Prostate Serum Antigen Levels Research Articles

Prostate-specific antigen level association with COVID-19 infection and vaccination

IntroductionThe associations among SARS-CoV-2 infection, vaccination and total serum prostate serum antigen (PSA) levels in men undergoing screening for prostate cancer are unknown. MethodsA retrospective analysis of data from a large health maintenance organization. Records of individuals aged 50 to 75 years with two serum PSA tests taken between March 2018 and November 2021 were included. Individuals with prostate cancer were excluded. Changes in PSA levels were compared between individuals who had at least 1 SARS-CoV-2 vaccination and/or infection between the two PSA tests and individuals who did not have an infection and were not vaccinated between the two PSA tests. Subgroup analyses were performed to assess the impact of the elapsed time between the event and the second PSA test on the results. ResultsThe study and control groups included 6,733 (29%) and 16 286 (71%) individuals, respectively. Although the median time between PSA tests was shorter in the study vs. the control group (440 vs. 469 days, P<.001), PSA elevation between the tests was higher in the study group (0.04 vs. 0.02, P<.001). The relative risk for PSA elevation ≥1 ng/dL was 1.22 (95% CI 1.1, 1.35). Among individuals who were vaccinated, PSA increased by 0.03 ng/dL (IQR -0.12, 0.28) and 0.09 ng/dL (IQR -0.05, 0.34) after 1 and 3 doses, respectively (P<.001). Multivariate linear regression showed that SARS-CoV-2 events (β 0.043; 95% CI 0.026-0.06) were associated with a greater risk for PSA elevation, after adjusting for age, baseline PSA and days between PSA tests. ConclusionSARS-CoV-2 infection and vaccinations are associated with a slight increase in PSA, with the third anti-COVID vaccine dose having a more prominent impact, but its clinical significance is unknown yet. Any significant increase in PSA must be investigated and cannot be dismissed as secondary to SARS-CoV-2 infection or vaccination.

Occupational and Environmental Exposure Influences the Inflammatory (Pro-and Anti-) Status in Benign Prostate Hyperplasia and Prostate Carcinoma Patients: A Retrospective Analysis.

Multiple diseases and disorders are connected with occupational and environmental exposure risk. It is also well-established that chemicals and chemical mixtures have an influence on the immune cells of humans. This is an important field of research that has been pursued extensively in relation to autoimmune illnesses, allergy/asthma, and lung cancer, but Prostate Carcinoma has received rare reports. Chronic chemical exposure is known to produce inflammation, which is one of the most prominent characteristics of all malignancies. Changes in the ratio of pro-inflammatory to anti-inflammatory molecules are thought to be a key factor in the emergence of inflammation. Prostate gland cells express the pro-inflammatory cytokine interleukin-18 (IL-18), which is a major facilitator of immunological responses. Conversely, interleukin-10 (IL-10) is an anti-inflammatory cytokine that is linked to immune responses and inhibits the development of an inflammatory environment. Our goal is to investigate the inflammatory status of IL-18 (pro-) and IL-10 (anti-) in a variety of occupationally exposed populations in patients with Benign Prostate Hyperplasia (BPH) and patients with Prostate Carcinoma. The present study was conducted with 664 subjects, comprising 285 Prostate Carcinoma patients, 94 BPH patients and 285 controls. The subjects of BPH and Prostate Carcinoma were screened and confirmed on the basis of Prostate Serum Antigen (PSA) and pathological biopsy. All subjects were categorized as per their occupational exposure into various groups. The pro-inflammatory and anti-inflammatory Interleukins (IL-18 and IL-10) and serum PSA levels were analysed by using corresponding quantitative ELISA kits. The results showed that as compared to control participants, the serum PSA levels were higher in the Prostate Carcinomaand BPH groups. When mean levels of IL-18 were compared between various occupational groups, Tanners (tanning industry), Agriculture, and Ordnance workers had significantly higher levels (P < 0.05) of IL-18 than sedentary workers. The pro-inflammatory cytokine (IL-18) levels were also found to be aggravated in Prostate Carcinomacompared to BPH and controls. According to the findings of the current study, the levels of inflammatory cytokines (IL-18 and IL-10) in various occupational groups of BPH, Prostate Carcinoma, and controls were altered. Long-term occupational exposure may have a negative influence on inflammation levels and the immune system; therefore, preventative measures should be explored for improved health.

