Prostate-specific Antigen Rate Research Articles

A phase 2, single-arm trial evaluating 131 I-PSMA-1095 targeted radioligand therapy for metastatic castration-resistant prostate cancer.

Metastatic castration-resistant prostate cancer (mCRPC) remains uniformly lethal. Prostate specific membrane antigen (PSMA) is a transmembrane glycoprotein overexpressed in prostate cancer. 131 I-PSMA-1095 (also known as 131 I-MIP-1095) is a PSMA-targeted radioligand which selectively delivers therapeutic radiation to cancer cells and the tumor microenvironment. We conducted a single-arm, phase 2 trial to assess efficacy and tolerability of 131 I-PSMA-1095 in mCRPC patients who had exhausted all lines of approved therapy. All patients underwent 18 F-DCFPyL PET and 18 F-FDG PET to determine PSMA-positive tumor volume, and patients with >50% PSMA-positive tumor volume were treated with up to four doses of 131 I-PSMA-1095. The primary endpoint was the response rate of prostate specific antigen (PSA). Secondary endpoints included rates of radiographic response and adverse events. Overall and radiographic progression-free survival were also analyzed. Eleven patients were screened for inclusion and nine patients received 131 I-PSMA-1095. The median baseline PSA was 162 µg/l, and six patients demonstrated a >50% PSA decrease. One patient demonstrated a confirmed radiographic response. Median overall survival was 10.3 months, and median progression-free survival was 5.4 months. Four patients experienced adverse events of grade 3 or higher, the most frequent being thrombocytopenia and anemia. 131 I-PSMA-1095 is highly active against heavily-pretreated PSMA-positive mCRPC, significantly decreasing tumor burden as measured by PSA. Adverse events, mainly hematologic toxicity, were not infrequent, likely related to off-target irradiation. This hematologic toxicity, as well as a higher logistical burden associated with use, could represent relative disadvantages of 131 I-PSMA-1095 compared to 177 Lu-PSMA-617.

A phase 2 expansion study of ARV-766, a PROTACandrogen receptor (AR) degrader, in metastatic castration-resistant prostate cancer (mCRPC).

TPS290 Background: Patients with mCRPC inevitably develop resistance to available therapies and lack curative options. In patients treated with novel hormonal agents (NHAs), mutations can develop in the ligand-binding domain (LBD) of the AR gene, some of which are associated with resistance to current therapies and disease progression. ARV-766 is a novel, potent, orally bioavailable proteolysis targeting chimera (PROTAC) protein degrader that degrades not only wild-type AR but also clinically relevant AR LBD mutants, including the most prevalent AR L702H, H875Y, and T878A mutations. Here we describe a phase 2 expansion study to evaluate the clinical activity and safety of ARV-766 in men with mCRPC who have experienced disease progression on prior NHA therapy. Methods: This phase 2 cohort expansion is part of an open-label, first-in-human, phase 1/2 clinical trial of ARV-766 in men (aged ≥18 years) with histologically, pathologically, or cytologically confirmed mCRPC and Eastern Cooperative Oncology Group performance status score of 0 or 1. Ongoing androgen deprivation therapy with a gonadotropin-releasing hormone analog or inhibitor or orchiectomy is required. Patients enrolled in the cohort expansion must have received 1–3 prior NHAs (eg, abiraterone or enzalutamide) and ≤2 prior chemotherapy regimens. Following completion of dose escalation in the phase 1 portion of the study, which is evaluating the safety and tolerability of ARV-766, 2 doses (100 mg and 300 mg administered orally once daily in 28-day cycles) were selected for the phase 2 cohort expansion. The primary objectives of the cohort expansion study are to evaluate the antitumor activity of ARV-766 based on the overall response rate (per Response Evaluation Criteria in Solid Tumors) and the rates of prostate-specific antigen (PSA) declines of 30% (PSA30) and 50% (PSA50). Enrollment in the phase 2 expansion study is ongoing. Clinical trial information: NCT05067140 .

Changes in prostate cancer incidence, mortality and survival in relation to prostate specific antigen testing in New South Wales, Australia

