Many tumour types have been reported to have deletion of 9p21 (refs 1-6). A candidate target suppressor gene, p16 (p16INK4a/MTS-1/CDKN2), was recently identified within the commonly deleted region in tumour cell lines. An increasing and sometimes conflicting body of data has accumulated regarding the frequency of homozygous deletion and the importance of p16 in primary tumours. We tested 545 primary tumours by microsatellite analysis with existing and newly cloned markers around the p16 locus. We have now found that small homozygous deletions represent the predominant mechanism of inactivation at 9p21 in bladder tumours and are present in other tumour types, including breast and prostate cancer. Moreover, fine mapping of these deletions implicates a 170 kb minimal region that includes p16 and excludes p15.
During the last decade much of the focus has been on improving the ability of this tumor marker to detect prostate cancer. PSA remains the best and most widely used tumor marker in urology today.
ContextThe incidence of localised prostate cancer is increasing worldwide. In light of recent evidence, current, radical, whole-gland treatments for organ-confined disease have being questioned with respect to their side effects, cancer control, and cost. Focal therapy may be an effective alternative strategy.ObjectiveTo systematically review the existing literature on baseline characteristics of the target population; preoperative evaluation to localise disease; and perioperative, functional, and disease control outcomes following focal therapy.Evidence acquisitionMedline (through PubMed), Embase, Web of Science, and Cochrane Review databases were searched from inception to 31 October 2012. In addition, registered but not yet published trials were retrieved. Studies evaluating tissue-preserving therapies in men with biopsy-proven prostate cancer in the primary or salvage setting were included.Evidence synthesisA total of 2350 cases were treated to date across 30 studies. Most studies were retrospective with variable standards of reporting, although there was an increasing number of prospective registered trials. Focal therapy was mainly delivered to men with low and intermediate disease, although some high-risk cases were treated that had known, unilateral, significant cancer. In most of the cases, biopsy findings were correlated to specific preoperative imaging, such as multiparametric magnetic resonance imaging or Doppler ultrasound to determine eligibility. Follow-up varied between 0 and 11.1 yr. In treatment-naïve prostates, pad-free continence ranged from 95% to 100%, erectile function ranged from 54% to 100%, and absence of clinically significant cancer ranged from 83% to 100%. In focal salvage cases for radiotherapy failure, the same outcomes were achieved in 87.2–100%, 29–40%, and 92% of cases, respectively. Biochemical disease-free survival was reported using a number of definitions that were not validated in the focal-therapy setting.ConclusionsOur systematic review highlights that, when focal therapy is delivered with intention to treat, the perioperative, functional, and disease control outcomes are encouraging within a short- to medium-term follow-up. Focal therapy is a strategy by which the overtreatment burden of the current prostate cancer pathway could be reduced, but robust comparative effectiveness studies are now required.
PURPOSE Germline testing (GT) is a central feature of prostate cancer (PCA) treatment, management, and hereditary cancer assessment. Critical needs include optimized multigene testing strategies that incorporate evolving genetic data, consistency in GT indications and management, and alternate genetic evaluation models that address the rising demand for genetic services. METHODS A multidisciplinary consensus conference that included experts, stakeholders, and national organization leaders was convened in response to current practice challenges and to develop a genetic implementation framework. Evidence review informed questions using the modified Delphi model. The final framework included criteria with strong (> 75%) agreement (Recommend) or moderate (50% to 74%) agreement (Consider). RESULTS Large germline panels and somatic testing were recommended for metastatic PCA. Reflex testing—initial testing of priority genes followed by expanded testing—was suggested for multiple scenarios. Metastatic disease or family history suggestive of hereditary PCA was recommended for GT. Additional family history and pathologic criteria garnered moderate consensus. Priority genes to test for metastatic disease treatment included BRCA2, BRCA1, and mismatch repair genes, with broader testing, such as ATM, for clinical trial eligibility. BRCA2 was recommended for active surveillance discussions. Screening starting at age 40 years or 10 years before the youngest PCA diagnosis in a family was recommended for BRCA2 carriers, with consideration in HOXB13, BRCA1, ATM, and mismatch repair carriers. Collaborative (point-of-care) evaluation models between health care and genetic providers was endorsed to address the genetic counseling shortage. The genetic evaluation framework included optimal pretest informed consent, post-test discussion, cascade testing, and technology-based approaches. CONCLUSION This multidisciplinary, consensus-driven PCA genetic implementation framework provides novel guidance to clinicians and patients tailored to the precision era. Multiple research, education, and policy needs remain of importance.
Word Count (text): 4,713Keywords: focal therapy, partial ablation, prostate cancer 2 ABSTRACT Context: focal therapy of prostate cancer has been proposed as an alternative to wholegland treatments.Objective: to summarise the evidence regarding sources of energy employed in focal therapy.Evidence Acquisition: Embase and Medline (PubMed) were searched from 1996 to 31 st October 2015 following the PRISMA statement. Ongoing trials were selected from electronic registries.Evidence Synthesis: thirty-seven articles reporting on 3,230 patients undergoing focal therapy were selected. 13 reported on high intensity focused ultrasound (HIFU), 11 on cryotherapy, three on photodynamic therapy (PDT), four on laser interstitial thermotherapy (LITT), two on brachytherapy, three on irreversible electroporation (IRE), and one on radiofrequency (RFA). HIFU, cryotherapy, PDT and brachytherapy have been assessed in up to stage 2b studies. LITT and IRE have been evaluated in up to stage 2a studies. RFA has been evaluated in one stage 1 study. Median follow-up varied between 4-61 months, and median rate of serious adverse events ranged between 0-10.6%. Pad-free leak-free continence and potency were obtained in 83.3-100% and 81.5-100%, respectively. In series with intentionto-treat, the median rate of significant and insignificant disease at control biopsy varied between 0-13.4% and 5.1-45.9%, respectively. Main limitations are the length of follow-up, the absence of a comparator arm, and study heterogeneity.Conclusion: focal therapy has been evaluated using seven sources of energy in single-arm retrospective and prospective development studies up to stage 2b. Focal therapy seems to 3 have minor impact on quality of life and genito-urinary function. Cancer-control is encouraging, although this needs to be verified in high quality comparative effectiveness studies.Patient summary: seven sources of energy have been employed to selectively ablate discrete areas of prostate cancer. There is high evidence that focal therapy is safe and has low detrimental impact on continence and potency. The oncological outcome has yet to be evaluated against standard of care.
Background: Prostate cancer affects one of six men during their lifetime. Dietary factors are postulated to influence the development and progression of prostate cancer. Low-fat diets and flaxseed supplementation may offer potentially protective strategies. Methods: We undertook a multisite, randomized controlled trial to test the effects of low-fat and/or flaxseedsupplemented diets on the biology of the prostate and other biomarkers. Prostate cancer patients (n = 161) scheduled at least 21 days before prostatectomy were randomly assigned to one of the following arms: (a) control (usual diet), (b) flaxseed-supplemented diet (30 g/d), (c) low-fat diet (<20% total energy), or (d) flaxseed-supplemented, low-fat diet. Blood was drawn at baseline and before surgery and analyzed for prostate-specific antigen, sex hormone-binding globulin, testosterone, insulin-like growth factor-I and binding protein-3, C-reactive protein, and total and
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