A clinical audit snapshot of Prostate Serum Antigen (PSA) test results for Pacific men from two Primary Health Care Clinics in the Auckland region, New Zealand

Prostate cancer is the most common malignancy registered in New Zealand and is the third most common cause of cancer death in men after lung cancer and bowel cancer. Prostate Serum Antigen (PSA) testing has been used to screen for prostate cancer. The following paper provides a clinical audit snapshot of Prostate Serum Antigen (PSA) test results for Pacific men from two Primary Health Care Clinics in the Auckland region, New Zealand. Two Auckland primary health care clinics provided anonymised data on prostate serum test results for their male patients along with ethnicity, age, and birthplace. Descriptive summaries of the data are presented as frequencies and percentages of positive test by age and by ethnic group. Logistic regression analysis was used to test for significant differences by ethnic group, age group and birthplace (NZ born versus overseas born). Two clinics which have predominately Pacific patients provided anonymised results of prostate serum antigen test results from 2009 – 2018. There were 5,787 prostate serum antigen level tests available from clinic 1 and clinic 2 had 493 patients. Most of the clinic patients tested were New Zealand born (5655, 90%) compared to overseas born (625, 10%). Samoans compared to Europeans were significantly more likely to have a positive test compared to Europeans &amp; other ethnicities. Cook Island Maori men were significantly less likely to have a positive test result compared to European and other ethnicities. Older individuals are more likely to have positive PSA results which shows that this is very similar and consistent with the current literature. Those being born overseas compared to being New Zealand born were significantly less likely to have positive serum antigen results.

IgG4-related prostatitis manifesting as urinary obstruction in a 28-year-old male

BackgroundImmunoglobulin G4-related disease (IgG4-RD) is a systemic lymphoproliferative disorder characterized by elevated serum IgG4 levels and tumefactive lesions that can involve nearly every organ system. Involvement of the prostate is rare but has been reported in limited cases.Case presentationA 28-year-old man of Asian descent with a history of sinusitis and priapism presented to hospital with rigors and voiding symptoms. He was diagnosed with IgG4-RD one month prior to presentation, following pathological analysis of a submandibular mass that demonstrated chronic sclerosing sialadenitis. On presentation, white blood cell count, C-reactive protein, and prostate serum antigen levels were all within normal limits. Examination was notable for a large, firm prostate, and a foley catheter was inserted. Contrast CT of the abdomen was unremarkable. Further workup revealed elevated serum IgG4 levels (9.22 g/L) and he was subsequently started on prednisone 35 mg daily. Imaging to screen for systemic IgG4-RD involvement demonstrated paravertebral soft tissue involvement and he was given rituximab 1000 mg IV × 2 doses. MRI revealed diffuse prostatitis. Five days after starting prednisone and one day after his first dose of rituximab, he successfully passed trial of void and was discharged home.ConclusionsIgG4-related prostatitis is a rare and underrecognized manifestation of IgG4-RD. Our case highlights the need to consider IgG4-related prostatitis as an etiology of urinary obstruction in young individuals. Resolution of symptoms following treatment with steroids may be diagnostic of IgG4-related prostatitis, and may potentially avoid the need for invasive diagnostic procedures such as prostate biopsy.

Gallium-68 prostate-specific membrane antigen PET-CT and the clinical management of prostate cancer.