BackgroundTo examine changes in prostate cancer incidence and mortality rates, and 5-year relative survival, in relation to changes in the rate of prostate specific antigen (PSA) screening tests and the use of radical prostatectomy (RP) in the Australian population. MethodsProstate cancer stage-specific incidence rates, 5-year relative survival and mortality rates were estimated using New South Wales Cancer Registry data. PSA screening test rates and RP/Incidence ratios were estimated from Medicare Benefits Schedule claims data. We used multiple imputation to impute stage for cases with “unknown” stage at diagnosis. Annual percentage changes (APC) in rates were estimated using Joinpoint regression. ResultsTrends in the age-standardized incidence rates for localized disease largely mirrored the trends in PSA screening test rates, with a substantial ‘spike’ in the rates occurring in 1994, followed by a second ‘spike’ in 2008, and then a significant decrease from 2008 to 2015 (APC −6.7, 95% CI −8.2, −5.1). Increasing trends in incidence rates were observed for regional stage from the early 2000s, while decreasing or stable trends were observed for distant stage since 1993. The overall RP/Incidence ratio increased from 1998 to 2003 (APC 9.6, 95% CI 3.8, 15.6), then remained relatively stable to 2015. The overall 5-year relative survival for prostate cancer increased from 58.4% (95% CI: 55.0–61.7%) in 1981–1985 to 91.3% (95% CI: 90.5–92.1%) in 2011–2015. Prostate cancer mortality rates decreased from 1990 onwards (1990–2006: APC −1.7, 95% CI −2.1, −1.2; 2006–2017: APC −3.8, 95% CI −4.4, −3.1). ConclusionsOverall, there was a decrease in the incidence rate of localized prostate cancer after 2008, an increase in survival over time and a decrease in the mortality rate since the 1990s. This seems to indicate that the more conservative use of PSA screening tests in clinical practice since 2008 has not had a negative impact on population-wide prostate cancer outcomes.

Race-Specific Trends in Prostate Cancer Screening and Presentation before and after the 2012 United States Preventive Services Task Force Statement.

Our goal was to assess temporal changes in the race-specific rates of prostate specific antigen (PSA) screening, prostate biopsy, overall prostate cancer detection and metastatic cancer at presentation among screen-eligible men in Kaiser Permanente Northern California before and after the 2012 United States Preventive Services Task Force Prostate Cancer Screening Statement. This was a retrospective study spanning the years 2006 to 2017 in screen-eligible Kaiser Permanente Northern California members (Black men ages 45-69, all other men ages 50-69) with no history of prostate cancer. We compared the race-specific biennial rates of PSA testing, prostate biopsy, overall prostate cancer incidence and metastatic cancer at presentation. A total of 422,664 to 567,660 men per biennial period were evaluated (72% White, 8% Black, 20% Asian). Following the 2012 United States Preventive Services Task Force statement, all races experienced similar declines in screening (22%-25%), biopsy (47%-57%) and overall cancer detection (34%-48%) rates. We found an increase in metastatic rates (39%-105%). Following the 2012 United States Preventive Services Task Force Statement, in men under the age of 70, PSA screening, biopsy and overall prostate cancer detection rates significantly decreased in a similar fashion across all races, while rates of metastatic disease significantly increased in all races.

Comparison of single incision robot-assisted laparoscopic radical prostatectomy with and without extraperitoneal special channel device

Objective: To compare the clinical effects of single-incision robot-assisted laparoscopic radical prostatectomy (RARP) with and without extraperitoneal special channel device. Methods: The clinical data of 70 patients who had undergone RARP in the Robotic Minimally Invasive Surgery Center of Sichuan Provincial People's Hospital from September 2020 to February 2021 were analyzed retrospectively, including 29 cases who were operated on without special channel device (group A) and 41 cases with special channel device (group B). All operations were performed by robot-assisted single-incision retrograde bladder neck exfoliation via extraperitoneal approach in patients by the same operator. The operation time, intraoperative blood loss, the bladder neck urethral anastomosis time, postoperative hospital stay, postoperative exhaust time, positive rate of incisal margin, indwelling time of urinary catheter, retention rate of postoperative erectile function, satisfaction rate of immediate postoperative urine control, positive rate of postoperative lymph node pathology, incision length, treatment cost and the rate of prostate specific antigen (PSA)lower than 0.2 μg/L at 6 weeks after operation were compared between the two groups. Results: All 70 cases were operated successfully. The difference of age[ (68.9±3.9) vs (69.4±5.4) years], preoperative PSA level[14.1(6.3, 19.8)vs13.7(5.8, 18.1)μg/L], prostate volume[44.8(30.7,172.6)vs 56.3(40.9,163.4)ml ] of the two groups was not statistically significant(all P>0.05). The difference of operation time [ (59.1±18.5) vs (59.6±18.0) min ], intraoperative blood loss [93(66,198)vs 95(68,203) ml ], bladder neck urethral anastomosis time [ (12.6±1.3) vs (13.7±2.8) min ], postoperative hospital stay [ (8.1±2.3) vs (9.1±1.3) d], postoperative exhaust time [ (1.4±0.6) vs (1.3±0.6) d], positive rate of incisal margin (20.7% vs 19.5%), indwelling time of the urinary catheter after operation [ (6.8±1.5) vs (7.1±2.0) d ], the retention rate of postoperative erectile function (31.0% vs 27.0%), the satisfaction rate of immediate postoperative urine control (79.3% vs 75.6%), the positive rate of postoperative lymph node pathology (17.2% vs 14.6%), the length of incision [ (5.1±0.5) vs (6.1±0.4) cm ], the rate of PSA lower than 0.2 μg/L at 6 weeks after operation (86.2% vs 83.0%) of the two groups was not statistically significant(all P>0.05). The operation cost of group A[(62 000±4 000) yuan]was lower than group B[(68 000±4 000) yuan] (P<0.05). Conclusion: Extraperitoneal non-special channel device single-incision RARP is safe and feasible.

