PSA Increase Research Articles

Efficacy of sequencing of cytotoxic and endocrine therapies in veterans with metastatic castration-resistant prostate cancer (mCRPC).

e16501 Background: The optimal sequencing of therapies in the treatment of mCRPC has not been established. We examined the efficacy of one to two lines of endocrine therapy with chemotherapy sequencied before or in between endocrine therapies versus without chemotherapy. Methods: We prospectively enrolled 103 male veterans from 2013 to 2016 receiving abiraterone or enzalutamide for mCRPC therapy. Participants received usual care. Through chart review, for each line of therapy, we analyzed progression-free survival (PFS), defined as PSA increase 25% and 2ng/mL above nadir and confirmed by a second value, and PSA response rate, defined as a 50% PSA reduction from baseline at treatment initiation, for participants receiving various sequences of endocrine therapies with or without docetaxel chemotherapy. Results: We observed no statistically significant differences between the above measures except for an improvement in PFS when comparing those that received two lines of endocrine therapy without chemotherapy between treatments to those with who received chemotherapy between treatments ( p-value = 0.027, Log-rank test). Conclusions: There were no compelling clinically significant differences noted in PFS or PSA response rate amongst the various sequences of endocrine and cytotoxic therapies. Our results suggest that various sequences of therapy may yield similar results. Larger randomized studies analyzing sequencing of therapies will help determine if cross-resistance arises with use of multiple therapies. [Table: see text]

A review of pomegranate in prostate cancer.

BackgroundPreclinical studies showing that pomegranate juice and its components inhibit prostate cancer led to multiple clinical trials to determine whether pomegranate products could slow the growth of prostate cancer. This review summarizes the preclinical data and discusses the results of the clinical trials.MethodsTrials targeted patients on active surveillance, neoadjuvant patients, patients with biochemical recurrence (BCR) following local therapy for prostate cancer, and patients with metastatic castration-resistant prostate cancer (mCRPC).ResultsIn the BCR patient population, early phase II trials of both pomegranate juice and extract showed significant lengthening of PSA doubling time (PSADT), and confirmed the safety of pomegranate products. While a placebo-controlled phase III trial determined that pomegranate extract did not significantly prolong PSADT in BCR patients, a preplanned subset analysis of patients with the manganese superoxide dismutase (MnSOD) AA genotype showed greater PSADT lengthening on the pomegranate extract arm. In the neoadjuvant population, a large trial demonstrated a significant increase in urolithin A and a non-significant reduction in 8-OHdG, a marker of oxidation in prostate cancer tissue, on the pomegranate arm vs. the placebo arm. In addition, a randomized clinical trial of a polyphenol-rich multi-component food supplement tablet, including 31.25% pomegranate extract, found significant slowing of PSA increase in the food supplement arm vs. placebo in men on active surveillance and those experiencing biochemical recurrence.ConclusionsPomegranate juice and extract are safe but did not significantly improve outcomes in BCR patients in a large placebo controlled trial. However a subset of BCR patients with the MnSOD AA genotype appear to respond positively to the antioxidant effects of pomegranate treatment. Phase II trials of 100% pomegranate products in neoadjuvant patients and patients with mCRPC were negative. A multi-component food supplement showed promising results in a phase II study in active surveillance and BCR patients.

Long‐term clinical impact of PSA surge in castration‐resistant prostate cancer patients treated with abiraterone

Early changes in PSA have been evaluated in association to treatment outcome. The aim of this study was to assess PSA surge phenomenon in castration-resistant prostate cancer (CRPC) patients treated with abiraterone and to correlate those variations with long-term treatment outcome. We retrospectively evaluated 330 CRPC patients in 11 Italian hospitals, monitoring PSA levels at baseline and every 4 weeks. Other clinical, biochemical and molecular parameters were determined at baseline. We considered PSA surge as PSA increase within the first 8 weeks from starting abiraterone more than 1% from baseline followed by a PSA decline. The log-rank test was applied to compare survival between groups of patients according to PSA surge. The impact of PSA surge on survival was evaluated by Cox regression analyses. A total of 330 patients with CRPC, median age 74 years (range, 45-90), received abiraterone (281 chemotherapy-treated and 49 chemotherapy-naïve). PSA surge was observed in 20 (7%) post-chemotherapy and 2 (4%) chemotherapy-naïve patients. For overall patients presenting PSA surge, timing of PSA peak from baseline was 5 ± 1.8 weeks and PSA rise from baseline was 21 ± 18.4%. The overall median follow-up was 23 months (range 1-62). No significant differences in progression-free survival and overall survival were observed between patients with and without PSA surge (P = 0.16 and =0.86, respectively). In addition, uni- and multivariate analyses showed no baseline factors related to PSA surge. PSA surge occurs in both chemotherapy-treated and chemotherapy-naïve patients treated with abiraterone resulting, however, in no long-term impact on outcome. Physicians and patients should be aware of PSA surge challenge to prevent a premature discontinuation of potentially effective therapy with abiraterone. Further larger and prospective studies are warranted to investigate this not infrequent phenomenon.

AR amplification eradication with high-dose testosterone (T) in patients with heavily pretreated mCRPC.

