Low Prostate-specific Antigen Levels Research Articles

A Case of Granulocyte Colony-Stimulating Factor-Related Aortitis that Developed during the Treatment of Advanced Prostate Cancer with Neuroendocrine Differentiation

An 81-year-old man with prostate cancer (cT3aN0M0), who had been undergoing hormonal therapy for 4 years and had maintained low prostate specific antigen levels, developed metastasized pelvic lymph nodes. A tissue biopsy revealed neuroendocrine differentiation of prostate cancer in the metastatic lymph nodes. Consequently, chemotherapy with carboplatin＋etoposide was initiated. During the first course, filgrastim was administered for 2 days due to a drop in his neutrophil count to 230/μl. During the second course, pegfilgrastim was administered as prophylaxis on day 4. However, on day 10 of the second course, he started to develop a fever and fatigue. Suspecting infection, antibiotics were administered, but failed to ameliorate his symptoms. On day 14, plain computed tomography revealed signs of aortic inflammation. Given the lack of improvement even after one week of antibiotic therapy, steroid treatment was initiated on the suspicion of granulocyte colony-stimulating factor (G-CSF) -induced aortitis, which rapidly improved his symptoms. Therefore, when encountering a case in which a fever remains unresponsive to antibiotics during chemotherapy with G-CSF agents, a differential diagnosis of aortic inflammation caused by G-CSF agents needs to be considered.

Biochemical Response of

BackgroundIn a subset of patients with oligorecurrent prostate cancer (PCa), salvage surgery with prostate-specific membrane antigen (PSMA) radioguided surgery (PSMA-RGS) seems to be of value. ObjectiveTo evaluate whether a lower level of postoperative prostate-specific antigen (PSA; <0.1 ng/ml) is predictive of therapy-free survival (TFS) following salvage PSMA-RGS. Design, setting, and participantsThis cohort study evaluated patients with biochemical recurrence after radical prostatectomy and oligorecurrent PCa on PSMA positron emission tomography treated with PSMA-RGS in three tertiary care centers (2014–2022). InterventionPSMA-RGS. Outcome measurements and statistical analysisPostsalvage surgery PSA response was categorized as <0.1, 0.1–<0.2, or >0.2 ng/ml. Kaplan-Meier and multivariable Cox regression models evaluated TFS according to PSA response. Results and limitationsAmong 553 patients assessed, 522 (94%) had metastatic soft tissue lesions removed during PSMA-RGS. At 2–16 wk after PSMA-RGS, 192, 62, and 190 patients achieved PSA levels of <0.1, 0.1–<0.2, and >0.2 ng/ml, respectively. At 2 yr of follow-up, TFS rate was 81.1% versus 56.1% versus 43.1% (p < 0.001) for patients with PSA <0.1 versus 0.1–<0.2 versus >0.2 ng/ml. In multivariable analyses, PSA levels of 0.1–0.2 ng/ml (hazard ratio [HR]: 1.9, confidence interval [CI]: 1.1–3.1) and ≥0.2 ng/ml (HR: 3.2, CI: 2.2–4.6, p < 0.001) independently predicted the need for additional therapy after PSMA-RGS. The main limitation is the lack of a control group. ConclusionsFor patients after salvage PSMA-RGS, a lower biochemical response (PSA <0.1 ng/ml) seems to predict longer TFS. This insight may help in counseling patients postoperatively as well as guiding the timely selection of additional therapy. Patient summaryWe studied what happened to prostate cancer patients in three European centers who had salvage surgery using a special method called prostate-specific membrane antigen–targeted radioguidance. We found that patients who had low prostate-specific antigen levels soon after surgery were less likely to need further treatment for a longer time.

Abstract 2824: Establishing prostate cancer models for orthotopic and bone metastatic growth using the 22Rv1cell line