The purpose of this study was to evaluate the use of Gallium-68 prostatic-specific membrane antigen (PSMA) PET-computerized tomography (CT) in patients with prostate cancer undergoing imaging for initial staging, biochemical failure or the evaluation of metastatic disease. This is a single institution retrospective study of 95 patients with prostate cancer who were referred for PSMA PET-CT scans. The National Comprehensive Cancer Network guidelines were used to generate treatment recommendations. Univariate and multivariate statistical analyses were performed to identify parameters associated with positive findings on a PET-CT PSMA scan. Mean age, Gleason score, and median prostate serum antigen (PSA) were: 72 years, 7.6 and 4 ng/ml, respectively. PSMA PET-CT was positive in 75.5% of the patients. A maximum standardized uptake value was 10.7 ± 8.8. PSMA avidity increased with rising PSA level: PSA ≤ 1 ng/ml: 5/15 patients (33%); PSA 1-5 ng/ml: 18/27 patients (67%), and PSA ≥ 5 ng/ml: 33/34 patients (97%). Following imaging in nine high-risk patients referred for staging, changes in treatment occurred in 6 (67%). Treatment recommendations changed in 27/35 (65%) patients referred due to biochemical failure; these included recurrences suitable for salvage therapy (n = 14), metastatic disease not suitable for salvage therapy (n = 10), and no lesion (n = 17). No changes in treatment occurred in any of the 35 patients referred to evaluate metastatic disease. PSMA PET-CT imaging may have a substantial impact on clinical management in prostate cancer patients at the time of initial staging or with biochemical failure; yet this modality does not appear useful in the management of patients with known metastatic disease.

The p21-activated kinase 4-Slug transcription factor axis promotes epithelial-mesenchymal transition and worsens prognosis in prostate cancer.

Epithelial-mesenchymal transition (EMT) facilitates cancer invasion and metastasis and thus accelerates cancer progression. p21-activated kinase 4 (PAK4) is a critical regulator of prostate cancer (PC) progression. Here, we report that PAK4 activation promotes PC progression through the EMT regulator Slug. We find that phosphorylated PAK4S474 (pPAK4) levels, an index of PAK4 activation, were tightly associated with Gleason score (p < 0.001), a clinical indicator of PC progression, but not with prostate serum antigen levels or tumor stage. Stable silencing of PAK4 in PC cells reduced their potential for EMT, cellular invasion, and metastasis in vivo. PAK4 bound and directly phosphorylated Slug at two previously unknown sites, S158 and S254, which resulted in its stabilization. The non-phosphorylatable form SlugS158A/S254A upregulated transcription of CDH1, which encodes E-cadherin, and thus suppressed EMT and invasion, to a greater extent than did wild-type Slug. The strong EMT inducer TGF-β elevated pPAK4 and pSlugS158 levels; PAK4 knockdown or introduction of a dominant-negative form of PAK4 inhibited both TGF-β-stimulated EMT and an increase in pSlugS158 levels. Finally, immunohistochemistry revealed a positive correlation between pPAK4 and pSlugS158 but an inverse correlation between pSlugS158 and E-cadherin. The results suggest that the PAK4-Slug axis represents a novel pathway that promotes PC progression.

A single mitochondrial DNA deletion accurately detects significant prostate cancer in men in the PSA \u2018grey zone\u2019

PurposeTo determine the clinical performance of a blood-based test for clinically significant (CS) prostate cancer (PCa) (grade group ≥ 2) intended for use in men with prostate serum antigen levels in the ‘grey zone’ (PSA < 10 ng/ml). The test quantifies a previously described 3.4 kb mitochondrial DNA (mtDNA) deletion.MethodsIn a first prospective study of an MRI-guided re-biopsy population (n = 126), the 3.4 kb deletion and 18S rRNA gene were amplified from plasma. A diagnostic threshold was selected from the coordinates of the receiver operating characteristic curve and tested in a second population of men who were (n = 92) biopsy naïve when the mtDNA deletion was assayed and for whom those diagnosed with cancer on initial biopsy were treated with radical prostatectomy.ResultsThe 3.4 kb deletion was a good predictor of CS PCa in the image-guided re-biopsy population [AUC 0.84, (95% CI 0.73–0.95)] and the selected threshold corresponded to a sensitivity of 87% [95% CI, 70–96%], specificity of 68% [95% CI, 47–85%] and negative predictive value (NPV) of 97%. Applying this threshold to the second population showed this deletion to be a strong predictor of CS cancer [AUC 0.98, (95% CI 0.94–1.02)], independent of PSA or age [sensitivity 100% (95% CI, 93–100%), specificity 90% (95%CI 73–98%) and NPV 100%].ConclusionThe 3.4 kb deletion in plasma is an accurate predictor of CS cancer for men in the PSA ‘grey zone’. Used in advance of biopsy for improved patient selection, this deletion may reduce the number of biopsies needed to diagnose CS prostate cancers.

