Changes In Prostate-specific Antigen Levels Research Articles

Neoadjuvant Exercise Therapy in Prostate Cancer

Observational data have shown that postdiagnosis exercise is associated with reduced risk of prostate cancer death. The feasibility and tumor biological activity of exercise therapy is not known. To identify recommended phase 2 dose of exercise therapy for patients with prostate cancer. This single-center, phase 1a dose-finding trial was conducted at a tertiary cancer center using a patientcentric, decentralized platform and included 53 inactive men with treatment-naive localized prostate cancer scheduled to undergo surgical resection between June 2019 and January 2023. Data were analyzed in June 2024. Six escalated exercise therapy dose levels ranging from 90 to 450 minutes per week of individualized, moderate-intensity treadmill walking, allocated using adaptive continual reassessment. All exercise therapy sessions were conducted remotely with real-time monitoring. Feasibility was evaluated by relative exercise dose intensity (REDI). A dose level was considered feasible if 70% or more of patients achieved an REDI of 75% or greater. Activity end points were changes in tumor cell proliferation (Ki67) and plasma prostate-specific antigen levels between pretreatment and postintervention. Safety and changes in patient physiology were also assessed. A total of 53 men were enrolled (median [IQR] age, 61 [56-66] years). All dose levels were feasible (≥75% REDI). The mean (95% CI) changes in Ki67 were 5.0% (-4.3% to 14.0%) for 90 minutes per week, 2.4% (-1.3% to 6.2%) for 150 minutes per week, -1.3% (-5.8% to 3.3%) for 225 minutes per week, -0.2% (-4.0% to 3.7%) for 300 minutes per week, -2.6% (-9.2% to 4.1%) for 375 minutes per week, and 2.2% (-0.8% to 5.1%) for 450 minutes per week. Changes in prostate-specific antigen levels were 1.0 ng/mL (-1.8 to 3.8) for 90 minutes per week, 0.2 ng/mL (-1.1 to 1.5) for 150 minutes per week, -0.5 ng/mL (-1.2 to 0.3) for 225 minutes per week, -0.2 (-1.7 to 1.3) for 300 minutes per week, -0.7 ng/mL (-1.7 to 0.4) for 375 minutes per week, and -0.9 ng/mL (-2.4 to 0.7) for 450 minutes per week. No serious adverse events were observed. Overall, 225 minutes per week (approximately 5 minutes per treatment at 5 times weekly) was selected as the recommended phase 2 dose. The results of this nonrandomized clinical trial suggest that neoadjuvant exercise therapy is feasible and safe with promising activity in localized prostate cancer. ClinicalTrials.gov Identifier: NCT03813615.

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

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

Plain language summary: Can declines in prostate-specific antigen level indicate how long patients with advanced prostate cancer will live when treated with enzalutamide?

This is a summary of a research article originally published in the Journal of Urology. The PROSPER study involved men who had a type of advanced prostate cancer called non-metastatic castration-resistant prostate cancer (nmCRPC). In patients with nmCRPC, their prostate cancer keeps growing even after traditional hormone treatments. In these patients, rising prostate-specific antigen (PSA) levels suggest that cancer is active but CT and bone scans show that it has not spread to other parts of the body. Everyone in this study received androgen deprivation therapy (ADT) either with the medicine enzalutamide or a placebo. Enzalutamide is a medicine that can slow or stop androgens, such as testosterone, from making prostate cancer grow. The main results of the PROSPER study showed that patients with nmCRPC treated with enzalutamide and ADT lived longer than patients treated with placebo and ADT. In this study, researchers wanted to know if the findings were different depending on how much patients' PSA level declined after enzalutamide treatment. Researchers also wanted to know if this made a difference in how long patients lived without the cancer spreading to other parts of their body. Researchers found that patients with a large decline in PSA level after treatment were more likely to live longer and without their cancer spreading. This study shows a link between PSA level changes and how long patients with nmCRPC live when treated with enzalutamide and ADT. These results may help health professionals monitor patients with different PSA level changes after enzalutamide treatment. Patients with a large decline in PSA level may not need to be monitored as closely as patients with a small decline in PSA level.

Nadir Prostate-specific Antigen as an Independent Predictor of Survival Outcomes: A Post Hoc Analysis of the PROSPER Randomized Clinical Trial.