251 Background: Patients (Pts) with mCRPC resistant to novel hormones (abi/enza) and taxanes pose a challenge for clinicians. Typically, once these agents are exhausted, clinical trials represent the best therapeutic option; however, many pts are not appropriate for clinical trials due to marrow suppression and/or extensive pre-treatments. Herein we present limited experience with three pts treated with high dose T when therapeutic clinical trial options were not available. Methods: Data was retrospectively collected at Tulane Cancer Center for pt treatment history, laboratory parameters, and circulating free-DNA genomic testing. High dose testosterone was used at a dose of 87.5-100 mg given daily as a 1% testosterone gel applied to the skin. Results: All the mCRPC patients were pre-treated with abi, enza, taxanes, & radium-223. All pts had RBC transfusions due to marrow suppression. All patients were previously treated on clinical trials. After starting high dose T, pt 1 demonstrated a clinical improvement in energy and appetite with a PSA decline from 530 to 45.8 ng/ml (-91.4%) over 30 days. At baseline, cfDNA analyses measured 15.9X AR amplification and 3.7X MYC amplification. The cfDNA also contained 9.8% of P53R273H mutation. Post high-dose T (serum T from castrate to 1462 ng/dL), both of the cfDNA measured amplifications returned to normal and P53 mutation declined to 0.5%. The PSA nadir occurred 30 days after T start; T was stopped 96 days after starting because of PSA rise to 280 ng/ml. The pt then restarted abi, despite prior resistance, and PSA declined from 280 to 65 ng/ml (-76.6%). The 2 other patients had PSA increases and clinical deterioration and high dose T was stopped after 2-3 weeks. Conclusions: Response to high dose T has been reported in occasional case reports going back over 60 years ago (see Brendler H et al. Arch Surg 1950;61:433–40). The frequency of favorable responses is unknown. In one case, a reversal of AR and MYC amplification was observed. The responding patient then was re-sensitized to abi, a drug to which he was previously resistant. Further research, such as the TRANSFORMER trial, is needed to understand the molecular changes and treatment options for this population.

2114 - Feasibility and acceptability of follow-up care for prostate cancer in primary care

Background The number of prostate cancer patients is high and will increase further due to the ageing population. Follow-up for prostate cancer will therefore put an increasing demand on health care capacity and costs. Increasing the role of the GP in follow-up for prostate cancer may help to limit the work load in secondary care and reduce costs. Before testing cost-effectiveness in a large trial, feasibility and acceptability should first be tested in a smaller sample. Methods We tested the feasibility and acceptability of a new clinical pathway for patients with prostate cancer in a stable phase aged ≥65 years and with comorbidity. Follow-up for prostate cancer was transferred to the GP and patients were followed for one year. We aimed to include 20 patients. Participating GPs and urologists jointly developed a protocol. Patient satisfaction regarding GP care was measured 0 and 12 months after transfer of care to the GP with the subscale ‘personalized care’ of the Consumer Quality Index GP-care. Next, patients, GPs and urologists were interviewed about their experiences. We considered the clinical pathway successful if no patients were referred back to the urologist except for an increase in PSA, and if the majority of patients and participating urologists and GPs were satisfied. Results Of the 20 patients included in the study, three were referred back to the urologist because of increasing PSA levels and one died (unrelated to prostate cancer). Most patients (73%) were satisfied with the transfer of care, indicated by a score of 3 or higher on the subscale ‘personalized care’. GPs and urologists were confident in GPs’ ability to provide follow-up for prostate cancer and preferred to continue this. Conclusions The new clinical pathway was successful. This warrants a larger study to provide evidence for the (cost-) effectiveness of GP-led prostate cancer follow-up.

Prostate-Specific Antigen Flare Phenomenon Induced by Abiraterone Acetate in Chemotherapy-Naive Patients With Metastatic Castration-Resistant Prostate Cancer

BackgroundProstate-specific antigen (PSA) flare is a well-known phenomenon in patients with prostate cancer treated with luteinizing hormone-releasing hormone agonist and chemotherapy. However, its incidence and the significance for the clinical outcomes of patients treated with abiraterone acetate (AA) are uncertain. Patients and MethodsA multicenter retrospective analysis of chemotherapy-naive patients treated with AA for metastatic castration-resistant prostate cancer (mCRPC) was conducted. The baseline characteristics, treatment history of mCRPC, and serum PSA kinetics during AA treatment were collected. The log-rank test was applied to compare progression-free survival (PFS) between patient groups with a PSA flare according to the different definitions and immediate PSA declines. ResultsThe data from 83 patients were analyzed. An immediate PSA decline of any amount was observed in 59 patients (71.1%). According to the various definitions of PSA flare, its incidence ranged from 6.0% to 10.8%. Although the median interval to the peak PSA level was 0.95 month, regardless of the PSA flare definition, the interval to the PSA nadir showed a wide range of 2.8 to 7.6 months. In PSA flare subgroup, the median PFS in patients with any PSA decline to less than the baseline and > 30% decline from the baseline was 12.4 months. The PFS duration of PSA flare patients did not significantly differ from that of patients with an immediate PSA decline of any amount and immediate > 30% decline without PSA flare. ConclusionThe PSA flare phenomenon is not rare event during AA treatment. A PSA decline during AA treatment, with or without a PSA flare, was associated with favorable clinical outcomes. Thus, AA should not be withdrawn early in patients with mCRPC in whom an initial, isolated PSA increase has been observed.

