Prostate-specific Antigen Rise Research Articles

An integrated radiology-pathology machine learning classifier for outcome prediction following radical prostatectomy: Preliminary findings

ObjectivesTo evaluate the added benefit of integrating features from pre-treatment MRI (radiomics) and digitized post-surgical pathology slides (pathomics) in prostate cancer (PCa) patients for prognosticating outcomes post radical-prostatectomy (RP) including a) rising prostate specific antigen (PSA), and b) extraprostatic-extension (EPE). MethodsMulti-institutional data (N = 58) of PCa patients who underwent pre-treatment 3-T MRI prior to RP were included in this retrospective study. Radiomic and pathomic features were extracted from PCa regions on MRI and RP specimens delineated by expert clinicians. On training set (D1, N = 44), Cox Proportional-Hazards models MR, MP and MRaP were trained using radiomics, pathomics, and their combination, respectively, to prognosticate rising PSA (PSA > 0.03 ng/mL). Top features from MRaP were used to train a model to predict EPE on D1 and test on external dataset (D2, N = 14). C-index, Kalplan-Meier curves were used for survival analysis, and area under ROC (AUC) was used for EPE. MRaP was compared with the existing post-treatment risk-calculator, CAPRA (MC). ResultsPatients had median follow-up of 34 months. MRaP (c-index = 0.685 ± 0.05) significantly outperformed MR (c-index = 0.646 ± 0.05), MP (c-index = 0.631 ± 0.06) and MC (c-index = 0.601 ± 0.071) (p < 0.0001). Cross-validated Kaplan-Meier curves showed significant separation among risk groups for rising PSA for MRaP (p < 0.005, Hazard Ratio (HR) = 11.36) as compared to MR (p = 0.64, HR = 1.33), MP (p = 0.19, HR = 2.82) and MC (p = 0.10, HR = 3.05). Integrated radio-pathomic model MRaP (AUC = 0.80) outperformed MR (AUC = 0.57) and MP (AUC = 0.76) in predicting EPE on external-data (D2). ConclusionsResults from this preliminary study suggest that a combination of radiomic and pathomic features can better predict post-surgical outcomes (rising PSA and EPE) compared to either of them individually as well as extant prognostic nomogram (CAPRA).

Stereotactic Body Radiation Therapy Salvage for Lymph Node Recurrent Prostate Cancer in the Era of PSMA PET Imaging.

Our understanding of patterns of prostate cancer recurrence after primary treatment of localized disease has significantly evolved since the development of positron emission tomography (PET) agents targeting prostate cancer. Previously, most biochemical recurrences were not associated with imaging correlates when restaging with computed tomography (CT), magnetic resonance imaging (MRI), or bone scintigraphy and, hence, were typically assumed to represent occult metastases. A rising prostate specific antigen (PSA) after previous local therapy prompting a PET scan showing uptake limited to regional lymph nodes is an increasingly common clinical scenario as advanced prostate cancer imaging becomes more widely utilized. The optimal management strategy for patients who have lymph node recurrent prostate cancer is both unclear and evolving, particularly in terms of local and regionally directed therapies. Stereotactic body radiation therapy (SBRT) utilizes ablative radiation doses with steep gradients to achieve local tumor control while sparing nearby normal tissues. SBRT is an attractive therapeutic modality due to its efficacy, favorable toxicity profile, and flexibility to administer elective doses to areas of potential occult involvement. The purpose of this review is to briefly describe how SBRT is being implemented in the era of PSMA PET for the management of solely lymph node recurrent prostate cancer. SBRT has been shown to effectively control individual lymph node tumor deposits within the pelvis and retroperitoneum for prostate cancer and is well-tolerated with a favorable toxicity profile. However, a major limitation thus far has been the lack of prospective trials supporting the use of SBRT for oligometastatic nodal recurrent prostate cancer. As further trials are conducted, its exact role in the treatment paradigm of recurrent prostate cancer will be better established. Although PET-guided SBRT appears feasible and potentially beneficial, there is still considerable uncertainty about the use of elective nodal radiotherapy (ENRT) in patients with nodal recurrent oligometastatic prostate cancer. PSMA PET has undoubtedly advanced imaging of recurrent prostate cancer, revealing anatomic correlates for disease recurrence that previously went undetected. At the same time, SBRT continues to be explored in prostate cancer with feasibility, a favorable risk profile, and satisfactory oncologic outcomes. However, much of the existing literature comes from the pre-PSMA PET era and integration of this novel imaging approach has led to greater focus on new and ongoing clinical trials to rigorously evaluate this approach and compare to other established treatment modalities utilized for oligometastatic, nodal recurrence of prostate cancer.