This post hoc analysis of PROSPER evaluated the relationship between depth of PSA decline and clinical outcomes in enzalutamide-treated men with nonmetastatic castration-resistant prostate cancer. PROSPER was an international, randomized, double-blind, placebo-controlled, phase 3 trial that demonstrated significantly improved metastasis-free survival and overall survival with androgen deprivation therapy plus enzalutamide vs placebo. A total of 905 enzalutamide-treated men were included in this post hoc analysis. Metastasis-free survival (primary endpoint) and overall survival (secondary endpoint) were evaluated for 4 mutually exclusive subgroups defined by PSA decline: <50% (reference); ≥50% to <90%; ≥90%, nadir ≥0.2 ng/mL; and ≥90%, nadir <0.2 ng/mL. Medians and 95% confidence intervals were determined using a 12-month landmark analysis; hazard ratios and P values were based on an unstratified Cox proportional analysis model. In enzalutamide-treated men, PSA declines of <50%, ≥50% to <90%, ≥90% with nadir ≥0.2 ng/mL, and ≥90% with nadir <0.2 ng/mL were associated with median metastasis-free survival in months (95% confidence intervals) of 22.1 (14.8-not reached), 34.2 (29.4-not reached), 36.6 (33.4-not reached), and not reached, respectively, and overall survival in months (95% confidence intervals) of 40.8 (31.7-44.9), 54.4 (49.0-67.0), 64.3 (63.4-not reached), and not reached, respectively. There was a statistically significant correlation between greater depth of PSA decline and improved clinical outcomes, suggesting a previously underappreciated relationship between changes in PSA levels and clinical outcomes in nonmetastatic castration-resistant prostate cancer.

Two-Year Analysis of a New Oral Testosterone Undecanoate (TU) Formulation in Hypogonadal Men: Efficacy, Impact on Psychosexual Function, and Safety

BackgroundLong-term data evaluating the efficacy and safety of oral testosterone undecanoate (oral TU; JATENZO) in adult hypogonadal men provides important information for healthcare professionals who prescribe testosterone replacement therapy (TRT). AimTo determine the efficacy and safety of long-term oral TU therapy, including its impact on total testosterone (T) levels and psychosexual functioning. MethodsHypogonadal men, between 18 and 75 years old, (mean age 56.2; 87.2% white) who completed a 12-month, open-label, multicenter, randomized, active-controlled trial were given the opportunity to enroll in a 12-month extension study. Among the 129 eligible TU-treated subjects, 86 chose this option, and 69 completed 24 months of uninterrupted oral TU therapy. OutcomesThe efficacy of oral TU was documented by measuring total serum T concentrations; sexual function was measured using the Psychosexual Daily Questionnaire (PDQ). For safety, liver function tests, cardiovascular endpoints, and prostate health were measured. ResultsOver 2 years, total serum T concentrations for patients treated with oral TU were in the eugonadal range (300–1,000 ng/dL [10–35 nmol/L]; mean ± SD: 617 ± 427 ng/dL [21 ± 15 nmol/L]) and increased significantly from baseline (P < .0001). For sexual function, mean score changes versus baseline for all PDQ domains at all time points were significantly improved (P < .0011 for all). For the sexual activity and sexual desire components, patient scores were consistently greater than validated thresholds for clinically meaningful change. Typical T-induced safety changes were observed, including a 3–6 mm Hg increase in systolic blood pressure (P < .05); a slight increase in hematocrit (P < .0001) that stayed <48% throughout the study; no clinically significant changes in prostate-specific antigen levels; and decreased high-density lipoprotein cholesterol (-9.8 ± 0.9 mg/dL from baseline; P < .0001). There were no clinically significant changes from baseline in liver function tests. Clinical ImplicationsOver 2 years of treatment, this novel oral TU formulation maintained total T concentrations in mideugonadal ranges, with improvements in sexual function and no clinically significant changes in liver function or other safety concerns previously associated with oral TRT. Strengths & LimitationsThese are the first long-term data to evaluate the efficacy and safety of a novel formulation of oral TU; the comparative long-term safety of oral TU would be strengthened by confirmatory studies versus other TRT formulations. ConclusionOral TU offers a safe and effective long-term treatment option for men with hypogonadism.Honig S, Gittelman M, Kaminetsky J, et al. Two-Year Analysis of a New Oral Testosterone Undecanoate (TU) Formulation in Hypogonadal Men: Efficacy, Impact on Psychosexual Function, and Safety. J Sex Med 2022;19:1750–1758.

MCRPC patients with PSA fluctuations under radioligand therapy have comparable survival benefits relative to patients with sustained PSA decrease

