PSA Changes Research Articles

Weight Loss, Pathological Changes, and Inflammatory Effects from a Short-Term Ketogenic Diet in Overweight and Obese Men with Untreated Prostate Cancer on Active Surveillance

Background and Aims: Active Surveillance (AS) is a favored strategy for the management of indolent prostate cancers (PCs). Overweight and obese men harbor an increased risk of cancer progression during AS. We aim to prospectively evaluate the feasibility and outcomes of a ketogenic diet (KD) weight-loss intervention in overweight men with PC. Materials and Methods: Men with PC and a BMI > 25 kg/m2 undergoing AS were placed on an 8-week ad libitum KD program before a scheduled surveillance biopsy to assess the impact on clinical grade group (CGG). Blood ketone levels were tracked to ensure compliance. BMI, PSA, and inflammatory marker data (TNF-α, TNFR1, TNFR2, sICAM-1, sVCAM-1, IL-6, IL1-RA, CRP, and SAA) were collected before and after the KD intervention. A Shapiro–Wilk test was performed to assess the normality of all continuous study variables. Paired t-tests and Wilcoxon rank sum tests were utilized to compare normally and non-normally distributed study outcomes, respectively. Results: Ten AS patients aged 62.1(±5.4) years were enrolled with an average BMI of 31.7 kg/m2 (±11.8). Post-KD intervention mean blood ketone levels were 0.32 (±0.12) mmol/L with a mean BMI reduction of 7.4% (p < 0.0003). There were no meaningful changes in PSA or inflammatory biomarkers (p > 0.05). Nine patients completed re-biopsy following a KD with four patients showing no evidence of cancer; one downgraded to a lower CGG; two had unchanged CGG scores; and two had higher CGG scores compared to baseline. Conclusions: Short-term KD interventions for BMI reduction are feasible in men undergoing AS for PC and may result in favorable pathological effects without inflammatory marker changes. Larger studies with longer follow-up are needed to explore whether KD-induced weight loss can improve clinical outcomes with AS in PC.

Preliminary efficacy, tolerability, and safety analysis of Darolutamide for metastatic castration‑resistant prostate cancer: a single-center, open-label study.

Darolutamide is a structurally unique second-generation androgen receptor antagonist that has been approved for indications in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) and metastatic hormone-sensitive prostate cancer (mHSPC). The aim is to assess the efficacy and safety of Darolutamide for mCRPC. In this single-center, open-label, phase 1 study, patients with previously untreated mCRPC were enrolled and received androgen deprivation therapy (ADT, goserelin acetate 3.6 mg every 28 days) and docetaxel (75 mg per square meter of body surface area every 21 days) with Denosumab (120 mg every 28 days) for bone metastases, Darolutamide (300 mg orally twice daily) in the experimental group, and the control group received the corresponding of placebo. Serum PSA changes were detected and recorded, and imaging changes and adverse events (AEs) were evaluated. The primary endpoints were the safety, tolerability, and antitumor efficacy and the second endpoint was the radiographic progression-free survival (rPFS). 37 patients with mCRPC were enrolled. The median time to PSA50 in the Darolutamide group was 1.5 months (95%CI 0.2619- 0.9545), significantly lower than that in the placebo group (3.0 months [95%CI 1.048- 3.818], p= 0.0259); The median time to PSA90 in the experimental group was 4 months (95%CI 0.3094- 1.437), 2 months shorter than that in the placebo group (6.0 months [95%CI 0.6961- 3.232]).With the median follow-up of 6 months, , the median decrease in serum PSA was -81.8% (range -60.4 to -99.9%) in the Darolutamide group and -69.4% (range -50.3 to -89.6%) in the placebo group. Tumor-related pain and AEs were not increased and the median rPFS was not reach. The combination of Darolutamide and docetaxel was well tolerated with more clinically beneficial than docetaxel alone in previously untreated mCRPC. Darolutamide rapidly reduced PSA levels and prolonged rPFS, and did not increase the incidence of AEs.

The Neutrophil-to-Lymphocyte Ratio as a Biomarker in Metastatic Castrate-Sensitive Prostate Cancer Patients Treated with Abiraterone Acetate

Given its known prognostic role, we aimed to investigate the role of neutrophil–lymphocyte ratio (NLR) as a biomarker in metastatic castration-resistant prostate cancer (mCRPC) patients receiving ADT, either as monotherapy or in conjunction with abiraterone acetate (AA) and prednisone. This retrospective cohort study analyzed the LATITUDE study of men with high-risk mCSPC. Patients were assigned to receive either AA, prednisone, and androgen deprivation therapy (ADT) or placebo plus ADT. Using a previously established NLR threshold of 2.5, we evaluated if this could predict clinical response to abiraterone. At baseline, there were no significant differences in NLR values between the treatment groups. Of the known baseline prognostic factors, NLR was associated with albumin levels and Eastern Cooperative Oncology Group performance scores. Moreover, the number of bone metastases was higher in patients with NLR ≥ 2.5. On multivariable analysis, baseline NLR ≥ 2.5 did not predict overall survival, PSA progression-free, or metastasis-free survival. However, changes in PSA and NLR at six months indicated distinct survival patterns between the placebo and AA groups, suggesting the potential for their combined assessment as a prognostic tool. Baseline NLR was not an independent predictor factor for response to AA in the LATITUDE study, though NLR changes at 6 months may predict better survival beyond PSA values alone. Further research is required to better understand in which patients with advanced prostate cancer NLR changes may be a useful prognostic tool.