MP57-01 THE DIAGNOSTIC ACCURACY OF 68GA-PSMA-PET/CT FOR DETECTION OF LYMPH NODE METASTASES IN THE SETTING OF SALVAGE LYMPH NODE DISSECTION

INTRODUCTION AND OBJECTIVES: Accurate imaging of lymph node metastases (LNM) is a prerequisite for metastases directed therapies such as salvage lymph node dissection (salvage-LND) in nodal recurrent prostate cancer (PCa). Our aim was to evaluate the diagnostic accuracy of 68PSMA-PET/CT (DKFZ-11) for nodal relapse of PCa according to different topographical locations and the size of tumor deposits in lymph nodes (LN). METHODS: 25 patients with the suspicion of nodal PCa-relapse after primary therapy underwent pelvic and/or retroperitoneal salvage-LND after a whole body PET/CT with 68Ga-PSMA showing PET-positive lesions. Time from PET/CT to salvage-LND was median 2.3 months. Diagnostic accuracy of PET/CT for dissected main-regions (pelvic left/right, retroperitoneal) and subregions (common, external, internal iliac, obturatoria, presacral, aortic-bifurcation, aortal, caval, interaortocaval) was determined by comparing histopathologic results with PET/CT-findings. Size ofmetastatic infiltration inLNwasmeasuredbasedonhistopathology. RESULTS: Mean PSA at salvage-LND was 3.03 ng/ml (SD 3.2 / median 1.74 ng/ml). Overall, 833 LN were resected in 25 patients, containing 98 LNM, corresponding to a mean of 33.3 LN and 3.9 LNM per patient. In 5 patients (8 subregions) tissue containing solid non-nodal local relapse was additionally resected. LN were removed in portions out of 10 subregions per patient leading to 251 subregions available for evaluation. Median 3 LN were removed per subregion. For 2/25 patients and in 7/251 subregions, the suspected tumor involvement was verified by follow-up PET/CT showing progress of the lesions and PSA increase. 35/60 (58.3%) of the main regions and 63/251 (25%) of the subregions were PET-positive. Sensitivity, specifity, positive predictive value (PPV), negative predictive value (NPV) and accuracy based on a main-region analysis was 92.1% (35/38), 100% (22/22), 100% (35/35), 88.0% (22/25) and 95.0% (57/60). Based on a subregion-analyses sensitivity, specifity, PPV, NPV and accuracy was 80.7 % (63/78), 100% (173/173), 100% (63/63), 92.0% (173/188) and 94.0% (236/251). Median diameter (6 mm) of tumor deposits in LNM removed from true-positive subregions was significantly different to LNM resected from false-negative subregions (2 mm) (p<0.0001). CONCLUSIONS: 68PSMA-PET/CT shows high diagnostic accuracy for detection of LNMand served therefore as an essential guidance for salvage-LND. LNM removed from false-negative subregions were significantly smaller compared to LNM removed from true-positive subregions.

Radium-223 in Heavily Pretreated Metastatic Castrate-Resistant Prostate Cancer

BackgroundRadium-223 is a bone-targeting radiopharmaceutical that extends survival in mCRPC. Postapproval data are limited, and the value of biochemical and radiologic monitoring during radium therapy is unknown. Patients and MethodsWe conducted a retrospective study of 29 patients with mCRPC who received radium-223 at 1 of 3 participating institutions between August 2013 and December 2014. Trend of PSA, radiographic changes, and association of biochemical and clinical variables with PSA trend were measured. ResultsThe median age of patients was 70 years, 79% of patients (N = 23) were European Americans, and 17% of patients (N = 5) were African Americans. Twenty patients (69%) had received at least 3 lines of prior therapies. Some 38% of patients (N = 11) received all 6 cycles of radium-223. Twenty patients (69%) had an increase in PSA during radium therapy, and 4 patients (14%) had a decline in PSA levels. Five patients had visceral metastases on computed tomography imaging performed during the course of radium-223. ConclusionsRadium therapy in mCRPC was associated with an increase in PSA in the majority of these heavily pretreated patients. The development of visceral disease was not uncommon, suggesting a need for follow-up computed tomography monitoring during radium-223 therapy. The significance of early increases in PSA and pain with radium-223 is still uncertain. Although pain and PSA flare have been reported in patients who subsequently have a dramatic response to therapy, we observed that a PSA increase or pain flare correlates to an improvement in bone scans only in a minority of patients.

Longitudinal tracking of subpopulation dynamics and molecular changes during LNCaP cell castration and identification of inhibitors that could target the PSA-/lo castration-resistant cells.

We have recently demonstrated that the undifferentiated PSA−/lo prostate cancer (PCa) cell population harbors self-renewing long-term tumor-propagating cells that are refractory to castration, thus representing a therapeutic target. Our goals here are, by using the same lineage-tracing reporter system, to track the dynamic changes of PSA−/lo and PSA+ cells upon castration in vitro, investigate the molecular changes accompanying persistent castration, and develop large numbers of PSA−/lo PCa cells for drug screening. To these ends, we treated LNCaP cells infected with the PSAP-GFP reporter with three regimens of castration, i.e., CDSS, CDSS plus bicalutamide, and MDV3100 continuously for up to ~21 months. We observed that in the first ~7 months, castration led to time-dependent increases in PSA−/lo cells, loss of AR and PSA expression, increased expression of cancer stem cell markers, and many other molecular changes. Meanwhile, castrated LNCaP cells became resistant to high concentrations of MDV3100, chemotherapeutic drugs, and other agents. However, targeted and medium-throughput library screening identified several kinase (e.g., IGF-1R, AKT, PI3K/mTOR, Syk, GSK3) inhibitors as well as the BCL2 inhibitor that could effectively sensitize the LNCaP-CRPC cells to killing. Of interest, LNCaP cells castrated for >7 months showed evidence of cyclic changes in AR and the mTOR/AKT signaling pathways potentially involving epigenetic mechanisms. These observations indicate that castration elicits numerous molecular changes and leads to enrichment of PSA−/lo PCa cells. The ability to generate large numbers of PSA−/lo PCa cells should allow future high-throughput screening to identify novel therapeutics that specifically target this population.