IntroductionIn men with metastatic castration-resistant prostate cancer (mCRPC) scheduled for prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT), biochemical response is assessed based on repeated measurements of prostate-specific antigen (PSA) levels. We aimed to determine overall survival (OS) in patients experiencing sustained PSA increase, decrease, or fluctuations during therapy.Materials and methodsIn this bicentric study, we included 176 mCRPC patients treated with PSMA-directed RLT. PSA levels were determined using blood samples prior to the first RLT and on the admission days for the following cycles. We calculated relative changes in PSA levels compared to baseline. Kaplan–Meier curves as well as log-rank test were used to compare OS of different subgroups, including patients with sustained PSA increase, decrease, or fluctuations (defined as change after initial decrease or increase after the first cycle).ResultsSixty-one out of one hundred seventy-six (34.7%) patients showed a sustained increase and 86/176 (48.8%) a sustained decrease in PSA levels. PSA fluctuations were observed in the remaining 29/176 (16.5%). In this subgroup, 22/29 experienced initial PSA decrease followed by an increase (7/29, initial increase followed by a decrease). Median OS of patients with sustained decrease in PSA levels was significantly longer when compared to patients with sustained increase of PSA levels (19 vs. 8 months; HR 0.35, 95% CI 0.22–0.56; P < 0.001). Patients with PSA fluctuations showed a significantly longer median OS compared to patients with sustained increase of PSA levels (18 vs. 8 months; HR 0.49, 95% CI 0.30–0.80; P < 0.01), but no significant difference relative to men with sustained PSA decrease (18 vs. 19 months; HR 1.4, 95% CI 0.78–2.49; P = 0.20). In addition, in men experiencing PSA fluctuations, median OS did not differ significantly between patients with initial decrease or initial increase of tumor marker levels (16 vs. 18 months; HR 1.2, 95% CI 0.38–4.05; P = 0.68).ConclusionInitial increase or decrease of PSA levels is sustained in the majority of patients undergoing RLT. Sustained PSA decrease was linked to prolonged survival and men with PSA fluctuations under treatment experienced comparable survival benefits. As such, transient tumor marker oscillations under RLT should rather not lead to treatment discontinuation, especially in the absence of radiological progression.

A phase I does-escalation and expansion study of epidiolex (cannabidiol) in patients with biochemically recurrent prostate cancer.

257 Background: There is a need for a low toxicity option for men with prostate cancer with biochemical recurrence (BCR) following primary curative therapy. Cannabinoids (CBD) have anti-tumor activity in preclinical studies, but products may vary in activity without clear standardization. As epidiolex is a standardized FDA approved oral CBD solution for treatment of certain types of seizures, we studied epidiolex in patients with BCR of prostate cancer to determine safety and dosing of this therapy to support future studies. Methods: We present an open-label, single center, phase I dose escalation study followed by a dose expansion. Patients with BCR prostate cancer after primary definitive local therapy (prostatectomy +/- salvage radiotherapy or primary definitive radiotherapy) were eligible. Majority of our patients’ prostate-specific antigen (PSA) doubling time was ≤ 12 months. All patients were screened for urine tetrahydrocannabinol (THC) prior to enrollment. With use of a Bayesian optimal interval design, patients received escalating doses of epidiolex starting at 600mg daily and up to 800mg daily. All patients were treated for 90 days followed by a 10 day taper. The Primary endpoints were safety and tolerability. Patients were monitored for both acute (30 days) and chronic (90 days) treatment-related toxicities. Secondary endpoints included change in PSA levels and testosterone levels from baseline throughout the treatment period. Results: A total of 21 patients were enrolled but four withdrew from the study (one patient was hospitalized with COVID-19 and three patients requested to stop due to grade 2 adverse events (AEs). There were seven patients included in the dose escalation phase. Four patients received 600mg daily; two of the four in this phase did not finish the first 30 days (one with COVID-19 and one withdrew). The other three patients received 800 mg daily. No dose-limiting toxicities were observed at any dose level so an additional 14 patients were enrolled at the 800mg dose. Treatment-related chronic AEs occurring in &gt;10% of patients were grade 1 or 2 diarrhea (47.6%), grade 1 or 2 nausea (23.8%) and grade 1 or 2 fatigue (19%). The mean PSA at baseline was 2.9 ng/ml. One patient developed oligo-metastasis disease, two patients progressed after the study period, and one patient died from a non-treatment or disease-related cause. Conclusions: Epidiolex at a dose of 800mg daily appears to be safe and tolerable in patients with BCR of prostate cancer, supporting a safe dose for future studies to determine if there is clinical activity to delay development of hormone refractory metastatic disease. Clinical trial information: NCT04428203.

Changes in prostate-specific antigen kinetics during androgen-deprivation therapy as a predictor of response to abiraterone in chemonaïve patients with metastatic castration-resistant prostate cancer

PurposeMetastatic castration-resistant prostate cancer (mCRPC) has a poor prognosis. Abiraterone acetate (AA), enzalutamide, and chemotherapy are first-line treatments for patients with mCRPC. This study examined prognostic factors for AA response in the form of prostate-specific antigen (PSA) kinetics throughout androgen-deprivation therapy (ADT) in chemonaïve patients with mCRPC.Materials and MethodsWe retrospectively included data from 34 chemonaïve patients with mCRPC who had received AA at some point between January 2017 and December 2018. We separated patients into two study arms according to the decrease in PSA percentages after use of AA for 3 months. We correlated PSA kinetics parameters with response and compared the two study groups with respect to PSA kinetics.ResultsThe patients’ median age was 77 years. In the total group of patients, 64% had a response to AA, whereas 35% did not. The ratio of the PSA level at nadir to the level during ADT was significantly higher in the AA-sensitive group (19.78 vs. 1.03, p=0.019).ConclusionsPatients who experienced a dramatic change in PSA level during ADT were more likely to be resistant to AA after progression to mCRPC. Chemotherapy rather than AA might be more suitable as a first-line treatment for these patients.

