Prostate-specific Antigen Progression Rate Research Articles

Urinary exosome-based androgen receptor-variant 7 detection in metastatic castration-resistant prostate cancer patients.

BackgroundAndrogen receptor variant 7 (AR-V7) detection provides important information for the clinical management of abiraterone in metastatic castration-resistant prostate cancer (mCRPC). We performed a non-invasive urine-derived exosomal AR-V7 analysis of mCRPC patients.MethodsA total of 34 mCRPC patients were recruited including 16 patients treated with abiraterone (ABI) with stable prostate-specific antigen (PSA)/radiograph response (the ABI-Sta group) and 18 were resistant to abiraterone (the ABI-Res group). Urine was collected from patients and healthy control patients for the analysis. Exosomal ribonucleic acid was isolated from urine. Urinary exosome-based androgen receptor-variant 7 was detected by quantitative real-time polymerase chain reaction assay. Characteristics of patients and survival data were collected. The correlation between AR-V7 expression and the therapeutic effect/survival outcomes of abiraterone was analyzed.ResultsUrine is the ideal biological sample for exosome separation and AR full-length analysis. Positive urine-derived exosomal AR-V7 was detected in 32.4% (11 of 34) of the mCRPC patients’ urine samples. Positive AR-V7 was more common in the ABI-Res patients than the ABI-Sta patients (50.0% vs. 12.5%, respectively; P=0.009), and was associated with a higher PSA progression rate and poorer overall survival (OS) (P=0.0031, and P=0.0012, respectively).ConclusionsThe present study showed that the detection of urine-derived exosomal AR-V7 provides a sensitive and feasible clinical workflow. The predicting role of urine-derived exosomal AR-V7 in mCRPC patients should be further verified using studies with greater sample sizes.

Appropriate Number of Docetaxel Cycles in Castration-Resistant Prostate Cancer Patients Considering Peripheral Neuropathy and Oncological Control

Background: The number of cycles of docetaxel required for castration-resistant prostate cancer (CRPC) is unclear. This study estimated peripheral neuropathy (PN) incidence and the optimal number of treatment cycles in patients receiving docetaxel for CRPC. Patients and Methods: The study retrospectively reviewed 82 patients receiving docetaxel for CRPC at an institution between January 2005 and January 2017. Docetaxel (70 or 75 mg/m²) was administered every 3 weeks, and prednisone 5 mg or dexamethasone 0.5 mg was administered twice a day. Results: PN (grade ≥2) was noted in 32 (39.0%) patients. The median cumulative dose of docetaxel associated with PN was 675 mg/m². No factor significantly predicted the occurrence of PN. The prostate-specific antigen progression rate, prostate cancer-specific survival, and overall survival were significantly better with ≥8 cycles of docetaxel than with <8 cycles (p < 0.05). Conclusion: The incidence of PN is high, and 8 treatment cycles are optimal for patients receiving docetaxel for CRPC.

Enzalutamide versus flutamide for castration-resistant prostate cancer after combined androgen blockade therapy with bicalutamide: study protocol for a multicenter randomized phase II trial (the OCUU-CRPC study)