PSMA-PET/CT response after metastasis-directed radiotherapy of bone oligometastases in prostate cancer

ObjectiveBone metastases are very common in advanced prostate cancer and can sensitively be detected utilizing PSMA-PET/CT. Therefore, our goal was to evaluate the suitability of PSMA-PET/CT-guided metastasis-directed external beam radiotherapy (MDT) as treatment option for patients with biochemical recurrence and oligometastatic bone lesions.Materials & methodsWe retrospectively examined 32 prostate cancer patients with biochemical recurrence and PSMA-positive oligometastatic disease limited to the bone (n = 1–3). A total of 49 bone lesions were treated with MDT. All patients received a post-radiotherapy PSMA-PET/CT-Scan. Changes in SUVmax, PSMA-positive tumor volume per lesion and PSA, as well as the correlation between the PET/CT-interval and SUVmax response were calculated.ResultsMDT lead to a SUVmax decrease in 46/49 (94%) of the lesions. The median relative decline of SUVmax was 60.4%, respectively. Based on PSMA-positive lesion volume with a SUV cut-off of 4, 46/49 (94%) of lesions showed complete response, two (4%) partial response and one lesion (2%) was stable on PSMA-PET/CT after MDT. Most of the treated patients (56.3%) showed an initial PSA decline at three months and a PSA nadir of median 0.14 ng/ml after a median time of 3.6 months after MDT. The median relative PSA change at three months after MDT was 3.9%.ConclusionMDT is a very effective treatment modality for prostate cancer bone oligometastases and lesion response to MDT can be assessed using the (semi-)quantitative parameters SUVmax and PSMA-positive lesion volume with established SUV cut-offs.

Impact of definitive radiotherapy on metabolic response measured with 68Ga-PSMA-PET/CT in patients with intermediate-risk prostate cancer.

To assess the early metabolic response of the primary tumor using Gallium-68 (68Ga)-labeled-prostate-specific membrane antigen positron emission tomography (68Ga-PSMA-PET/CT), as well as the relationship between PSMA change in the primary tumor and PSA response after definitive radiotherapy (RT), either alone or in combination with androgen deprivation therapy (ADT) in intermediate risk prostate cancer (IR-PCa) patients. The clinical data of 71 IR-PCa patients treated with RT alone (36 patients, 50.7%) or RT and ADT (35 patients, 49.3%) were retrospectively analyzed. The difference between pre- and Posttreatment primary tumor PSMA expression and serum PSA values measured 4 months after completion of treatment were compared between treatment arms. Correlation between primary tumor metabolic response and serum PSA changes was analyzed. The median duration between pre- and Posttreatment 68Ga-PSMA-PET/CT for the entire patient population was 6.9 months (range, 5.6-8.4 months), and it was similar in both treatment arms. A decrease in primary tumor maximum standardized uptake value (SUVmax) was seen in 66 patients (93.0%), with a median value of 61.2%, which is significantly lower in patients undergoing RT alone than those undergoing RT and ADT (45.1 ± 30.6% vs. 59.1 ± 24.7%; p = 0.004). The complete metabolic response rate was significantly higher in patients undergoing RT and ADT than those treated with RT alone (40% vs. 0%; p < 0.001). Although moderate and positive correlation between pretreatment SUVmax and oosttreatment SUVmax was observed, there was no significant correlation between SUV change and PSA change. For patients treated with RT and ADT, posttreatment SUVmax was significantly lower and SUV change was significantly higher in patients with PSA nadir than in those without. Our preliminary results show that RT, with or without ADT, significantly reduces primary tumor SUVmax and serum PSA levels. Nonetheless, our findings indicate that early treatment response using 68Ga-PSMA-PET/CT is not feasible for those treated with RT alone, and it may only be useful in better distinguishing patients with and without PSA nadir for those who received both RT and ADT.

Efficacy of Palmitoylethanolamide, Epilobium and Calendula suppositories for the treatment of patients with chronic prostatitis/chronic pelvic pain syndrome type III.

The management of chronic prostatitis/ chronic pelvic pain syndrome type III (CP/CPPS) has been always considered complex due to several biopsychological factors underlying the disease. In this clinical study, we aimed to evaluate the efficacy of the treatment with Palmitoylethanolamide, Epilobium and Calendula extract in patients with CP/CPPS III. From June 2023 to July 2023, we enrolled 45 consecutive patients affected by CP/CPPS type III in three different institution. We included patients aged between 18 and 75 years with symptoms of pelvic pain for 3 months or more before the study, a total National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score ≥ 12 point and diagnosed with NIH category III, according to 4-glass test Meares-Stamey test. Patients were then allocated to receive rectal suppositories of PEA, Epilobium and Calendula, 1 suppository/ die for 1 month. All patients have been tested with standard urinalysis in order to assess urinary leukocytes (U-WBC). The primary endpoint of the study was the reduction of NIHCPSI. The secondary outcomes were the change of peak flow, post-void residual (PVR), IIEF-5, VAS score, PSA and decrease of U-WBC. A total of 45 patients concluded the study protocol. At baseline, the median age of all the patients included in the cohort was 49 years, the median PSA was 2.81 ng/ml, the median NIH-CPSI was 18.55, the median IIEF-5 was 18.27, the median U-WBC was 485.3/mmc, the median VAS score was 6.49, the median PVR was 26.5 ml and the median peak flow was 16.3 ml/s. After 1 month of therapy we observed a statistically significant improvement of NIH-CPSI, U-WBC, PSA, IIEF-5, peak flow, PVR and VAS. In this observational study, we showed the clinical efficacy of the treatment with PEA, Epilobium and Calendula, 1 suppository/die for 1 month, in patients with CP/CPPS III. The benefits of this treatment could be related to the reduction of inflammatory cells in the urine that could imply a reduction of inflammatory cytokines. These results should be confirmed in further studies with greater sample size.