Abstract Prostate cancer is the second most common cancer in men with new cases diagnosed in 1.4 million men each year. Luckily the 5-year survival rates in developed countries are high reaching over 90%. However, approximately one third will develop a metastatic disease. In metastatic patients, prostate cancer almost always progresses despite the androgen deprivation therapy and is then referred to as “castration-resistant (mCRPC)”. Bone is involved in 80% of patients with metastasis, and the bone lesions are typically osteoblastic. The 22Rv1 human prostate carcinoma cell line is androgen sensitive and shown to express androgen receptor (AR). They also express low levels of prostate-specific membrane antigen (PSMA). The aim of this study was to establish orthotopic and intratibial preclinical in vivo prostate cancer models that can be used in drug development when targeting cancer cells and their local environment. Male athymic nude mice (5-6 weeks old) and NOG mice (over 20 weeks old) were used in the study. 2.5 × 105 22Rv1 cells (ATCC) were inoculated orthotopically into the prostate of NOG mice, and 5 × 105 cells were inoculated intratibially into the bone marrow cavity of athymic nude mice. Tumor growth was followed by PSA measurements every second week using Human PSA ELISA assay. In addition, in the intratibial model, tumor-induced bone changes were monitored by X-ray imaging of the hind limbs. Prostates and hind limbs were collected at sacrifice, fixed in 10% NBF, and processed to paraffin blocks for further histological analysis. Sections of prostate were stained with hematoxylin-eosin (HE) and AR. Tumor-bearing and contralateral (healthy) tibias were stained with HE - OrangeG, MGT, TRAP, and AR. The observed tumor take rate was 92% in the orthotopic and 100% in the intratibial models. Confirmed by IHC, tumors formed in both the orthotopic and intratibial models expressed AR. 22Rv1 cells formed osteoblastic - lytic mixed bone lesions in the intratibial model. Based on lesion areas, randomization of the tumor bearing mice in the intratibial model can be done after 2 weeks from cancer cell inoculation. Taken together, the 22Rv1 prostate cancer models are relatively fast growing, express AR and present good take rates. Furthermore, the intratibial model represents robust tumor-induced changes in bone with strong osteoblastic component. Thus, these models have several advantages in efficacy studies of novel drug candidates for prostate cancer. Citation Format: Justyna Zdrojewska, Katja Fagerlund, Jenni H. Mäki-Jouppila, Mari I. Suominen. Establishing prostate cancer models for orthotopic and bone metastatic growth using the 22Rv1cell line [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2824.

Three- and Seven-month Prostate-specific Antigen Levels as Prognostic Markers for Overall Survival in Metastatic Hormone-sensitive Prostate Cancer: Results from SWOG S1216, a Phase 3 Randomized Trial of Androgen Deprivation Plus Orteronel or Bicalutamide

BackgroundA robust decrease in prostate-specific antigen (PSA) in response to androgen deprivation therapy (ADT) has been evaluated as a prognostic factor in patients with metastatic hormone-sensitive prostate cancer (mHSPC) since 2006, but the treatment of mHSPC has since evolved to include intensified therapy. ObjectiveWe assessed the association of PSA levels at 3 (PSA-3mo) and 7 (PSA-7mo) mo with overall survival (OS) in patients with mHSPC treated with ADT combined with either bicalutamide or orteronel in the S1216 phase 3 clinical trial. Design, setting, and participantsPSA responses to treatment of patients in the S1216 trial were categorized as: complete response (CR) if PSA was ≤0.2 ng/ml, partial response if PSA was >0.2 and ≤4 ng/ml, and no response (NR) if PSA was >4 ng/ml. Outcome measurements and statistical analysisA Cox analysis (adjusted for treatment arm and three stratification factors: performance status, severity of disease, and early vs late induction) was used for OS association. While PSA-7mo association was a prespecified objective, PSA-3mo association was also evaluated. Results and limitationsA total of 1251 and 1231 patients from the S1216 study were evaluable for PSA-3mo and PSA-7mo, respectively. A PSA-7mo CR was associated with improved OS compared with NR (HR: 0.20; p < 0.0001). A PSA-3mo CR showed a similar association to NR (HR: 0.34; p < 0.0001). The association of a PSA response with survival did not differ by treatment arm at either time point. ConclusionsThe PSA-3mo and PSA-7mo responses were strongly associated with OS; taken with other emerging prognostic biomarkers, these markers may allow for early identification of patients at the highest risk of death, aid with counseling in clinical practice, and permit design of future clinical trials targeting these patients. Patient summaryA low prostate-specific antigen level at 3 or 7 mo after starting treatment for metastatic hormone-sensitive prostate cancer predicts longer survival regardless of the first treatment given with androgen deprivation therapy.

Mortality Risk for Docetaxel-Treated, High-Grade Prostate Cancer With Low PSA Levels