Advanced nanoengineered-customized point-of-care tools for prostate-specific antigen.

Change in the level of human prostate-specific antigen (PSA) is a major element in the development and progression of prostate cancer (PCa). Most of the methodologies are currently restricted to their application in routine clinical screening due to the scarcity of adequate screening tools, false reading, long assay time, and cost. Innovative techniques and the integration of knowledge from a variety of domains, such as materials science and engineering, are needed to provide sustainablesolutions. The convergence of precision point-of-care (POC) diagnostic techniques, which allow patients to respond in real time to changes in PSA levels, provides promising possibilities for quantitative and quantitative detection of PSA. This solution could be interesting and relevant for use in PCa diagnosis at the POC. The approaches enable low-cost real-time detection and are simple to integrate into user-friendly sensor devices. This review focuses on the investigations, prospects, and challenges associated with integrating engineering sciences with cancer biology to develop nanotechnology-based tools for PCa diagnosis. This article intends to encourage the development of new nanomaterials to construct high-performance POC devices for PCa detection. Finally, the review concludes with closing remarks and a perspective forecast.

Assessment of volumetric parameters derived from 68Ga-PSMA PET/CT in prostate cancer patients with biochemical recurrence: an institutional experience.

The aim of this study was to evaluate the relationship between volumetric parameters calculated using semiautomatic quantification of lesions detected in 68Ga-labeled prostate-specific membrane antigen PET-computed tomography (68Ga-PSMA PET/CT) and clinical characteristics in prostate cancer (PCa) patients with biochemical recurrence. A total of 85 consecutive PCa patients with biochemical recurrence who underwent 68Ga-PSMA PET/CT at our institution from January 2019 to March 2020 were retrospectively assessed. 68Ga-PSMA PET/CT-derived volumetric parameters, including whole-body PSMA tumor volume (wbPSMA-TV) and whole-body total lesion PSMA (wbTL-PSMA), as well as the established maximum and mean standardized uptake value (SUVmax and SUVmean), were calculated for each patient. All PET-derived parameters were analyzed for correlation with prostate-specific antigen (PSA) levels and for association with Gleason scores. Eighty-five patients with a mean age of 68.9 ± 7.8 years (range, 47-83 years) and a mean PSA level of 40.9 ± 92.1 ng/ml (range, 0.2-533.2 ng/ml) were analyzed. Volumetric parameters, that is, wbPSMA-TV and wbTL-PSMA, demonstrated a statistically significant correlation with PSA levels (r = 0.403 and r = 0.556, respectively, all at P < 0.001) and only the means of wbTL-PSMA were significantly different between the Gleason score groups (P < 0.05). The results of our study indicate that 68Ga-PSMA PET/CT might be a valuable tool for the detection and follow-up of recurrence in PCa patients. 68Ga-PSMA PET/CT-derived quantitative volumetric parameters demonstrated a highly significant correlation with changes in PSA levels. Larger prospective studies are needed to help reveal the full potential of parameters such as PSMA-TV and TL-PSMA derived from PET imaging with 68Ga-PSMA.

The Predictive Role of Prostate-Specific Antigen Changes Following Transurethral Resection of the Prostate for Patients with Localized Prostate Cancer.

Simple SummaryA part of localized prostate cancer (PC) was an incidental finding in patients who received transurethral resection of the prostate (TURP) for urinary symptoms. The present study examined whether changes in prostate-specific antigen (PSA) levels after TURP possess a predictive value for localized PC. Our data revealed that patients at intermediate risk who are associated with tumor involvement ≤5% in TURP specimens, PSA_TURP ≤ 4 ng/mL, and ≥68% PSA reduction following TURP might be suitable for conservation management instead of immediate local therapy. Moreover, for patients with no pre-TURP PSA, Gleason score (GS) < 7, and low PSA_TURP could potentially be utilized to select which patients could be considered for conservative management after TURP. The findings suggest the pathologic finding of TURP and changes in PSA could be used as adjuvant markers to guide a risk-adaptive strategy for patients with localized PC.Regarding localized prostate cancer (PC), questions remain regarding which patients are appropriate candidates for conservative management. Some localized PC was an incidental finding in patients who received transurethral resection of the prostate (TURP) for urinary symptoms. It is known that TURP usually affects the level of prostate-specific antigen (PSA). In the present study, we examined whether changes in PSA levels after TURP possess a predictive value for localized PC. We retrospectively reviewed the clinical data of 846 early-stage PC patients who underwent TURP for urinary symptoms upon diagnosis at our hospital. Of 846 patients, 687 had tumor involvement in TURP specimens, and 362 had post-TURP PSA assessment. Our data revealed that, in addition to low GS and PSA levels at diagnosis, ≤5% tumor involvement in TURP specimens, greater PSA reduction (≥68%) following TURP, and post-TURP PSA ≤ 4 were significantly associated with better progression-free survival (PFS). Survival analysis revealed that the addition of prostate-directed local therapy significantly improved PFS in intermediate- and high-risk groups, but not in the low-risk group. Moreover, in the intermediate-risk group, local therapy improved PFS only for patients who were associated with post-TURP PSA > 4 ng/mL or <68% PSA reduction following TURP. We also found that local therapy had no obvious improvement in PFS for those with post-TURP ≤ 4 ng/mL regardless of pre-TURP PSA. In conclusion, conservative management is considered for patients at low or intermediate risk who have greater PSA reduction following TURP and low post-TURP PSA. Therefore, the levels of PSA following TURP might be helpful for risk stratification and the selection of patients for conservative management.