Prostate Cancer Screening and Incidence among Aging Persons Living with HIV.

The risk of prostate cancer among persons living with human immunodeficiency virus (PWH) is not well understood and may be obscured by different opportunities for detection. We identified 123,472 (37,819 PWH and 85,653 comparators) men enrolled in the Veterans Aging Cohort Study, a prospective national cohort of PWH and demographically matched, uninfected comparators in 2000-2015. We calculated rates of prostate specific antigen (PSA) testing by human immunodeficiency virus (HIV) status and fit multivariable Poisson models comparing the rates of PSA testing, prostate biopsy, and cancer incidence. The mean age at enrollment was 52 years. Rates of PSA testing were lower in PWH versus uninfected comparators (0.58 versus 0.63 tests per person-year). Adjusted rates of PSA screening and prostate biopsy were lower among PWH (incidence rate ratio [IRR] 0.87, 95% CI 0.75-0.84 and IRR 0.79 95% CI 0.74-0.83, respectively). The crude IRR for prostate cancer was lower in PWH versus controls (IRR 0.90, 95% CI 0.83-0.97). However, in a multivariable model adjusting for PSA testing, cancer incidence was similar by HIV status (IRR=0.93, 95% CI 0.86-1.01, p=0.08). Among patients who received a prostate biopsy, incidence of prostate cancer did not differ significantly by HIV status (IRR 1.06, 95% CI 0.98-1.15, p=0.15). Among incident cancers, there were significant differences in the distributions of Gleason grade (p=0.05), but not cancer stage (p=0.14) by HIV status. When accounting for less PSA testing among PWH, the incidence of prostate cancer was similar by HIV status. These findings suggest that less screening contributed to lower observed incidence of prostate cancer in PWH.

Abstract PO-100: Ancestry-related variation in Sphingosine Kinase Type 1-Interacting Protein (SKIP) and Sphingosine Kinase 1 (SPHK1) and response to secondary hormonal therapy in metastatic castration-resistant prostate cancer

Abstract The number of cases and deaths from prostate cancer (PCa) is highest for African American (AA) men compared with men of other racial and ethnic groups, and AA men more frequently have more aggressive disease. However, recent studies have shown that AA PCa patients have a better response to certain therapeutic regimens than white PCa patients. We conducted a DoD Prostate Cancer Clinical Trials Consortium (PCCTC) prospective study of secondary hormonal therapy (HT) in metastatic castration-resistant PCa (mCRPC) patients stratified by race, Abi-Race. This study enrolled 50 AA and 50 white patients with mCRPC and received abiraterone and prednisone daily until disease progression or adverse event. AA men had higher rates of Prostate Specific Antigen (PSA) response and time to PSA progression. Herein we focus on correlative science in the context of Abi-Race to determine novel relationships between ancestry-related genetic variation and response and time to progression on secondary HT in mCRPC. An exploratory genome-wide analysis assessing the role of genotypic and local ancestry variation with respect to time to progression identified a missense variant in Sphingosine Kinase Type 1-Interacting Protein (SKIP) with predicted pathogenicity and potentially high ancestral variation. SKIP plays a role in modulating the conversion of sphingosine to sphingosine-1-phosphate (S1P) by regulating Sphingosine Kinase 1 (SPHK1) activity within the cytosol. S1P is a potent lipid mediator that plays a role in multiple cancer-promoting biofunctions. SKIP directly binds and inhibits SPHK1 activity, resulting in the decreased production of S1P and S1P-associated cell signaling. The relationship between SKIP and SPHK1 and response to secondary HT in mCRPC was investigated. We knocked down SKIP or SPHK1 in LN95 prostate cancer cells and assessed resulting alterations in proliferation with or without abiraterone. Knockdown of SKIP increased proliferation in untreated cells and knockdown cells were more resistant to treatment with abiraterone compared with the control group. Conversely, knockdown of SPHK1 decreased proliferation in untreated cells and knockdown cells were more sensitive to treatment with abiraterone compared with the control group. In addition, we are measuring changes in sphingosine and S1P in serum samples we collected from fasting Abi-Race patients at baseline and cycle 4 of treatment to investigate ancestry-related sphingosine and S1P variations and associated outcomes. Lastly, we are further investigating the potential function of the variant in SKIP associated with time to progression on secondary HT in mCRPC. These findings will further the understanding of ancestry-related biological factors that influence response to secondary HT in mCRPC and could have direct implications for the timing and selection of AA patients for secondary HT and those needing additional therapy. Ultimately, such strategies have the potential to mitigate prostate cancer disparities. Citation Format: Sean A. Piwarski, Tyler A. Allen, Dadong Zhang, Alexander B. Sibley, Patrick Healy, Brendon M. Patierno, Bonnie L. LaCroix, Rick A. Kittles, Kouros Owzar, Terry Hyslop, Steven R. Patierno, Daniel J. George, Jennifer A. Freedman. Ancestry-related variation in Sphingosine Kinase Type 1-Interacting Protein (SKIP) and Sphingosine Kinase 1 (SPHK1) and response to secondary hormonal therapy in metastatic castration-resistant prostate cancer [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-100.