Patients with high-grade prostate cancer with low levels of prostate-specific antigen (PSA; <4 ng/mL) are at high risk of mortality, necessitating an improved treatment paradigm. To assess for these patients whether adding docetaxel to standard of care (SOC) treatment is associated with decreased prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM). PubMed search from 2000 to 2022. Five prospective randomized clinical trials (RCTs) performed in the US, France, and the United Kingdom evaluating SOC treatment with radiotherapy and androgen deprivation therapy (ADT) or with radical prostatectomy vs SOC plus docetaxel. Individual data were included from patients with nonmetastatic prostate cancer, a PSA level of less than 4 ng/mL, and a Gleason score of 8 to 10. Patients initiated treatment between February 21, 2006, and December 31, 2015 (median follow-up, 7.1 [IQR, 5.4-9.9] years). Data were analyzed on December 16, 2022. Hazard ratio (HR) of ACM and subdistribution HR (sHR) of PCSM adjusted for performance status (1 vs 0 or good health), Gleason score (9 or 10 vs 8), tumor category (T3-T4 vs T1-T2 or TX), and duration of ADT (2 years vs 4-6 months). From a cohort of 2184 patients, 145 patients (6.6%) in 4 RCTs were eligible (median age, 63 [IQR, 46-67] years). Thirty-one patients died, and of these deaths, 22 were due to prostate cancer. Performance status was 0 for 139 patients (95.9%) and 1 for 6 patients (4.1%). A reduced but nonsignificant risk of ACM (HR, 0.51 [95% CI, 0.24-1.09]) and PCSM (sHR, 0.42 [95% CI, 0.17-1.02]) was associated with patients randomized to SOC plus docetaxel compared with SOC. The risk reduction in ACM (HR, 0.46 [95% CI, 0.21-1.02]) was more pronounced among patients with a performance status of 0 and was significant for PCSM (sHR, 0.30 [95% CI, 0.11-0.86]). Adding docetaxel to SOC treatment for patients who are in otherwise good health with a PSA level of less than 4 ng/mL and a Gleason score of 8 to 10 was associated with a significant reduction in PCSM and therefore has the potential to improve prognosis.

Low PSA radiographic disease progression on C11-choline PET.

For men with prostate cancer, radiographic progression may occur without a concordant rise in prostate-specific antigen (PSA). Our study aimed to assess the prevalence of radiographic progression using C-11 choline positron emission tomography (PET) imaging in patients achieving ultra-low PSA values and to evaluate clinical outcomes in this patient population. In a single institution study, we reviewed the prospectively maintained Mayo Clinic C-11 Choline PET metastatic prostate cancer registry to identify patients experiencing radiographic disease progression (rDP) on C-11 choline PET scan while the PSA value was less than 0.5ng/mL. Disease progression was confirmed by tissue biopsy or response to subsequent therapy. Clinicopathologic variables were abstracted by trained research personnel. Overall survival was estimated using the Kaplan-Meier method. Intergroup differences were assessed using the log-rank test. A univariate and multivariate Cox regression model was performed to investigate variables associated with poor survival after rDP. A total of 1323 patients within the registry experienced rDP between 2011 and 2021, including 220 (16.6%) men with rDP occurring at low PSA level. A median (interquartile range [IQR]) of 54.7 (19.7-106.9) months elapsed between the time of prostate cancer diagnosis and low PSA rDP, during which 173 patients (78%) developed castration-resistant prostate cancer (CRPC). Sites of low PSA rDP included local recurrence (n = 17, 8%), lymph node (n = 90, 41%), bone (n = 94, 43%) and visceral metastases (n = 19, 9%). Biopsy at the time of rDP demonstrated small-cell or neuroendocrine features in 21% of patients with available tissue. Over a median (IQR) follow-up of 49.4 (21.3-95.1) months from the time of low PSA rDP, 46% (n = 102) of patients died. Factors associated with poorer survival outcomes include advanced age at rDP, CRPC status, bone and visceral metastasis (p value <0.05). Visceral metastases were associated with decreased overall survival (p = 0.009 by log-rank) as compared with other sites of rDP. Men with prostate cancer commonly experience metastatic progression at very low or even undetectable PSA levels. Periodic imaging, even at low absolute PSA values, may result in more timely identification of disease progression.

Diagnostic Performance of PSMA-Based 18F-DCFPyL PET/CT in Prostate Cancer Patients After Definitive Treatment With PSA Level ≤0.2 ng/mL.

