIGAND THERAPY WITH 177 Lu-PSMA-I&amp;T IN PATIENTS WITH METASTATIC CASTRATION-RESISTANT PROSTATE CANCER: ONCOLOGICAL OUTCOMES AND TOXICITY PROFILE

You have accessJournal of UrologyCME1 Apr 2023MP11-07 RADIOLIGAND THERAPY WITH 177Lu-PSMA-I&T IN PATIENTS WITH METASTATIC CASTRATION-RESISTANT PROSTATE CANCER: ONCOLOGICAL OUTCOMES AND TOXICITY PROFILE Mehmet Onur Demirkol, Baris Esen, Melis Sen, Burcu Ucar, Sevgilay Kurtuldu, Nil Molinas Mandel, Sevil Bavbek, Okan Falay, Derya Tilki, and Tarik Esen Mehmet Onur DemirkolMehmet Onur Demirkol More articles by this author , Baris EsenBaris Esen More articles by this author , Melis SenMelis Sen More articles by this author , Burcu UcarBurcu Ucar More articles by this author , Sevgilay KurtulduSevgilay Kurtuldu More articles by this author , Nil Molinas MandelNil Molinas Mandel More articles by this author , Sevil BavbekSevil Bavbek More articles by this author , Okan FalayOkan Falay More articles by this author , Derya TilkiDerya Tilki More articles by this author , and Tarik EsenTarik Esen More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003226.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prostate-specific membrane antigen (PSMA) targeted radioligand therapy (RLT) with 177Lu-PSMA-617 is associated with prolonged overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC). Data regarding the oncological efficacy and toxicity profile of 177Lu-PSMA-I&T is limited. Herein, we aimed to investigate the oncological outcomes and toxicity profile of 177Lu-PSMA-I&T RLT in patients with mCRPC. METHODS: A total of 33 consecutive patients with mCRPC were treated with a total of 88 cycles (median 2 cycles, range 1-7) of 177Lu-PSMA-I&T RLT. The 177Lu-PSMA-I&T was given with a median activity of 7.5 GBq (IQR: 6.7 – 8.1) per cycle. Response to RLT were assessed according to prostate-specific antigen (PSA) changes and imaging response. Oncological outcomes were reported using clinical progression-free survival (cPFS), and overall survival (OS). Time interval from the first RLT cycle to any radiological or biochemical progression was considered clinical progression-free survival (cPFS). Common Toxicity Criteria for Adverse Events (CTCAE) criteria were utilized to assess toxicity. RESULTS: The mean patient age at the time of the first RLT cycle was 71.6 ± 10.7 years. Any PSA decline was detected in 22 (69%) cases after RLT. The number of patients achieving PSA declines of ≥30% and ≥50% were 18 (56%) and 11 (34%), respectively (Figure 1). The cPFS and OS after first cycle of RLT was 6.3 and 21.4 months, respectively. During RLT, nephrotoxicity occurred in 4 cases (12.1%); CTCAE grade according to estimated glomerular filtration rate worsening from I to II (n=2), II to III (n=1), III to IV (n=1). Six patients (18.2%) experienced a grade I/II myelotoxicity and 3 cases (9.1%) had grade III/IV myelotoxicity. CONCLUSIONS: 177Lu-PSMA-I&T RLT achieved a good PSA response (≥30%) in more than half of the patients with mCRPC with an acceptable toxicity profile. Further studies are required to assess the role of 177Lu-PSMA-I&T RLT in mCRPC. Source of Funding: European Urological Scholarship Programme through a 1-year research scholarship (to B.E.) © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e125 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mehmet Onur Demirkol More articles by this author Baris Esen More articles by this author Melis Sen More articles by this author Burcu Ucar More articles by this author Sevgilay Kurtuldu More articles by this author Nil Molinas Mandel More articles by this author Sevil Bavbek More articles by this author Okan Falay More articles by this author Derya Tilki More articles by this author Tarik Esen More articles by this author Expand All Advertisement PDF downloadLoading ...