MP29-20 FACTORS ASSOCIATED WITH POOR SURVIVAL OUTCOMES IN PROSTATE CANCER (PCA) PATIENTS WITH RADIOGRAPHIC DISEASE PROGRESSION IN THE SETTING OF LOW PSA

You have accessJournal of UrologyCME1 Apr 2023MP29-20 FACTORS ASSOCIATED WITH POOR SURVIVAL OUTCOMES IN PROSTATE CANCER (PCA) PATIENTS WITH RADIOGRAPHIC DISEASE PROGRESSION IN THE SETTING OF LOW PSA Mohamed Ahmed, Jack Andrews, Ahmed Mahmoud, Matthew Lee, Elizabeth Bearrick, Daniel Childs, A. Tuba Kendi, Matthew Tollefson, Stephen Boorjian, R. Jeff Karnes, and Eugene Kwon Mohamed AhmedMohamed Ahmed More articles by this author , Jack AndrewsJack Andrews More articles by this author , Ahmed MahmoudAhmed Mahmoud More articles by this author , Matthew LeeMatthew Lee More articles by this author , Elizabeth BearrickElizabeth Bearrick More articles by this author , Daniel ChildsDaniel Childs More articles by this author , A. Tuba KendiA. Tuba Kendi More articles by this author , Matthew TollefsonMatthew Tollefson More articles by this author , Stephen BoorjianStephen Boorjian More articles by this author , R. Jeff KarnesR. Jeff Karnes More articles by this author , and Eugene KwonEugene Kwon More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003257.20AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Recent studies, including a post-hoc analysis of the ARCHES trial, highlight radiographic disease progression (rDP) occurring without concordant rise in prostate specific antigen (PSA). In a previous study by our group, we reported that almost 40% of patients on 2nd generation hormone therapy experience rDP with non-rising PSA and have poor survival outcomes. The current analysis more specifically focuses on the subgroup of patients with rDP occurring at low PSA (<0.5 ng/dL) and describes factors associated with poorer survival outcomes in this patient population. METHODS: In a single institution study, we reviewed the prospectively maintained Mayo Clinic C-11 Choline PET registry for patients treated between 2011 and 2021, who experienced rDP at low PSA (value < 0.5 ng/mL). Disease progression on C-11 choline PET was confirmed by either tissue biopsy or subsequent response to therapy. We investigated factors associated with poor cancer-specific survival outcomes in univariable and multivariable cox regression analyses. RESULTS: In total, 220 (16%) patients experiencing rDP at low PSA were identified. Median (IQR) age at rDP was 67.91 (61.10 – 73.87) yrs., median (IQR) primary Gleason score was 9 (7-9), and median (IQR) PSA was 0.17 (0 – 0.32) ng/ml. 75% of the patients (n=166) had CRPC disease status at time of rDP. Prior systemic treatments included 2nd generation HT in 18% (n= 40) and chemotherapy in 31% (n=70). Sites of rDP were divided into 7% local (n=16), 42% lymph nodes (n=91), 43% bone (n=95), and 8% visceral metastases (n=18). Over a median follow-up duration of 55 months, 46% of patients (n=100) reported death. Factors associated with poor survival outcomes are demonstrated in table-1 and include age at rDP, CRPC status, and disease location (P-value <0.05). CONCLUSIONS: We found that radiographic disease progression commonly occurs at low PSA (<0.5 ng/mL). CRPC-disease status and the development of visceral metastases are associated with particularly poor survival outcomes. To identify early progression, monitoring with imaging may be warranted, even in the patients with low PSA. Source of Funding: none © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e390 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mohamed Ahmed More articles by this author Jack Andrews More articles by this author Ahmed Mahmoud More articles by this author Matthew Lee More articles by this author Elizabeth Bearrick More articles by this author Daniel Childs More articles by this author A. Tuba Kendi More articles by this author Matthew Tollefson More articles by this author Stephen Boorjian More articles by this author R. Jeff Karnes More articles by this author Eugene Kwon 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 ...

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.

Factors associated with poor survival outcomes in patients with prostate cancer (PCa) with radiographic disease progression in the setting of low PSA.

60 Background: Recent studies, including a post-hoc analysis of the ARCHES trial, highlight radiographic disease progression (rDP) occurring without concordant rise in prostate specific antigen (PSA). In a previous study by our group, we reported that almost 40% of patients on 2nd generation hormone therapy experience rDP with non-rising PSA and have poor survival outcomes. The current analysis more specifically focuses on the subgroup of patients with rDP occurring at low PSA (&lt;0.5 ng/dL) and describes factors associated with poorer survival outcomes in this patient population. Methods: In a single institution study, we reviewed the prospectively maintained Mayo Clinic C-11 Choline PET registry for patients treated between 2011 and 2021, who experienced rDP at low PSA (value &lt; 0.5 ng/mL). Disease progression on C-11 choline PET was confirmed by either tissue biopsy or subsequent response to therapy. We investigated factors associated with poor cancer-specific survival outcomes in univariable and multivariable cox regression analyses. Results: In total, 220 (16%) patients experiencing rDP at low PSA were identified. Median (IQR) age at rDP was 67.91 (61.10 – 73.87) yrs., median (IQR) primary Gleason score was 9 (7-9), and median (IQR) PSA was 0.17 (0 – 0.32) ng/ml. 75% of the patients (n=166) had CRPC disease status at time of rDP. Prior systemic treatments included 2nd generation HT in 18% (n= 40) and chemotherapy in 31% (n=70). Sites of rDP were divided into 7% local (n=16), 42% lymph nodes (n=91), 43% bone (n=95), and 8% visceral metastases (n=18). Over a median follow-up duration of 55 months, 46% of patients (n=100) reported death. Factors associated with poor survival outcomes are demonstrated in the table and include age at rDP, CRPC status, and disease location (P-value &lt;0.05). Conclusions: We found that radiographic disease progression commonly occurs at low PSA (&lt;0.5 ng/mL). CRPC-disease status and the development of visceral metastases are associated with particularly poor survival outcomes. To identify early progression, monitoring with imaging may be warranted, even in the patients with low PSA. [Table: see text]