Class III β-tubulin expression as a predictor of docetaxel-resistance in metastatic castration-resistant prostate cancer.

About half of the patients treated with docetaxel in the setting of metastatic castration-resistant prostate cancer (CRPC) are non-responders. Therefore, a marker of response would be beneficial for clinical decision-making. We evaluated class III β-tubulin (βIII-tubulin) expression as a predictor of resistance in this setting, which previously has been correlated with lack of response to taxanes in other cancers. Patients with CRPC were included if they were treated with at least 3 cycles of docetaxel between 1990 and 2011. βIII-tubulin expression was assessed by immunostaining, which was performed in tissue samples obtained either via biopsy or prostatectomy at the time of diagnosis. Rates of prostate-specific antigen (PSA) response and overall survival (OS) following docetaxel treatment were compared between patients with high (2+ or 3+ staining) vs. low (0 or 1+ staining) βIII-tubulin expression. Of 73 patients, 26 (35%) had a high expression of βIII-tubulin. A PSA decline of 10% or greater occurred in 65% of patients with a high βIII-tubulin expression vs. 89% with a low βIII-tubulin expression (p = 0.0267). The median OS for patients with a high βIII-tubulin expression was 17.4 (95% CI 8.7–21.0) months vs. 19.8 (95% CI 16.6–23.6) months for patients with a low expression (p = 0.039). Our results show that a high βIII-tubulin expression is a negative prognostic factor in metastatic CRPC patients treated with docetaxel.

Serum testosterone level is a useful biomarker for determining the optimal treatment for castration-resistant prostate cancer

ObjectiveOur aim was to evaluate the usefulness of serum testosterone to guide treatment decision for castration-resistant prostate cancer (CRPC). MethodsWe conducted a retrospective analysis of 115 patients with CRPC treated with either abiraterone (n = 43) or enzalutamide (n = 72). A serum testosterone level was measured at time of starting of abiraterone or enzalutamide. We determined whether serum testosterone influenced the outcomes of androgen receptor (AR)-targeted therapy. ResultsIn the very-low testosterone group (<5 ng/dl), the rate of prostate-specific antigen (PSA) response was significantly higher among patients treated with abiraterone compared to enzalutamide (62 vs. 32%, respectively; P = 0.033), with no difference in the low testosterone group (5–<50 ng/dl) (93 vs. 81%, respectively; P = 0.429). During the median follow-up of 26 months, PSA progression-free survival was significantly longer in the low testosterone group than in the very-low testosterone group (12.2 vs. 4.5 months, P<0.001). In the very-low testosterone group, enzalutamide use (HR 3.07, 95% CI 1.36–6.94; P = 0.007), primary androgen deprivation therapy <12 months (HR 2.50, 95% CI 1.23–5.08; P = 0.011) and bone metastases (HR 2.60, 95% CI 1.20–5.64; P = 0.015) were significantly associated with PSA progression. ConclusionPatients with a serum testosterone level ≥5 ng/dl were more likely to receive therapeutic benefits from AR-targeted therapy compared to those with serum testosterone levels <5 ng/dl. However, even for those with a very low serum testosterone level, the efficacy of abiraterone was slightly higher than that of enzalutamide. Therefore, serum testosterone level is a useful biomarker for informing treatment selection for CRPC.

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

168 Background: In Asia, including Japan, combined androgen blockade (CAB) therapy with bicalutamide is widely administered for metastatic prostate cancer. Alternative anti-androgen therapy (AAT) with flutamide after CAB therapy with bicalutamide was common before the androgen receptor-targeted therapy era. The objective of the OCUU-CRPC study was to compare the efficacy and safety between second-line hormonal therapy of enzalutamide and flutamide as alternative AAT after CAB therapy that included bicalutamide in patients with CRPC. Methods: A total of 104 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) and flutamide (375 mg/day) groups. The primary endpoint for the drug efficacy was the response rate of prostate-specific antigen (PSA; i.e., declined by ≥50%) at 3 months. Results: Between January 2015 and February 2018, 103 patients were randomly assigned, 52 to enzalutamide and 51 to flutamide. 25 (48%) and 38 (75%) patients, respectively, discontinued their assigned treatment before study end, mainly due to progressive disease. Median follow-up time was 13.4 months (IQR 9.6–23.8) in the enzalutamide group and 17.0 months (9.7–24.4) in the flutamide group. Enzalutamide resulted in significant improvements in the response rate of PSA at 3 months (84.6% vs 31.4%; p&lt; 0.001). Enzalutamide significantly improved in all secondary endpoints: the PSA progression rate at 3 months (HR, 0.17; 95% CI, 0.05 to 0.47; p&lt; 0.01) and at 6 months (HR, 0.22; 95% CI, 0.09 to 0.50; p&lt; 0.01); and PSA response rate at 6 months (75.0% vs 29.4%; p&lt; 0.01); and time to PSA progression (median: not reached vs 6.6 months; HR, 0.29; 95% CI, 0.15 to 0.54; p&lt; 0.01). The observed adverse event profile was consistent with that from phase III enzalutamide trials. Conclusions: Enzalutamide significantly reduced risk of progression compared with flutamide in patients with CRPC after CAB therapy with bicalutamide. This trial is registered with ClinicalTrials.gov, number. Clinical trial information: NCT02346578.

