Early Prostate Cancer Patients Research Articles

The superior detection rate of total-body [68Ga]Ga-PSMA-11 PET/CT compared to short axial field-of-view [68Ga]Ga-PSMA-11 PET/CT for early recurrent prostate cancer patients with PSA < 0.2ng/mL after radical prostatectomy.

[68Ga]Ga-PSMA PET imaging has been extensively utilized for the detection of biochemical recurrence (BCR) in prostate cancer. However, the detection rate declines to merely 10-40% when PSA levels are < 0.2ng/mL employing short axial field-of-view (SAFOV) PET. Prior studies exhibited superior detection rates with total-body [68Ga]Ga-PSMA-11 PET compared to SAFOV [68Ga]Ga-PSMA-11 PET in BCR patients with PSA > 0.2ng/mL. Nevertheless, the diagnostic utility of total-body [68Ga]Ga-PSMA-11 PET for BCR patients when PSA is < 0.2ng/mL remains unclear. This study aimed to assess whether total-body [68Ga]Ga-PSMA-11 PET/CT could improve the detection rate compared to SAFOV [68Ga]Ga-PSMA-11 PET/CT in BCR patients with PSA < 0.2ng/mL. Eighty BCR patients with PSA < 0.2ng/mL underwent total-body [68Ga]Ga-PSMA-11 PET/CT. These patients were matched by baseline qualities to another 80 patients who received SAFOV [68Ga]Ga-PSMA-11 PET/CT. The detection rates of total-body [68Ga]Ga-PSMA-11 PET/CT and SAFOV [68Ga]Ga-PSMA-11 PET/CT were compared utilizing a chi-square test and stratified analysis. Image quality of total-body [68Ga]Ga-PSMA PET/CT and SAFOV [68Ga]Ga-PSMA-11 PET/CT was assessed based on subjective scoring and objective parameters. The objective parameters measured were SUVmax, SUVmean, standard deviation (SD) of SUV, and signal-to-noise ratio (SNR) of liver and gluteus maximus. The image quality of total-body [68Ga]Ga-PSMA PET/CT was superior to that of SAFOV [68Ga]Ga-PSMA-11 PET/CT in both early and delayed scans. The detection rate of total-body [68Ga]Ga-PSMA PET/CT for BCR patients with PSA < 0.2ng/mL was significantly higher than that of SAFOV [68Ga]Ga-PSMA-11 PET/CT (73.75% vs. 43.75%, P < 0.001). Total-body [68Ga]Ga-PSMA PET/CT resulted in noteworthy modifications to the treatment regimen when contrasted with SAFOV [68Ga]Ga-PSMA-11 PET/CT. In BCR patients with PSA < 0.2ng/mL, total-body [68Ga]Ga-PSMA-11 PET/CT not only demonstrated a significantly higher detection rate compared to SAFOV [68Ga]Ga-PSMA-11 PET/CT but also led to significant alterations in treatment regimens.

68Ga-PSMA PET/CT in early relapsed prostate cancer patients after radical therapy

Biochemical recurrence (BCR) of prostate cancer (PCa) occurs in about 25% of patients treated with radical prostatectomy (RP) and up to 45% in patients who receive external beam radiotherapy (RT). Early diagnosis of PCa recurrence is of high importance for successful salvage therapy. The aim of the present study is to analyze the efficacy of 68 Ga-PSMA PET/CT in detecting the presence of local and/or systemic disease in patients with a history of PCa who have BCR. A total of 52 PCa patients with BCR referred for 68 Ga-PSMA PET/CT were recruited from the American University of Beirut Medical Center between November 2017 and December 2019. We compared the performance of PSMA PET/CT to the results and clinical factors based on follow up: PSA, PSA kinetics, primary treatment, and Gleason score. The relationship between the PET/CT findings and clinical indicators of disease were assessed by univariate and multivariate logistic regression. From a total of 52 patients, 34 (65.4%) had positive PSMA-PET/CT scans. Among those, 8/34 (23.5%) received primary RT. For all patients with a positive PSMA-PET: the detection rate was 2/4 (50%) for PSA < 0.2, 5/10 (50%) for PSA 0.2–0.49, 3/6 (50%) for PSA 0.5–0.99, 6/12 (50%) for PSA 1–1.99, 8/9 (88.9%) for PSA 2–3.99, and 10/11 (90.9%) for PSA 4–10.PSMA-PET/CT positivity was significantly associated with PSA level at time of PET scan, PSA doubling time, Gleason score and TNM staging. However, it did not show a significant correlation with radiotherapy as primary treatment, ongoing androgen deprivation therapy (ADT), time to relapse, and initial PSA before therapy. In our single center prospective trial, 68 Ga-PSMA PET/CT successfully detected the recurrence of PCa in patients with BCR. Scan positivity was significantly associated with PSA level at time of PET scan, PSA doubling time, Gleason score, and TNM staging. PSMA- PET/CT is a highly promising modality in the work up of patients with PCa in the setting of BCR for earlier detection of disease recurrence.