Patient outcomes following a response biomarker-guided approach to treatment using 177Lu-PSMA-I&T in men with metastatic castrate-resistant prostate cancer (Re-SPECT).

177LuPSMA is an effective treatment in metastatic castrate-resistant prostate cancer with trials adopting a standardised dose interval. Adjusting treatment intervals utilising early response biomarkers may improve patient outcomes. This study evaluated progression-free survival (PFS) and overall survival (OS) based on treatment interval adjustment utilising 177LuPSMA 24-h SPECT/CT (177Lu-SPECT) and early prostate-specific antigen (PSA) response. Retrospective analysis of a clinical 177Lu-PSMA-I&T treatment programme. In all, 125 men were treated with 6-weekly 177LuPSMA-I&T [median 3 cycles, interquartile range (IQR): 2-4], median dose 8.0 GBq [95% confidence interval (CI): 7.5-8.0]. Imaging screening involved 68GaPSMA-11 PET/diagnostic CT. 177Lu-SPECT/diagnostic CT was acquired following each therapy, and clinical assessments 3-weekly. Following dose 2 (week 6), a composite PSA and 177Lu-SPECT/CT imaging response [partial response (PR), stable disease (SD), and progressive disease (PD)] determined ongoing management. Response group (RG) 1 (marked reduction in PSA/imaging PR) break in treatment until subsequent PSA rise, then re-treatment. RG 2 (stable or reduced PSA and/or imaging SD) 6-weekly treatments until six doses, or no longer clinically benefitting. RG 3 (rise in PSA and/or imaging PD) recommended for an alternative treatment. Overall PSA50% response rate (PSARR) was 60% (75/125), median PSA-PFS 6.1 months (95%CI: 5.5-6.7), and median OS 16.8 months (95%CI: 13.5-20.1). 35% (41/116) were classified as RG 1, 34% (39/116) RG 2, and 31% (36/116) RG 3. PSARRs by RG were 95% (38/41), 74% (29/39), and 8% (3/36); median PSA-PFS rates were 12.1 months (95%CI: 9.3-17.4), 6.1 months (95%CI: 5.8-9.0), and 2.6 months (95%CI: 1.6-3.1); and OS rates were 19.2 months (95%CI: 16.8-20.7), 13.2 months (95%CI: 12.0-18.8), and 11.2 months (95%CI: 8.7-15.6) for RG 1, 2, and 3, respectively. The median months of 'treatment holiday' for RG 1 was 6.1 months (IQR: 3.4-8.7). Nine men had received prior 177LuPSMA-617 and were retreated with 177LuPSMA-I&T, with a PSARR of 56% on re-treatment. Personalising dosing regimens using early response biomarkers with 177LuPSMA has the potential to achieve similar treatment responses to continuous dosing while allowing treatment breaks or intensification. Further evaluation of early response biomarker-guided treatment regimens in prospective trials is warranted. Lutetium-PSMA therapy is a new therapy for metastatic prostate cancer that is well tolerated and effective. However, not all men respond equally, with some responding very well and others progressing early. Personalising treatments require tools that can accurately measure treatment responses, preferably early in the treatment course, so adjustments to treatment can be made. Lutetium-PSMA can measure tumour sites after each therapy by taking whole body 3D images at 24 h using a small radiation wave from the treatment itself. This is called a SPECT scan. Previous work has shown that both prostate-specific antigen (PSA) response and changes in tumour volume on a SPECT scan can predict how patients will respond to treatment as early as dose 2. This study demonstrates that stratifying how men are treated based on the results of the 6-week SPECT scan and PSA response potentially allows a third of men to have break in treatment and that these men have both longer time to disease progression and OS. Men with an increase in tumour volume and increase in PSA early in treatment (6 weeks) had shorter time to disease progression and OS. Men with early biomarker disease progression were offered alternative treatments early in an attempt to allow the opportunity to allow a more effective potential therapy, if one was available. The study is an analysis of a clinical programme, and was not a prospective trial. As such, there are potential biases that could influence results. Hence, while the study is encouraging for the use of early response biomarkers to guide better treatment decisions, this must be validated in a well-designed clinical trial.

Current role of PSMA-PET imaging in the clinical management of prostate cancer.