PYGOPUS2 expression in prostatic adenocarcinoma is a potential risk stratification marker for PSA progression following radical prostatectomy

AimsProstate cancer (PrCa) is the most frequently diagnosed non-cutaneous cancer in men. Without clear pathological indicators of disease trajectory at diagnosis, management of PrCa is challenging, given its wide-ranging manifestation...

Switching from an LHRH Antagonist to an LHRH Agonist: A Case Report of 10 Finnish Patients with Advanced Prostate Cancer.

IntroductionLuteinizing hormone-releasing hormone (LHRH) analogues are widely used for the treatment of advanced hormone-dependent prostate cancer. However, there are currently no clinical guidelines for switching between LHRH analogues. It has been reported that there may be clinical benefits for patients switching between different formulations of LHRH agonists, as well as from an LHRH agonist to LHRH antagonist, but there are no published data on switching from an LHRH antagonist to an LHRH agonist. In this paper, we summarize the clinical notes of 10 patients with hormone-sensitive advanced prostate cancer who switched from an LHRH antagonist to an LHRH agonist.MethodsPatients with T3N0M0–T4N1M1 prostate cancer experiencing injection site reactions, such as pain and swelling, with monthly degarelix (Firmagon®) subcutaneous injections were switched to the 3-monthly leuprorelin acetate implant (Leuprorelin Sandoz®) subcutaneous injections.ResultsMean patient age was 75 years (SD 8.3; range 59–85) and Gleason scores ranged from 7 to 9. The mean [±standard deviation (SD)] duration of degarelix treatment was 5 ± 3.7 months (range 2–13). After switching, prostate serum antigen levels were comparable or reduced from those measured prior to switching, showing that efficacy was not compromised. Throughout the course of treatment, no patients reported injection site reactions. Patients reported increased satisfaction with the leuprorelin acetate implant versus degarelix, mainly because of a lack of injection site reactions and reduced frequency of injection.ConclusionThis is the first report of the clinical experience and potential cost implications of switching from an LHRH antagonist to an LHRH agonist. These data are consistent with other experiences of switching between LHRH analogues in terms of efficacy, safety, and potential cost savings, and provide preliminary evidence that the switch from an LHRH antagonist to an agonist is safe and equally efficacious.

Salvage Stereotactic Body Radiotherapy for Isolated Lymph Node Recurrent Prostate Cancer: Single Institution Series of 94 Consecutive Patients and 124 Lymph Nodes.

The purpose of the study was to evaluate the prostate serum antigen (PSA) response, local control, progression-free survival (PFS), and toxicity of stereotactic body radiotherapy (SBRT) for lymph node (LN) oligorecurrent prostate cancer. Between May 2012 and October 2015, 124 lesions were treated in 94 patients with a median dose of 24 Gy in 3 fractions. Seventy patients were treated for a single lesion and 25 for > 1 lesion. In 34 patients androgen deprivation (AD) was combined with SBRT. We evaluated biochemical response according to PSA level every 3 months after SBRT: a 3-month PSA decrease from pre-SBRT PSA of more than 10% identified responder patients. In case of PSA level increase, imaging was performed to evaluate clinical progression. Toxicity was assessed every 6 to 9 months after SBRT. Median follow-up was 18.5 months. In 13 patients (14%) Grade 1 to 2 toxicity was reported without any Grade 3 to 4 toxicity. Biochemical response, stabilization, and progression were observed in 64 (68%), 10 (11%), and 20 (21%) of 94 evaluable patients. Clinical progression was observed in 31 patients (33%) after a median time of 8.1 months. In-field progression occurred in 12 lesions (9.7%). Two-year local control and PFS rates were 84% and 30%, respectively. Age older than 75 years correlated with better biochemical response rate. Age older than 75 years, concomitant AD administered up to 12 months, and pelvic LN involvement correlated with longer PFS. SBRT is safe and offers good in-field control. At 2 years after SBRT, 1 of 3 patients is progression-free. Further investigation is warranted to identify patients who benefit most from SBRT and to define the optimal combination with AD.