To assess the clinical effect of radium 223 (Ra223) in patients with progressive symptomatic bone metastases on a background of metastatic castrate resistant prostate cancer (mCRPC).

347 Background: Ra223 is the first radiopharmaceutical shown in the ALSYMPCA trial to improve survival and achieve a tolerable safety profile in patients with symptomatic bone metastases. It remains unclear as to where Ra223 is best placed in the treatment pathway of CRPC. We assessed the effect of Ra223 in mCRPC in terms of biochemical and clinical response. Methods: Retrospective analysis of mCRPC patients treated with Ra223 via CDF between Dec 2013-May 2015. Clinical benefit assessed by pain response. Toxicities graded as per CTCAE V 4. Results: 58 patients, median follow up 11.6 (1.0-18.1) months. Median age 71 (54-84); median WHO PS 1 (0-2). 58 patients received 50kBq/kg, median number of cycles 5 (1-6). 43% and 33% completed 6 and 3 cycles respectively. Median number of previous treatments 3 (1-6). 52%, 17% and 5 % received prior Docetaxel, Bisphosphonates and Strontium respectively. Median time from radiotherapy for symptomatic bone metastases to initiation of Ra 223 was 433 days. Incidence of Grade (G) 3/ 4 events 5% ; 2% G3 anaemia, 3% G3 neutropenia and 0% G3 thrombocytopenia. No treatment related deaths. 5% developed a skeletal related event, mean time of development from completion of Ra223 was 218 days. Median PSA pre v post treatment was 225 and 418. Median ALP (Alkaline Phosphatase) pre v post treatment was 292 and 138. Median Hb (Haemoglobin) pre v post treatment was 118 and 103. 50% patients had a clinical response. Whilst no significant association was seen between clinical benefit and change in PSA (p 0.973) or ALP (p 0.455) across this cohort, a number of patients had a sharp increase in PSA and decrease in ALP with no clinical benefit and clinical benefit respectively. 36/58 (62%) are alive; 16/58 (44%) alive with progressive disease. Median PFS 7.23 months (95% c.i. 5.73, 7.93) and median OS 8.33 months ((95% c.i. 5.65-13.50). Conclusions: Ra223 is safe and effective in pre-treated mCRPC patients. PSA response is not clinically meaningful whereas ALP may be a useful adjunct in measuring response. The optimum sequence is yet to be defined but better selection and earlier use in patients with predominant bone only disease should be considered.

Defining the optimal PSA range for the maximal predictive efficacy of PSA density to detect prostate cancer on biopsy: Results from a multi-institutional and prospective contemporary cohort.

70 Background: PSA density (PSAD) is an important predictor of prostate cancer (PCa). We assessed whether the predictive accuracy of PSAD varied based on the range of PSA or whether the patient had a previous negative prostate biopsy (PB). Methods: We assessed a prospective cohort of men who were referred for a PB due to suspicion of PCa at 26 different sites across USA. The area under the receiver operating characteristic curve (AUC) was used to assess the added predictive accuracy of PSAD versus PSA across 3 different PSA ranges ( &lt; 4, 4 – 10, &gt; 10 ng/mL) and in men with or without a prior negative PB for the detection of any and significant (Gleason ≥ 7) PCa. Results: Of the 1,290 men, 585 (45%) and 284 (22%) had any and significant PCa, respectively. PSAD was significantly more predictive than PSA for detecting any PCa in the PSA ranges of 4 – 10 (AUC 0.70 vs 0.53, P &lt; 0.00001) and &gt; 10 (AUC 0.84 vs 0.65, P &lt; 0.00001) ng/mL. Similarly, for significant PCa, PSAD was more predictive than PSA in the PSA ranges of 4 – 10 (AUC 0.72 vs 0.57, P &lt; 0.00001) and &gt; 10 (AUC 0.82 vs 0.68, P = 0.0001) ng/mL. Furthermore, PSAD was significantly more predictive than PSA in detecting PCa in men that had a prior negative PB (AUC 0.69 vs 0.56, P = 0.0001 for any PCa and AUC 0.81 vs 0.70, P = 0.0042 for significant PCa), and those that didn’t (AUC 0.72 vs 0.67, P = 0.0001 for any PCa and AUC 0.77 vs 0.73, P = 0.0026 for significant PCa). However the difference between the AUC of PSAD and PSA (ΔAUC) was a lot more pronounced in men that had a prior negative PB (ΔAUC = 0.13 for any PCa and ΔAUC = 0.11 for significant PCa) as opposed to those that didn’t (ΔAUC = 0.05 for any PCa and ΔAUC = 0.04 for significant PCa), suggesting that PSAD is a much better predictor than PSA alone in men who have undergone a previous PB. Conclusions: As PSA increases, the predictive accuracy of PSAD over PSA appears to improve for the detection of any PCa and significant PCa. Additionally, PSAD has a more pronounced predictive value over PSA in detecting any and significant PCa in men who have undergone a prior negativePB. We support the use of PSAD testing to avoid unnecessary biopsies in men who have elevated PSA secondary to an enlarged prostate.