Testosterone replacement therapy (TRT) in patients with locoregional prostate cancer (LPC) treated with prior androgen deprivation therapy (ADT): A single center review.

e24045 Background: In LPC, ADT may be combined with radiation therapy (RT) for 4-24 months. Post-ADT, a significant proportion of men experience prolonged hypogonadism. TRT can alleviate symptoms and improve metabolic outcomes. Contrary to longstanding concerns, there is no substantial evidence of increased prostate cancer recurrence in patients (pts) treated with single modalities (surgery or RT). However, sparse data ( &lt; 100 cases published to our knowledge) exist regarding recurrence risk of LPC with TRT after prior ADT, where baseline T levels may fall below the androgen receptor saturation point. Methods: We retrospectively abstracted clinical data from hospital records of men with stage I – IVA PC, treated with prior concurrent ADT and RT and subsequently received TRT between January 2014 and September 2023. Extracted data included demographics, cancer diagnosis/staging, ADT/TRT treatment details and PSA and clinical outcomes. The co-primary endpoints were change in PSA and incidence of PC recurrence. Results: 21 pts met criteria. Median age was 77. ISUP Grade Groups (GG) included: GG1: 2, GG2: 2, GG3: 8, GG4: 2, and GG5: 7. AJCC 8th ed. stages were: I: 2, II: 7, III: 7, IV-A: 5. The median duration of prior ADT was 8 months (IQR 5 – 17) and the median interval from RT to TRT was 19 months (IQR: 12 – 44). Prior to TRT, the median testosterone level was 30.5 ng/dL (IQR: 17-76). TRT formulations included: injection: 6, oral: 4, topical: 13. The median follow-up period from the start of TRT was 13 months, and the median duration on TRT was 10 months (IQR: 5-22). TRT was ongoing in 15 (71.4%) pts and discontinued in 6 (28.6%). Reasons for discontinuation included testosterone recovery (1), hospice (not PC related) (2), no perceived benefit (2), MD concern for PSA rise (1). After TRT, the median testosterone level was 336 ng/dL (IQR: 207-462). Median PSA pre- and post-TRT were undetectable and 0.08 ng/dL, respectively. None of the subjects experienced PC recurrence or PC-specific mortality. One pt showed PSA bounce without recurrence. Median BMI was unchanged before (28.3 kg/m2) and after (27.7 kg/m2) TRT (p = 0.48). Due to the nature of the study, quality of life measures and metabolic parameters could not be systematically abstracted. Conclusions: In men with LPC who remained hypogonadal long-term after prior ADT and RT, we found that TRT was not associated with a significant rise in median PSA and no cases of PC recurrence were documented. This included many with a history of very high-risk cancers (eg. GG ≥ 4, Stage ≥ III). This study adds to the sparse existing literature in this clinical setting and together they support the case for a prospective trial utilizing TRT in patients who remain hypogonadal after ADT and radiation.

Assessment of PSA responses and changes in the rate of tumor growth (g-rate) with immune checkpoint inhibitors in US Veterans with prostate cancer

We examined data from US Veterans with prostate cancer (PC) to assess disease response to immune checkpoint inhibitors (ICI) as monotherapy or combined with abiraterone or enzalutamide to assess ICI efficacy in the real-world. We queried the VA corporate data warehouse (CDW) to identify Veterans with a diagnosis of PC who received ICI for any malignancy and had ≥1 PSA measurement while receiving ICI. To evaluate ICI monotherapy, we restricted analysis to Veterans who had not received LHRH agonists/antagonists, PC-directed medical therapy, or radiation/extirpative surgery of the bladder/prostate within and preceding the duration of ICI administration. For ICI combination analysis, we identified Veterans who received abiraterone or enzalutamide for PC while on ICI. We calculated rates of tumor (PSA) growth (g-rates), comparing them to a 1:2 matched reference cohort. We identified 787 Veterans with PC and ≥1 PSA measurement while receiving an ICI. Median duration of ICI therapy was 155 days. 223 Veterans received ICI monotherapy, with only 17(8%) having a reduction in PSA (median decline = 43%). 12 (5%) had PSA declines >30% (PSA30) which included 6 (3%) who had PSA reductions greater than 50% (PSA50). Median g-rates for ICI plus abiraterone (n = 20) or enzalutamide (n = 31) were 0.000689/d-1 and 0.002819/d-1, respectively, and were statistically insignificant compared to g-rates of matched cohorts receiving abiraterone (g = 0.000925/d-1, P = 0.73) or enzalutamide (g = 0.001929/d-1, P = 0.58) alone. Our data align with clinical trial data in PC, demonstrating limited benefit from ICI monotherapy and predicting no survival benefit from simultaneous abiraterone or enzalutamide with an ICI using g-rate.