Prostate Stem Cell Antigen Expression in Radical Prostatectomy Specimens Predicts Early Biochemical Recurrence in Patients with High Risk Prostate Cancer Receiving Neoadjuvant Hormonal Therapy.

We aimed to identify tissue biomarkers that predict early biochemical recurrence (BCR) in patients with high-risk prostate cancer (PC), toward the goal of increasing the benefits of neoadjuvant hormonal therapy (NHT). In 2005–2012, prostatectomy specimens were collected from 134 PC patients who had received NHT and radical prostatectomy. The expression of 13 tissue biomarkers was assessed in the specimens via immunohistochemistry. Time to BCR and factors predictive of BCR were determined by using the Cox proportional hazards model. During the follow-up period (median, 57.5 months), 67 (50.0%) patients experienced BCR. Four (3.0%) patients were tumor-free in the final pathology assessment, and 101 (75.4%) had negative resection margins. Prostate stem cell antigen (PSCA) was the only significant prognostic tissue biomarker of BCR [hazard ratio (HR), 2.58; 95% confidence interval (CI), 1.06–6.27; p = 0.037] in a multivariable analysis adjusted by the clinicopathological variables that also significantly predicted BCR; these were seminal vesicle invasion (HR, 2.39; 95% CI, 1.32–4.34), initial prostate serum antigen level (HR 1.01; 95% CI, 1.001–1.020), prostate size (HR, 0.93; 95% CI, 0.90–0.97), and the Gleason score of preoperative biopsies (HR, 1.34; 95% CI, 1.01–1.79). We suggest that PSCA is a useful tissue marker for predicting BCR in patients with high risk PC receiving NHT and radical prostatectomy.

Portulaca oleracea chemopreventive effects in rats injected with 1, 2 dimethylhydrazine (824.3)

Purslane (Portulcace Oleracea) is a widely eaten medicinal plant. This study investigated the chemopreventative effects of purslane in rats injected subcutaneously with dimethylhydrazine (DMH. The objective of this study were: 1) To determine the effects of purslane on colon‐induced carcinogenesis by 1, 2‐Dimethylhydrazine injections; 2) To determine the effects of three levels of purslane‐base diets (PBD) on colon neoplasia, ki67, and cyclooxygenase‐2 expression; 3) To determine the effects of three levels of PBD on prostate function and prostate specific antigen (PSA). Forty animals were divided among four treatment groups and fed PBD for eight weeks. The animals were injected subcutaneously with dimethylhydrazine (20 mg/kg body weight) two times per week for three weeks to stimulate cancer development. Prostates and serum were collected for prostate serum antigen level determination and prostate function. Colon tissues were processed for ki67, and cyclooxygenase 2 immunohistochemical analyses. Levels of prostate serum antigen (PSA), and prostate weight decreased, as purslane levels increased. Expression of ki67 and COX‐2 varied among treatment groups however, ki67 and COX‐2 expression was highest among groups with histological lesions suggestive of lymphoma. No colon cancer was identified however, suggestive lymphoma carcinogenesis was highest among animals fed the 5 % PBD compared to the 7 %. Purslane may be effective in the reduction of weight gain, prostate serum antigen level, and prostate weight, however, no protective effect was observed for lymphoma carcinogenesis and its effect on colon cancer is unclear.

Phase I study of BIBF 1120 with docetaxel and prednisone in metastatic chemo-naive hormone-refractory prostate cancer patients