Effect of combined use of atorvastatin and hormonal therapy on serum prostate-specific antigen, urinary function, and quality of life of early prostate cancer patients in intensive care unit

Purpose: To determine the effects of combined use of atorvastatin and hormonal therapy on serum levels of prostate-specific antigen (PSA), urinary function parameters, and quality of life (QOL) of intensive care unit (ICU) patients with early prostate cancer (PCa).&#x0D; Methods: The clinical data for 90 PCa patients treated in ICU of Chenzhou First People's Hospital, Chenzhou, China from July 2019 to July 2020 were retrospectively analyzed. The patients were divided into a reference group given intensity-modulated radiotherapy (n = 45), and a study group treated with intensity-modulated radiotherapy + atorvastatin + hormonal therapy (n = 45) sequentially as they were admitted. After the treatments, serum PSA levels of the patients were measured using enzyme-linked immunosorbent assay (ELISA), while QOL was measured based on Expanded Prostate Cancer Index Composite (EPIC). Urinary parameters were determined by measuring various urodynamic indicators.&#x0D; Results: Compared with the reference group, the study group had significantly lower post-treatment serum levels of PSA and blood lipids, higher levels of urinary function indicators (except for residual urine volume), and higher scores in IIEF-5 and EPIC (p &lt; 0.001). &#x0D; Conclusion: These results demonstrate that the combined use of atorvastatin and hormonal therapy is a reliable method for improving urinary function and QOL in early PCa patients. Moreover, the combined treatment has potentials for reducing serum levels of PSA and blood lipids in PCa patients. These findings may be useful in the establishment of improved therapy for early PCa.&#x0D; Keywords: Atorvastatin; Hormonal therapy; Early prostate cancer; Serum PSA; Urinary function; Quality of life

18F]Fluciclovine PET/CT Improves the Clinical Management of Early Recurrence Prostate Cancer Patients.

Simple SummaryIn the challenge between increasingly sensitive PET radiopharmaceuticals for the evaluation of prostate cancer patient in biochemical relapse, the choice of the most accurate PET tracer must be guided by literature data, but above all tailored to the patient’s profile. In describing our single-center experience, we aimed to identify biochemical and clinical–histological factors to be considered in patient selection and the semiquantitative parameters that can help the interpretation of malignant from benign lesions, in order to optimize the performance of this imaging method. These data in combination with a significant impact on therapeutic decision making can be useful to further validate the [18F]Fluciclovine PET/CT clinical application.We investigated the [18F]Fluciclovine PET/CT reliability in the early detection of recurrent prostate cancer (PCa) and its impact on therapeutic decision making. We retrospectively analyzed 58 [18F]Fluciclovine PET/CT scans performed to identify early PCa recurrence. Detection rate (DR) and semiquantitative analysis were evaluated in relation to biochemical and clinical–histological features. Clinical follow-up data were collected and considered as gold standard to evaluate sensitivity, specificity, accuracy, positive and negative predictive value (PPV, NPV). The impact of [18F]Fluciclovine PET/CT on clinical management was also assessed. Overall DR resulted as 66%, while DR was 53%, 28%, and 7% in prostate/bed, lymph nodes, and bone, respectively. DR significantly increased with higher PSA values (p = 0.009) and 0.45 ng/mL was identified as the optimal cut-off value. Moreover, SUVmax and SUVmean resulted significant parameters in interpreting malignant from benign findings. [18F]Fluciclovine PET/CT reached a sensitivity, specificity, PPV, NPV, and accuracy of 87.10%, 80.00%, 87.10%, 80.00%, and 84.31%, respectively. Therapeutic strategy was changed in 51% of patients. Our results support [18F]Fluciclovine PET/CT as a reliable tool for early restaging of PCa patients, especially for local recurrence detection, leading to a significant impact on clinical management. Semiquantitative analysis could improve specificity in interpreting malignant from benign lesions.