The effect of a fermented soy beverage among patients with localized prostate cancer prior to radical prostatectomy

BackgroundFermented soy products have shown to possess inhibitory effects on prostate cancer (PCa). We evaluated the effect of a fermented soy beverage (Q-Can®), containing medium-chain triglycerides, ketones and soy isoflavones, among men with localized PCa prior to radical prostatectomy.MethodsWe conducted a placebo-controlled, double-blind randomized trial of Q-Can®. Stratified randomization (Cancer of the Prostate Risk Assessment (CAPRA) score at diagnosis) was used to assign patients to receive Q-Can® or placebo for 2–5 weeks before RP. Primary endpoint was change in serum PSA from baseline to end-of-study. We assessed changes in other clinical and pathologic endpoints. The primary ITT analysis compared PSA at end-of-study between randomization arms using repeated measures linear mixed model incorporating baseline CAPRA risk strata.ResultsWe randomized 19 patients, 16 were eligible for analysis of the primary outcome. Mean age at enrollment was 61, 9(56.2%) were classified as low and intermediate risk, and 7(43.8%) high CAPRA risk. Among patients who received Q-Can®, mean PSA at baseline and end-of-study was 8.98(standard deviation, SD 4.07) and 8.02ng/mL(SD 3.99) compared with 8.66(SD 2.71) to 9.53ng/mL(SD 3.03), respectively, (Difference baseline – end-of-study, p = 0.36). There were no significant differences in Gleason score, clinical stage, surgical margin status, or CAPRA score between treatment arms (p > 0.05), and no significant differences between treatment arms in end-of-study or change in lipids, testosterone and FACT-P scores (p > 0.05).ConclusionsShort exposure to Q-Can® among patients with localized PCa was not associated with changes in PSA levels, PCa characteristics including grade and stage or serum testosterone. Due to early termination from inability to recruit, study power, was not achieved.

P101 Investigating the association between clinical enthesitis and central sensitisation in psoriatic arthritis

Abstract Background/Aims Psoriatic Arthritis (PsA) is an inflammatory arthritis with enthesitis as its characteristic clinical feature. Enthesitis can be clinically challenging to differentiate from the widespread pain associated with Fibromyalgia (FM), the prototype of central sensitisation (CS) present in up to 30% of PsA patients. Algometry is used in CS research to quantify pressure pain threshold (PPT), reflecting increased pain sensitivity when reduced. Ultrasound is a valuable tool to evidence entheseal inflammatory changes in PsA. This study investigates associations between CS, i.e., FM, and entheseal ultrasound outcomes to better characterise pain mechanisms in PsA enthesitis. Methods A total of 20 patients with active PsA about to start a new immunosuppressant were recruited. Ultrasound evaluation of non-dominant knee (left for all patients) using dynamic B-mode and power Doppler was performed alongside the Leeds Enthesitis Index (LEI) collection to assess enthesitis. PPT was measured with algometry at the non-dominant knee (enthesitis), trapezius and calf muscle (CS areas), and collection of the ACR 2011 FM criteria was used to determine the presence of CS. Non-dominant areas were selected because they are less likely to exhibit biomechanical ultrasound alterations; moreover, the non-dominant side is generally more sensitive than the dominant side, thus enabling more precise PPT measurements. Correlations and t-tests were used to test associations between variables collected. SPSS was used to analyse the data. Results The 30% of patients met the FM criteria and presented higher LEI scores and lower PPT evoked threshold than FM-negative patients. Total FM scores significantly correlated with LEI scores (r = 0.69, p &amp;lt; 0.001) and calf PPTs (r=-0.53, p=-0.014), but not with knee and trapezius PPTs (r=-0.49, p = 0.09; r=-0.30, p = 0.19), or US enthesitis (r=-0.04, p = 0.86). PPTs in the areas investigated did not show significant correlations with US enthesitis, while an indirect association was observed between LEI with calf PPT (r=-0.51, p = 0.02) and trapezius PPT (r=-0.41, p = 0.06). No significant correlation was demonstrated between LEI and left knee enthesitis (r=-0.32, p = 0.17). Conclusion FM is frequent in PsA and can mimic entheseal pain, as suggested by the strong correlation with the LEI scores. In our cohort, LEI scores did not efficiently capture inflammatory enthesitis, demonstrated by the lack of association with ultrasound data. Moreover, the association between objective measurement of CS, including calf and trapezius PPTs, supports that LEI score may primarily reflect the presence of central sensitisation rather than inflammation. Therefore, relying solely on clinical detection of enthesitis may result in inappropriate treatment escalation. Ultrasound, conversely, serves as a dependable tool for confirming enthesitis and providing valuable information for making informed treatment decisions. Disclosure N.M. Aldehmi: None. N. Basu: None. J. Dale: None. A. Najm: None. F. Sunzini: None.

Association between SPECT/CT total tumor volume (TTV) and new lesions (NLs) in early cycles of 177Lu-PSMA-617 (LuPSMA) and progression-free and overall survival (PFS and OS) in men with metastatic castration-resistant prostate cancer (mCRPC).

40 Background: LuPSMA is a newly established treatment in patients with mCRPC, but PSA and survival outcomes vary widely, and predictors of treatment responses are needed. LuPSMA delivers radiation to tumor tissues that can also be imaged with SPECT/CT which provides semiquantitative estimates of TTV and identification of NLs. This study investigates the use of SPECT/CT in early cycles to predict LuPSMA outcomes. Methods: Between June and December 2022, mCRPC patients who initiated the 2nd cycle of LuPSMA with SPECT/CT 24 hours post-treatment were retrospectively reviewed. We evaluated associations between TTV and the appearance of NLs at the start of the 2nd or 3rd cycle with PFS and OS using Cox regression analysis. NLs were classified as non-PSMA-avid with no or low uptake (&lt; liver) with corresponding findings on CT and PSMA-avid (uptake &gt; liver). All analyses were adjusted for change in PSA relative to baseline. Results: Sixty-six mCRPC patients (median age, 73.5) received a median of 4 (IQR: 3-5) cycles of LuPSMA. Median follow-up starting at 2nd cycle was 26 weeks (IQR: 21-36) with 47/66 (71%) alive at the time of the analysis. A reduction of ≥50% in PSA (PSA50) was noted in 33/66 (50%) patients. Changes in PSA and TTV at 2nd and 3rd cycle were apparently concordant in 50/66 (76%) and 42/51 (82%) and were significantly correlated (r= 0.55 and 0.56, both p&lt;0.001). Patients with higher absolute TTV adjusted for PSA change at 2nd cycle had worse PFS and OS (HR=1.3 and 2.26) with consistent results at 3rd cycle (Table). NLs were detected in 13/66 (7/13 PSMA-avid, 6/13 non-PSMA-avid) and 7/51 patients (5/7 PSMA-avid, 2/7 non-PSMA-avid) at 2nd and 3rd cycle, respectively. Patients with NLs at 2nd cycle had higher risks of progression and death (HR=4.53 and 6.28). Conclusions: Higher SPECT/CT TTV at 2nd and 3rd cycle and detection of NLs at 2nd cycle were associated with higher risks of progression and death. Although changes in PSA and TTV were correlated, absolute SPECT/CT TTV in early cycles provided a complementary ability to predict outcomes of LuPSMA. [Table: see text]