Non Selective Inhibition of COX Activity Reversed Inflammation and Reactive Oxygen Radicals Mediated Prostate Cancer Risk and Decreased Disease Progression in Preclinical Model

Prostate cancer (PCa) represents the most frequent urologic diagnosis in elderly males. We have previously shown that exposure of prostate to lipopolysaccharide (LPS) promotes cancer risk. We investigated the effect of non-selective cyclooxygenase (COX) inhibition on prostate inflammation-mediated cancer risk in vivo. The prostates of male rats were inoculated with E. coli as sources of inflammatory molecules (LPS) and were treated with COX inhibitor, aspirin 2 mg/Kg orally for 14 days or PBS. Oxidative stress was induced with two 2 mls of hydrogen peroxide orally twice daily or PBS for 14 days; they were either treated with COX inhibitor or PBS for another 14 days. Blood was collected and analyzed for acid phosphatase and PSA. Data showed presences of LPS in the prostate of the rats resulted in gradual increase in PSA when compared to control (P P 2O2 had 2.5 fold increase in acid phosphatase (ACP) compared control (P P ity in rats.

Double métastase ganglionnaire d’un adénocarcinome prostatique et d’un carcinome urothélial et revue de la littérature

Tumor collision is the encounter of two tumors from two different topographical sites. Cases of metastatic lymph node collision are exceptional. We report the case of a metastatic lymph node collision of an urothelial carcinoma and a prostatic adenocarcinoma. A 61-year-old man was hospitalized for a right nephroureterectomy with peri-ureteral lymph node dissection. He was followed since 2004 for prostatic adenocarcinoma and treated with radical prostatectomy then radiation therapy 4 years later due to a new increase of PSA. In the follow-up, an urothelial carcinoma of the lower right ureter was discovered in 2014. Histological analysis of a peri-ureteral lymph node showed a double metastasis of urothelial and prostatic origin. The prostatic adenocarcinoma was composed of acinar and ductal subtypes. Immunohistochemical study including CK7, CK20, PSA, GATA3, P63 antibodies confirmed the distinct phenotype of the 2 tumors. Metastatic collision of urothelial carcinoma and prostatic adenocarcinoma has been reported in 4 cases only. Our review of literature shows that prostatic adenocarcinoma always precedes the urothelial carcinoma. Immunohistochemical study, when carried out for distinguishing both tumors, should include CK7, CK20 and PSA. GATA3, androgen receptor and P63 could be added in a second time.

Predictors of Participation in Prostate Cancer Screening among Older Men in Jordan.

Participation is one of the major factors affecting the long-term success of population-based prostate cancer screening programs. The aim of this study was to explore strong factors linked to participation in prostate cancer screening among older Jordanian adults using the Health Belief Model (HBM). Data were obtained from Jordanian older adults, aged 40 years and over, who visited a comprehensive health care center within the Ministry of Health. A pilot test was conducted to investigate the internal consistency of the the Champion Health Belief Model Scale for prostate cancer screening and the clarity of survey questions. Sample characteristics and rates of participation in prostate cancer screening were examined using means and frequencies. Important factors associated with participation in prostate cancer screening were examined using bivariate correlation and multivariate logistic regression analysis. About 13% of the respondents had adhered to prostate cancer screening guidelines over the previous decade. Four out of the seven HBM-driven factors (perceived susceptibility, benefits and barriers to PSA test, and health motivation) were statistically significant. Those with greater levels of susceptibility, benefits of PSA test and health motivation and lower levels of barriers to PSA testing were more likely to participate in prostate cancer screening. Family history, presence of urinary symptoms, age, and knowledge about prostate cancer significantly predicted the participation in prostate cancer screening. Health professionals should focus more on the four modifiable HBM-related factors to encourage older adults to participate in prostate cancer screening. Intervention programs, which lower perceived barriers to PSA testing and increase susceptibility, benefits of PSA testing and health motivation, should be developed and implemented.

Early side effects and first results of radioligand therapy with (177)Lu-DKFZ-617 PSMA of castrate-resistant metastatic prostate cancer: a two-centre study.

BackgroundRadioligand therapy (RLT) with 177Lu-DKFZ-617 PSMA (Lu-PSMA) (prostate-specific membrane antigen) is a novel targeted therapy of metastatic prostate cancer. We analysed retrospectively the early side effects and the response rate in the first patients, who received a therapy with Lu-PSMA in our departments.MethodsRLT was performed in ten hormone- and/or chemo-refractory patients with distant metastases and progressive disease (mean age 73.5 years). 68Ga-PSMA HBED-CC PET/CT was performed in all patients prior to RLT. The median PSA level prior to the therapy was 298.5 ng/ml (range 5–853 ng/ml). All patients received CBC, renal and liver function tests the day before and 2 days after application (mean administered activity 5.6 GBq, range 4.1–6.1 GBq), followed by further tests every 2 weeks. All patients were contacted by telephone every week regarding side effects or any positive and negative changes.ResultsEight weeks after the therapy, seven patients (70 %) experienced a PSA decline, of whom six experienced more than 30 % and five more than 50 %. Three patients showed a progressive disease according to the PSA increase. No patient experienced any side effects immediately after injection of Lu-PSMA. Relevant hematotoxicity (grade 3 or 4) occurred 7 weeks after the administration in just one patient. The same patient showed a leucopenia grade 2. Two patients showed a disturbance of only 1 hematologic cell line, whereas one patient showed a reduction of grades 1 and 2 in leucocytes and thrombocytes, respectively. Six patients did not show any hematotoxicity during the 8 weeks after therapy. There was no relevant nephrotoxicity (grade 3 or 4).ConclusionsOur initial results indicate that RLT with Lu-PSMA is safe and seems to have low early side-effect profile. A relevant PSA decline was detected in 70 % of patients.