Cost implications of PSA screening differ by age

BackgroundMultiple guidelines seek to alter rates of prostate-specific antigen (PSA)-based prostate cancer screening. The costs borne by payers associated with PSA-based screening for men of different age groups—including the costs of screening and subsequent diagnosis, treatment, and adverse events—remain uncertain. We sought to develop a model of PSA costs that could be used by payers and health care systems to inform cost considerations under a range of different scenarios.MethodsWe determined the prevalence of PSA screening among men aged 50 and higher using 2013-2014 data from a large, multispecialty group, obtained reimbursed costs associated with screening, diagnosis, and treatment from a commercial health plan, and identified transition probabilities for biopsy, diagnosis, treatment, and complications from the literature to generate a cost model. We estimated annual total costs for groups of men ages 50-54, 55-69, and 70+ years, and varied annual prostate cancer screening prevalence in each group from 5 to 50% and tested hypothetical examples of different test characteristics (e.g., true/false positive rate).ResultsUnder the baseline screening patterns, costs of the PSA screening represented 10.1% of the total costs; costs of biopsies and associated complications were 23.3% of total costs; and, although only 0.3% of all screen eligible patients were treated, they accounted for 66.7% of total costs. For each 5-percentage point decrease in PSA screening among men aged 70 and older for a single calendar year, total costs associated with prostate cancer screening decreased by 13.8%. For each 5-percentage point decrease in PSA screening among men 50-54 and 55-69 years old, costs were 2.3% and 7.3% lower respectively.ConclusionsWith constrained financial resources and with national pressure to decrease use of clinically unnecessary PSA-based prostate cancer screening, there is an opportunity for cost savings, especially by focusing on the downstream costs disproportionately associated with screening men 70 and older.

Preliminary results of a study on focal low dose rate prostate brachytherapy using Cesium 131.

151 Background: Prostate cancer patients continue to seek out minimally invasive therapies with equal disease eradication, but with less morbidity, lower cost and multiple salvage options. Our objective was to evaluate PSA response and determine rate of prostate specific antigen (PSA) kinetics in patients undergoing permanent low dose rate (LDR) focal prostate brachytherapy at a single institution. Methods: Between 4/2015 – 1/2017, 52 patients, of which 25% of patients were diagnosed with prostate cancer using a stereotactic transperineal mapping biopsy approach, while 75% had a standard transrectal prostate biopsy, were treated with LDR focal prostate brachytherapy. Dose to target was 115 Gy using Cesium-131. 30 patients (57.7%) were considered low risk, 21 pts (40.4%) were intermediate, and 1 patient (1.9%) was high risk. Treatment was limited to the side of the gland where the cancer was diagnosed. Because there is no agreed upon standard regarding PSA control, we are choosing to call the percent change in PSA the “Impact PSA”. Results: Median pre-treatment prostate volume was 51.6 cm3 (range 18 – 129 cm3), while the median target volume was 17.8 cm3 (range 7.6 – 39.4 cm3). Additionally, the median prostate volume treated was 33.73% (range 17.6 – 95.3%). Our data demonstrates that patients in whom 25-50% of the gland treated, resulted in an Impact PSA of approximately 25% - 50% decrease in total PSA between 3 - 6 months, with continued decreases of 55% at 1 year, and 77% at 2 years. Conclusions: Focal therapy outcomes are highly variable and related to volume of ablation. For low volume disease, LDR focal brachytherapy may be a viable option for patients. Optimal outcome assessment after focal therapy is yet to be determined. Since there is untreated gland with the potential to produce PSA, perhaps stable patterns in PSA kinetics, rather than a nadir, is more valuable. We will continue to follow-up with this cohort to report long term results and closely study the Impact PSA.