P1039 - %p2PSA and phi predict the pathological reclassification of first-year protocol biopsy during Active surveillance for early prostate cancer patients: From the PRIAS-JAPAN study

P1039 - %p2PSA and phi predict the pathological reclassification of first-year protocol biopsy during Active surveillance for early prostate cancer patients: From the PRIAS-JAPAN study

The psychological impact of early prostate cancer: A prospective evaluation.

210 Background: Early prostate cancer is often considered as being associated with a good prognosis and quality of life. However, early prostate cancer research mainly focus on its medical aspects, rarely considering its psychological impact. We aimed to prospectively analyze the correlation between illness perception, quality of life (QOL) and psychological distress among prostate cancer patients, in comparison to healthy controls. Methods: Early prostate cancer patients and healthy controls were prospectively recruited through convenience sampling. Participants filled questionnaires of demographic, illness perception (IPQ-R), QOL (MOS SF-36) and anxiety and depression (HADS). We compared the illness perception, QOL and psychological distress between patients and healthy controls. Results: 51 early prostate cancer patients and 65 healthy men controls were included. Median age was 69. Patients and healthy participants differed in illness perception ['consequences' (p&lt;.001), 'emotional representations' (p&lt;.001)] and psychological distress (p&lt;.01). There was a correlation between the patient illness perception and QOL (p&lt;.05) and psychological distress (p&lt;.05). Among patients, the correlation between psychological distress and QOL was mediated by illness perception (p&lt;.05), while it was not among controls. Conclusions: Diagnosis of early prostate cancer may have a psychological impact. Among early prostate cancer patients, a correlation may exist between illness perception, and quality of life (QOL) and psychological distress. Our results emphasize the need to identify patient distress and to implement therapeutic interventions also in a disease which usually is associated with a good prognosis.

Abstract 283: Identification of a high-risk subgroup in primary prostate cancers presenting with targetable immune biology

Abstract Background Recent studies have demonstrated limited success of immune checkpoint therapies in unselected prostate cancer. We therefore assessed an immune based DNA Damage Repair Deficiency (DDRD) assay, that we have previously reported represents activation of the cGAS STING pathway in the TCGA dataset of primary prostate cancers, to investigate the presence of targetable immune biology in prostate cancer. In addition we applied a second assay (the prostate cancer metastatic signature-PCM) that predicts risk of metastatic recurrence for early prostate cancer to assess if immune therapy could have a role in treating high risk disease. Methods 498 samples in the TCGA dataset with RNA sequencing data were scored with the PCM and DDRD assays. Integrative analysis was performed on 488 of those samples with matched RNA sequencing, promoter site methylation, somatic mutation and somatic copy number variation. Gene expression of n=6 immune checkpoint targets was investigated with the subgroups identified using T-tests. The prevalence of immune infiltration in each subgroup was tested by applying a cut off to the leukocyte fraction. The viability of reproducing those subgroups with RNA sequencing alone was tested in the TCGA dataset and an independent validation dataset of 321 resected primary prostate cancers. Cox proportional hazards regression analysis was performed for biochemical recurrence and metastatic events in both datasets. Results Integrative analysis of the TCGA dataset identified four patient subgroups characterised primarily by variances in copy number and genomic mutation. One of these subgroups ‘Metastatic-like DDRD' had significantly higher PCM scores and DDRD immune scores compared to the other subgroups (p &amp;lt; 2E-12). This subgroup of patients showed elevated leukocyte fraction and expression of immune checkpoint genes: CD274 (PDL1), CTLA4, ICOS, IDO1, HAVCR2 (TIM3) &amp; LAG3 (p &amp;lt; 2E-6). Genomic instability with amplification of 8q and a larger prevalence of somatic mutations including that of TP53 was also detected in this subgroup. The ‘Metastatic-like DDRD' subgroup was found to have a significant association with poor survival outcome in TCGA (multivariable: p &amp;lt; 0.008), a result that has also been replicated in an independent dataset in both univariate (p &amp;lt; 0.001) and multivariable analysis (p &amp;lt; 0.01). Conclusions We have identified and validated a poor prognostic subgroup, representing 10-20% of early prostate cancer patients that are at increased risk of developing metastatic disease and present with targetable immune biology. These patients may represent a viable target population for immune checkpoint and DNA damaging therapies in prostate cancer. Citation Format: Emma Reilly, Andrena McCavigan, Steven M. Walker, Nuala McCabe, Eileen Parkes, Denis P. Harkin, Richard D. Kennedy, Laura A. Knight. Identification of a high-risk subgroup in primary prostate cancers presenting with targetable immune biology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 283.