Background:BIBF 1120 is an oral, potent, tyrosine kinase inhibitor that simultaneously targets vascular endothelial growth factor receptors 1–3, platelet-derived growth factor receptors α and β, and fibroblast growth factor receptors 1–3, as well as FLT3 and Src. Currently, the molecule is in phase III development for second-line non-small cell lung cancer and first-line ovarian cancer patients.Methods:This phase I dose-escalation study assessed the safety and maximum tolerated dose of continuous daily treatment with BIBF 1120 plus standard-dose docetaxel (75 mg m−2, every 3 weeks) and prednisone (5 mg BID) in patients with metastatic, chemo-naive, hormone-refractory prostate cancer (HRPC). Secondary objectives were characterisation of BIBF 1120 and docetaxel pharmacokinetics (PK), and preliminary antitumour activity.Results:Patients received BIBF 1120 100 mg BID (n=3), 150 mg BID (n=3), 200 mg BID (n=3), and 250 mg BID (n=12). The most frequent drug-related adverse events were diarrhoea (71.4%), asthenia (61.9%), nausea (28.6%), vomiting (28.6%), and alopecia (23.8%). The maximum tolerated dose was 250 mg BID of BIBF 1120. Overall, reversible grade 3/4 liver enzyme elevations occurred in six of twelve patients at this dose level. Among 19 assessable patients, 13 (68.4%) showed a ⩾50% reduction in prostate serum antigen levels from baseline and among 6 evaluable patients with measurable lesions 1 patient experienced a partial response by Response Evaluation Criteria In Solid Tumours criteria. Pharmacokinetic analysis showed no interactions between BIBF 1120 and docetaxel/prednisone.Conclusion:Based on the overall safety profile, 200 mg BID was the recommended dose for the combination of BIBF 1120 with the standard dose of 75 mg m−2 of docetaxel and prednisone that might be further investigated in HRPC patients. This combination was well tolerated, with preliminary signs of efficacy and no indication of PK interaction between BIBF 1120 and docetaxel.

Genetic polymorphisms of CYP17A1, vitamin D receptor and androgen receptor in Italian heredo-familial and sporadic prostate cancers

Background: Searching for genetic and environmental factors predisposing to prostate cancer, common single-nucleotide polymorphisms in CYP17A1, CYP19A1, VDR genes, and the number of CAG repeats from AR were investigated in Italian heredo-familial prostate cancer (HFPC) patients controlled for dietary intake and life style habits. Methods: We evaluated differences between HFPC and sporadic cancers, in the pattern of common single-nucleotide polymorphisms in CYP17A1, CYP19A1, VDR genes, and the CAG repeat from AR, controlling for dietary intake and lifestyle habits in a regionwide population. Ninety-five patients with HFPC were identified and 378 sporadic prostate cancers were randomly selected as controls. Dietary intake and lifestyle habits were determined through self-administered questionnaires in all patients. Genotyping of polymorphisms for CYP17A1, CYP19A1, VDR, and the CAG repeat from AR was carried out using pyrosequencing. Results: HFPC cases were significantly younger than controls, whereas similar proportions of localized tumours, favourable histology, and abnormal prostate serum antigen levels (4–19 ng/ml) were detected in the two groups. A statistically evident gene–gene interaction was found: a 5-fold higher probability [odds ratio (OR) = 4.83; 95% confidence interval (CI): 1.37–17.02] of HFPC was observed in the subgroup profiling VDR1 T/T genotypes coupled with VDR2 T/T genotype. Among nutrients, an increase in HFPC risk (OR = 3.14; 95% CI: 1.12–8.81) was found only for zinc, when associated with the VDR2 T/T genotype. Conclusions: Significant evidence for positive interactions between VDR1 and VDR2 genotypes was demonstrated, suggesting that high-risk multigenic polymorphism profiles could variously sustain HFPC tumorigenesis.

Characteristics of in vitro prostate cancer models grown in human serum

Objective To compare growth, prostate serum antigen (PSA) production and integrin expression (α2β1, αvβ3, vitronectin receptor VR) in established in vitro models of prostate cancer, when growth media is supplemented with human serum (HS) from healthy men instead of fetal calf serum (FCS), the current standard supplement. Methods The cell lines RWPE, 22Rv1, and LNCaP representing increasing degrees of invasiveness, were cultured in growth media containing 1% HS or 10% FCS. Growth, PSA levels and integrin expression were measured using trypan blue exclusion, ELISA assays, monoclonal antibodies and flow cytometry respectively. Results There were no differences in growth or PSA production by cell lines cultured in HS versus FCS. Expression of the α2β1 integrin was observed to be significantly lower (p< 0.01) in 22Rv1s cultured in HS. 22Rv1 and LNCaP cell lines had lower α2β1 expression compared to RWPE (p<0.05). Expression of the αvβ3, VR was very minimal in all cell lines, although LNCaP expressed greater VR when cultured in HS compared to FCS (p = 0.03). Conclusions Cell lines representing human prostate cancer expressed differences in integrins reported to be involved in cell adhesion and angiogenesis when cultured using HS instead of FCS, despite the lack of change in growth and PSA production. This change in expression is significant in regard to standard culture methods and demonstrates that attempts to make culture methods more closely resemble human conditions must be considered. (Funding: CIHR grant; Elizabeth Donald Fellowship in Human Nutrition)