Real-world clinical outcomes of patients treated with Lu-177-PSMA-617 for metastatic castration-resistant prostate cancer (mCRPC): A single-institution experience.

83 Background: The radiopharmaceutical Lu177-PSMA-617 (LuPSMA) was FDA approved in March 2022 for patients with mCRPC previously treated with both an androgen receptor signaling inhibitor (ARSI) and a taxane, if eligible based on PSMA PET. However, data regarding real world LuPSMA treatment outcomes are limited. Methods: This is a retrospective analysis of the first 100 mCRPC patients who received at least 1 cycle of LuPSMA at a single institution from June 2022 to August 2023. Demographic and clinical characteristics as well as laboratory values were collected. Central review of qualifying PSMA PET/CT was performed to assess disease distribution. A PSA decrease of 30%, 50%, or 90% from baseline at any point during treatment was the primary measure of response (PSA30, PSA50, and PSA90 respectively). Results: Of the 100 patients identified, 2 were excluded from analysis due to prior receipt of LuPSMA on clinical trial. Three patients were still receiving LuPSMA at the time of data collection. Median age was 72 (range, 50 - 93) and median number of treatments received was 4.0. On baseline PET/CT, 43 patients (44%) had bone + nodal metastases only, 19 (19%) had bone metastases only, 8 (8%) had nodal metastases only, and 11 (11%) had liver metastases. As for prior therapies, 47% had received ≥2 ARSIs (n=47/98), 48% had received 2 prior taxanes (n= 47/98), 42% had received 1 prior taxane (n=41/98), 17% received radium-223 (n=17/98), and 10% were treated off-label with no prior chemotherapy (n=10/98). Median follow up from the start of LuPSMA treatment was 7.6 months (range= 0.6-14.1 months, n=98). During treatment, 21 (21%) patients achieved a PSA90 response, 51 (52%) patients achieved a PSA50 response and 60 (61%) patients achieved a PSA30 response. An increase or no change in baseline PSA was seen in 28% (n=26/94 evaluable patients). Among patients with an initial rise in PSA after the first treatment, 10% had a subsequent reduction from baseline PSA (n=3/29). Conclusions: In this cohort of heavily pretreated mCRPC patients, we observed a PSA50 response of 54% and 21% of patients experiencing a PSA reduction ≥90%. This data supports the clinical benefit of LuPSMA in real-world clinical practice. Characterization of response rates within subgroups by prior treatment and disease characteristics are ongoing.

Bilateral Subcapsular Orchidectomy as Surgical Castration: A Reasonable Aesthetic Alternative to Bilateral Total Orchidectomy in Patients with Metastatic Hormone-sensitive Prostate Cancer

Background: The study highlights the historical significance of bilateral orchidectomy as the traditional 'gold standard' for surgical androgen deprivation in treating advanced prostate cancer. The study presented aims to compare total orchidectomy and subcapsular orchidectomy, considering factors such as androgen ablation, disease progression control, and patient satisfaction. Objective: This study aims to compare the effectiveness and patient satisfaction of bilateral subcapsular orchidectomy and bilateral total orchidectomy treatment in managing hormone-sensitive metastatic prostate cancer. Methods and materials: In this prospective study of 18 months at North East Medical College Hospital, 40 participants with Metastatic Carcinoma of Prostate underwent bilateral orchidectomy, among them 20 subcapsular and 20 total orchidectomy. The research focused on evaluating the impact of these treatments on serum testosterone levels, serum PSA levels, employing as outpatient procedures and a 3-month follow-up, utilizing a satisfaction scoring scale. Data, including age, Gleason Grade Group, PSA, and testosterone levels at diagnosis &amp; at 3-month follow-up were recorded and analyzed using IBM SPSS-21 software. Result: The study compared Bilateral Subcapsular Orchidectomy and Bilateral Simple Orchidectomy for Hormone-Sensitive Metastatic Carcinoma of Prostate in 40 patients. The highest frequency was in the 71-75 age group (30%), with a mean age of 66.67 ± 2.21 years. Gleason grade group 3 dominated (40%), followed by 2 (25%). Pre-operative PSA levels were 31.14±1.27 ng/ml for Subcapsular and 35.21±1.70 ng/ml for Total Orchidectomy, decreasing post-operatively to 8.25±0.41 ng/ml and 7.32±0.80 ng/ml, respectively. Pre-operative testosterone levels were 513.21±3.01 ng/dl for Subcapsular and 498.40±2.10 ng/dl for Total Orchidectomy, decreasing post-operatively to 21.14±2.84 ng/dl and 16.90±1.08 ng/dl, respectively, with non-significant p-values. Surgery related Satisfaction scores in the Follow-Up phase were significantly higher for Subcapsular Orchidectomy, 2.91±0.31 comparing with Total Orchidectomy, 2.05±0.45. The results emphasize better patient satisfaction after subcapsular orchidectomy, while maintaining similar cancer control in the form of PSA and testosterone level changes. Conclusion: In conclusion, our study advocates for the reconsideration of bilateral subcapsular orchidectomy as a preferred method for surgical androgen ablation in metastatic prostatic carcinoma, offering comparable efficacy to traditional total orchidectomy approach while prioritizing patient satisfaction and psychological well-being. This suggests a potential paradigm shift in the landscape of cost-effective androgen deprivation therapy within the urological field.