Personalized risk stratification for patients with early prostate cancer (PRONTO): A Canadian team biomarker project.

109 Background: Current practice stratifies men with prostate cancer into risk groups based primarily on Gleason grade. When applied to biopsy samples, the Gleason grading is inaccurate due to sampling error and inter-observer variation. The result is that men either receive unnecessary surgical treatment, or they don’t receive adequate treatment, leading to worse outcomes. Previously published genomic tests have not successfully distinguished indolent low grade (G6 or GG1) cancers from their more aggressive intermediate grade (G7 or GG2 and 3) counterparts. PRONTO is specifically aimed at creating a multi-modal risk stratification tool to improve treatment stratification following a core biopsy diagnosis. Methods: PRONTO links 7 projects, each with novel diagnostic assays for risk stratification that focus on analysis of copy number variations (CNV), DNA hypermethylation, trans-differentiation, cancer metabolism, or the tumor microenvironment. We merged the best transcripts from each project into a single NanoString gene expression assay, measuring 393 transcripts, in a cohort of 365 cases of radical prostatectomy from low-to-intermediaterisk patients. To minimize sampling error, we took multiple samples, and obtained high grade, low grade and benign areas for each radical prostatectomy case. Results: Our primary goal was to develop a multivariate molecular classifier of grade that distinguished G6 from G7 (3+4 or 4+3). Cases were randomly partitioned into five equally sized groups. A supervised machine learning algorithm (random forests) was trained on samples from four of the groups, and then evaluated by testing on the fifth group. This process was repeated for each of the five groups, yielding a combined clinical and molecular classifier. DNA methylation profiles and CNV profiles are currently being integrated into our classifier Conclusions: We have developed a multivariate classifier that distinguishes low grade from intermediate grade prostate cancer. It will be clinically validated in biopsy samples from large cohorts of early prostate cancer patients.

Exploration of the cGAS-STING pathway in prostate cancer.

103 Background: Recent studies have demonstrated limited success of immune checkpoint therapies in unselected prostate cancer. We therefore assessed an immune based DNA Damage Repair Deficiency (DDRD) assay, that we have previously reported represents activation of the cGAS STING pathway, in the TCGA prostate cancer dataset to investigate the presence of targetable immune biology in prostate cancer. In addition we applied a second assay (the prostate cancer metastatic signature-PCM) that predicts the risk of metastatic recurrence for early prostate cancer, in order to assess if immune therapy could have a role in treating high risk disease. Methods: 498 samples with RNA sequencing data were scored with the PCM and DDRD assays. Integrative analysis was performed on 488 samples with RNA sequencing, promoter site methylation, somatic mutation and somatic copy number variation. Gene expression of n = 6 immune checkpoint targets was investigated with the subgroups identified using T-tests. The prevalence of immune infiltration in each subgroup was tested by applying a cut off to the leukocyte fraction. Cox proportional hazards regression analysis of 441 patients was assessed for biochemical recurrence. Results: Integrative analysis identified four patient subgroups characterised primarily by variances in copy number and genomic mutation. One of these subgroups ‘Metastatic-like DDRD’ had significantly higher PCM scores and DDRD immune scores compared to the other subgroups (p &lt; 2E-12). This subgroup of patients showed elevated leukocyte fraction and expression of immune checkpoint genes: CD274 (PDL1), CTLA4, ICOS, IDO1, HAVCR2 (TIM3) &amp; LAG3 (p &lt; 2E-6). Genomic instability with amplification of 8q and a larger prevalence of somatic mutations including that of TP53 was also detected in this subgroup. These patients had an increased risk of biochemical relapse in both univariate (p &lt; 2E-5) and multivariate (p &lt; 0.008) analysis. Conclusions: We identified a poor prognostic subgroup, representing 17% of early prostate cancer patients that are at increased risk of developing metastatic disease and present with targetable immune biology. These patients may represent a viable target population for immune checkpoint and DNA damaging therapies in prostate cancer.

Clinical efficacy of combination therapy with an alpha blocker and low-dose sildenafil on post-therapy lower urinary tract symptoms after low-dose-rate brachytherapy for prostate cancer.