The effect of bicycling on PSA levels: a systematic review and meta-analysis.

Recent literature has suggested that bicycling may be associated with increases in serum PSA levels, a diagnostic and prognostic marker for prostate cancer. To further investigate this relationship, we conducted a systematic review and meta-analysis of current literature in this field. MEDLINE, CENTRAL, CINAHL and SPORTDiscus were searched using MeSH terms and keywords for English publications related to bicycle riding and PSA. Studies were included if PSA was measured relative to cycling activity in healthy men who were free of any prostatic condition. Case studies were excluded. Eight studies met our inclusion criteria, comprising 912 participants that engaged in, or self-reported, bicycling activity. Six studies investigated the acute pre-post change in PSA following bicycling activity that ranged from a single cycling bout of 15 min to a 4-day cycling event. Following cycling activity, two studies reported total PSA increased from baseline by up to 3.3-fold, free PSA increased in one study by 0.08±0.18 ng ml(-)(1) and did not change in four studies. One study compared PSA in elite/professional cyclists versus non-cyclists and demonstrated no significant difference in PSA measurements between groups. Data from six studies were meta-analyzed and demonstrated no significant increase in PSA associated with cycling from pre to post (mean change +0.027 ng ml(-)(1), s.e.m.=0.08, P=0.74, 95% confidence interval (CI)=-0.17-0.23). Our findings suggest that there is no effect of cycling on PSA; however, the limited number of trials and the absence of randomized controlled trials limit the interpretation of our results. Additionally, the median sample size only consisted of 42 subjects. Therefore, our study may have low statistical power to detect a difference in PSA. Although, a higher sample size may demonstrate statistical significance, it may not be clinically significant. Studies of higher empirical quality are needed.

MP62-15 YOUNG AGE PREDICTS FOR TRANSIENT ELEVATION IN PSA AFTER DEFINITIVE STEREOTACTIC BODY RADIATION THERAPY FOR PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Localized V1 Apr 2015MP62-15 YOUNG AGE PREDICTS FOR TRANSIENT ELEVATION IN PSA AFTER DEFINITIVE STEREOTACTIC BODY RADIATION THERAPY FOR PROSTATE CANCER Seth Blacksburg, Matthew Witten, Aaron Katz, and Jonathan Haas Seth BlacksburgSeth Blacksburg More articles by this author , Matthew WittenMatthew Witten More articles by this author , Aaron KatzAaron Katz More articles by this author , and Jonathan HaasJonathan Haas More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2389AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Stereotactic Body Radiation Therapy (SBRT) is a standard therapeutic option for men with prostate adenocarcinoma. There is a small body of literature characterizing a PSA bump after treatment with SBRT. Despite this, there is a paucity of data addressing rates of transient PSA increase immediately after SBRT treatment and what factors portend for this rare occurrence. This study reports outcomes on initial PSA after SBRT therapy for men who have undergone definitive radiation for prostate cancer. METHODS Between May 2006 and February 2014, 921 patients with prostate cancer were treated with SBRT delivered via Cyberknife robotic-based therapy. The mean age was 67 years old. 68.5% of patients were Caucasian, 17.4% African American, and 14.1% were another ethnicity. Patients were divided into prognostic risk groups with 44.7%, 43.5%, and 11.1% of patients falling in the low, intermediate, and high risk stratifications. Gleason scores were < 6 in 44.4%, 7 in 41.3%, and 8-10 in 14.2%. 37 patients also received supplemental external beam radiation (median dose 4500cGy) and 8.9% of patients received Androgen Deprivation Therapy (ADT) as part of their treatment regimen. Pre-treatment PSA was 0.8 – 205 ng/ml (median 6.1). RESULTS At three months' follow-up, 2.8% of patients had a PSA elevated above their baseline value. 27.8% of patients age ≤50 (p<.0001) and 8.4% of patients age ≤60 (p=.001) experienced an increased in baseline PSA. African Americans were more likely to experience a transient increase in PSA over Caucasians (7.8% vs. 3.0%, p=.06). Patients treated with fewer beams were also more likely have a temporary rise in PSA (p=.056). Gleason Score, Risk grouping, prostate volume, ADT, and EBRT did not predict for rise on Pearson Chi-Square analysis. On multivariate analysis, only age ≤50 (p<.0001) portended for increased PSA at 3 months' time. CONCLUSIONS This represents the largest series evaluating elevation of PSA after definitive SBRT for prostate cancer. Temporary rise in baseline PSA after SBRT is a rare occurrence. Despite that, a significant cohort of younger patients can experience transient elevation, which can cause patient and physician unease. Patient age ≤50 was found to be the only predictor of this otherwise rare occurrence. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e786 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Seth Blacksburg More articles by this author Matthew Witten More articles by this author Aaron Katz More articles by this author Jonathan Haas More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

PD39-12 THE CO-OCCURRING SYNDROME - OVERLAP OF ED AND BPH AND THEIR CLINICAL CORRELATES IN AGING MEN: RESULTS FROM THE NATIONAL HEALTH AND NUTRITION EXAMINATION SURVEY.