Psoriatic arthritis: the role of self-reported non-adherence, non-trough drug levels, immunogenicity and conventional synthetic DMARD co-therapy in adalimumab and etanercept response.

The aim of this study was to assess the relationship between self-reported non-adherence, non-trough drug levels, immunogenicity and conventional synthetic DMARD (csDMARD) co-therapy in TNF inhibitor (TNF-i) drug response in PsA. Serum samples and adherence questionnaires were collected at baseline, 3, 6 and 12 months for PsA patients prescribed TNF-i. Non-trough adalimumab (ADL) and etanercept (ETN) drug levels were measured at 3 and 6 months using commercially available ELISAs. Clinical response was assessed using PsA response criteria (PsARC) and change in 28-joint DAS (ΔDAS28) between baseline and 3, 6 and 12 months. In 244 PsA patients (52.5% ADL and 47.5% ETN), self-reported non-adherence was associated with PsARC non-response over 12 months using generalized estimating equation (GEE) modelling (P = 0.037). However, there was no significant difference between non-trough ADL or ETN drug levels based on self-reported non-adherence. Higher ETN levels at 3 months were associated with PsARC response at 3 (P = 0.015), 6 (P = 0.037) and 12 months (P = 0.015) and over 12 months using GEE modelling (P = 0.026). Increased ADL drug levels at 3 months were associated with greater ΔDAS28 at 3 months (P = 0.019). ADL anti-drug antibody-positive status was significantly associated with lower 3- and 6-month ADL levels (P < 0.001) and ΔDAS28 and PsARC response at 3, 6 and 12 months. Meanwhile, MTX co-therapy was associated with a reduction in immunogenicity at 3 and 6 months (P = 0.008 and P = 0.024). Although both were associated with reduced response, the objectively measured non-trough drug levels showed more significant associations with drug response than self-reported non-adherence measures.

Early response monitoring during [177Lu]Lu-PSMA I&T therapy with quantitated SPECT/CT predicts overall survival of mCRPC patients: subgroup analysis of a Swiss-wide prospective registry study

PurposeTo assess early tumor response with quantitated SPECT/CT and to correlate it with clinical outcome in metastatic castration–resistant prostate cancer (mCRPC) patients treated with 177Lutetium-PSMA I&T therapy.MethodsSingle-center, observational study, part of the prospective Swiss national cancer registry study investigating the safety and efficacy of [177Lu]Lu-PSMA I&T (EKNZ: 2021–01271) in mCRPC patients treated with at least two cycles of [177Lu]Lu-PSMA I&T 6-weekly. After the first and second cycle quantitated SPECT/CT (Symbia Intevo, Siemens) was acquired 48 h after injection (three fields of view from head to thigh, 5 s/frame) and reconstructed using xQuant® (48i, 1 s, 10-mm Gauss). Image analysis: The PSMA-positive total tumor volumes (TTV) were semi-automatically delineated using a SUV threshold of 3 with MIMencore® (version 7.1.3, Medical Image Merge Software Inc.). Changes in TTV, highest tumor SUVmax, and total tumor SUVmean between cycles 1 and 2 were calculated and grouped into a) stable or decrease and b) increase. Serum PSA levels were assessed at each therapy cycle and at follow-up until progression or death. Changes in TTV, PSA, SUVmax, and SUVmean were correlated with PSA-progression-free survival (PSA-PFS) and the overall survival (OS) using the Kaplan–Meier methodology (log-rank test).ResultsBetween 07/2020 and 04/2022, 111 patients were screened and 73 finally included in the data analysis. The median follow-up was 8.9 months (range 1.4–26.6 months). Stable or decreased TTV at cycle 2 was associated with longer OS (hazard ratio (HR) 0.28, 95% confidence interval (CI) 0.09–0.86, p < 0.01). Similar, stable, or decreased PSA was associated with longer OS (HR 0.21; CI 0.07–0.62, p < 0.01) and PSA-PFS (HR 0.34; 95% CI 0.16–0.72, p < 0.01). Combining TTV and PSA will result in an augmented prognostic value for OS (HR 0.09; CI 0.01–0.63; p < 0.01) and for PSA-PFS (HR 0.11; CI 0.02–0.68; p < 0.01). A reduction of SUVmax or SUVmean was not prognostically relevant, neither for OS (p 0.88 and 0.7) nor for PSA-PFS (p 0.73 and 0.62, respectively).ConclusionSix weeks after initiating [177Lu]Lu-PSMA I&T, TTV and serum PSA appear to be good prognosticators for OS. Combined together, TTV + PSA change demonstrates augmented prognostic value and can better predict PSA-PFS. Larger studies using TTV change prospectively as an early-response biomarker are warranted for implementing management change towards a more personalized clinical practice.