Urological issues in cyclists

Cycle use has grown rapidly over the last few years in the UK. British Cycling membership has increased threefold since the 2012 Olympic and Paralympic Games, and this is likely to rise in the wake of the Coronavirus pandemic. As urologists, day-to-day encounters with cyclists are commonplace, who may present with acute traumatic injuries or chronic overuse injuries. The aim of this literature review was to evaluate the effect of cycling on conditions presenting to the urology clinic, in particular those of raised prostate-specific antigen (PSA), haematuria and soft-tissue lesions (‘cyclist nodules’). Furthermore, the review aimed to summarize the relationship between cycling and pudendal nerve entrapment (PNE) syndromes. A PubMed search of the literature on cycling and genitourinary disorders was performed. The literature suggests no significant change in PSA levels after a bout of cycling. Age appears to have no effect on the change in PSA experienced following a bout of cycling, in particular when comparing those &lt;50 years of age to those &gt;50 years of age. Haematuria appears to be rare with cycling but has been described, even with stationary bike riding. It is imperative to exclude coexisting urinary-tract pathological conditions, and cycling-induced haematuria should always be considered a diagnosis of exclusion. Perineal nodular induration (‘cyclist nodules’) is a rare condition, related to pressure and repetitive micro-trauma between the perineum and saddle. Pudendal Nerve Entrapment (PNE) represents the most common bicycling-associated urogenital complaint. Numbness in the perineum, penis, scrotum or buttocks—‘genital numbness’—is the most common and most recognized symptom of pudendal compression. Despite several studies demonstrating a link between elite cyclists and erectile dysfunction, for the average cyclist riding may actually have a protective effect on sexual function.

Association between prostate-specific antigen and serum testosterone: A systematic review and meta-analysis.

Serum testosterone assays are an important tool in the clinical evaluation of a number of endocrine disorders including male hypogonadism. However, serum testosterone has a limited role in real clinical use due to its inaccuracy. We aimed to assess the association between prostate-specific antigen (PSA) and testosterone as well as the effects of various types of testosterone replacement therapy (TRT) for PSA level. Two electronic databases were screened: PubMed (1966 through December 2018) and Cochrane Library (1993 through December 2018). The first strategy compared the overall increase in PSA following testosterone treatment compared with placebo. The second strategy analyzed the overall association between PSA and testosterone among the observational studies. In the first strategy, 22 articles were included in the final analysis. In the second strategy, 18 studies were included. Testosterone replacement therapy (TRT) showed a significant change in PSA level compared to that in the placebo group (mean difference [MD]: 0.13, 95% CI: 0.01-0.25, P=.04). Compared to placebo, only intramuscular (IM) TRT shows a significant change in PSA level group (MD: 0.16, 95% CI: 0.01-0.30, P=.04), as neither the oral nor topical type showed a significant change in PSA. In the second strategy analysis, there was no overall correlation found between PSA and testosterone (z=0.04, 95% CI: -0.04 to 0.12, P=.04; r=0.039). However, in the subgroup of non-BPH (benign prostate hyperplasia), a significant correlation between PSA and testosterone (z=0.07, 95% CI: 0.01-0.13, P=.009; r=0.089) was found. We found that TRT, particularly IM TRT, significantly changed the PSA level compared with the placebo group. Furthermore, there was a significant correlation between PSA and testosterone in patients with non-BPH. According to these findings, we suggest the possibility of PSA as a surrogate marker of testosterone.

Do testosterone supplements enhance response to phosphodiesterase 5 inhibitors in men with erectile dysfunction and hypogonadism: a systematic review and meta-analysis.