To investigate the efficacy of tamsulosin monotherapy and tamsulosin with low-dose sildenafil combination therapy on lower urinary tract symptoms (LUTS) following low-dose-rate (LDR) brachytherapy in early prostate cancer patients. From March 2008 to June 2014, of the 212 prostate cancer patients with a Gleason score ≤7 who received LDR brachytherapy, 80 patients with a prostate volume ≤35g and progressed LUTS following implantation were selected. All 80 patients took tamsulosin 0.4-mg monotherapy until 1month after implantation. Then, the patients were divided into two groups; 45 patients received tamsulosin 0.4-mg monotherapy, and 35 patients received tamsulosin 0.4-mg plus sildenafil 25-mg combination therapy due to erectile dysfunction. LUTS were compared between the two groups using the International Prostate Symptom Score (IPSS), the mean maximum flow rate (Q max) and the pre-implantation post-voiding residual (PVR) volume at 1 and 3months after implantation. The pre-implantation total IPSS, Q max and PVR for the monotherapy and combination therapy groups were 14.0±6.7, 14.3±3.2ml/s and 36.3±16.7ml and 15.3±5.6, 13.7±4.5ml/s and 39.0±23.4ml, respectively. At 1 month post-implantation, both groups showed increases in total IPSS and PVR, but no statistically significant differences were observed (P=0.078, P=0.23). At 3 months post-implantation, the combination therapy group showed a greater decrease in total IPSS compared with the monotherapy group (P=0.035), but there were no statistically significant differences in the Q max and PVR between the two groups. Tamsulosin plus low-dose sildenafil combination therapy is a beneficial treatment for post-implantation progression of LUTS.

Safety and efficacy of iodine-125 permanent prostate brachytherapy in patients with J-pouch anastomosis after total colectomy for ulcerative colitis

PurposeTo ascertain the safety and efficacy of permanent prostate brachytherapy (PPB) in early prostate cancer patients who have undergone previous total proctocolectomy and J-pouch anastomosis for inflammatory bowel disease. Methods and materialsWe identified 10 patients with a previous history of prostate cancer and J-pouch anastomosis from our institutional review board–approved database. Seven patients had PPB and 3 had prostatectomy. Only patients treated with PPB were included. Patient records were reviewed to collect data on treatment-related toxicity and oncological outcomes. ResultsAll 7 patients who underwent PPB had low- to intermediate-risk prostate cancer. The mean prostatic volume was 24.40 mL and the average number of iodine-125 seeds implanted was 84. Postimplant dosimetric calculations showed a mean prostate volume receiving 100% of the prescribed dose (V100) of 88.76%, V150 of 45.23%, V200 of 16.79%, radiation dose delivered to 90% of the prostate of 147.89 Gy, volume of ileal pouch receiving 100% of the prescribed dose of 0.164 mL, and volume of ileal pouch receiving 50% of the prescribed dose of 1.38 mL. After a mean follow-up of 19 months, none of the patients had evidence of biochemical failure or clinical failure. There were no long-term genitourinary side effects detected. Two patients had Common Terminology Criteria for Adverse Events version 4.0 grade II gastrointestinal side effects, of which symptoms resolved to baseline in 1 patient, whereas the other patient progressed to chronic active enteritis (pouchitis). ConclusionLow- to intermediate-risk prostate cancer patients with J-pouch anastomosis after total colectomy for inflammatory bowel disease are candidates for definitive treatment with PPB. Caution should be exercised while deploying the most posterior row of seeds to minimize enteral pouch radiation doses.

Risk of Pathologic Upgrading or Locally Advanced Disease in Early Prostate Cancer Patients Based on Biopsy Gleason Score and PSA: A Population-Based Study of Modern Patients