The aim of this study was to investigate the role of 18F-DCFPyL PET/CT in the evaluation of prostate cancer (PC) patients after definitive treatment and with low-level prostate-specific antigen (PSA) level of ≤0.2 ng/mL. This retrospective study was conducted in PC patients who received definitive treatments with PSA level of ≤0.2 ng/mL and underwent 18F-DCFPyL PET/CT within a 1-week interval of PSA examination, and without interval treatment change or history of other cancer. Patient and tumor characteristics at initial diagnosis, treatment regimens, and findings on 18F-DCFPyL PET/CT were collected. Patients with minimal 6-month (median, 11 months; range, 6-21 months) follow-up or definitive biopsy results of the suspected PET/CT findings were included. Imagine findings were reached with consensus among experienced board-certified nuclear medicine physicians. Comprehensive follow-up and/or biopsy results were used as definitive determination of presence or absence of disease. Comparisons between groups of positive and negative 18F-DCFPyL PET/CT were done by using descriptive statistics. A total of 96 18F-DCFPyL PET/CTs from 93 patients met the inclusion criteria. The median Gleason score (GS) of positive group is 8 (range, 6-10), whereas negative group is 7 (range, 6-10). The median age of positive group is 71 (range, 50-90), whereas negative group is 69 (range, 45-88). There were 49 positive (51%) and 47 negative 18F-DCFPyL PET/CTs (49%). Detection rates at PSA level of ≤0.1 and 0.2 ng/mL were 58.7% (27/46) and 44% (22/50), respectively. The scan-based sensitivity, specificity, positive predictive value, and negative predictive value are 100%, 95%, 96%, and 100% in group with PSA level of ≤0.1 ng/mL, and 100%, 97%, 95%, and 100% in group with PSA level of 0.2 ng/mL, respectively. Sites of involvement on positive 18F-DCFPyL PET/CTs were prostate bed, pelvic lymph nodes, bone, chest and supraclavicular lymph nodes, lung, and adrenal glands. The SUVmax value on positive lesions ranged from 1.9 to 141.4; the smallest positive lymph node was 0.4 cm. High GS of 8-10, known metastatic status (M1), presence of extraprostatic extension, presence of seminal vesicle invasion, and very high-risk PC are significantly associated with positive 18F-DCFPyL PET/CT results (P < 0.05). Of all analyzed treatment regimes, upfront surgery (radical prostatectomy with or without pelvic lymph node dissection) had strong correlation with negative PET/CT results (P < 0.001). If patients received ADT only, or ADT plus chemotherapy, the PET/CT results were most likely positive (P = 0.026). For other treatment regimes, there were no statistical differences between the groups (P > 0.05). In the presence of low PSA level in PC patients after definitive treatment, 18F-DCFPyL PET/CT is most beneficial in detection of disease in patients with GS of 8 or higher at the time of diagnosis, and the ones who have history of ADT only, or ADT plus chemotherapy. There is excellent negative prediction value of 18F-DCFPyL PET/CT. However, there is no cutoff PSA level for 18F-DCFPyL PET/CT indication and no correlation between PSA level and SUVmax of positive lesions on 18F-DCFPyL PET/CT.

A-035 Association between Obesity and Prostate Specific Antigen level in Diabetes Mellitus Type2

Abstract Background Body mass index (BMI) is a simple index commonly used to classify obesity. It is defined as a person’s weight(kg) divided by the square of his height (m). An inverse relationship between obesity and prostate-specific antigen (PSA) has been reported by previous studies with lower PSA levels found in groups with a higher body mass index (BMI). The main objective of this current study is to assess the association between body mass index (BMI) and PSA in male patients with diabetes mellitus. Methods This study uses a case-control experimental procedure to assess adult men between 40–75 years old, attending University of Nigeria Teaching Hospital, Enugu State, Nigeria. Eighty-six (86) of the volunteers recruited for this study were patients diagnosed with type II diabetes, and sixty (60) others were non-diabetic patients used as controls. Consent was sorted from these patients, and a questionnaire was given to the participants in which data about their age, family history of diabetes, and prostate condition was collected. Their hospital folders were used to confirm their diabetic status and prostate gland health. Body Mass Index (BMI) was calculated after measuring weight (kg) and height(m). Blood samples were assayed to determine the fasting blood sugar (FBS) using Glucose Oxidase enzymatic method, and total prostate-specific antigen (tPSA) concentration was determined using Enzyme-Linked Immunosorbent Assay (ELISA). The Body mass index (BMI), as a “gold standard” approach for obesity classification, was used to group the patients as; underweight (below 18.5), normal weight (18.5–24.9), pre-obesity (25.0–29.9), obesity class I (30–34.9), obesity class II (35.0–34.9), and obesity class III (40 and above). The Statistical Package for Social Sciences (SPSS) version 22.0 was used to analyze data generated and compared between groups using student T-test. Statistical difference was at a P value of 0.05 or higher. Results The result of this study demonstrated a significant difference in the BMI of diabetic men (test) and non-diabetic men (control). Moreso, lower tPSA was observed in obese men compared to normal BMI in both test and control. Hemodilution caused by elevated plasma volume, which may reduce serum concentration of soluble tumor markers, may be responsible for lower PSA levels in obese men. Conclusion Obesity may hinder the ability to detect prostate cancer at an earlier stage. Therefore, BMI should be considered while determining a PSA threshold for prostate disorders screening.

Prostate-specific membrane antigen positron emission tomography detected local failure after post-prostatectomy radiation therapy: Low rates of out-of-field recurrence validates current Australian prostate bed contouring guidelines.