BackgroundEnzalutamide is an oral androgen receptor targeted agent that has been shown to improve survival in PREVAIL trials and has been approved for patients with chemo-naïve metastatic castration-resistant prostate cancer (CRPC). Meanwhile, flutamide is a non-steroidal oral anti-androgen that was commonly used before the approval of bicalutamide. The objective of the OCUU-CRPC study is to compare the efficacy and safety between second-line hormonal therapy of enzalutamide and flutamide as alternative anti-androgen therapy (AAT) after combined androgen blockade (CAB) therapy that included bicalutamide in patients with CRPC.MethodsA total of 100 patients with CRPC with or without distant metastases after disease progression who received CAB therapy with bicalutamide were randomly assigned at a 1:1 ratio according to distant metastases to the enzalutamide (160 mg/day, 4 × 40 mg capsules once daily) and flutamide (375 mg/day; 3 × 125 mg tablets thrice daily) groups. The primary endpoint for the drug efficacy is the response rate of prostate-specific antigen (PSA) (i.e., the ratio of patients whose PSA declined by ≥50% from baseline) at 3 months. Meanwhile, the secondary endpoints are PSA progression rate at 3 and 6 months, PSA response rate at 6 months, change in quality of life, PSA progression-free survival, and safety. The patient registration started in January 2015 and will end in March 2018, and the follow-up period is 6 months after the last patient registration. The main result will be reported in March 2019.DiscussionIn the OCUU-CRPC study, we compare the efficacy and safety of enzalutamide or alternative AAT with flutamide in participants with CRPC who were previously treated with a CAB therapy with bicalutamide. The expected results of this study will be that enzalutamide is superior to flutamide in terms of PSA response. A longer time to disease progression with enzalutamide over flutamide may translate to better overall survival. However, flutamide may be more accessible for patients owing to its lower cost than enzalutamide.Trial registrationThe OCUU-CRPC study was prospectively registered at clinicaltrials.gov (NCT02346578, January 2015) and University Hospital Medical Information Network (UMIN000016301, January 2015).

Primary androgen deprivation therapy for prostate cancer in koreans: a retrospective multicenter study.

PurposeTo evaluate the characteristics of patients who received primary androgen deprivation therapy (PADT) for prostate cancer and the clinical efficacy of this treatment.Materials and MethodsTwo hundred forty patients treated by PADT were reviewed. These patients could not receive definitive therapy owing to old age, patient need, and medical comorbidity. The patients were divided into three groups according to the extent of prostate cancer: localized, locally advanced, and metastatic. Then, prostate-specific antigen (PSA) progression in these groups was analyzed.ResultsThe median age of the patients was 73.0 years, and the median pretreatment PSA level was 47.0 ng/mL. Of the patients, 91.7% were treated with combined androgen blockade, and 8.3% were treated with monotherapy. Clinical factors for PSA progression were a PSA nadir and a high clinical stage. Estimated PSA recurrence-free median survival time in each group was 57, 24, and 12 months, respectively. A PSA nadir of >0.2 ng/mL and metastatic stage were independent factors for expecting a poor response to PADT (hazard ratio 4.26, p<0.001; and 2.60, p<0.001).ConclusionsPatients with localized or locally advanced prostate cancer who did not receive definitive therapy had lower PSA progression rates than those at metastatic stage during PADT. Further, a PSA nadir of ≤0.2 ng/mL showed better progression-free survival. Therefore, PADT can be another therapeutic option in well-selected patients with localized or locally advanced prostate cancer and PSA change should be checked carefully.

Biopsy of men with PSA level of 2.6 to 4.0 ng/mL associated with favorable pathologic features and PSA progression rate: A preliminary analysis

Objectives To compare the pathologic outcomes and prostate-specific antigen (PSA) progression rates of patients who underwent radical prostatectomy because of prostate cancers and whose cancer was detected at a PSA level of 2.6 to 4.0 ng/mL versus those with cancer detected after the PSA level rose to greater than 4.0 ng/mL. Some studies have suggested that clinically significant prostate cancer is detected more frequently in an organ-confined stage with a PSA level between 2.6 and 4.0 ng/mL than with a PSA level greater than 4 ng/mL. However, it is uncertain whether this will affect clinical outcomes. Methods From 1991 to 2001, 20,788 men enrolled in a prostate cancer screening study had an initial PSA level of less than 2.6 ng/mL. Of these patients, 523 had a PSA level that rose to greater than 2.5 ng/mL and had prostate cancer detected. Of the 297 patients who subsequently underwent radical prostatectomy, 223 had a preoperative PSA level of 2.6 to 4.0 ng/mL and 74 had a preoperative PSA level greater than 4.0 ng/mL. The median follow-up was 4 years. The pathologic stage, mean tumor volume, Gleason score, possibly insignificant cancer rate, possibly rapidly progressive cancer rate, and PSA progression rate were compared between the two groups. Results The patients with a preoperative PSA level between 2.6 and 4.0 ng/mL had more favorable pathologic outcomes in terms of cancer volume, pathologic stage, and possibly rapidly progressive cancer rate. The possibly insignificant cancer rates were not different between the groups. A trend was noted for patients with a preoperative PSA level between 2.6 and 4.0 ng/mL to have a lower PSA progression rate. Conclusions Biopsy in men with PSA levels between 2.6 and 4.0 ng/mL may detect clinically significant prostate cancer more frequently at an organ-confined stage, with a lower PSA progression rate. Additional study in a larger population with longer follow-up is needed to confirm this trend.