Radiation oncologists rely on available clinical information (biopsy Gleason score and prostate-specific antigen [PSA]) to determine the optimal treatment regimen for each prostate cancer patient. Existing published nomograms correlating clinical to pathologic extent of disease were based on patients treated in the 1980s and 1990s at select academic institutions. We used the Surveillance, Epidemiology, and End Results (SEER) database to examine pathologic outcomes (Gleason score and cancer stage) in early prostate cancer patients based on biopsy Gleason score and PSA concentration. This analysis included 25,858 patients whose cancer was diagnosed between 2010 and 2011, with biopsy Gleason scores of 6 to 7 and clinical stage T1 to T2 disease, who underwent radical prostatectomy. In subgroups based on biopsy Gleason score and PSA level, we report the proportion of patients with pathologically advanced disease (positive surgical margin or pT3-T4 disease) or whose Gleason score was upgraded. Logistic regression was used to examine factors associated with pathologic outcomes. For patients with biopsy Gleason score 6 cancers, 84% of those with PSA <10 ng/mL had surgical T2 disease with negative margins; this decreased to 61% in patients with PSA of 20 to 29.9 ng/mL. Gleason score upgrading was seen in 43% (PSA: <10 ng/mL) to 61% (PSA: 20-29.9 ng/mL) of biopsy Gleason 6 patients. Patients with biopsy Gleason 7 cancers had a one-third (Gleason 3 + 4; PSA: <10 ng/mL) to two-thirds (Gleason 4 + 3; PSA: 20-29.9 ng/mL) probability of having pathologically advanced disease. Gleason score upgrading was seen in 11% to 19% of patients with biopsy Gleason 4 + 3 cancers. Multivariable analysis showed that higher PSA and older age were associated with Gleason score upgrading and pathologically advanced disease. This is the first population-based study to examine pathologic extent of disease and pathologic Gleason score upgrading based on clinically available information in modern patients. These data inform the selection of radiation therapy strategies and an understanding of whether prostatectomy alone is likely to be curative for patients with early prostate cancers.

Association of "DNA damage signature" with poor outcome in early prostate cancer.

13 Background: Whole genome and matching normal tissue analyses in prostate cancer patients have shown that widespread genomic changes occur in multiple distant regions of the genome simultaneously (Baca et al., Cell. 2013). The inherent genomic instability in prostate cancers causes activation of pathways involved in DNA damage, which could be a prognostic and potentially predictive marker for treatment with agents impacting DNA repair (e.g. PARP inhibitors). Using a published dataset, a “DNA damage signature” was generated to test its role as a potential prognostic marker. Methods: A 10-gene signature was generated, using the top 9 genes (MXD3, ZMYND19, BANF1, TOMM40, UBE2S, SNRPF, RPP21, CDK2AP2 and H2AFX) correlated with H2AFX expression, which is known to be unregulated upon DNA damage. TP53 was added due to its significant role in this pathway. This signature was then assessed in The Cancer Genome Atlas dataset (TCGA, unpublished data at NCI) as a discovery set and then validated in the MSK dataset (Taylor et al., 2010) using mutation, copy number, mRNA and proteomic data. Results: Genes in the signature were altered in 31% (77/246) of patients, by amplification and over expression compared to normal. The most frequent alterations were found in TP53 (15%), MXD3 (7%), BANF1 (7%), UBE28 (7%) and CDK2AF2 (7%). Analysis of protein changes associated with alteration in genomic signature showed upregulation of FOXO3, BCL2L1, BAK1 and PCNA (P&lt;0.05). There were significant correlations between the signature and Gleason score (p=0.0015), PTEN (p=0.003) &amp; RAD51 gene expression (p&lt;0.001), but not with ERG,PSA, PIK3CA or BRCA2. Patients with alterations were associated with poor disease free survival (DFS) (p=0.002). When expression was assessed in the validation set, 73%(62/85) samples showed altered gene signatures and those with alterations also had poor DFS (p=0.003). Conclusions: The DNA damage signature can be used to define a group of patients with poor outcome and has the potential to be used as prognostic marker in treatment decisions in early prostate cancer patients.

Difference in the rate of rectal complications following prostate brachytherapy based on the prostate-rectum distance and the prostate longitudinal length among early prostate cancer patients.