MP44-08 RELATIONSHIP BETWEEN COVID 19 VACCINATION AND PSA LEVEL

You have accessJournal of UrologyCME1 Apr 2023MP44-08 RELATIONSHIP BETWEEN COVID 19 VACCINATION AND PSA LEVEL David Ahlborn, Ilene Staff, Tara Mclaughlin, Joseph Tortora, Jeff Mather, and Joseph Wagner David AhlbornDavid Ahlborn More articles by this author , Ilene StaffIlene Staff More articles by this author , Tara MclaughlinTara Mclaughlin More articles by this author , Joseph TortoraJoseph Tortora More articles by this author , Jeff MatherJeff Mather More articles by this author , and Joseph WagnerJoseph Wagner More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003290.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Some reports have indicated that the COVID vaccine could affect parameters used for some cancer screenings. The effect of COVID vaccination on breast cancer screening mammograms has been hotly debated and anecdotal reports of a rise in prostate-specific antigen (PSA) after COVID vaccination have appeared in the media. We explored the relationship between PSA levels and COVID vaccination. METHODS: With IRB approval, we queried the electronic medical record for men who received at least two mRNA COVID vaccine injections (Pfizer or Moderna), at least one PSA test within two years prior to the first vaccine injection and at least one PSA within one year of their second injection and before any third injection. PSA results were grouped according to the timing of the post vaccination PSA. The pre-vaccine PSA closest to the first injection was used. Both within and between subject analyses were conducted. Wilcoxon signed rank tests were performed to compare PSAs pre- and post- vaccine for each time defined group. McNemar tests were used to assess the percentage of patients crossing a 4.0 ng/dl threshold when compared with their pre-vaccine PSA. Difference in relative PSA change across the groups was compared using a Kruskal Wallis test. RESULTS: 5713 men met inclusion criteria. Median pre-vaccine PSA was 1.2 ng/dl (IQR 0.6-2.7 ng/dl). The median time difference between vaccine injection 1 and 2 was 22 days (IQR 21-28 days). Within each time group, a significant increase in PSA was observed pre to post and a higher proportion of men went above 4.0 relative to those going below. However, no significant differences were observed across groups (Table 1). CONCLUSIONS: Due to the lack of intergroup differences, PSA increases most likely reflect natural progression rather than any temporal effect of vaccination. Source of Funding: Unfunded © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e613 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information David Ahlborn More articles by this author Ilene Staff More articles by this author Tara Mclaughlin More articles by this author Joseph Tortora More articles by this author Jeff Mather More articles by this author Joseph Wagner More articles by this author Expand All Advertisement PDF downloadLoading ...

The role of prostate-specific antigen changes in predicting overall survival after progressive-site directed therapy for oligoprogressive castration-resistant prostate cancer.

None declared.

Clomiphene citrate: A potential alternative for testosterone therapy in hypogonadal males.

Hypogonadism is a worldwide problem among men causing sexual, physical and mental problems. Testosterone therapy is the first-choice treatment for male hypogonadism, with several side effects, that is, subfertility. Clomiphene citrate (CC) is an alternative off-label therapy for a certain group of hypogonadal males, especially for those with an active or future child wish. There is scarce literature in usage of CC for men with hypogonadism. The aim of this retrospective study was to evaluate the effectiveness and safety of CC for hypogonadal males. In this single-centre study, men treated with CC for hypogonadism were evaluated retrospectively. Primary outcome was hormonal evaluation including total testosterone (TT), free testosterone (FT), luteinizing hormone (LH) and follicle stimulating hormone (FSH). Secondary outcomes were hypogonadal symptoms, metabolic and lipid parameters, haemoglobin (Hb), haematocrit (Ht), prostate specific antigen (PSA), side effects, the effect of a trial without medication and potential predictors for biochemical and clinical response. In total, 153 hypogonadal men were treated with CC. Mean TT, FT, LH and FSH increased during treatment. TT increased from 9 to 16 nmol/L, with a biochemical increase in 89% of the patients. In patients who continued CC treatment, an increased level of TT persisted after 8 years of treatment. With CC treatment, 74% of the patients experienced hypogonadal symptom improvement. LH at the lower normal range before CC treatment was predictive for better TT response. During CC therapy, few side effects were reported and no clinical important changes in PSA, Hb and Ht were found. Clomiphene citrate is an effective therapy on short and long term, improving both clinical symptoms and biochemical markers of male hypogonadism with few side effects and good safety aspects.

Serial stereotactic body radiation therapy for oligometastatic prostate cancer detected by novel PET-based radiotracers.