Transrectal ultrasound-guided biopsy of the prostate gland: value of 12 versus 6 cores.

We investigated the effect on prostate carcinoma detection of 12 versus 6 core biopsies at transrectal ultrasound (TRUS), when all biopsies are taken from the lateral peripheral zone. This was a prospective study of 202 consecutive men, ages 51 to 81 years, referred for TRUS-guided biopsy of the prostate gland. All patients had prostate serum antigen levels higher than 4.0 ng/mL and/or abnormal digital rectal examination. In each case three biopsies were taken from the peripheral zones of the right and left lobes of the prostate. Biopsies were taken at the apex, midway between the apex and the base, and at the base. A second set of biopsies was taken from the same regions and analyzed separately. In total, twelve biopsies were taken. Note was subsequently made of additional carcinoma diagnosis increase in Gleason grade, and new diagnoses of carcinoma in the opposite side of the gland diagnosed on the second set of biopsies alone. Seventy-eight of the 202 men (38.6%) had prostatic carcinoma diagnosed on TRUS-guided biopsy. Of these 78 patients, six were diagnosed with malignancy based on the second set of biopsies alone, a 2.9% increase in the 202 patients, representing an increased yield of 8.3% (95% confidence interval, 5.3-28.6%). In nine cases (12.5%; 95% confidence interval, 6.2-22.9%), the Gleason tumor grade was increased on the second set of sextant biopsies; in an additional nine cases, carcinoma was detected in the opposite side of the gland. There were two complications (1%). A 12- versus six-core biopsy strategy for TRUS-guided biopsy of the prostate gland improves detection and histologic grading of prostate carcinoma. The added benefit of additional biopsies was lower in this series than in some prior studies using extensive biopsy protocols.

The role of endorectal coil MRI in patient selection and treatment planning for prostate seed implants

Purpose: To assess the role of endorectal coil magnetic resonance imaging (MRI) staging for patients undergoing seed implantation (SI) with or without external beam radiotherapy (EBRT).Methods and Materials: Between October 1994 and December 1998, 390 patients underwent prostate SI (98% Pd-103, 2% I-125). Seventy-six percent of patients had a prostate serum antigen (PSA) < 10, 17% had PSA of 10–20, and 7% of patients had PSA of > 20. Ten percent of patients had a Gleason score (GS) of 4–5, 54% had GS 6, 29% had GS 7, and 7% had GS ≥ 8. Monotherapy was employed in 46% of patients, and the remaining 54% received combined EBRT and SI. Three hundred twenty-seven were staged by high-resolution phased array pelvic coil, or in most cases, an endorectal coil MRI. The MRI findings were used to guide stage-appropriate treatment recommendations, and to assist in the preplanning and optimization of seed distributions. The criteria utilized to determine MRI-based stage were founded on the reported literature from the University of Pennsylvania. All MRI studies were reviewed by C.A., D.B., or W.H., who were unaware of clinical stage at the time of their review. The biopsy report was available to them as the only clinical correlate.Results: Of the 327 patients staged by MRI, 70% were upstaged from the digital rectal examination-based clinical stage; 26% of T1, T2 patients were upstaged to T3. Perineural invasion and the percentage of positive cores predicted for T3 MRI stage (p < 0.0001 for both variables). MRI findings changed the overall treatment recommendation in 60/327 (18%) patients. The majority of these patients were advised to receive combined therapy instead of monotherapy after the MRI documented more extensive disease. The seed distribution was modified in 183/327 (56%) patients, mostly related to preplanned extracapsular coverage of bulky or extraprostatic disease seen on MRI. With a mean follow-up of 38 months (range 3–72), PSA freedom from progression (FFP) was 94% at 5 years. Cox regression analysis showed that only the percentage of positive cores (p = 0.001) and failure to have MRI staging (p = 0.0008) predicted for failure. Pretreatment PSA level, Gleason score, perineural invasion, and external beam radiotherapy did not significantly predict for PSA failure. We compared our MRI T3 intermediate-risk group patients treated by combined therapy with a previous study of T3 intermediate-risk group treated by radical prostatectomy (RP) at the University of Pennsylvania. Our 36-month PSA FFP was 94% compared with 21% for the previous study’s RP patients.Conclusion: MRI is a valuable staging procedure for prostate cancer patients treated by SI. PSA FFP results appear to be improved by MRI staging. MRI T3 disease can be treated more effectively by SI + EBRT than by RP.