Despite the developments of the last few years, metastatic castration-resistant prostate cancer (PC) remains a deadly disease. Until recently, almost all guidelines recommended magnetic resonance imaging (MRI) or computed tomography (CT) for the initial staging and local/systematic recurrence. Positron emission tomography/computed tomography (PET/CT) with prostate-specific membrane antigen (PSMA) at the present stage, emerged as a promising diagnostic imaging tool for PC. PSMA PET/CT alone or in combination with multiparametric magnetic resonance imaging (mpMRI) can improve the detection of clinically significant PC, especially for Prostate Imaging Reporting & Data System (PI-RADS) = 3 lesions. In addition, PSMA PET/CT is more accurate than CT and bone scan for intermediate to high-risk disease at the initial staging. Contrariwise, a negative PET is not useful for surgeons to avoid a pelvic nodal dissection. PET-PSMA imaging is appropriate for prostate-specific antigen (PSA) persistence or PSA rise from undetectable level after radical prostatectomy or for PSA rise above nadir after definitive radiotherapy. Also, it is recommended for patients fit for curative salvage treatment. It should be noted that in patients, candidates for radionuclide therapy with Lutetium-177 (117Lu), a PSMA strong expression from PET/CT at baseline is considered necessary. This review summarizes the evolution of PSMA PET/CT and its current role in the management of PC.

Utility of Directly Measured Free Testosterone in Predicting Benefit of Testosterone Therapy in Men with Hypogonadal Symptoms and Normal Total Testosterone

Introduction: Currently symptomatically hypogonadal men with normal total testosterone (TT) levels but low enzyme-linked immunoassay (EIA) free testosterone (FT) are not offered Testosterone Therapy (TTh), despite the evidence that they may benefit. Objective: To determine whether low EIA-FT could help predict response to TTh in men with hypogonadal symptoms and TT >300. Methods: A total of 86 consecutive men with hypogonadal symptoms were prospectively analyzed with normal TT (>300 ng/dL) and low FT (<7.9 pg/mL). The TT and FT were measured by a single laboratory (LabCorp). Subjects began testosterone cypionate intramuscular 200 mg q2 weeks with 3- and 6-month follow-up. The population was divided into two groups based on initial TT levels: Group 1: 300–399 ng/dL; Group 2: 400–660 ng/dL. Clinical response to TTh was determined by improvements in hypogonadal symptoms, changes in International Index of Erectile Function (IIEF-5) questionnaire, and subjective changes in libido, energy, and vitality. Safety parameters were assessed with periodic checks of T, estradiol, hematocrit, and prostate-specific antigen (PSA). Results: Mean age was 62 years. Mean IIEF-5 score before TTh was 12.8; after 3 and 6 months, the scores were 14.1 and 14.7, respectively. Eighty-seven percent of men reported subjective improvement in energy/libido after 3 months of TTh, 61% of patients reported substantial improvement, 26% reported a modest improvement, and 13% reported no improvement. After 6 months of TTh, 77 patients (89.5%) reported substantial improvement, 7 (8.1%) with more mild but noticeable improvement, and only 2 (2.3%) with no improvement. Erectile function after 6 months of TTh improved, but it did not reach statistical significance (mean 12.8 ≥ 14.7, p = 0.07). Group 1 showed a greater rise in their IIEF-5 score after 6 months compared with patients in Group 2. Ten men (11.6%) and 3 men (4.8%) developed erythrocytosis and a rise in PSA respectively at 6 months. Conclusion: Our data suggest that many men with hypogonadal symptoms, normal TT, and low EIA-FT respond well, and safely, to TTh.

The effect of testosterone therapy on haematocrit and prostate specific antigen in the real-life setting

Testosterone therapy (TT) is commonly prescribed in men with androgen deficiency. TT has several common side effects. Moreover, the effect of TT on serum prostate specific antigen (PSA) levels has been a matter of debate over the last decade. We aimed to investigate the effect of TT on PSA and haematocrit levels in a cohort of men with androgen deficiency. Complete demographic, clinical and laboratory data from 106 consecutive hypogonadal men treated with TT were analysed. Health-significant comorbidities were scored with the Charlson Comorbidity Index (CCI). Serum hormones, complete blood count and PSA were measured in every patient at baseline and after 3 months of TT. Descriptive statistics and logistic regression models tested the association between clinical parameters and haematocrit and PSA values. Overall, median (IQR) patient's age and BMI were 54 (44-64) years and 26.2 (34.6-29) kg/m2, respectively. Above all, 63 (59.4%), 32 (30.2%) and 11 (10.4%) men were treated with T undecanoate, enanthate and gel formulation, respectively. Out of 106 men, 28 (26.4%) and 12 (11.3%) participants had PSA and haematocrit worsening (any degree), respectively. Patients who had PSA worsening (60.5 vs. 50.1 years, p=0.04) and haematocrit worsening (63 vs. 55 years, p=0.03) were older. At univariable logistic regression analysis, older age (OR 1.1, p<0.01) and lower baseline PSA values (OR 0.6; p=0.04) were associated with PSA worsening after TT. Similarly, older age (OR 1.2, p=0.04) and lower baseline haematocrit values (OR 0.7; p=0.03) were associated with haematocrit worsening after TT. After accounting for clinical and laboratory values no independent predictors of haematocrit rising were found. Approximately 20% and 10% of hypogonadal men treated with TT experienced PSA and haematocrit worsening. The degree of change was not meaningful and we failed to find any independent predictor of PSA and haematocrit rising in the real-life setting. None