Radiopharmaceuticals, including Ga-68-prostate specific membrane antigen (PSMA)-11 and F-18-Fluciclovine, are increasingly used to inform therapies for prostate cancer (CaP). Stereotactic body radiation therapy (SBRT) to PET-detected oligometastatic CaP has been shown to improve progression free survival (PFS) and delay androgen deprivation therapy (ADT) compared to observation. For men who subsequently develop oligorecurrent CaP, outcomes following second SBRT are unknown. A retrospective cohort study was conducted. Eligibility criteria included patients with oligometastatic (1-5 lesions) CaP detected on PSMA or Fluciclovine PET who underwent 2 consecutive SBRT courses to tracer-avid sites. Data on stage, tracer type, concurrent systemic therapy, and prostate-specific antigen (PSA) responses for first SBRT (SBRT1) and second SBRT (SBRT2) were collected. Outcomes included PSA decline ≥50% (PSA50), PFS after SBRT2, and ADT initiation or intensification-free survival after SBRT2. Factors potentially associated with PSA50 after SBRT2 was evaluated with multivariable logistic regression. Factors potentially associated with PFS and ADT initiation/intensification-free survival after SBRT2 were evaluated with separate multivariable Cox proportional-hazards models. Twenty-five patients were identified. At SBRT2, oligorecurrence was detected on PSMA and Fluciclovine PET in 17 (68%) and 8 (32%) patients, respectively. Fifteen (60%) patients had castration-sensitive disease and 10 (40%) had castration-resistant disease. After SBRT2, 16 (64%) achieved a PSA50 response, median PFS was 11.0mo, and median ADT initiation/intensification-free survival was 23.2mo. On multivariable analysis, maximum percent change in PSA after SBRT1 (OR 0.94, 95%CI 0.88-0.99, P = 0.046) and concurrent change in systemic therapy (OR 21.61, 95%CI 1.12-417.9, P = 0.042) were associated with PSA50 responses after SBRT2. PSA50 response after SBRT1 was associated with improved PFS (HR 0.36, 95%CI 0.00-0.42, P = 0.008) and ADT initiation/intensification-free survival (HR 0.07, 95%CI 0.01-0.68, P = 0.021) after SBRT2. From SBRT1 to last follow-up (median 48 months), 7 (28%) patients remained ADT-free. Serial SBRT for oligometastatic CaP detected on PSMA or Fluciclovine PET is feasible and can achieve PSA declines, with or without systemic therapy. Degree of biochemical response to first SBRT warrants further study as a potential predictor of PSA response, PFS, and ADT initiation/intensification-free survival following a subsequent SBRT course. This preliminary evidence provides rationale for larger, prospective studies of this strategy.

Prostate-specific antigen kinetics contributes to decision making for biopsy referral: the predictive implication for PSA retest in patients with elevated PSA levels.

It is common to repeat prostate-specific antigen (PSA) measurements for men with PSA elevation before prostate biopsy. In this scenario, they may have considerable psychological distress in fear of the presence of cancer until retests. We assessed possible clinical factors causing transient PSA rise and explored the parameters predictive of subsequent PSA change. As interfering conditions, the history of ejaculation, bicycling, and any types of infections were assessed using the questionnaire. The pattern of PSA change was compared in association with the various clinical factors. Predictive significance of PSA kinetics such as coefficient of variation (CV) and PSA velocity (PSAV) for PSA values at retest was evaluated. The rate of reversion to the normal range was 38.3% at retest. The rate of 12.8% of men showed a large increase by ≥20%, whereas 38.2% of men showed a large decline by ≥20% from the baseline. Men with younger age (≤60 years), small prostate (<20cc), and prior history of ejaculation or infections showed significantly larger PSA decrease than their counterparts. Those with large CV or PSAV before the baseline more frequently showed PSA decrease below the age-specific cutoff or decline by ≥10% from the baseline at retest. These parameters associated with PSA kinetics had independent predictive values for relevant PSA change at retest. Ejaculation and any types of infections should be avoided before PSA tests. Men with large PSA fluctuation before the baseline are likely to show a significant PSA decrease at retest. This predictive information may help both physicians to determine whether to proceed to an immediate biopsy and patients to reduce their psychological burden.