Prospective study of sex hormone levels and risk of prostate cancer.

Sex steroids, particularly androgens, have been implicated in the pathogenesis of prostate cancer. Data from previous studies comparing circulating hormone levels in men with and without prostate cancer are difficult to interpret, since the studies were limited in size, hormone levels were analyzed in blood drawn after the diagnosis of cancer, nonrepresentative control subjects were used, and hormone and hormone-binding protein levels were not simultaneously adjusted. We conducted a prospective, nested case-control study to investigate whether plasma hormone and sex hormone-binding globulin (SHBG) levels in healthy men were related to the subsequent development of prostate cancer. Among participants in the Physicians' Health Study who provided plasma samples in 1982, we identified 222 men who developed prostate cancer by March 1992. Three hundred ninety control subjects, matched to the case patients on the bases of age, smoking status, and length of follow-up, were also identified. Immunoassays were used to measure the levels of total testosterone, dihydrotestosterone (DHT), 3 alpha-androstanediol glucuronide (AAG), estradiol, SHBG, and prolactin in the stored (at -82 degrees C) plasma samples. Correlations between individual hormone levels and between hormone levels and SHBG in the plasma of control subjects were assessed by use of Spearman correlation coefficients (r). Odds ratios (ORs) and 95% confidence intervals (CIs) specifying the prostate cancer risk associated with quartile levels of individual hormones, before and after adjustment for other hormones and SHBG, were calculated by use of conditional logistic regression modeling. Reported P values are two-sided. No clear associations were found between the unadjusted levels of individual hormones or SHBG and the risk of prostate cancer. However, a strong correlation was observed between the levels of testosterone and SHBG (r = .55), and weaker correlations were detected between the levels of testosterone and the levels of both estradiol (r = .28) and DHT (r = .32) (all P < .001). When hormone and SHBG levels were adjusted simultaneously, a strong trend of increasing prostate cancer risk was observed with increasing levels of plasma testosterone (ORs by quartile = 1.00, 1.41, 1.98, and 2.60 [95% CI = 1.34-5.02]; P for trend = .004), an inverse trend in risk was seen with increasing levels of SHBG (ORs by quartile = 1.00, 0.93, 0.61, and 0.46 [95% CI = 0.24-0.89]; P for trend = .01), and a non-linear inverse association was found with increasing levels of estradiol (ORs by quartile = 1.00, 0.53, 0.40, and 0.56 [95% CI = 0.32-0.98]; P for trend = .03). No associations were detected between the levels of DHT or prolactin and prostate cancer risk; for AAG, a marker of 5 alpha-reductase activity, only suggestive evidence of a positive association was found. The results were essentially unchanged when case patients diagnosed within 4 years of plasma collection, case patients diagnosed with localized (i.e., nonaggressive) disease, or control subjects with elevated prostate serum antigen levels (> 2.5 ng/mL) were excluded from the analyses. High levels of circulating testosterone and low levels of SHBG-both within normal endogenous ranges-are associated with increased risks of prostate cancer. Low levels of circulating estradiol may represent an additional risk factor. Circulating levels of DHT and AAG do not appear to be strongly related to prostate cancer risk.