BackgroundCombining testosterone and phosphodiesterase 5 inhibitors (PDE5-Is) has become increasingly common in the treatment of men with erectile dysfunction (ED) and low testosterone levels, but combination therapy involving PDE5-Is and testosterone is highly debated, with strong reasons for and against argued by the various opinion leaders. PDE5-Is can be given prior to, alongside or after the commencement of any testosterone replacement therapy. Meanwhile, combination of PDE5-Is and testosterone is reported to better increase testosterone levels and thus improve International Index of Erectile Function (IIEF) score in hypogonadal men. The objective of this meta-analysis was to assess whether testosterone therapy (TTh) can possibly enhance the reaction to PDE5-Is in men with ED and hypogonadism.MethodsRelevant studies and available data were extensively collected form Medline, Embase, and Cochrane Library databases until June 2019. We calculated standard mean differences (SMDs) with their 95% confidence intervals (CIs) for IIEF including IIEF-5 and IIEF-EFD. Trial sequential analysis (TSA) was performed to explore whether the sample size of the accumulated evidence is sufficient.ResultsThere were 8 studies including 913 patients. The pooled SMD of erectile function (EF) component change was 0.663 [(0.299 to 1.027); P<0.0001], which concluded that combination therapy (TTh plus PDE5-Is) is superior to PDE5-Is monotherapy group. We also conducted a subgroup analysis according to trial follow-up, baseline serum total testosterone, baseline EF score and PDE5-Is type, which may explain for the underlying source of heterogeneity in part. The frequency of adverse events and change in PSA levels did not differ between the 2 groups. None of the patients experienced an increase in the prostate specific antigen (PSA) level above 4 ng/mL. Hematocrit increased significantly more in the testosterone group than in the placebo group but not greater than 0.54.ConclusionsIn summary, the present results confirm that combination therapy is effective and safe. TTh can enhance the reaction to PDE5-Is in men with ED and hypogonadism, but this effect also depends on the specific diagnosis and initial response to PDE5-Is. Most patients with adverse events during treatment are mild, and have a stable overall safety of combination therapy.

Association Between New Unconfirmed Bone Lesions and Outcomes in Men With Metastatic Castration-Resistant Prostate Cancer Treated With Enzalutamide

For men with metastatic castration-resistant prostate cancer (mCRPC) whose condition is responding to enzalutamide, new unconfirmed bone lesions detected at posttreatment scinitigraphy may reflect an osteoblastic reaction that represents healing, known as pseudoprogression, which can lead to premature discontinuation of therapy. To determine the association between new unconfirmed lesions detected on a follow-up bone scintigram (bone scan) and outcomes in enzalutamide-treated men with mCRPC. This post hoc, retrospective secondary analysis of 1672 enzalutamide-treated men from 2 phase 3, randomized mCRPC studies (PREVAIL and AFFIRM) before or after treatment with docetaxel was conducted from April 12, 2018, to July 25, 2019. Participants were men from the enzalutamide groups of the 2 studies with a decrease in prostate-specific antigen level at any time or with stable disease or soft-tissue disease responding to treatment based onradiologic findings. Enzalutamide, 160 mg once daily. The clinical significance of new lesions detected on the first (early) or second (late) posttreatment bone scan, without an unfavorable change in prostate-specific antigen level or soft-tissue progression, was investigated. Associations of new unconfirmed lesions with radiographic progression-free survival, overall survival, decrease in prostate-specific antigen level, objective response in soft tissue, and quality of life were evaluated. Among the 643 men (median age, 72 years [range, 43-93 years]) in PREVAIL, early and late unconfirmed lesions were observed in 177 men (27.5%) with stable disease or disease responding to enzalutamide. Among the 404 men (median age, 70 years [range, 41-88 years]) in AFFIRM, early and late unconfirmed lesions were observed in 73 men (18.1%) with stable disease or disease responding to enzalutamide. In PREVAIL, men with new unconfirmed lesions had median radiographic progression-free survival (hazard ratio [HR], 1.37 [95% CI, 0.81-2.30]; P = .23) and median overall survival (HR, 1.25 [95% CI, 0.85-1.83]) in the chemotherapy-naive setting similar to men those of men without such new lesions. In AFFIRM, the median overall survival (HR, 1.94 [95% CI, 1.10-3.44]) was reduced among men with unconfirmed bone lesions, but the median radiographic progression-free survival was not reduced (HR, 1.21 [95% CI, 0.83-1.75]; P = .32). Quality of life over time was similar regardless of the presence of new unconfirmed lesions detected on a follow-up bone scan in either setting. These results suggest that new unconfirmed lesions detected on follow-up bone scans may represent pseudoprogression in men with mCRPC and are indicative of a favorable treatment response to enzalutamide. The detection of new unconfirmed bone lesions in men with mCRPC that responded to treatment with enzalutamide after docetaxel appears to be associated with worse overall survival and may represent true progression, thus highlighting the need for improved functional bone metastasis imaging. ClinicalTrials.gov Identifiers: NCT01212991 and NCT00974311.

18F-choline positron emission tomography/computed tomography for the detection of prostate cancer relapse: assessment of maximum standardized uptake value correlation with prostate-specific antigen levels.