The Australian Faculty of Radiation Oncology Genitourinary Group (FROGG) developed prostate bed clinical target volume (CTV) contouring guidelines which were subsequently used to develop the National EviQ guidelines for adjuvant and salvage post-prostatectomy radiotherapy (PPRT). These guidelines were based mainly upon consensus agreement. With the advent of prostate-specific membrane antigen (PSMA) positron emission tomography (PET), sites of recurrence can now be detected with low prostate-specific antigen (PSA) levels following radical prostatectomy. We evaluated sites of recurrence in patients treated with FROGG/EviQ CTVs to inform upcoming modifications of these guidelines. At our institution, we use the FROGG/EviQ guidelines for PPRT. From 2015, patients with PSA failure following PPRT have been re-staged using PSMA PET imaging. We identified patients with PET-avid local, nodal, and distant recurrences, fusing them with original treatment plans to determine whether recurrences were within or outside the prostate bed CTV. Regional nodal failures were reviewed to determine if they were within current elective node contouring guidelines. Ninety-four patients had positive PSMA PET following PPRT. Nine (9.6%) recurrences were local, seven being local-only. One local recurrence (1.1%) was just superior to the contoured prostate bed CTV, located within the vas deferens. Seventy-three (77.7%) patients had a component of node failure, with 56 (59.6%) having node-only failure. Sites of nodal relapses were covered by standard contouring guidelines 60.3% of the time. The low recurrence rate outside of current prostate bed CTV contouring guidelines is consistent with other studies using contemporary contouring, and validates the efficacy of the current FROGG/EviQ prostate bed CTV definition.

Association of TyG index with prostate-specific antigen (PSA) in American men: results from NHANES, 2003–2010

BackgroundIn recent years, triglyceride-glucose index (TyG) was a new indicator of insulin resistance, and it has been widely reported that it may be associated with serum prostate-specific antigen (PSA) concentrations.AimsWe intended to investigate the possible connection between serum PSA concentration and the TyG index.MethodsThis is a cross-sectional study of adults with complete data on TyG and serum PSA concentrations (ng/ml) from the NHANES, 2003–2010. The TyG index is obtained by the formula below: TyG = Ln [triglycerides (mg/dL) × fasting glucose(mg/dL)/2]. Multivariate regression analysis and subgroup analysis were used to examine the connection between the TyG index and serum PSA levels.ResultsMultiple regression analysis of the weighted linear model showed that individuals with a higher TyG index had lower PSA levels. Subgroup analyses and interaction tests showed no apparent dependence on age, race/ethnicity, BMI, household income ratio, education level, and marital status on this negative association (all interactions p > 0.05).ConclusionsTyG index is related to lower serum PSA concentrations in adult men from the USA. Further comprehensive prospective studies are needed to confirm our findings.

Diagnosis of high-grade prostate cancer in patients with unexpectedly low prostate specific antigen levels: a rare case series

Link of Video Abstract: https://youtu.be/PfhZ7H4kszQ Background: Prostate cancer is regarded as one of the most common leading causes of male cancer-related death worldwide. Clinicians agree that prostate specific antigen (PSA) is the best prostate cancer predictor. High PSA levels increase prostate cancer risk in most men. However, other research suggests that prostate cancer with low PSA levels is aggressive. In this uncommon case series, we present three high-grade prostate cancer patients with low PSA. Case Description: Between 2018 and 2019, three patients were referred for further therapeutic management after initial evaluation and treatment from secondary hospitals. All patients underwent complete diagnostic procedures including Laboratory examination, Pathological examination, and Radiologic imaging. PSA levels were 0.67 ng/mL, 4.0 ng/ml, and 4.93 ng/mL in the first, second, and third patients, respectively. The first two of three patients had a Gleason score (GS) of 9 (5+4), and one patient presented with GS of 8 (5+3). Distant metastatic disease was not found in our series. All of the patients underwent hormonal therapy, and none of them underwent radical prostatectomy. Follow-ups were completed in all patients, with the survival of 3 months, 4 months, and 12 months respectively. Conclusion: High-grade prostate cancer in patients with low PSA levels emphasizes the need for rigorous history taking and physical examination and quick investigation of new biomarkers and criteria for prostate cancer detection. These patients' prognosis and optimal therapy are unknown. These patients have a worse prognosis than those with high PSA values, according to multiple studies.

Choline PET/CT in recurrent prostate cancer.

Biochemical recurrence (BR) occurs in up to 40% of patients with prostate cancer (PCa) treated with primary radical prostatectomy (RP). Choline PET/CT may show, in a single-step examination, the site of tumor recurrence earlier than traditional imaging methods, particularly at low prostate-specific antigen (PSA) levels, thus influencing subsequent treatment. Patients with recurrent and non-metastatic prostate cancer (nmPCa), who were assessed with choline PET/CT, were included in the analysis. Based on imaging results, the following therapeutic strategies were chosen: radiotherapy to the prostatic bed, androgen deprivation therapy (ADT), and chemotherapy or stereotactic body radiotherapy (SBRT) to either the pelvic lymph nodes or distant metastases. We assessed the impact of age, PSA levels, Gleason score (GS), and adjuvant therapy on oncological outcomes. Data from 410 consecutive nmPCa patients with BR who underwent RP as primary treatment were analyzed. One hundred seventy-six (42.9%) patients had a negative choline PET/CT, and 234 (57.1%) patients resulted positive. In the multivariate analysis, only chemotherapy and PSA at recurrence were significant independent prognostic factors on overall survival (OS). In the PET-positive subgroup, the number of relapses, PSA post-prostatectomy, and chemotherapy impacted on OS. PSA (post-surgery and at recurrence) affected progression-free survival (PFS) in the univariate analysis. In the multivariate analysis, GS, the number of relapse sites, and PSA (post-surgery and at recurrence) were significant prognostic factors for disease-free survival (DFS). Choline PET/CT provides better accuracy than conventional imaging for the assessment of nmPCa with BR after prostatectomy, thereby enabling salvage strategies and improving quality of life.