PurposeTo investigate the difference in rectal complications rate following prostate low dose rate (LDR) brachytherapy based on prostate-rectum distance and prostate longitudinal length among early prostate cancer patients.Materials and MethodsFrom March 2008 to February 2013, 245 prostate cancer patients with a Gleason score ≤7 were treated with 125-I LDR brachytherapy. Among them, 178 patients with prostate volume 20-35 mL and a follow-up period ≥6 months were evaluated for radiation proctitis. Magnetic resonance imaging (MRI) was performed for a prebrachytherapy evaluation, and prostate-rectum distance and prostate longitudinal length were measured. The radiation proctitis was confirmed and graded via colonoscopy based on the radiation therapy oncology group (RTOG) toxicity criteria.ResultsTwenty-three patients received a colonoscopy for proctitis evaluation, and 12 were identified as grade 1 on the RTOG scale. Nine patients were diagnosed as grade 2 and 2 patients were grade 3. No patient developed grade 4 proctitis. The rectal-complication group had a mean prostate-rectum distance of 2.51±0.16 mm, while non-rectal-complication control group had 3.32±0.31 mm. The grade 1 proctitis patients had a mean prostate-rectum distance of 2.80±0.15 mm, which was significantly longer than 2.12±0.31 mm of grades 2 and 3 patient groups (p=0.045). All 11 patients of grades 2 and 3 had a prostate longitudinal length of 35.22±2.50 mm, which was longer than group 1, but the difference was not statistically significant (p=0.214).ConclusionsAs the prostate-rectum distance increased, fewer postimplantation rectal symptoms were observed. Patients with a shorter prostate-rectum distance in MRI should receive modified implantation techniques or radical prostatectomy.

Treatment Decision-making for Early Prostate Cancer Patients - What Can Nurses Do

This review investigates the topic of treatment for early cancer patients. The research question to be addressed is What can oncology nurses do to support men with early cancer in making treatment decisions? Reports of primary research found by CIHNAL and Ovid search engines using the term prostate cancer decision-making are reviewed. A total of 18 studies have been identified. It is found that men with cancer all need support and information when making treatment decisions. However, little has been said about the types of support and information needed or the best way to deliver them. The undesirable situation is coupled with people's seemingly innate wish to solve crises quickly and making decisions based on individual experience and misconception. As such, reciting treatment options simply and handing out generic literature cannot ensure that the patient and his family members fully understand the options available. It is argued that individualized treatment, with informed decision made jointly by the patient, his family and a treating team, offers the best chance for satisfactory outcomes. Nurses can make use of their research to design interventions and inform the patient of the treatment approach to better assist men in making treatment decisions. It is hoped that individualized and patient-centered treatment will become the norm in healthcare.

Treatment of early‐stage prostate cancer among rural and urban patients

Geographic barriers and limited availability of cancer specialists may influence early prostate cancer treatment options for rural men. This study compares receipt of different early prostate cancer treatments between rural and urban patients. Using 2004-2006 SEER Limited-Use Data, 51,982 early prostate cancer patients were identified (T1c, T2a, T2b, T2c, T2NOS; no metastases) who were most likely to benefit from definitive treatment (< 75 years old, Gleason score < 8, PSA ≤ 20). Definitive treatment included radical prostatectomy, daily external beam radiation for 5 to 8 weeks, brachytherapy, or combination external beam radiation/brachytherapy. Adjusted definitive treatment rates were calculated by rural-urban residence overall, and for different sociodemographic and cancer characteristics, and different states based on logistic regression analyses, using general estimating equation methods to account for clustering by county. Adjusted definitive treatment rates were lower for rural (83.7%) than urban (87.1%) patients with early-stage prostate cancer (P ≤ .01). Rural men were more likely than urban men to receive non-definitive surgical treatment and no initial treatment. The lowest definitive treatment rates were among rural subgroups: 70 to 74 years (73.9%), African Americans (75.6%), American Indians/Alaska Natives (77.8%), single/separated/divorced (76.8%), living in New Mexico (69.3%), and living in counties with persistent poverty (79.6%). Between 2004 and 2006, this adjusted analysis found that men who were living in rural areas were less likely to receive definitive treatment for their early-stage prostate cancer than those living in urban areas. Certain rural patient groups with prostate cancer need particular attention to ensure their access to appropriate treatment. Rural providers, rural health care systems, and cancer advocacy and support organizations should ensure resources are in place so that the most vulnerable rural groups (men between 60 and 74 years of age; African American men; men who are single, separated, or divorced; and men living in rural New Mexico) can make informed prostate cancer treatment choices based on their preferences.

Brachytherapy Alone May Be Sufficient For Most Early Prostate Cancer Patients

Brachytherapy Alone May Be Sufficient For Most Early Prostate Cancer Patients

Role of lymphotoxin-a and interleukin-17A in human prostate cancer.