Patients with prostate cancer are monitored by prostate-specific antigen (PSA) evaluation and PET [PET/computed tomography (CT)]. The aim of our study was to evaluate correlations between PSA levels and standardized uptake values (SUV) in patients with recurrent prostate cancer. We analyzed 282 prostate cancer patients undergoing PET-CT due to suspicion of recurrence. Levels of PSA and PSA change per month were analyzed, together with maximum standardized uptake value (SUVmax). PET/CT results were positive in 175 patients (62.1%) and negative in 107 patients (37.9%). In the positive group, PSA levels were significantly higher. The ROC curve analysis indicated PSA level of 1.70 ng/ml and PSA level change in time of 0.12 ng/ml are the optimal cut-off values. Patients were divided into subgroups: with metastases (M), local relapse (L), and local relapse and metastases (M + L). The latest PSA levels, were similar in subgroups L and M: 5.00 (2.98-10.30) ng/ml and 3.90 (1.27-14.08) ng/ml, but lower than in subgroup M + L: 12.43 (6.08-49.36) ng/ml. PSA level change in time was similar in the subgroups L and M: 0.63 (0.09-1.00) ng/ml/month and 0.33 (0.02-1.73) ng/ml/month, but lower in subgroup M + L: 2.21 (0.22-10.34) ng/ml/month, P < 0.05. SUVmax was significantly (P < 0.05) lower in subgroup L than in M and L + M: 3.00 (2.30-4.00), 4.60 (2.70-7.40), and 4.90 (3.80-8.00), respectively. PSA level significantly correlated with SUVmax in patients from subgroups L (R = 0.424; P < 0.05) and M (R = 0.314; P < 0.01). Positive correlation between PSA change and SUVmax was observed in subgroup M + L (R = 0.561; P < 0.01) and M (R = 0.270; P < 0.05). The study confirmed that patients with high PSA level and fast PSA increase are likely to be diagnosed with both, local relapse and metastases. Moreover, SUVmax values in metastatic lesions are usually higher.

Abstract 430: Prostate specific antigen (PSA) as a diagnostic and prognostic marker of prostate cancer

Abstract Since several decades, prostate specific antigen (PSA) is regarded as a specific marker for healthy and neoplastic prostate tissues, and PSA level changes in blood and tissue are discussed as prognostic markers of prostate cancer. Using a custom-made mouse monoclonal anti-PSA antibody, we studied expression of PSA in a tissue microarray (TMAs) comprising 17,456 prostate cancers with long-term follow-up data. PSA staining was typically present in the cytoplasm and pronounced at the apical cell pole. PSA expression was often reduced (15%) or even completely lost (1%). Reduction of PSA expression was significantly linked to adverse features of prostate cancer, including advanced stage, high classical and quantitative Gleason grade, presence of lymph node metastasis, a positive surgical margin, increased cell proliferation, and reduced time to recurrence (p&amp;lt;0.0001 each). Complete lack identified a small subset of patients with the worst prognosis. There was also in impact of the subcellular localization of PSA expression: Loss of the apical staining pattern worsened the prognosis in cancers with otherwise identical levels of cytoplasmic staining. In a multivariable analysis including pT stage, Gleason grade, nodal stage, and resection margin status, loss of PSA expression proved to predict outcome independently from these parameters. Of note, PSA even stratified the prognosis of 971 cancers harboring PTEN deletions in our cancer set. In conclusion, gradual reduction of PSA staining, including a loss of the apical staining pattern, is a strong and independent prognostic marker in prostate cancer. Citation Format: Ronald Simon, Martina Kluth, Kristine Fischer, Sarah Bonk, Claudia Hube-Magg, Doris Höflmayer, Maximilian Lennartz, Florian Lutz, Guido Sauter, Franziska Büscheck, Ria Uhlig, David Dum, Andreas M. Luebke, Corinna Wittmer, Frank Jacobsen, Eike Burandt, Stefan Steurer, Waldemar Wilczak, Sarah Minner. Prostate specific antigen (PSA) as a diagnostic and prognostic marker of prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 430.

PO-519 Can PSA level and its change in time predict localization of proastate cancer relapse, assesed by PET-CT with 18F-Choline?

