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A Prospective Study of Intraprostatic Inflammation, Focal Atrophy, and Progression to Lethal Prostate Cancer.

ABSTRACT: BACKGROUND:Inflammation and focal atrophy are common features adjacent to prostate tumors. Limited evidence exists on whether these features have prognostic significance. METHODS:In the Health Professionals Follow-Up Study and Physicians' Health Study, we studied 1,035 men diagnosed with prostate cancer. A genitourinary pathologist centrally reviewed tumor and normal areas of hematoxylin and eosin slides from prostate cancer specimens for the presence of acute and chronic inflammation, and four subtypes of focal atrophy. Cox proportional hazards models adjusted for potential confounders were used to estimate HRs and 95% confidence intervals (CI) for the association of these features with lethal prostate cancer, defined as development of metastatic disease or death during follow-up. RESULTS:During a median of 12 years of follow-up, 153 men developed lethal prostate cancer. A total of 84% of men had histologic evidence of chronic inflammation and 30% had acute inflammation. Both chronic and acute inflammation were inversely associated with lethal prostate cancer in age- and lifestyle-adjusted models. Chronic inflammation remained inversely associated with lethal prostate cancer after additionally adjusting for prognostic clinical features (HR = 0.45; 95% CI, 0.30-0.69 for mild and HR = 0.51; 95% CI, 0.33-0.80 for moderate to severe). None of the atrophic lesions were associated with lethal prostate cancer. CONCLUSIONS:Our data suggest that the presence of inflammation, particularly chronic inflammation, in prostate cancer tissue is associated with better prognosis among patients with prostate cancer. IMPACT:This is the largest prospective cohort study to examine the association between inflammation, focal atrophy, and lethal prostate cancer.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC6941930 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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A Prospective Study of Intraprostatic Inflammation, Focal Atrophy, and Progression to Lethal Prostate Cancer.

Zhang Yiwen Y Zhou Cindy Ke CK Rencsok Emily M EM Fall Katja K Lotan Tamara L TL Loda Massimo M Giunchi Francesca F Platz Elizabeth A EA De Marzo Angelo M AM Mucci Lorelei A LA Fiorentino Michelangelo M Ebot Ericka M EM

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20190918 12

<h4>Background</h4>Inflammation and focal atrophy are common features adjacent to prostate tumors. Limited evidence exists on whether these features have prognostic significance.<h4>Methods</h4>In the Health Professionals Follow-Up Study and Physicians' Health Study, we studied 1,035 men diagnosed with prostate cancer. A genitourinary pathologist centrally reviewed tumor and normal areas of hematoxylin and eosin slides from prostate cancer specimens for the presence of acute and chronic inflamma ...[more]

PMID: 31533941

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Project description:Radiation therapy (RT) is a curative treatment option for localized prostate cancer. Prostate irradiation with focal dose escalation to the intraprostatic dominant nodule (IDN) is an emerging treatment option that involves the prophylactic irradiation of the whole prostate while increasing RT doses to the visible prostatic tumor. Because of the lack of large multicentre trials, a systematic review was performed in an attempt to get an overview on the feasibility and efficacy of focal dose escalation to the IDN. A bibliographic search for articles in English, which were listed in MEDLINE from 2000 to 2016 to identify publications on RT with focal directed boost to the IDN, was performed. The review was completed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Twenty-two articles describing 1,378 patients treated with RT using focal boost were identified and fulfilled the selection criteria. Intensity-modulated radiation therapy (IMRT) was used in 720 patients (52.3%), volumetric modulated arc therapy was used in 45 patients (3.3%), stereotactic body radiation therapy (SBRT) in 113 patients (8.2%), and low-dose rate and high-dose rate brachytherapy (BT) were used in 305 patients (22.1%) and 195 patients (14.1%), respectively. Use of androgen deprivation therapy varied substantially among series. Biochemical disease-free survival at 5 years was reported for a cohort of 812 (58.9%) patients. The combined median biochemical disease-free survival for this group of patients was 85% (range: 78.8-100%; 95% confidence interval: 77.1-82.7%). The average occurrence of grade III or worse gastrointestinal and genitourinary late toxicity was, respectively, 2.5% and 3.1% for intensity-modulated RT boost, 10% and 6% for stereotactic body RT, 6% and 2% for low-dose rate BT, and 4% and 4.3% for high-dose rate BT. This review shows encouraging results for focal dose escalation to the IDN with acceptable short- to medium-term side effects and biochemical disease control rates. However, owing to the heterogeneity of patient population and the short follow-up, the results should be interpreted with caution. Considering that the clinical endpoint in the studies was biochemical recurrence, the use and duration of androgen deprivation therapy administration should be carefully considered before driving definitive conclusions. Randomized trials with long-term follow-up are needed before this technique can be generally recommended.