Molecular detection of the COVID-19 genome in prostatic tissue of patients with previous infection

COVID-19 infection has been linked to worsening or de novo lower urinary tract symptoms and transient serum prostate-specific antigen rise in patients with benign prostatic hyperplasia. This pilot study aimed to examine prostatic tissue for evidence for direct involvement with the COVID-19 (SARS-CoV-2) infection. Fourteen patients with previous documented COVID-19 infection who underwent prostate enucleation had their prostate specimens examined for COVID-19 RNA. The specimens were examined using a SARS-CoV-2 test, an in vitro diagnostic test based on reverse transcription polymerase chain reaction technology that analyses the presence of RNA for the SARS-CoV-2 strain. Among the 14 patients, COVID infection was severe in three, mild in seven, and asymptomatic in four patients. The COVID-19 genome was successfully identified in the prostate specimen of a single patient. Although this patient had mild COVID-19 infection, he had positive COVID tests for 40 days after the initial infection. Identification of the COVID-19 genome in prostate tissue is a further step toward better understanding its effect on the genitourinary tract. This study’s findings provide some explanation for the proposed association with lower urinary tract symptoms and rise in serum prostate-specific antigen levels. Larger studies are needed to further investigate this association.

Radiographic progression in the absence of prostate-specific antigen (PSA) progression in patients with metastatic hormone-sensitive prostate cancer (mHSPC): Post hoc analysis of ARCHES.

5072 Background: Enzalutamide (ENZA) + androgen deprivation therapy (ADT) significantly reduced the risk of radiographic progression and increased overall survival in men with mHSPC, regardless of baseline PSA levels (ARCHES; NCT02677896). This post hoc analysis investigated concordance between PSA progression and radiographic progression in patients with mHSPC. Methods: Patients with mHSPC (n=1150) were randomized 1:1 to ENZA (160 mg/day) + ADT or placebo (PBO) + ADT. The concordance between radiographic progression and PSA progression, as defined by Prostate Cancer Clinical Trials Working Group 2 (PCWG2) criteria, and between any rise in PSA above nadir was assessed. Results: In total, 267/1150 patients in ARCHES had radiographic progression (ENZA + ADT, n=79; PBO + ADT, n=188). At radiographic progression, the median (range) PSA for ENZA + ADT-treated patients was 2.25 ng/mL (0–1062.3 ng/mL) and 17.47 ng/mL (0–1779.5 ng/mL) for PBO + ADT-treated patients. Most patients (67%) treated with ENZA + ADT did not have PCWG2-defined PSA progression at radiographic progression, compared with 43% of those treated with PBO + ADT (Table). The median absolute and percentage rise in PSA from nadir to radiographic progression was 0.77 ng/mL and 200%, respectively, with ENZA + ADT compared with 12.23 ng/mL and 367%, respectively, with PBO + ADT. Conclusions: In this post hoc analysis of ARCHES, we found frequent discordance between radiographic progression and PSA progression by PCWG2 criteria or any PSA rise over nadir in patients with mHSPC treated with ENZA + ADT. Thus, regular imaging is recommended to detect radiographic progression among patients treated with potent androgen receptor pathway inhibitors, such as ENZA + ADT, as serial PSA monitoring alone may not be sufficient to detect radiographic progression in many patients. Clinical trial information: NCT02677896. [Table: see text]

PD22-09 DISTINGUISHING BETWEEN PROSTATE SPECIFIC ANTIGEN BOUNCE AND BIOCHEMICAL RECURRENCE FOLLOWING STEREOTACTIC BODY RADIOTHERAPY FOR PROSTATE CANCER

