50 research outputs found
Padeliporfin vascular-targeted photodynamic therapy versus active surveillance in men with low-risk prostate cancer (CLIN1001 PCM301): an open-label, phase 3, randomised controlled trial
BACKGROUND: Vascular-targeted photodynamic therapy, a novel tissue-preserving treatment for low-risk prostate cancer, has shown favourable safety and efficacy results in single-arm phase 1 and 2 studies. We compared this treatment with the standard of care, active surveillance, in men with low-risk prostate cancer in a phase 3 trial. METHODS: This randomised controlled trial was done in 47 European university centres and community hospitals. Men with low-risk, localised prostate cancer (Gleason pattern 3) who had received no previous treatment were randomly assigned (1:1) to vascular-targeted photodynamic therapy (4 mg/kg padeliporfin intravenously over 10 min and optical fibres inserted into the prostate to cover the desired treatment zone and subsequent activation by laser light 753 nm with a fixed power of 150 mW/cm for 22 min 15 s) or active surveillance. Randomisation was done by a web-based allocation system stratified by centre with balanced blocks of two or four patients. Best practice for active surveillance at the time of study design was followed (ie, biopsy at 12-month intervals and prostate-specific antigen measurement and digital rectal examination at 3-month intervals). The co-primary endpoints were treatment failure (histological progression of cancer from low to moderate or high risk or death during 24 months' follow-up) and absence of definite cancer (absence of any histology result definitely positive for cancer at month 24). Analysis was by intention to treat. Treatment was open-label, but investigators assessing primary efficacy outcomes were masked to treatment allocation. This trial is registered with ClinicalTrials.gov, number NCT01310894. FINDINGS: Between March 8, 2011, and April 30, 2013, we randomly assigned 206 patients to vascular-targeted photodynamic therapy and 207 patients to active surveillance. Median follow-up was 24 months (IQR 24-25). The proportion of participants who had disease progression at month 24 was 58 (28%) of 206 in the vascular-targeted photodynamic therapy group compared with 120 (58%) of 207 in the active surveillance group (adjusted hazard ratio 0路34, 95% CI 0路24-0路46; p<0路0001). 101 (49%) men in the vascular-targeted photodynamic therapy group had a negative prostate biopsy result at 24 months post treatment compared with 28 (14%) men in the active surveillance group (adjusted risk ratio 3路67, 95% CI 2路53-5路33; p<0路0001). Vascular-targeted photodynamic therapy was well tolerated. The most common grade 3-4 adverse events were prostatitis (three [2%] in the vascular-targeted photodynamic therapy group vs one [<1%] in the active surveillance group), acute urinary retention (three [2%] vs one [<1%]) and erectile dysfunction (two [1%] vs three [1%]). The most common serious adverse event in the vascular-targeted photodynamic therapy group was retention of urine (15 patients; severe in three); this event resolved within 2 months in all patients. The most common serious adverse event in the active surveillance group was myocardial infarction (three patients). INTERPRETATION: Padeliporfin vascular-targeted photodynamic therapy is a safe, effective treatment for low-risk, localised prostate cancer. This treatment might allow more men to consider a tissue-preserving approach and defer or avoid radical therapy. FUNDING: Steba Biotech
Three dimensional ultrasound and prostate cancer.
Three-dimensional ultrasound (3-D US) is a non-invasive method of producing whole volume images of solid structures. Early work on prostate imaging identified several advantages over 2-D imaging with a good ability to detect intraprostatic lesions. Several 3-D transrectal ultrasound (3-D TRUS) systems are now available for prostate imaging. Initial work using gray scale ultrasound appears promising with reported overall staging accuracies of up to 94%. These results were favourable when compared to other modalities for local staging of prostate cancer. Several adjuncts to 3-D gray scale TRUS have been investigated. A greater sensitivity for cancer detection has been achieved with the addition of power colour Doppler and contrast agents. Further clinical applications for 3-D TRUS include assessing placement of brachytherapy seeds and for cyroablation techniques. Computer enhancement with image registration has shown that 3-D US images can be manipulated to derive more information. Although the results of gray scale imaging alone or with adjuncts and post processing appear promising, these techniques remain largely experimental
Gli1 appears to be constitutively expressed in the lumenal epithelial cells of the prostate but not in the basal cell layer or the mesenchyme
DNA promoter methylation in urothelial cancer: a feature of the invasive phenotype and a novel therapeutic target
Loss of intercellular expression of beta-dystroglycan is a common event in prostate cancer and is significantly associated with loss of differentiation
Microsatellite instability as predictor of survival in patients with invasive upper urinary tract transitional cell carcinoma.