Project description:BACKGROUND:Radical whole-gland therapy can lead to significant genitourinary and rectal side-effects for men with localised prostate cancer. We report on whether selective focal ablation of unifocal and multifocal cancer lesions can reduce this treatment burden. METHODS:Men aged 45-80 years were eligible for this prospective development study if they had low-risk to high-risk localised prostate cancer (prostate specific antigen [PSA] ?15 ng/mL, Gleason score ?4?+?3, stage ?T2), with no previous androgen deprivation or treatment for prostate cancer, and who could safely undergo multiparametric MRI and have a general anaesthetic. Patients received focal therapy using high-intensity focused ultrasound, delivered to all known cancer lesions, with a margin of normal tissue, identified on multiparametric MRI, template prostate-mapping biopsies, or both. Primary endpoints were adverse events (serious and otherwise) and urinary symptoms and erectile function assessed using patient questionnaires. Analyses were done on a per-protocol basis. This study is registered with ClinicalTrials.gov, number NCT00561314. FINDINGS:42 men were recruited between June 27, 2007, and June 30, 2010; one man died from an unrelated cause (pneumonia) 3 months after treatment and was excluded from analyses. After treatment, one man was admitted to hospital for acute urinary retention, and another had stricture interventions requiring hospital admission. Nine men (22%, 95% CI 11-38) had self-resolving, mild to moderate, intermittent dysuria (median duration 5·0 days [IQR 2·5-18·5]). Urinary debris occurred in 14 men (34%, 95% CI 20-51), with a median duration of 14·5 days (IQR 6·0-16·5). Urinary tract infection was noted in seven men (17%, 95% CI 7-32). Median overall International Index of Erectile Function-15 (IIEF-15) scores were similar at baseline and at 12 months (p=0·060), as were median IIEF-15 scores for intercourse satisfaction (p=0·454), sexual desire (p=0·644), and overall satisfaction (p=0·257). Significant deteriorations between baseline and 12 months were noted for IIEF-15 erectile (p=0·042) and orgasmic function (p=0·003). Of 35 men with good baseline function, 31 (89%, 95% CI 73-97) had erections sufficient for penetration 12 months after focal therapy. Median UCLA Expanded Prostate Cancer Index Composite (EPIC) urinary incontinence scores were similar at baseline as and 12 months (p=0·045). There was an improvement in lower urinary tract symptoms, assessed by International Prostate Symptom Score (IPSS), between baseline and 12 months (p=0·026), but the IPSS-quality of life score showed no difference between baseline and 12 months (p=0·655). All 38 men with no baseline urinary incontinence were leak-free and pad-free by 9 months. All 40 men pad-free at baseline were pad-free by 3 months and maintained pad-free continence at 12 months. No significant difference was reported in median Trial Outcomes Index scores between baseline and 12 months (p=0·113) but significant improvement was shown in median Functional Assessment of Cancer Therapy (FACT)-Prostate (p=0·045) and median FACT-General scores (p=0·041). No histological evidence of cancer was identified in 30 of 39 men biopsied at 6 months (77%, 95% CI 61-89); 36 (92%, 79-98) were free of clinically significant cancer. After retreatment in four men, 39 of 41 (95%, 95% CI 83-99) had no evidence of disease on multiparametric MRI at 12 months. INTERPRETATION:Focal therapy of individual prostate cancer lesions, whether multifocal or unifocal, leads to a low rate of genitourinary side-effects and an encouraging rate of early absence of clinically significant prostate cancer. FUNDING:Medical Research Council (UK), Pelican Cancer Foundation, and St Peters Trust.

Project description:ObjectiveTo determine morphological and biological control as well as toxicity and quality of life (QoL) of men with localized prostate cancer (PCa) treated with MRI-guided focal boost radiotherapy.Material and methods30 patients with PCa and a visible dominant intraprostatic lesion (DIL) identified on mpMRI were included in a prospective Phase II trial. Matching point registration of planning CT and T2W, diffusion-weighted and a gradient-recalled echo (GRE) MRI images made in treatment position was used for prostate and tumour delineation. Treatment consisted on 35 daily fractions of 2.17 Gy with a concomitant focal boost to the DIL of 2.43 Gy using volumetric modulated arc therapy (VMAT) and image-guided radiation therapy (IGRT) with intraprostatic fiducial markers. Biochemical failure was analysed using PSA nadir +2 ng/mL criteria and local control using mpMRI evaluation at 6-9 months following RT. Acute and late toxicity were defined according to CTCAE v.4.0 and RTOG/EORTC scales and QoL was assessed using IPSS, EPIC short-form and UCLA-PCI questionnaires.ResultsThe median radiation dose to the prostate was 77.6 Gy (IQR 77.3-78.1), and to the DIL was 85.5 Gy (IQR 85.0-86.0). With a median follow up of 30.0 months (IQR 25.5-40.27), all patients remain free of biochemical relapse. An mpMRI complete response was observed in 25 patients during the first post-treatment evaluation at 6 months. The remaining five patients achieved a complete disappearance of the DIL both on T2 and DWI on the second mpMRI performed at 9 months following treatment. Six out of 30 (20%) patients presented acute Grade 2 urinary toxicity with no Grade 3 acute complications. Acute rectal toxicity was only found in 2 (6.6%) patients (both Grade 1). Only late Grade 1 urinary and rectal complications were observed in 3/30 patients, respectively, with no Grade 2 or more late toxicity. The urinary, bowel and sexual bother EPIC scores were slightly and insignificantly increased in the first 3 months post-treatment, returning to normal afterwards.ConclusionsmpMRI-guided focal boost using VMAT hypofractionated technique is associated with an excellent morphological and functional response control and a safe toxicity profile.Advances in knowledgeIn the present trial, we examined the potential role of mpMRI for radiological assessment (functional and morphological) of treatment response in high-risk prostate cancer patients treated with MRI-guided focal radiotherapy dose intensification to dominant Intraprostatic lesion.

Dataset Information

A Prospective Study of Intraprostatic Inflammation, Focal Atrophy, and Progression to Lethal Prostate Cancer.

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A Prospective Study of Intraprostatic Inflammation, Focal Atrophy, and Progression to Lethal Prostate Cancer.

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