Vascular Targeted Photodynamic Therapy with Padeliporfin for Low Risk Prostate Cancer Treatment: Midterm Oncologic Outcomes

We assessed the midterm oncologic outcomes of vascular targeted photodynamic therapy with padeliporfin for low risk prostate cancer treatment. We prospectively assessed all patients treated with vascular targeted photodynamic therapy for low risk prostate cancer at our center. Patients were followed every 6 months. All patients underwent prostate biopsies 6 months after treatment or when there was biological or clinical progression. The primary end point was progression-free survival. Secondary end points were absent clinically significant cancer in the treated lobes, radical therapy and the prostate specific antigen rate. Variables were compared with the chi-square, Mann-Whitney or Wilcoxon test. Progression-free survival is reported with Kaplan-Meier curves. A total of 82 men were treated with vascular targeted photodynamic therapy. Median followup was 68 months (range 6 to 89). Median progression-free survival was 86 months (95% CI 82-90). Median prostate specific antigen decreased significantly by 41% 6 months after treatment and it remained stable during followup (p <0.001). A total of 115 lobes were treated and absent clinically significant cancer was achieved in 94 (82%). Of the 82 patients 20 (24%) underwent radical therapy, including radical prostatectomy in 18 and brachytherapy in 2, at a median of 22 months (range 6 to 86). Study limitations include a single arm design, small population size and midterm followup. Padeliporfin vascular targeted photodynamic therapy for low risk prostate cancer achieved an 82% rate of absent clinically significant cancer in treated lobes and 76% of patients avoided radical therapy at a median followup of 68 months. However, longer followup is required to determine long-term outcomes.

Prospecting for prostate cancer with precision medicine

With the high false positive rate of prostate-specific antigen (PSA) for detection of prostate cancer, new reliable biomarkers for prostate cancer diagnosis and prognosis have been the topic of extensive research efforts. Preferably, the biomarkers should be present in biofluids that can be sampled with non- or minimally-invasive methods, to allow repeated analysis. In addition to many and varied analyses applied to blood specimens, three prostate-relevant body fluids have been investigated, namely, urine (1-3), seminal fluid (4,5) and expressed prostatic secretion (EPS) (6-8).

An Examination of Clinical Outcomes in Patients Experiencing Biochemical Relapse in a Cohort of 966 Permanent Prostate Brachytherapy Monotherapy Patients

Low rates of prostate specific antigen (PSA) relapse are observed following permanent prostate brachytherapy monotherapy (PPBM). We report a large single institution experience of outcomes following such relapse. We examined 966 consecutive pts treated with I-125 PPBM between 4/98 and 1/13 with at least one post PPBM serum PSA to identify pts who experienced PSA relapse by the nadir + 2 (Phoenix) criteria. Survival estimates used the Kaplan-Meier method. Characteristics of the 966 pt cohort include median age of 69 years (range 42-86) and NCCN risk group of low (n=685, 71%) or intermediate (n=281, 29%). Overall survival (OS) at 5 and 10 years was 94% (95% confidence interval (CI) 92-95) and 74% (95% CI 69-78). Ten year prostate cancer-specific mortality (PCSM) was 2% (95% CI 0-3) overall and 1% (95% CI 0-3) vs 4% (95% CI 0-8, p=0.02) for low vs intermediate risk prostate cancer. Freedom from PSA relapse at 5 and 10 years is 97% (95% CI 95-98) and 85% (95% CI 80-90). PSA relapse was detected in 45 pts at a median of 52 (IQR 36-67) months after PPBM with a median PSA at relapse of 3.9 (IQR 2.7-6) ng/dL. Characteristics of pts with relapse include NCCN low risk (n=20) or intermediate risk (n=25) at initial diagnosis. Relapse was found to be local (n= 10, 22%), nodal (n=9, 20%), local and nodal (n=1, 2%), distant (n=9, 20%), local and distant (n=1, 2%) or biochemical only (n=15, 33%). Positive prostate biopsy was found in 12 of 23 (52%) (representing 12 local relapses in 966 pts (1.2%)). Biopsy pathology showed the same Gleason score (n=3), higher Gleason score (n=8) or new neuroendocrine features (n=1) compared to initial diagnosis. Locoregional salvage therapy for local and/or nodal relapse was prostatectomy and lymph node dissection (n=4), external beam radiotherapy (n=2), cryotherapy (n=1) or no local treatment (n=13). Locoregional therapy without (n=3) androgen deprivation therapy (ADT) resulted in persistent PSA in 1 pt and undetectable PSA for >72 months in 2 pts. Locoregional therapy with ADT (n=4) resulted in PSA relapse in 1 pt at 36 months following salvage treatment and no PSA relapse at 5, 7 and 21 months in the remaining pts. ADT was given to 28 pts a median of 6 (IQR 3-17) months after PSA relapse with subsequent PSA decline in all pts. Median time to disease progression after ADT initiation was 36 months. One patient was treated with chemotherapy (carboplatin) as the initial management strategy after PSA relapse. Median OS after PSA relapse for patients with low or intermediate risk disease was 74 vs 52 months (p=0.07), respectively. Mortality occurred in 18 pts. Cause of death was prostate cancer (n=7), lung cancer (n=2), non-malignant causes (n=6) or unknown causes (n=3). PCSM occurred in pts with metastatic disease at PSA relapse (n=3), nodal disease (n=3) or in pts with PSA relapse only who subsequently developed evidence of metastases after progression on ADT (n=2). Of 10 pts with local relapse only, mortality occurred in 4 pts from metastatic lung cancer (n=2) or neurodegenerative disease (n=2). PCSM at 5 years after PSA relapse for the whole cohort is 40% (95% CI 21-64) and is 27% (95% CI 9-59) vs 63% (95 CI 25-90, p=0.06) for low and intermediate risk pts, respectively. Excellent long term results for patients undergoing PPBM similar to other reports are observed. Patients experiencing biochemical relapse have a decrement in subsequent PCSM. Consequently, these data may provide insight into selection of management approaches.