You have accessJournal of UrologyCME1 May 2022PD22-09 DISTINGUISHING BETWEEN PROSTATE SPECIFIC ANTIGEN BOUNCE AND BIOCHEMICAL RECURRENCE FOLLOWING STEREOTACTIC BODY RADIOTHERAPY FOR PROSTATE CANCER Ashley Monaco, Jessica Sommer, Jordan Mendelson, Jonathan Haas, Anthony Corcoran, and Aaron Katz Ashley MonacoAshley Monaco More articles by this author , Jessica SommerJessica Sommer More articles by this author , Jordan MendelsonJordan Mendelson More articles by this author , Jonathan HaasJonathan Haas More articles by this author , Anthony CorcoranAnthony Corcoran More articles by this author , and Aaron KatzAaron Katz More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002564.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: While prostate specific antigen (PSA) bounce following radiation therapy for prostate cancer (PCa) treatment is well established, the parameters to predict this occurrence and differentiate it from biochemical recurrence (BCR) following stereotactic body radiotherapy (SBRT) are unknown. The purpose of this study is to investigate associations between pre-treatment and post-treatment variables among patients experiencing PSA bounce, BCR, or neither following SBRT. METHODS: An IRB-approved PCa database was reviewed for patients who underwent primary SBRT. Patients with less than 18 months of follow-up or were missing >3 PSA measurements following SBRT were excluded. Patients were divided into outcome groups experiencing PSA bounce, BCR, or neither. PSA bounce was defined as a rise of >0.2 ng/mL over the pre-rise nadir followed by a decline without intervention. BCR was defined by Phoenix criteria. Pre-treatment and post-treatment characteristics were analyzed between groups. Results that were significant when comparing PSA bounce to BCR were then analyzed in a multivariate logistic regression model to determine predictors for PSA bounce. RESULTS: We analyzed 170 men with a median age of 72 (52-87) years with an average follow-up time of 75 + 21 months, of which 28 (16%) experienced PSA bounce and 42 (25%) had BCR (Table 1). Pre-treatment D’Amico and Capra risk, Gleason group, PSA, prostate volume, prostate density and post-treatment PSA velocity were not associated with PSA bounce when compared to BCR or non-BCR/bounce cohorts. Compared to those who did not experience PSA bounce/BCR, those with PSA bounce were younger (p <.05), had lower PSA doubling time (p <.001), and took longer to reach PSA nadir (p <.001). Compared to BCR group, men with PSA bounce had lower PSA nadir and took longer to reach nadir, both of which were significant predictors for PSA bounce (OR: 4.3, p <.05; OR: 0.90, p <.001). PSA bounce occurred significantly earlier than BCR (16 vs. 33 months; p <.001). CONCLUSIONS: While there is overlap among patients who experience PSA bounce or BCR following SBRT, the timing of which the PSA rise occurs, the PSA nadir value, and the time to PSA nadir are useful variables in the management of a rising PSA in patients following SBRT. Source of Funding: Department of Urology, NYU Langone Hospital – Long Island © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e407 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ashley Monaco More articles by this author Jessica Sommer More articles by this author Jordan Mendelson More articles by this author Jonathan Haas More articles by this author Anthony Corcoran More articles by this author Aaron Katz More articles by this author Expand All Advertisement PDF DownloadLoading ...

High-dose Radiotherapy or Androgen Deprivation Therapy (HEAT) as Treatment Intensification for Localized Prostate Cancer: An Individual Patient–data Network Meta-analysis from the MARCAP Consortium

BackgroundThe relative benefits of radiotherapy (RT) dose escalation and the addition of short-term or long-term androgen deprivation therapy (STADT or LTADT) in the treatment of prostate cancer are unknown. ObjectiveTo perform a network meta-analysis (NMA) of relevant randomized trials to compare the relative benefits of RT dose escalation ± STADT or LTADT. Design, setting, and participantsAn NMA of individual patient data from 13 multicenter randomized trials was carried out for a total of 11862 patients. Patients received one of the six permutations of low-dose RT (64 to <74 Gy) ± STADT or LTADT, high-dose RT (≥74 Gy), or high-dose RT ± STADT or LTADT. Outcome measurements and statistical analysesMetastasis-free survival (MFS) was the primary endpoint. Frequentist and Bayesian NMAs were performed to rank the various treatment strategies by MFS and biochemical recurrence–free survival (BCRFS). Results and limitationsMedian follow-up was 8.8 yr (interquartile range 5.7–11.5). The greatest relative improvement in outcomes was seen for addition of LTADT, irrespective of RT dose, followed by addition of STADT, irrespective of RT dose. RT dose escalation did not improve MFS either in the absence of ADT (hazard ratio [HR] 0.97, 95% confidence interval [CI] 0.80–1.18) or with STADT (HR 0.99, 95% CI 0.8–1.23) or LTADT (HR 0.94, 95% CI 0.65–1.37). According to P-score ranking and rankogram analysis, high-dose RT + LTADT was the optimal treatment strategy for both BCRFS and longer-term outcomes. ConclusionsConventionally escalated RT up to 79.2 Gy, alone or in the presence of ADT, does not improve MFS, while addition of STADT or LTADT to RT alone, regardless of RT dose, consistently improves MFS. RT dose escalation does provide a high probability of improving BCRFS and, provided it can be delivered without compromising quality of life, may represent the optimal treatment strategy when used in conjunction with ADT. Patient summaryUsing a higher radiotherapy dose when treating prostate cancer does not reduce the chance of developing metastases or death, but it does reduce the chance of having a rise in prostate-specific antigen (PSA) signifying recurrence of cancer. Androgen deprivation therapy improves all outcomes. A safe increase in radiotherapy dose in conjunction with androgen deprivation therapy may be the optimal treatment.