OBJECTIVES: To establish whether high microsatellite instability (MSI) (present in almost 20% of cases) and loss of MSH2 protein expression (sometimes used to predict MSI status) are prognostic factors of overall survival for patients with invasive upper urinary tract transitional cell carcinoma (UUT-TCC). UUT-TCC has a poor prognosis (overall survival less than 50% at 5 years). METHODS: The files of 80 patients who underwent nephroureterectomy for invasive UUT-TCC (Stage pT2 or worse) between 1990 and 2002 were reviewed. The following data were collated: age at diagnosis, prior history of cancer, tobacco consumption, tumor stage and grade, and disease progression. MSI was determined by polymerase chain reaction/fragment analysis and MSH2 protein expression by immunohistochemistry on retrieved tumor tissue. RESULTS: The median patient age was 71.5 years. The male/female ratio was 2.8. High MSI and loss of MSH2 expression were encountered in the tumors of 14 (17%) and 21 (26%) of the 80 patients, respectively. High MSI was significantly associated with patients with a better prognosis (Stage T2-T3N0M0; P = 0.02). The mean overall survival was 22.5 +/- 18 months (range 6 to 78). In univariate analyses, age, stage, tumor grade, high MSI, and loss of MSH2 expression were related to better overall survival (37 +/- 22 months, P = 0.003; 34 +/- 22 months, P = 0.02). Only stage, age, and high MSI were prognostic factors in a multivariate analysis (P < 0.05). CONCLUSIONS: MSI and expression of MSH2 are useful prognostic factors in invasive UUT-TCC. However, other than age and stage, only MSI was an independent factor. High MSI indicates a better prognosis, especially in patients younger than 71 years with Stage T2-T3N0M0
Tissue microarray immunohistochemistry and cluster analysis confirms the validity of candidate proteins in prostate cancer identified by proteomic analysis of urine
Proteomic analysis of voided urine after prostatic massage from patients with prostate cancer: a pilot study.
OBJECTIVES: Serum prostate-specific antigen measurements are widely used for the early detection of prostate cancer but lack specificity, thus warranting the search for additional biomarkers. METHODS: Two-dimensional gel electrophoresis followed by matrix-assisted laser desorption ionization-time of flight-mass spectroscopy (MALDI-TOF-MS) analysis was used to investigate the protein profiles of voided urine after prostatic massage from 6 patients with histologically confirmed prostate cancer and 6 age-matched patients with benign prostatic hyperplasia. RESULTS: The median number of protein spots per gel was lower in the urine from the patients with cancer (median 143 spots, range 118 to 163) than in the urine from those with benign prostatic hyperplasia (median 154 spots, range 142 to 209), although the difference was not statistically significant. MALDI-TOF-MS analysis identified six commonly expressed proteins: alpha-enolase, isocitrate dehydrogenase, beta-2-microglobulin, alpha-1-microglobulin, complex-forming glycoprotein HC, and PRO2044. Of the five protein spots seen in a subset of patients with cancer, one was identified as calgranulin B/MRP-14. Immunohistochemical staining of prostatic tissue showed greater expression of calgranulin B/MRP-14 in 2 of 7 well-differentiated, 1 of 12 moderately differentiated, and 0 of 8 poorly differentiated tumors relative to adjacent benign tissue; expression of calgranulin A/MRP-8, a heterodermic binding partner of calgranulin B/MRP-14, was absent. CONCLUSIONS: The role of urinary calgranulin B/MRP-14 as a potential novel marker for prostate cancer needs additional investigation
Promoter hyper-methylation of calcium binding proteins S100A6 and S100A2 in human prostate cancer.
BACKGROUND: S100A6 and S100A2 are members of the S100 family of calcium binding proteins, which are down regulated in prostate cancer, however the molecular mechanism(s) underlying their loss of expression is unknown. METHODS: The promoter and exon 1 region of the S100A6 and S100A2 genes was sequenced in bisulfite modified DNA from non-malignant, benign prostatic hyperplasia (BPH), malignant and metastatic prostate tissues and in cell lines. Immunohistochemistry was performed to correlate S100A2 expression with methylation status. RESULTS: S100A6 methylation was absent or occurred at isolated sites in 14/14 cases of non-malignant epithelium and 5/5 cases of BPH tissues, whereas methylation was seen in 14/27 (52%) cases of prostatic cancer (P<0.0001), 2/2 cases of metastatic cancer and in the CWR22 prostatic cancer xenograft. Critical CpG sites within the S100A2 promoter were methylated in LNCaP, LNCaP-LN3, and CWR22 cells but not in Du145, PC3 or BPH45 cells. In tissues, S100A2 methylation was seen in 32/34 (94%) cases of adenocarcinoma and 5/5 cases of metastatic cancer. However, S100A2 methylation was also seen in 9/12 (75%) cases of non-malignant tissues and in 5/5 cases of BPH. Immunostaining, showed absent S100A2 expression all 41 cases of prostatic cancer, whereas staining was seen in the basal cells of non-malignant epithelium. CONCLUSIONS: Loss of S100A6 and S100A2 proteins is frequent in human prostatic cancer. A major mechanism underlying the loss of S100A6 expression appears to involve promoter hyper-methylation. However, mechanisms other than methylation of the known promoter are involved in silencing S100A2 in the prostate