High RhoA expression at the tumor front in clinically localized prostate cancer and association with poor tumor differentiation.

Ras homolog gene family, member A (RhoA) has been reported as essential to the invasion process and aggressiveness of numerous cancers. However, there are only sparse data on the expression and activity of RhoA in clinically localised prostate cancer. In numerous cancers, tumour cells at the invasive front demonstrate more aggressive behaviour in comparison with the cells in the central regions. In the present study, the expression and activity of RhoA was evaluated in 34 paraffin-embedded and 20 frozen prostate tissue specimens obtained from 45 patients treated with radical prostatectomy for clinically localised cancer. The expression patterns of RhoA were assessed by immunohistochemical staining and western blotting. Additional comparisons were performed between the tumour centre, tumour front and distant peritumoural tissue. RhoA activity was assessed by G-LISA. Associations between RhoA expression and the clinical features and outcome of the patients were also analysed. The present study found an increasing gradient of expression from the centre to the periphery of index tumour foci. RhoA expression was significantly increased at the tumour front compared to the tumour centre, which was determined using immunohistochemistry (P=0.001). Increased RhoA expression was associated with poor tumour differentiation in the tumour front (P=0.044) and tumour centre (P=0.039). Subsequent to a median follow-up period of 52 months, the rate of prostate-specific antigen (PSA) relapse was increased in patients with higher RhoA expression at the tumour front when compared with patients with lower RhoA expression (62.5 vs. 35.0%), although the difference was not significant (P=0.09). There was no association between RhoA expression and the PSA level or pathological stage in the present study. In conclusion, RhoA expression was increased at the tumour front and was associated with poor tumour differentiation in the tumour front and tumour centre, indicating the potential role of RhoA in prostate cancer. RhoA expression may also act as a prognostic factor in prostate cancer. The present data provide a foundation for novel therapeutic approaches by targeting RhoA in prostate cancer.

Association of GPs' risk attitudes, level of empathy, and burnout status with PSA testing in primary care.

BackgroundRates of prostate specific antigen (PSA) test ordering vary among GPs.AimTo examine whether GPs’ risk attitude, level of empathy, and burnout status are associated with PSA testing.Design and settingRegister and questionnaire study including 129 solo GPs (active in the Central Denmark Region) and 76 672 of their adult male patients with no history of or current prostate cancer diagnosis.MethodPSA tests from 2012 were retrieved from a register and classified as incident (that is, the first PSA test within 24 months), repeated normal, or repeated raised tests. This was merged with information on GPs’ risk attitudes, empathy, and burnout status from a 2012 survey.ResultsPatients registered with a GP with a high score on anxiety caused by uncertainty (odds ratio [OR] 1.03, 95% confidence interval [CI] = 1.00 to 1.06, P = 0.025) or concern about bad outcomes (OR 1.04; 95% CI = 1.00 to 1.08, P = 0.034) were more likely to have an incident PSA test, whereas those registered with a GP with increased tolerance for ambiguity were less likely (OR 0.98, 95% CI = 0.96 to 1.00, P = 0.025). Patients registered with a GP reporting high tolerance for ambiguity (OR 0.96, 95% CI = 0.94 to 0.99, P = 0.009) or high propensity to risk-taking (OR 0.97, 95% CI = 0.93 to 1.00, P = 0.047) were less likely to have a repeated normal PSA test.ConclusionVarious aspects of GPs’ risk-taking attitudes were associated with patients’ probability of having an incident and a repeated normal PSA test. The probability of having a repeated raised PSA test was not influenced by any of the psychological factors. Burnout and empathy were not associated with PSA testing.