The prognostic potential of alkaline phosphatase and lactic acid dehydrogenase in bmCRPC patients without significant PSA response under enzalutamide

BackgroundIn patients with bone metastatic castration-resistant prostate cancer (bmCRPC) on systemic treatment, it is difficult to differentiate between continuous rise of prostate specific antigen (PSA) representing progression, and PSA-surge, which is followed by clinical response or stable disease. The purpose of this study was to evaluate the prognostic value of dynamic changes of alkaline phosphatase (ALP) and lactic acid dehydrogenase (LDH) levels as a predictor of clinical efficacy or therapeutic resistance of patients who do not show a sufficient initial PSA decline of ≥50% from baseline during early therapy with Enzalutamide.MethodsForty-eight men with bmCRPC on Enzalutamide 07/2010-09/2019 with initially rising PSA were analyzed. We monitored PSA, LDH and ALP at week 0, 2, 4, and every 4 weeks thereafter and analyzed the correlation between ALP rising at 12 weeks with or without LDH-normalization and the association with survival. For this we used Kaplan Meier analysis and uni- and multivariate cox-regression models.ResultsIn Kaplan-Meier analysis, ALP rising at 12 weeks with or without LDH-normalization was associated with significantly worse median progression-free survival (PFS) of 3 months vs. 5 months (Log rank P = 0.02) and 3 months vs. 5 months (P = 0.01), respectively and overall survival (OS) with 8 months vs. 15 months (P = 0.02) and 8 months vs. 17 months (P < 0.01). In univariate analysis of PFS, ALP rising at 12 weeks alone, ALP rising at 12 weeks without LDH-normalization and application of Enzalutamide after chemotherapy showed a statistically significant association towards shorter PFS (hazard ratio (HR): 0.51, P = 0.04; HR: 0.48, P = 0.03; HR: 0.48, P = 0.03). Worse OS was significantly associated with ALP rising at 12 weeks alone, ALP rising at 12 weeks without LDH-normalization, and application of Enzalutamide after chemotherapy (HR: 0.47, P = 0.02; HR: 0.36, P < 0.01; HR: 0.31, P < 0.01). In multivariate analysis only the application of Enzalutamide after chemotherapy remained an independent prognostic factor for worse OS (HR: 0.36, P = 0.01).ConclusionsDynamic changes of ALP (non-rise) and LDH (normalization) under therapy with Enzalutamide may be associated with clinical benefit, better PFS, and OS in patients with bmCRPC who do not show a PSA decline.

Prostate Cancer Screening Using a Quick One-Step PSA Test

Background and aim: A one-step prostate-specific antigen (PSA) test was studied in a large population to improve the convenience and lower the cost of prostate cancer (PC) screening. The PSA rapid test kit aids in the diagnosis of PC by detecting human PSA in serum or plasma at or above a threshold level of 4 ng/mL. The aim of this study is to screen PC using a Quick One-Step PSA Test. Materials and Methods: Between July 2020 and August 2021, at National institute of urology and nephrology, Cairo, Egypt, Male attendees were offered PC screening utilizing the PSA quick test. A total of 305 men's blood samples were tested. The test was interpreted by two independent observers. Following that, the remaining serum samples were examined using a standard quantitative technique. Results: Of 305 participants, 118 had a PSA value of less than 4 ng/mL, and 55 presented a PSA value higher than 4 ng/mL. A total of 63 participants had a PSA value between 4 and 10 ng/mL. A total of 12 participants presented a PSA value &gt; 10 ng/mL; 10 was judged as positive. The intensity of the color reaction was implying a strong positive correlation between the two methods (correlation test: P&lt; 0.0001). Conclusion: The one-step test is a good preliminary screening method from which positive results may be quantified to provide a semi-quantitative estimate of the degree of PSA rise. The test is inexpensive, easy to do, and provides results in a timely manner.

Prostate Cancer Screening Using a Quick One-Step PSA Test

Background and aim: A one-step prostate-specific antigen (PSA) test was studied in a large population to improve the convenience and lower the cost of prostate cancer (PC) screening. The PSA rapid test kit aids in the diagnosis of PC by detecting human PSA in serum or plasma at or above a threshold level of 4 ng/mL. The aim of this study is to screen PC using a Quick One-Step PSA Test. Materials and Methods: Between July 2020 and August 2021, at National institute of urology and nephrology, Cairo, Egypt, Male attendees were offered PC screening utilizing the PSA quick test. A total of 305 men's blood samples were tested. The test was interpreted by two independent observers. Following that, the remaining serum samples were examined using a standard quantitative technique. Results: Of 305 participants, 118 had a PSA value of less than 4 ng/mL, and 55 presented a PSA value higher than 4 ng/mL. A total of 63 participants had a PSA value between 4 and 10 ng/mL. A total of 12 participants presented a PSA value &gt; 10 ng/mL; 10 was judged as positive. The intensity of the color reaction was implying a strong positive correlation between the two methods (correlation test: P&lt; 0.0001). Conclusion: The one-step test is a good preliminary screening method from which positive results may be quantified to provide a semi-quantitative estimate of the degree of PSA rise. The test is inexpensive, easy to do, and provides results in a timely manner.

Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography Is Associated with Improved Oncological Outcome in Men Treated with Salvage Radiation Therapy for Biochemically Recurrent Prostate Cancer

BackgroundRadiolabeled prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) has shown superior diagnostic accuracy to conventional imaging for the detection of prostate cancer deposits . Consequently, clinical management changes have been reported in patients with biochemical recurrence (BCR) of disease after robot-assisted radical prostatectomy (RARP). We hypothesized that, due to the exclusion of patients with metastatic disease on PSMA-PET/CT, those who underwent local salvage radiation therapy (SRT) after restaging PSMA-PET/CT for BCR may have better oncological outcomes than patients who underwent “blind” SRT. ObjectiveTo compare the oncological outcome of a patient cohort that underwent PSMA-PET imaging prior to SRT with that of a patient cohort that did not have PSMA-PET imaging before SRT. Design, setting, and participantsWe included 610 patients who underwent SRT, of whom 298 underwent PSMA-PET/CT prior to SRT and 312 did not. No additional hormonal therapy was prescribed. Outcome measurements and statistical analysisTo compare both cohorts, case-control matching was performed, using the prostate-specific antigen (PSA) value at the initiation of SRT, pathological grade group, pathological T stage, surgical margin status, and biochemical persistence after RARP as matching variables. The outcome variable was biochemical progression at 1 yr after SRT, defined as either a rise of PSA ≥0.2 ng/ml above the nadir after SRT or the start of additional treatment. Results and limitationsAfter case-control matching, 216 patients were matched in both cohorts (108 patients per cohort). In the patient cohort without PSMA-PET/CT prior to SRT, of 108 patients, 23 (21%) had biochemical progression of disease at 1 yr after SRT, compared with nine (8%) who underwent restaging PSMA-PET/CT prior to SRT (p = 0.007). ConclusionsPSMA-PET/CT is found to be associated with an improved oncological outcome in patients who undergo SRT for BCR after RARP. Patient summaryPerforming prostate-specific membrane antigen positron emission tomography/computed tomography imaging in patients with biochemical recurrence of disease after robot-assisted radical prostatectomy, before initiating salvage radiation therapy, resulted in improved short-term oncological outcomes.

Salvage Prostate Stereotactic Body Radiation Therapy After Definitive Cryoablation

PurposeWhole gland cryoablation is a guideline-approved definitive treatment for localized prostate cancer, and is being explored for partial gland ablation. However, there is limited data regarding management of cryoablation failures. Stereotactic body radiation therapy (SBRT) is a well-established method of primary treatment for prostate cancer. Here we review salvage SBRT after cryoablation failures. Methods and MaterialsA large database of patients treated with definitive SBRT was interrogated to identify those who underwent primary cryoablation. All patients were determined to have progressive disease based on a rising prostate specific antigen and/or postcryoablation biopsy. All patients were treated with SBRT over 5 treatment fractions using a robotic radiosurgical platform. Baseline cryoablation characteristics and pre- and posttreatment Expanded Prostate Cancer Index Composite questionnaires were analyzed. Acute and late toxicity was evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Cancer outcomes after salvage SBRT were stratified by disease and treatment characteristics. ResultsA total of 51 patients were identified who underwent cryoablation followed by salvage SBRT. The majority (47%) were found to have intermediate-risk disease at the time of SBRT salvage and most commonly were treated with 3500 cGy in 5 fractions to the prostate and seminal vesicles. Only 1 grade 3+ toxicity was identified. Patient-reported quality of life metrics after SBRT salvage followed prior patterns observed in the de novo SBRT setting. With a median follow-up of 40 months, 76% of the cohort demonstrated disease control. Median time to prostate cancer recurrence was 57.5 months, and recurrence was predominantly seen in patients with underlying high-risk disease. ConclusionsThis is the largest cohort of patients treated with any radiation therapy salvage after cryoablation and the first institution to report SBRT as a modality of salvage. Salvage SBRT after cryoablation results in low rates of high-grade toxicity, acceptable changes in patient-reported quality of life, and durable rates of long-term oncologic control.

Clinical characteristics and outcomes for patients with non\u2011metastatic castration-resistant prostate cancer

This study used linked, routinely-collected datasets to explore incidence, clinical characteristics and outcomes of prostate cancer (PC) patients who experience a rise in prostate-specific antigen (PSA) levels despite androgen deprivation therapy (ADT), without evidence of metastases in their patient record, termed non-metastatic castration-resistant PC (nmCRPC). Routinely collected administrative data in Wales were used to identify patients diagnosed with PC and nmCRPC from 2000–2015. Logrank tests and Cox proportional hazard models were used to compare time-to-events across subgroups defined by PSA doubling time and age. Of 38,021 patients identified with PC, 1,465 met nmCRPC criteria. PC incidence increased over the study period, while nmCRPC categorizations reduced. Median time from PC diagnosis to nmCRPC categorization was 3.07 years (95% confidence interval [CI] 2.91–3.26) and from nmCRPC categorization to metastases/death was 2.86 years (95% CI 2.67–3.09). Shorter PSA doubling time (≤ 10 months, versus > 10 months) was associated with reduced time to metastases or death (2.11 years [95% CI 1.92–2.30] versus 5.22 years [95% CI 4.87–5.51]). Age was not significantly associated with time to metastases/death. Our findings highlight key clinical characteristics and outcomes for patients with nmCRPC prior to the introduction of recently approved treatments.