DEFINING PROSTATE SPECIFIC ANTIGEN PROGRESSION AFTER RADICAL PROSTATECTOMY: WHAT IS THE MOST APPROPRIATE CUT POINT?

The most appropriate definition of biochemical progression after radical prostatectomy and radiation therapy is uncertain. We analyzed the effect of using various prostate specific antigen (PSA) end point definitions for defining biochemical progression after radical prostatectomy and attempted to determine the best PSA cut point to use. Aspects of the American Society for Therapeutic Radiology and Oncology (ASTRO) definition of biochemical failure after radiation therapy are also analyzed in our radical prostatectomy cases. A total of 2,782 men with clinically localized prostate cancer (cT1-T2) who had undergone radical prostatectomy between 1987 and 1993 were reviewed. All patients had regular PSA determinations from surgery through followup. Analysis was limited to patients who did not receive adjuvant treatment within 90 days of radical prostatectomy. Biochemical, PSA progression-free percent after radical prostatectomy was determined by the Kaplan-Meier method using several PSA cut points, including 0.2, 0.3, 0.4 and 0.5 ng./ml. or greater, as well as 0.4 ng./ml. or greater and increasing. Progression-free percent was also assessed using the ASTRO definition, which is 3 increases in PSA. To determine which PSA level was most appropriate to define progression after radical prostatectomy, the percentage of patients with a continued PSA increase after reaching each cut point was determined. The relationship between the maximum PSA within 3 years of surgery and subsequent development of clinical disease was also assessed. Progression-free percent was dependent on the PSA cut point used. Biochemical progression-free percentages for cut points 0.2, 0.3, 0.4 and 0.5 ng./ml. or greater were 62%, 72%, 76% and 78% at 5 years, and 43%, 54%, 59% and 61% at 10 years, respectively. A subsequent increase in PSA was noted in 49%, 62% and 72% of patients who had PSA 0.2, 0.3 and 0.4 ng./ml., respectively. Subsequent clinical progression (local or systemic) was directly related to the maximum PSA attained within 3 years of radical prostatectomy (p=0.0001). Progression-free percent for definitions requiring multiple increases in PSA were dependent on when the event was said to occur. Backdating of events at or before the first PSA (ASTRO definition) resulted in poorer, short-term progression-free percent (78% at 5 years), with little apparent likelihood of long-term failure (78% at 10 years). Coding the event at the last PSA increase when all event criteria had been met resulted in more realistic progression-free percent estimates (85% at 5 and 59% at 10 years). Biochemical, PSA progression rates vary markedly depending on the method used to define PSA failure. Methods that require multiple increasing PSA values, for example the ASTRO definition, give misleading results, especially if the event time is backdated. Standards for defining PSA progression would allow more consistent and comparable progression estimates after radical prostatectomy. PSA 0.4 ng./ml. or greater may be the most appropriate cut point to use since a significant number of patients with lower PSA do not have a continued increase in it.

WHY NEOADJUVANT ANDROGEN DEPRIVATION PRIOR TO RADICAL PROSTATECTOMY IS UNNECESSARY

Neoadjuvant hormonal therapy (NHT) prior to radical prostatectomy has been advocated for downstaging of tumors and reducing the rates of positive surgical margins with the expectation that disease-free survival will be improved. Despite the apparent favorable impact on pathologic findings, randomized trials to date show no benefit of NHT in prostate-specific antigen progression rates. Consequently, there is serious concern about the validity and biologic significance of the apparent downstaging and decreased rate of positive margins, and no evidence exists that there is improved time to progression and survival; therefore, the authors do not recommend NHT outside of a clinical trial.