212 Background: Infiltrating immune cells have been implicated in prostate carcinogenesis. Murine studies suggest that B-cell-derived lymphotoxin (LT)a may be a key effector in the evolution to castrate-resistant prostate cancer (CRPC) (Ammirante et al, Nature 2011). Lymphotoxin a has also been implicated in the progression of murine fibrosarcoma, where it complements interleukin (IL)-17A, to synergistically enhance NFkB signaling. This interaction may also apply to human prostate cancer since IL-17-producing Th17 cells are abundant in these tumors. However, the role of LTα in human as distinct from murine prostate cancer remains unclear. Clinical validation is vital since murine models poorly recapitulate the behavior of prostate cancer in man. Methods: Serum levels of LTα and IL-17A were measured by ELISA in patients with benign (n=22) and malignant prostate disease (n=87). Samples were from 29 early prostate cancer patients (amenable to radical therapy), 28 with androgen-sensitive (AS) disease and 30 with CRPC. Data were not normally distributed and thus were analyzed by Mann-Whitney U test. Results: Serum LTαand IL-17A were significantly elevated in patients with both CRPC and early stage prostate cancer, compared to those with benign disease. LTαwas significantly raised in CRPC compared to AS disease. IL-17A was significantly higher in the early stage disease compared to AS prostate cancer. Conclusions: Based upon these data, we hypothesize that B-cell derived LTα synergises with Th17 derived IL-17A from the earliest stage of primary tumor development. In support of this, blockade of LTα in prostate cancer-prone (TRAMP) mice delays primary tumor onset and inhibits metastasis. Furthermore, NSAIDs protect more strongly against lifetime risk of prostate cancer in those individuals with an LTα over-producer polymorphism. Prostate cancer preferentially metastasizes to local lymph nodes and bone – sites at which mature B-cells are plentiful. Consequently, tumor-trophic effects of LTα would become increasingly efficient with disease progression. Our data are incompatible with and thus refute the clinical relevance of a role for androgen ablation in promoting LTα-driven CRPC.

CD10 and Endothelin-1 are Inversely Expressed in Early Prostate Cancer and Predict Psa Failure after Radical Prostatectomy

Background: Loss of the membrane endopeptidase CD10 plays an important role in the development of neuropeptide-mediated androgen-independent prostate cancer cell growth. The aim of this study was to investigate the potential prognostic value of the CD10/neuropeptide axis with regard to prostate-specific antigen (PSA) failure after radical prostatectomy in early prostate cancer patients. Methods: Tumor samples from 70 early prostate cancer patients who underwent radical prostatectomy were immunohistochemically evaluated for expression of CD10 and endothelin-1 (ET-1). The examined parameters were prospectively correlated with time to PSA failure and combined with Gleason grade and pathological TNM stage. Results: Membranous and apical cytoplasmic expression of CD10 was directly correlated with time to PSA failure ( P < 0.001). Cytoplasmic ET-1 was inversely correlated with time to PSA relapse ( P = 0.002). CD10 and ET-1 were inversely interrelated ( P < 0.001). CD10 expression (P = 0.012) and stage ( P = 0.013) were independent predictors of biochemical recurrence. Conclusion: CD10 and ET-1 follow inverse patterns of expression in tumors of early prostate cancer patients, in accordance with their biological roles and molecular interrelations. Evaluation of CD10 expression in early prostate cancer might contribute to a better prediction of PSA relapse-free survival after radical prostatectomy.

Alcohol Drinking, Non-alcoholic Beverages and Risk of Advanced Prostate Cancer among Uruguayan Men

Background: Loss of the membrane endopeptidase CD10 plays an important role in the development of neuropeptide-mediated androgen-independent prostate cancer cell growth. The aim of this study was to investigate the potential prognostic value of the CD10/neuropeptide axis with regard to prostate-specific antigen (PSA) failure after radical prostatectomy (RP) in early prostate cancer (PC) patients. Methods: Tumor samples from 70 early PC patients who underwent RP were immunohistochemically evaluated for expression of CD10 and endothelin-1 (ET-1). The examined parameters were prospectively correlated with time to PSA failure and combined with Gleason grade and pathological TNM stage. Results: Membranous and apical cytoplasmic expression of CD10 was directly correlated with time to PSA failure ( P < 0.001). Cytoplasmic ET-1 was inversely correlated with time to PSA relapse ( P = 0.002). CD10 and ET-1 were inversely interrelated ( P < 0.001). CD10 expression (P = 0.012) and stage ( P = 0.013) were independent predictors of biochemical recurrence. Conclusion: CD10 and ET-1 follow inverse patterns of expression in tumors of early PC patients, in accordance with their biological roles and molecular interrelations. Evaluation of CD10 expression in early PC might contribute to a better prediction of PSA relapse-free survival after RP.