Intravesical Injection of Botulinum Toxin Type A in Men without Bladder Outlet Obstruction and Post-Deobstructive Prostate Surgery.

A significant proportion of men without bladder outlet obstruction (BOO) have been reported to have overactive bladders (OAB). This article aimed to review the specific group of reports on the use of botulinum toxin type A (BTX-A) injections into the bladder wall. Original articles reporting men with small prostates without BOO were identified through a literature search using the PubMed and EMBASE databases. Finally, we included 18 articles that reviewed the efficacy and adverse effects of BTX-A injections in men. Of the 18 articles screened, 13 demonstrated the therapeutic efficacy and adverse effects of BTX-A injections in men. Three studies compared BTX-A injection response between patients without prior prostate surgery and those undergoing prior prostate surgery, including transurethral resection of the prostate and radical prostatectomy (RP). Patients with prior RP experienced better efficacy and had a low risk of side effects. Two studies focused on patients who had undergone prior surgery for stress urinary incontinence, including male sling and artificial urethral sphincter surgery. The BTX-A injection was a safe and effective procedure for this specific group. OAB in men was found to have a different pathophysiology mechanism from that in female patients, which may decrease the efficacy of BTX-A injection in men. However, patients with small prostates and low prostate-specific antigen levels demonstrated better efficacy and tolerability after BTX-A injection. Although intravesical injection of BTX-A was a good option for controlling refractory OAB in men, the evidence-based guidelines are still limited. Further research is necessary to better understand the role of BTX-A injections on various aspects and histories. Therefore, treating patients using strategies tailored to their individual conditions is important.

Clinical practice in prostate PET imaging.

Positron emission tomography (PET) imaging in prostate cancer has advanced significantly in the past decade with prostate cancer targeted radiopharmaceuticals now playing a growing role in diagnosis, staging, and treatment. This narrative review focuses on the most commonly used PET radiopharmaceuticals in the USA: prostate-specific membrane antigen (PSMA), fluciclovine, and choline. 18F-fluorodeoxyglucose (FDG) is used in many other malignancies, but rarely in prostate cancer. Previous literature is discussed regarding each radiopharmaceutical's utility in the settings of screening/diagnosis, initial staging, biochemical recurrence, advanced disease, and evaluation prior to targeted radiopharmaceutical therapy and radiation therapy. PET imaging has demonstrated utility over traditional imaging in various scenarios; however, there are few head-to-head studies comparing PET radiopharmaceuticals. PSMA radiopharmaceuticals are the newest tracers developed and have unique properties and uses, especially at low prostate-specific antigen (PSA) levels. However, each PET radiopharmaceutical has different properties which can affect image interpretation. Choline and fluciclovine have minimal urinary activity, whereas PSMA agents can have high urinary activity which may affect locoregional disease evaluation. Of the three radiopharmaceuticals, only PSMA is approved for both diagnostic and therapeutic indications with 177Lu-PSMA. A variety of diagnostic PET radiotracers for prostate cancer allows for increased flexibility, especially in the setting of supply chain and medication shortages. For the time being, keeping a diverse group of PET radiopharmaceuticals for prostate cancer is justifiable.

The impact of salvage radiotherapy initiation at PSA ≤ 0.5 ng/mlon metastasis-free survival in patients with relapsed prostate cancer following prostatectomy.

Salvage radiation therapy (SRT) is indicated for biochemical failure after radical prostatectomy. Prior data have shown that initiation of SRT at lower PSA levels improves subsequent biochemical control, yet given the long natural history of prostate cancer questions remain regarding optimal timing of SRT. We analyzed the impact of prostate specific antigen (PSA) level at time of salvage radiotherapy with regard to both biochemical relapse-free (bRFS) as well as metastasis-free survival (MFS) in patients with biochemically recurrent prostate cancer. Using prospective institutional tumor registry data, univariate and multivariable-adjusted Cox proportional hazards models were constructed to assess association between outcomes and clinical and pathologic prognostic features, including pre-SRT PSA, interval from prostatectomy to SRT, androgen deprivation therapy (ADT), and adverse pathologic features. We identified 397 patients who received salvage RT between 1985 and 2016: 187 (45.8%) received SRT initiated when pre-RT PSA was ≤0.5 ng/ml; 212 (52.0%) patients had pre-SRT PSA > 0.5 ng/ml. Independent of pathologic risk status and ADT use, pre-SRT PSA ≤ 0.5 ng/mlwas the most significant predictor of bRFS (HR 0.39, 95% CI [0.27, 0.56]) as well as MFS (HR = 0.58, 95% CI [0.37, 0.91]). Seminal vesicle invasion was also associated with shorter interval to biochemical failure, HR = 1.79, 95% CI [1.07, 2.98], and eventual metastases, HR = 2.07, 95% CI [1.14, 3.740]. Initiation of salvage RT while PSA levels remain ≤0.5 ng/ml was associated with improved MFS. Consideration for salvage RT initiation while PSA levels remain low is warranted to minimize risk of future prostate cancer metastasis.