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Epidemiology and Natural History1 Apr 2015PD39-12 THE CO-OCCURRING SYNDROME - OVERLAP OF ED AND BPH AND THEIR CLINICAL CORRELATES IN AGING MEN: RESULTS FROM THE NATIONAL HEALTH AND NUTRITION EXAMINATION SURVEY. Arthur L. Burnett, Kathryn Egan, Minhyung Suh, Kevin T. McVary, Claus Roehrborn, David Wong, Xiao Ni, and Raymond Rosen Arthur L. BurnettArthur L. Burnett More articles by this author , Kathryn EganKathryn Egan More articles by this author , Minhyung SuhMinhyung Suh More articles by this author , Kevin T. McVaryKevin T. McVary More articles by this author , Claus RoehrbornClaus Roehrborn More articles by this author , David WongDavid Wong More articles by this author , Xiao NiXiao Ni More articles by this author , and Raymond RosenRaymond Rosen More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2407AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Erectile dysfunction (ED) and benign prostatic hyperplasia (BPH) are highly prevalent, age-related conditions in men, with frequent co-occurrence of the two disorders worldwide. Despite this, little is known about specific factors associated with co-occurring ED/BPH and the potential increased health risks associated with co-occurrence. Using a nationally representative population of U.S. men, we established a descriptive profile of men with co-existent ED/BPH, ED only, or BPH only compared to men with neither, and, 2) we identified specific determinants of co-occurring ED/BPH in multivariable regression analyses and association differences by disease status. METHODS Complete data on prostate conditions and erectile function were collected in men age ≥40 years (N=2,142) from the 2001-2004 National Health and Nutrition Examination Surveys (NHANES) and standardized medical examinations. Analyses were weighted to account for survey design, nonresponse bias, and the probability of selection into the sample. ED and BPH were defined by self-report and/or medication use. Descriptive analyses examined the distribution of covariates by ED/BPH. Odds ratios (OR) with 95% confidence intervals were calculated using multinomial logistic regression. RESULTS Of 393 men with BPH, 57.8% had co-existent ED, confirming the moderately strong conditional probability between the conditions (p<0.0001). The overall prevalence in men aged ≥40 years of co-occurring ED/BPH was 10.6%, while 24.4% and 7.7% of men reported ED only and BPH only. After age 60, the odds of reporting ED only, BPH only, or ED/BPH almost tripled for each decade of increasing age, corresponding to an increase in the prevalence of each condition. The unadjusted odds of ED/BPH increased 1.3 times per unit increase in PSA (ng/mL) and 1.1 times per unit increase in C-reactive protein (mg/L). In addition to age, other predisposing factors for ED/BPH included higher BMI or presence of obesity (OR=2.5), increased use of prescription medications (antidiabetics (OR=2.9), proton pump inhibitors (OR=2.3)), increased number healthcare visits (OR=3.5), and more frequent urinary symptoms (voiding difficulty (OR=9.7)). CONCLUSIONS We identified a substantial overlap between ED and BPH in the NHANES surveys and related clinical correlates, such as obesity. Our findings support the need for clinicians to actively investigate the presence of either condition in at risk men. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e834-e835 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Arthur L. Burnett More articles by this author Kathryn Egan More articles by this author Minhyung Suh More articles by this author Kevin T. McVary More articles by this author Claus Roehrborn More articles by this author David Wong More articles by this author Xiao Ni More articles by this author Raymond Rosen More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MP86-06 IMPACT OF PSA SCREENING ON STAGE MIGRATION OF PROSTATE CANCER: TRENDS IN CLINICOPATHOLOGIC CHARACTERISTICS OVER THE PAST 14 YEARS

biopsy is often omitted for patients with gray zone PSA and/or comorbidity. We investigated changes of PSA level among patients with dutasteride and its association with the positive rate of prostate cancer at a subsequent biopsy in real-life setting. METHODS: From November, 2009 to March, 2014, we experienced 321 patients (49-97: mean 73.6 years old) with prostate hypertrophy who were prescribed dutasteride for more than six months (6-44: mean 20.4 months) in our institute. We retrospectively investigated their age, initial serum PSA, initial prostate volume, previous prostate biopsy, change in serum PSA, change in prostate volume and dosing period of dutasteride. Patients with failure of PSA decrease by half or recurrent increase of PSA after PSA decrease by half underwent subsequent biopsy that provide 12 cores of peripheral zone (PZ) or PZþ 2 cores of transition zone (TZ). RESULTS: Mean PSA was decreased by 47.5% (6.7 to 3.2ng/ ml); mean prostate volume 73% (53.6 to 39.1ml) six months after dosing. Among twenty seven patients (27/321: 8.4%) who underwent subsequent biopsy, prostate cancer was detected in 13 patients (13/27: 48%). The positive rate of prostate cancer was significantly higher in patients with failure of PSA decrease by half (10/12: 83%) than patients with recurrent increase of PSA after PSA reduction by half (3/15: 20%, p1⁄40.0007). Low initial prostate volume and high initial PSAD were associated with positive biopsy (p1⁄40.001 and 0.048). CONCLUSIONS: Failure of PSA reduction by half from baseline following 5 alpha reductase inhibitor is associated with high positive rate of prostate cancer at subsequent biopsy and is an independent contributing factor for positive biopsy in the present study. It is necessary to find optimal PSA parameter in a real-life clinic for effective detection of prostate cancer.