Negative Delta-Prostate-Specific Antigen Time Ratio as Potential New Marker of Progression-Free Survival in Castration-Resistant Prostate Cancer Patients Treated With First-Line Enzalutamide or Docetaxel

Purpose: We propose a new potential marker of progression-free survival (PFS) called negative delta-prostate-specific antigen (PSA) time ratio (NDPSATR) and compare it with conventional PSA response, defined as PSA decline ≥50% at 12 weeks from pretreatment baseline (PSAR50) in metastatic castration-resistant prostate cancer (mCRPC) patients treated with first-line enzalutamide (ENZ) or docetaxel (DTX).Materials and Methods: All patients diagnosed as mCRPC at Ajou University Hospital from 2016 were included. Delta-PSA days is PSA change between 2 consecutive measurements during a regimen multiplied by interval days. A negative delta-PSA days value represents a positive PSA response. NDPSATR is calculated by dividing the sum of days on negative delta-PSA days by total days on the regimen. Student t-test was used to compare mean values and Kaplan-Meier survival curves for PFS were obtained.Results: Of 57 patients identified, 22 and 35 were treated with ENZ and DTX, respectively. Rates of PSAR50 for ENZ and DTX were 72.7% and 20.6%, respectively. Mean NDPSATR for ENZ and DTX were 0.40 and 0.46, respectively and the difference was not statistically significant. For ENZ, median PFS (mPFS) of PSAR50 and non-PSAR50 were 14.3 and 4.8 months, respectively and there was significant difference in PFS (p=0.002). For DTX, mPFS of PSAR50 and non-PSAR50 were 15.0 and 6.5 months, respectively but there was no significant difference in PFS (p=0.055). At cutoff value of 0.4, rate of NDPSATR ≥0.4 for ENZ and DTX were 36.4% and 62.9%, respectively. For ENZ, mPFS of NDPSATR ≥0.4 and NDPSATR &lt;0.4 were not achieved and 14.1 months, respectively and there was no significant difference in PFS (p=0.895). For DTX, mPFS of NDPSATR ≥0.4 and NDPSATR &lt;0.4 were 9.7 and 6.3 months, respectively and there was a significant difference in PFS (p=0.045).Conclusions: NDPSATR ≥0.4 may be a good marker of PFS in CRPC patients treated with DTX and may replace PSAR50.

Associations of quantitative whole-body PSMA-PET metrics with PSA progression status under long-term androgen deprivation therapy in prostate cancer patients: a retrospective single-center study

PurposeTo evaluate whether quantitative whole-body (WB) PSMA-PET metrics under long-term androgen deprivation therapy (ADT) and/or androgen receptor signaling inhibitors (ARSi) are associated with PSA progression.MethodsPatients who underwent at least 2 68Ga-PSMA-11 PET/CT scans between October 2016 and April 2021 (n = 372) and started a new line of ADT ± ARSi between PET1 and PET2 were retrospectively screened for inclusion. We investigated the association between PCWG3-defined PSA progression status at PET2 and the following PSMA-PET parameters: appearance of new lesions on PET2, ≥ 20% increase in WB-PSMA tumor volume (WB-PSMA-VOL), progression of disease (PD) by RECIP 1.0, and ≥ 30% increase in WB-PSMA-SUVmean from PET1 to PET2. Spearman’s rank correlation coefficients and Fisher’s exact test were used to evaluate the associations.ResultsThirty-five patients were included: 12/35 (34%) were treated with ADT only and 23/35 (66%) with ARSi ± ADT. The median time between PET1 and PET2 was 539 days. Changes (%) in median PSA levels, WB-PSMA-SUVmean, and WB-PSMA-VOL from PET1 to PET2 were -86%, -23%, and -86%, respectively. WB-PSMA-VOL ≥ 20%, new lesions, RECIP-PD, and WB-PSMA-SUVmean ≥ 30% were observed in 5/35 (14%), 9/35 (26%), 5/35 (14%), and 4/35 (11%) of the whole cohort, in 3/9 (33%), 7/9 (78%), 3/9 (33%), and 2/9 (22%) of patients with PSA progression at PET2, and in 2/26 (8%), 2/26 (8%), 2/26 (8%), and 2/26 (8%) of patients without PSA progression at PET2 (p = 0.058, p < 0.001, p = 0.058, p = 0.238, respectively). Changes in PSA were correlated to percent changes in WB-PSMA-VOL and WB-PSMA-SUVmean (Spearman ρ: 0.765 and 0.633, respectively; p < 0.001).ConclusionChanges in PSA correlated with changes observed on PSMA-PET, although discordance between PSA and PSMA-PET changes was observed. Further research is necessary to evaluate if PSMA-PET parameters can predict progression-free survival and overall survival and serve as novel endpoints in clinical trials.

Top-down holmium laser enucleation of the prostate (HoLEP) versus traditional HoLEP for the treatment of benign prostatic hyperplasia (BPH): 1-year outcomes of a randomized controlled trial.

The top-down holmium laser enucleation of the prostate (HoLEP) technique recently emerged as a safe and effective modification of traditional HoLEP. In our randomized controlled trial, we compared intraoperative and postoperative outcomes of traditional and top-down HoLEP for the treatment of benign prostatic hyperplasia (BPH) in patients with a prostate size ≥80 g. One-hundred patients with BPH and a prostate volume ≥80 cc participated in this prospective randomized controlled trial. Outcome measures were collected and compared, including IPSS, QoL, flow rate, PVR, IIEF-15, PSA, and TRUS prostate volume changes. Perioperative complications were also recorded. All patients were followed up at 1, 3, 6, and 12 months. There were no significant differences in preoperative baseline characteristics between the two surgical groups. The median prostate volume for the traditional and top-down HoLEP groups was 107 and 102 cc, respectively. The operative parameters and postoperative outcomes were comparable for both cohorts. The median enucleation time for traditional HoLEP was 60 min, which was not significantly longer than that of top-down HoLEP (52 min) (p = 0.07). At 3 months follow-up, there was no statistically significant difference in transient stress urinary incontinence (SUI) in the traditional HoLEP (4.1%) versus the top-down HoLEP group (2.2%), (p = 0.61). There were no significant differences in functional and sexual outcomes between the two groups at 12 months. The HoLEP procedure significantly improves patients' urinary functional outcomes and has comparable postoperative outcomes regardless of the technique utilized.