1398P Overall survival (OS) in patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC) who received prior androgen deprivation therapy (ADT) and reached low prostate-specific antigen (PSA) levels treated further with enzalutamide (ENZA): Post hoc analyses of ARCHES

In the phase 3 ARCHES trial, >90% of men with mHSPC received prior ADT and achieved a range of PSA values (≤0.2, >0.2−4, and >4 μg/L) before randomization. This post hoc analysis examined the effect of treatment intensification with ENZA + ADT versus continuing ADT alone on OS and other efficacy outcomes by baseline PSA categories.

Machine learning model for the prediction of prostate cancer in patients with low prostate-specific antigen levels: A multicenter retrospective analysis.

ObjectiveThe aim of this study was to develop a predictive model to improve the accuracy of prostate cancer (PCa) detection in patients with prostate specific antigen (PSA) levels ≤20 ng/mL at the initial puncture biopsy.MethodsA total of 146 patients (46 with Pca, 31.5%) with PSA ≤20 ng/mL who had undergone transrectal ultrasound-guided 12+X prostate puncture biopsy with clear pathological results at the First Affiliated Hospital of Guangxi Medical University (November 2015 to December 2021) were retrospectively evaluated. The validation group was 116 patients drawn from Changhai Hospital(52 with Pca, 44.8%). Age, body mass index (BMI), serum PSA, PSA-derived indices, several peripheral blood biomarkers, and ultrasound findings were considered as predictive factors and were analyzed by logistic regression. Significant predictors (P < 0.05) were included in five machine learning algorithm models. The performance of the models was evaluated by receiver operating characteristic curves. Decision curve analysis (DCA) was performed to estimate the clinical utility of the models. Ten-fold cross-validation was applied in the training process.ResultsProstate-specific antigen density, alanine transaminase-to-aspartate transaminase ratio, BMI, and urine red blood cell levels were identified as independent predictors for the differential diagnosis of PCa according to multivariate logistic regression analysis. The RandomForest model exhibited the best predictive performance and had the highest net benefit when compared with the other algorithms, with an area under the curve of 0.871. In addition, DCA had the highest net benefit across the whole range of cut-off points examined.ConclusionThe RandomForest-based model generated showed good prediction ability for the risk of PCa. Thus, this model could help urologists in the treatment decision-making process.

Event-free survival after radical prostatectomy according to prostate-specific membrane antigen-positron emission tomography and European Association of Urology biochemical recurrence risk groups.

To assess European Association of Urology (EAU) risk groups for biochemical recurrence (BCR) of prostate cancer relative to prostate-specific membrane antigen-positron emission tomography (PSMA-PET) status and oncological outcomes. A retrospective analysis of a study that incorporated PSMA-PET for men with BCR after radical prostatectomy (RP) was undertaken. EAU risk groups were considered relative to clinical variables, PSMA-PET findings, and deployment of salvage radiotherapy (SRT). The primary oncological outcome was event-free survival (EFS) and this was analysed relative to clinical and imaging variables. An 'event' occurred if prostate-specific antigen (PSA) level rose >0.2 ng/mL above nadir or additional therapies were introduced. A total of 137 patients were included, most of whom had EAU high-risk disease (76%) and/or low PSA levels (80% <0.5 ng/mL) at the time of PSMA-PET. EAU risk group was not associated with regional nodal/distant metastasis on PSMA-PET. Regional nodal/distant metastasis on PSMA PET (compared to negative/local recurrence: hazard ratio [HR] 2.2; P = 0.002) and SRT use (vs no SRT: HR 0.44; P = 0.004) were associated with EFS. EAU high-risk status was not significantly associated with worse EFS (HR 1.7, P = 0.12) compared to EAU low-risk status. Among patients who received SRT, both regional/distant metastasis on PSMA-PET (HR 3.1; P < 0.001) and EAU high-risk status (HR 2.9; P = 0.04) were independently associated with worse EFS, which was driven by patients in the EAU high-risk group with regional/distant metastases (38%; HR 3.1, P = 0.001). In patients with post-RP BCR, PSMA-PET findings and receipt of SRT predicted EFS. In patients receiving SRT, PSMA status combined with EAU risk grouping was most predictive of EFS. These findings suggest that the EAU risk groups could be improved with the addition of PSMA-PET.