Editorial Comment

In 2008, the United States Preventive Services Task Force (USPSTF) recommended against prostate-specific antigen (PSA) screening for men aged >75 years and extended this to men of all ages in a 2011 draft recommendation that was finalized in 2012. 1 Moyer V.A. Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2012; 157: 120 Crossref PubMed Scopus (1608) Google Scholar Similar recommendations against PSA were issued by the Canadian Preventive Health Task Force in 2014. 2 Canadian Task Force on Preventive Health Care. Available at: http://canadiantaskforce.ca/ctfphc-guidelines/2014-prostate-cancer/. Accessed May 1, 2015. Google Scholar These guidelines have generated significant controversy and contrast with the recommendations of numerous professional societies for shared decision making about PSA. 3 AUAEarly detection of prostate cancer: American Urological Association Guideline. 2013http://www.auanet.org/education/guidelines/prostate-cancer-detection.cfm Google Scholar Trends in Prostate-specific Antigen Screening, Prostate Biopsies, Urology Visits, and Prostate Cancer Treatments From 2000 to 2012UrologyVol. 86Issue 3PreviewTo determine whether the rates of prostate-specific antigen (PSA) screening, related biopsies and subsequent prostate cancer utilization decreased between 2000 and 2012 in a large, managed care organization. Full-Text PDF ReplyUrologyVol. 86Issue 3PreviewWe thank Drs. Brawley1 and Loeb2 for their thoughtful comments about screening for prostate cancer and the results reported here at Kaiser Permanente Southern California. The evidence about prostate-specific antigen screening for prostate cancer is controversial, particularly in an age where risk stratification is inexact. However, there is little controversy regarding when prostate cancer screening is no longer beneficial, and as such, we have chosen to focus our efforts in reducing unnecessary overscreening, overdiagnosis, and overtreatment in older men. Full-Text PDF

Editorial Comment

This study documents changes in prostate cancer screening patterns in a defined medical practice. 1 Wallner L.P. Hsu J.W. Loo R.K. Palmer-Toy D.E. Schottinger J.E. Jacobsen S.J. Trends in prostate-specific antigen screening, prostate biopsies, urology visits, and prostate cancer treatments from 2000 to 2012. Urology. 2015; 86: 498-505 Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar Since 2008, there is a decline especially among older men without a change in the rate of prostate cancer diagnosis. The pattern suggests that the doctors in the study became more discriminating in their decision to screen. This may be a model for the teaching about and use of prostate cancer screening. Trends in Prostate-specific Antigen Screening, Prostate Biopsies, Urology Visits, and Prostate Cancer Treatments From 2000 to 2012UrologyVol. 86Issue 3PreviewTo determine whether the rates of prostate-specific antigen (PSA) screening, related biopsies and subsequent prostate cancer utilization decreased between 2000 and 2012 in a large, managed care organization. Full-Text PDF ReplyUrologyVol. 86Issue 3PreviewWe thank Drs. Brawley1 and Loeb2 for their thoughtful comments about screening for prostate cancer and the results reported here at Kaiser Permanente Southern California. The evidence about prostate-specific antigen screening for prostate cancer is controversial, particularly in an age where risk stratification is inexact. However, there is little controversy regarding when prostate cancer screening is no longer beneficial, and as such, we have chosen to focus our efforts in reducing unnecessary overscreening, overdiagnosis, and overtreatment in older men. Full-Text PDF Editorial CommentUrologyVol. 86Issue 3PreviewIn 2008, the United States Preventive Services Task Force (USPSTF) recommended against prostate-specific antigen (PSA) screening for men aged >75 years and extended this to men of all ages in a 2011 draft recommendation that was finalized in 2012.1 Similar recommendations against PSA were issued by the Canadian Preventive Health Task Force in 2014.2 These guidelines have generated significant controversy and contrast with the recommendations of numerous professional societies for shared decision making about PSA. Full-Text PDF

The impact of socio-economic deprivation on incidence, treatment and mortality from prostate cancer in England, 1990–2010

Objective: To explore any association between socio-economic deprivation and prostate cancer diagnosis and/or treatment. Patients and methods: Data was extracted as follows: We gained the incident cases and staging from the National Cancer Data Repository, survival from the Cancer Information System, mortality from the Office for National Statistics, treatment data from Hospital Episode Statistics and National Clinical Analysis and Specialised Applications Team. Our analysis regarding socio-economic deprivation was controlled for age distribution. Results: We recorded 518,453 diagnoses of prostate cancer; 174,579 prostate cancer deaths; 33,889 prostatectomies and 21,351 radiotherapy treatments. Incidence is increasing in all groups, but the highest is amongst the least deprived. Mortality is decreasing, with survival consistently better in the least deprived. Prostatectomies are more frequent in the least deprived; however, this gap is narrowing. Conclusions: Prostate cancer incidence, survival and treatment are associated with socio-economic deprivation. Prostatectomy rates show a decrease in the gap of inequality. Multiple potential confounding factors, such as rates of prostate specific antigen (PSA) testing and access to health care are associated with socio-economic deprivation. The unifying influences of Improving Outcomes Guidance and the National Treatment Guidelines are intended to counteract the above inequalities. Particularly in prostate cancer, where long-term gain depends on multiple factors, individualised treatment decisions are paramount.