MP87-13 IMPACT OF PRE-TREATMENT PSA LEVEL ON CANCER CONTROL AFTER EARLY SALVAGE RADIATION THERAPY POST RADICAL PROSTATECTOMY: NEED FOR PATIENT STRATIFICATION ACCORDING TO PROSTATE CANCER FEATURES

You have accessJournal of UrologyProstate Cancer: Advanced III1 Apr 2015MP87-13 IMPACT OF PRE-TREATMENT PSA LEVEL ON CANCER CONTROL AFTER EARLY SALVAGE RADIATION THERAPY POST RADICAL PROSTATECTOMY: NEED FOR PATIENT STRATIFICATION ACCORDING TO PROSTATE CANCER FEATURES Nicola Fossati, R. Jeffrey Karnes, Cesare Cozzarini, Claudio Fiorino, Steven Joniau, Wolfgang Hinkelbein, Karin Haustermans, Bertrand Tombal, Shahrokh F. Shariat, Pierre I. Karakiewicz, Gregor Goldner, Francesco Montorsi, Hein Van Poppel, Thomas Wiegel, and Alberto Briganti Nicola FossatiNicola Fossati More articles by this author , R. Jeffrey KarnesR. Jeffrey Karnes More articles by this author , Cesare CozzariniCesare Cozzarini More articles by this author , Claudio FiorinoClaudio Fiorino More articles by this author , Steven JoniauSteven Joniau More articles by this author , Wolfgang HinkelbeinWolfgang Hinkelbein More articles by this author , Karin HaustermansKarin Haustermans More articles by this author , Bertrand TombalBertrand Tombal More articles by this author , Shahrokh F. ShariatShahrokh F. Shariat More articles by this author , Pierre I. KarakiewiczPierre I. Karakiewicz More articles by this author , Gregor GoldnerGregor Goldner More articles by this author , Francesco MontorsiFrancesco Montorsi More articles by this author , Hein Van PoppelHein Van Poppel More articles by this author , Thomas WiegelThomas Wiegel More articles by this author , and Alberto BrigantiAlberto Briganti More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1958AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Early salvage radiotherapy (eSRT) represents an option for biochemical recurrence (BCR) after radical prostatectomy (RP). However, the optimal PSA level for eSRT initiation is still unclear. We hypothesized that the association between PSA at eSRT and cancer control is not linear and that it is significantly associated with prostate cancer features at RP. METHODS We evaluated a multi-institutional cohort of 716 node-negative patients with early undetectable postoperative PSA (<0.1 ng/ml), who experienced BCR after RP. All patients received eSRT, defined as local radiation to prostate and seminal vesicle bed, delivered at PSA ≤0.5 ng/ml. BCR after eSRT was defined as two consecutive PSA values ≥0.2 ng/ml. Multivariable Cox regression analyses tested the association between pre-eSRT PSA level and BCR. Covariates consisted of pathologic stage, pathologic Gleason score, and surgical margin status. Locally weighted scatter plot smoothing (lowess) methods were used to explore the relation between pre-eSRT PSA level and BCR-free survival rate at 5 years after eSRT according to cancer characteristics at RP. RESULTS Median follow-up after eSRT was 47 months. 5-year BCR-free survival rate was 81%. At multivariable analysis, pre-eSRT PSA level was associated with BCR after eSRT (hazard ratio [HR]: 4.89; p<0.0001). Moreover, pathologic stage ≥pT3b (HR: 2.07; p=0.007), pathologic Gleason score ≥8 (HR: 2.69; p=0.0002), and negative surgical margins (HR: 2.50; p<0.0001) were associated with BCR and were identified as risk factors. Overall, using lowess methods, we observed a decrease of 5-years BCR-free survival rate from 87% to 75% for pre-eSRT PSA level ranging from 0.1ng/ml to 0.5ng/ml. Overall, the 5-years BCR risk increased by 3% per 0.1ng/ml of PSA level. However, when patients were stratified according to the number of risk factors (≤1 vs. ≥2), the effect of increasing PSA at eSRT on cancer control was higher in men with more aggressive disease. Specifically, patients with ≥2 pathologic risk factors showed an increased risk of 5-years BCR equal to 10% per 0.1ng/ml of PSA level vs. 1.5% in patients with a single risk factor (p<0.001). CONCLUSIONS Cancer control after eSRT depends on pretreatment PSA level. This effect is highest in men with at least two of the following features: pT3b/pT4 disease, pathologic Gleason score ≥8, and negative surgical margins. In these patients eSRT should be administered at the very first sign of PSA increase in order to maximize cancer control. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e1089 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Nicola Fossati More articles by this author R. Jeffrey Karnes More articles by this author Cesare Cozzarini More articles by this author Claudio Fiorino More articles by this author Steven Joniau More articles by this author Wolfgang Hinkelbein More articles by this author Karin Haustermans More articles by this author Bertrand Tombal More articles by this author Shahrokh F. Shariat More articles by this author Pierre I. Karakiewicz More articles by this author Gregor Goldner More articles by this author Francesco Montorsi More articles by this author Hein Van Poppel More articles by this author Thomas Wiegel More articles by this author Alberto Briganti More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...