IntroductionPatients with prostate cancer after treatment are routinely monitored by Prostate Specific Antigen (PSA) level evaluation and occasionally referred to Positron Emission Tomography (PET-CT) for verification and assessment of relapse and/or metastases. The aim of our study was to evaluate the value of measurements of PSA level and its changes by quantitative PET parameter Standardised Uptake Values (SUV) in patients with recurrent prostate cancer.Material and methodsWe retrospectively collected PET-CT, performed using Discovery IQ scanner (GE Healthcare), 3 and 20 min after injection of 18F-choline (3 MBq/kg). Biopsy-proven prostate cancer patients undergoing a PET-CTscan due to the suspicion of recurrence after treatment were enrolled into the study and subgroup of subjects with recurrent disease, confirmed by positive PET-CT were analysed. Plasma levels of PSA at the time of PET-CT and PSA level change per month (ΔPSA) prior to the scan were analysed, together with SUVmax. Results are shown as median values and interquartile range.Results and discussionsThe study cohort included three subgroups, diagnosed by visual PET-CT evaluation: 27 patients with only local cancer recurrence (R), 110 with distant metastases (M) and 35 subjects with both local recurrence and metastases (R+M). PSA levels at the time of PET-CT were similar in R and M groups: 5,00 (2,98–10,30) ng/ml and 3,90 (1,27–14,08) ng/ml, but significantly (p<0,05) lower than in R+M group: 12,43 (6,08–49,36) ng/ml. ΔPSA was similar in R and M groups: 0,63 (0,09–1,00) ng/ml/month and 0,33 (0,02–1,73) ng/ml/month, but lower than in R+M: 2,21 (0,22–10,34) ng/ml/month, p<0,05. SUVmax was significantly (p<0,05) lower in R subjects than in both M and R+M groups: 3,00 (2,30–4,00); 4,60 (2,70–7,40) and 4,90 (3,80–8,00), respectively.ConclusionPSA levels and PSA changes in time are higher in patients with simultaneous local recurrence and metastatic spread than in patients with either isolated local recurrence or distant metastases. Local recurrence present with lower values of SUVmax than metastases.

PO-101 Relation between PSA level, its dynamics and performance of 18F-choline PET-CT in recurrent prostate cancer

IntroductionPET-CT using 18F-choline is widely used in diagnosis of prostate cancer local recurrence and metastases, whereas Prostate Specific Antigen (PSA) measurement is routinely used for biochemical monitoring. The purpose of our study was to evaluate performance of PET-CT with 18F-choline in relation to the PSA level or its change in time, in patients with biochemically diagnosed recurrent prostate cancer.Material and methods263 consecutive prostate cancer patients with elevation of PSA after treatment were included into the study. PSA values were evaluated at the time of PET scan (not more than 30 days before) and the PSA level change (ΔPSA) was calculated as a per month difference between two recent measurements. PET-CT was performed using Discovery IQ scanner (GE Healthcare ), 3 and 20 min after injection of 18F-choline (3 MBq/kg). Data are shown as median values (quartiles).Results and discussionsIn 164 patients, in whom PET-CT scan was positive and has shown local recurrence or metastases both the PSA level [5,85(2,09;17,37)] ng/ml and ΔPSA [0,54 (0,06;2,00)] ng/ml/month were significantly (p<0.01) higher than in 99 subjects with negative PET-CT: 1,23 (0,25;3,59) ng/ml and 0,00 (-0,11;0,10) ng/ml/month, respectively. The ROC curve analysis has indicated that PSA level of 1,70 ng/ml and ΔPSA of 0,12 ng/ml/month are the optimal cut-off values, with sensitivity 80, 9% and 70,2% and specificity 69.1% and 84.3%, for PSA and ΔPSA respectively.ConclusionDiagnostic performance of 18F-choline PET-CT in patients with recurrent prostate cancer is dependent on the level of PSA and its change in time. The calculated cut-off values can be used to select patients who would benefit from PET-CT.

Computer vision detects subtle histological effects of dutasteride on benign prostate.

To determine whether a computer vision-based approach applied to haematoxylin and eosin (H&E) prostate biopsy images can distinguish dutasteride-treated tissue from placebo, and identify features associated with degree of responsiveness to 5α-reductase inhibitor (5ARI) therapy. Our study population comprised 100 treatment-adherent men without prostate cancer assigned to dutasteride or placebo in the REDUCE trial, who had slides available from mandatory year-4 biopsies. Half of the men also provided slides from a year-2 biopsy. We obtained 20× whole-slide images and used specialized software to generate a library of 1 300 epithelial and stromal features from objects comprising superpixels and several types of nuclei, including spatial relations among objects between and within each hierarchical level. We used penalized logistic regression and fivefold cross-validation to find optimal combinations of histological features in the year-4 biopsies. Feature data from the year-2 biopsies were fitted to a final model for independent validation. Two pathologists, blinded to treatment, scored each image for focal atrophy and histological features previously linked to 5AR1 treatment. Consensus classification by pathologists obtained a discrimination accuracy equivalent to chance. A 21-feature computer vision model gave a cross-validation area under the curve of 0.97 (95% confidence interval [CI] 0.95-0.99) in the year-4 biopsies and 0.79 (95% CI: 0.65-0.92) in the set-aside year-2 biopsies. Histology scores were not correlated with change in prostate-specific antigen level, serum dihydrotestosterone level or gland volume. Key features associated with dutasteride treatment included greater shape and colour uniformity in stroma, irregular clustering of epithelial nuclei, and greater variation in lumen shape. The present findings show that a computer vision approach can detect subtle histological effects attributable to dutasteride, resulting in a continuous measure of responsiveness to the drug that could eventually be used to predict individual patient response in the context of BPH treatment or cancer chemoprevention.