Association between obesity and frequency of high-grade prostate cancer on biopsy in men: A single-center retrospective study.

The present study aimed to investigate the relationship between BMI and the prostate cancer (PCa) risk at biopsy in Italian men. Retrospective analyses of the clinical data of 2,372 consecutive men undergoing ultrasound-guided multicore (≥10) prostate biopsy transrectally between May 2010 and December 2018 were performed. BMIs were categorized, according to Western countries' classification of obesity, as follows: <18.5 kg/m2 (underweight), 18.5-24.99 kg/m2 (normal weight), 25-30 kg/m2 (overweight) and >30 kg/m2 (obese). The distribution of patients undergoing biopsy was compared with a model population from the official survey data. Patient characteristics and the relationships between characteristics were investigated using correlation analysis, ANOVA, Kruskal-Wallis and Dunn's tests. The present study estimated the influence on cancer incidence not only of BMI but also of other patient characteristics using multi-variable logistic modelling and compared, using the models, the expected outcomes for patients who differed only in BMI. From a sample of 2,372 men, the present study enrolled 1,079 men due to a lack of clinical data [such as prostate specific antigen (PSA) and BMI data] in the other patients undergoing prostate biopsy. Their distribution was significantly different from the model distribution with the probability of undergoing biopsy increasing with increasing BMI. The median age was 69.4 years. The median BMI was 26.4 kg/m2, while the median PSA level was 7.60 ng/ml. In total, the biopsies detected PCa in 320 men (29.7%) and high-grade PCa (HGPCa) in 218 men (20.2%). Upon applying the aforementioned Western countries' criteria for BMI categories, there were 4 (0.4%) underweight, 318 (29.5%) of normal weight, 546 (50.6%) overweight, and 211 (19.6%) obese patients. ANOVA/Kruskal-Wallis tests revealed that overweight and obese men were younger than the normal-weight men, while there was no statistical difference in their PSA values. Furthermore, 29.3% of normal-weight men, 29.5% of overweight men and 29.9% of obese men were diagnosed with PCa, while 19.5% of normal-weight men, 20.1% of overweight men and 21.8% of obese men were affected by severe cancer. BMI was found to be positively correlated with PCa risk and negatively correlated with both age and PSA level. Age and PSA level were both positively correlated with PCa risk, while digital rectal examination (DRE) outcome was strongly indicative of PCa discovery if the test outcome was positive. Logistics models attributed a positive coefficient to BMI when evaluated against both PCa risk and HGPCa risk. In patients having a negative DRE outcome who differed only in BMI, logistic regression showed a 60% increased risk of PCa diagnosis in obese patients compared with in normal-weight patients. This risk difference increased when other characteristics were less indicative of PCa (younger age/lower PSA), while it decreased when patient characteristics were more indicative (older age/higher PSA, positive DRE). In conclusion, the present study demonstrated that, in men with higher BMIs, the risk of PCa is higher. The relative difference in risk between low and high BMI is most pronounced in younger patients having a lower PSA level and a negative DRE outcome.

Diagnostic performance of positron emission tomography combined with computed tomography with 18F-PSMA-1007 for detecting local recurrence of prostate cancer after radical prostatectomy

In the situation of biochemical recurrence (BCR) of prostate cancer (PCa) it is important to distinguish between local recurrence in the prostate bed and systemic disease progression. Conventional imaging modalities have a limited role, especially in patients with low prostate specific antigen (PSA) levels. In recent years, the role of positron emission tomography combined with computed tomography (PET/CT) with PSMA-labeled ligands has grown, but there is currently no consensus on the role and effectiveness of the method in detecting local recurrence of the disease. The aim of the study was to analyze the diagnostic performance of 18F-PSMA‐1007 PET/CT in detecting local recurrence of prostate cancer. The study included 57 patients with BCR after radical prostatectomy, who underwent PET/CT with 18F-PSMA-1007 and according to its results there were no distant and/or regional metastases. Local recurrence was clinically verified in 53 (93.0%) patients. The sensitivity of PET/CT in detecting local recurrence was 58.5 %, specificity ‒ 75.0, positive predictive value ‒ 96.9, negative predictive value ‒ 12.0 %. According to multivariate analysis, only PSA level was significantly associated with truepositive PET/CT findings (p = 0.02). According to multivariate analysis, PSA level is an independent predictive factor of 18F-PSMA‐1007 PET/CT sensitivity in detecting local recurrence (p &lt; 0.05). In the subgroup of patients with a low PSA level sensitivity was only 20.0 %. Therefore, a negative PET/CT scan at PSA level &lt;0.5 ng/ml is not a reason for delay the initiation of salvage radiation therapy.