Association of Prostate Specific Antigen Kinetics after Testosterone Recovery with Subsequent Recurrence: Secondary Analysis of a Phase III Randomized Controlled Trial.

The combination of short-term androgen deprivation therapy (ST-ADT) with prostate radiotherapy (RT) is a standard of care for patients with localized prostate cancer (LPCa). After cessation of ST-ADT, it takes about 8 to 10 months for the testosterone (T) to recover to supracastrate levels, which could drive changes in PSA kinetics. It largely remains unknown whether early changes in PSA kinetics after T recovery could predict for subsequent biochemical relapse. We performed a secondary analysis of a phase III randomized controlled trial in which patients with newly diagnosed LPCa with Gleason score £7, clinical stage T1b to T3a, and PSA <30 ng/mL were randomly allocated to neoadjuvant and concurrent ADT for 6 months starting 4 months before prostate RT (76 Gy in 38 fractions over 7.5 weeks) or concurrent and adjuvant ADT for 6 months starting simultaneously with prostate RT. Clinical assessment and laboratory investigations were repeated 1 month after completion of ADT, every 4 months for the first 2 years, every 6 months for the next 3 years, and annually thereafter. We calculated the PSA doubling time (PSADT) based on PSA values up to 18 months after recovery of T to a supracastrate level (>50 ng/dL). Patients with ³3 PSA measurements after T recovery to supracastrate level were included in this analysis. Fine and Gray cumulative incidence of biochemical recurrence (BCR) was calculated in patients with PSADT at or above median versus below median. Deaths were considered as competing events. All endpoints were calculated from the time of T recovery to supracastrate level. Subdistribution hazard ratios (sHR) with 95% confidence intervals (CI) were estimated for association of PSADT with relative incidence of recurrence using competing risk regression after adjusting for tumor stage, pre-treatment PSA, Gleason score, treatment regimen, and age at randomization. Overall, 311 patients were eligible for this analysis. Median PSADT was 8 months. Cumulative incidence of BCR at 10 years was 31.0% and 20.7% in patients with PSADT <8 months and ³8 months, respectively. Longer PSADT was associated with a significantly lower risk of cumulative incidence of BCR (sHR for PSADT as a continuous variable 0.43, 95% CI: 0.28-0.66; sHR for PSADT ³8 months 0.54, 95% CI: 0.30-0.99). After adjustment for time to recovery of T to supracastrate level in addition to the aforementioned variables, longer PSADT (³8 months) was associated with lower risk of cumulative incidence of BCR (sHR: 0.53, 95% CI: 0.27-1.01). These findings suggest that early PSA kinetics within 18 months of recovery of T to a supracastrate level predict for subsequent biochemical failure. Taking account of early changes in PSA after testosterone recovery may allow for recognition of potential failures earlier in the disease course and thereby permit greater personalization of management decisions.

Early biochemical and radiographic response after one cycle of [177Lu]Lu-PSMA I&T radioligand therapy in metastatic castration-resistant prostate cancer patients

PurposeThe aim of this study was to investigate very early radiographic PSMA PET response after one cycle of [177Lu]Lu-PSMA I&T radioligand therapy (RLT) of metastatic castration-resistant prostate cancer (mCRPC) and to assess its role in predicting overall response and survival.MethodsThis retrospective study enrolled 40 mCRPC patients who were treated with a median of 3 (2–9) [177Lu]Lu-PSMA I&T RLT cycles. Biochemical response was based on the relative change of serum PSA according to PCWG3 criteria, while radiographic response referred to the relative change of PSMA-derived total viable tumor volumes expressed as total lesion PSMA (TLP).ResultsAfter one cycle of RLT, biochemical partial response (PR) was seen in 8/40 (20.0%), stable disease (SD) in 22/40 (55.0%), and progressive disease (PD) in 10/40 (25%) patients. In PSMA PET, very early molecular PR was observed in 12 (30.0%), SD in 19 (47.5%), and PD in 9 (22.5%) subjects. The PSA and TLP nadir were achieved after a median of 1 (1–5) and 2 (1–6) cycles, respectively. Nineteen (47.5%) patients showed overall biochemical PR, 11 (27.5%) had SD, and 10 (25%) experienced PD. In PSMA-directed PET, 4 patients experienced molecular complete response (CR), 24 (60.0%) had PR, 4 (10.0%) SD, and 8 (20.0%) PD. Early biochemical or radiographic response was not associated with longer overall survival (OS). Overall biochemical responders had a nearly significantly longer median OS (22.7 months) than non-responders (14.4 months, p = 0.08). Early PSA progression was associated with shorter OS (12.2 months), compared to biochemical SD/PR (18.7 months, p = 0.09).ConclusionIn this retrospective cohort, there was no association between early PSMA PET radiographic response and overall survival; hence, treatment should not be prematurely discontinued. In contrast, early PSA progression after one cycle of [177Lu]Lu-PSMA I&T RLT was an indicator of overall progression and poor clinical outcome.