Subgroup Of Prostate Cancer Patients Research Articles

Deficiency in DNA Damage Repair Proteins Promotes Prostate Cancer Cell Migration through Oxidative Stress

Introduction: DNA damage repair gene deficiency defines a subgroup of prostate cancer patients with early metastatic progression and unfavorable disease outcome. Whether deficiency in DNA damage repair genes directly promotes metastatic dissemination is not completely understood. Methods: The migratory behavior of prostate cancer cells was analyzed after siRNA-mediated knockdown of DNA damage repair and checkpoint proteins, including BRCA2, ATM, and others, using transwell migration assays, scratch assays and staining for F-actin to ascertain cell circularity. Cells deficient in BRCA2 or ATM were tested for oxidative stress by measuring reactive oxygen species (ROS). The effects of ROS inhibition on cell migration were analyzed using the antioxidant N-acetylcysteine (NAC). The correlation between BRCA2 deficiency and oxidative stress was ascertained via immunohistochemistry for methylglyoxal (MG)-modified proteins in 15 genetically defined primary prostate cancers. Results: Prostate cancer cells showed a significantly increased migratory activity after the knockdown of BRCA2 or ATM. There was a significant increase in ROS production in LNCaP cells after BRCA2 knockdown and in PC-3 cells after BRCA2 or ATM knockdown. Remarkably, the ROS scavenger NAC abolished the enhanced motility of prostate cancer cells after the knockdown of BRCA2 or ATM. Primary prostate cancers harboring genetic alterations in BRCA2 showed a significant increase in MG-modified proteins, indicating enhanced oxidative stress in vivo. Conclusions: Our results indicate that DNA damage repair gene deficiency may contribute to the metastatic dissemination of prostate cancer through enhanced tumor cell migration involving oxidative stress.

Recent Advances in Prostate Cancer Treatment and Drug Discovery.

Novel drugs, drug sequences and combinations have improved the outcome of prostate cancer in recent years. The latest approvals include abiraterone acetate, enzalutamide and apalutamide which target androgen receptor (AR) signaling, radium-223 dichloride for reduction of bone metastases, sipuleucel-T immunotherapy and taxane-based chemotherapy. Adding abiraterone acetate to androgen deprivation therapy (ADT) in order to achieve complete androgen blockade has proven highly beneficial for treatment of locally advanced prostate cancer and metastatic hormone-sensitive prostate cancer (mHSPC). Also, ADT together with docetaxel treatment showed significant benefit in mHSPC. Ongoing clinical trials for different subgroups of prostate cancer patients include the evaluation of the second-generation AR antagonists enzalutamide, apalutamide and darolutamide, of inhibitors of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) pathway, of inhibitors of DNA damage response, of targeted alpha therapy and of prostate-specific membrane antigen (PSMA) targeting approaches. Advanced clinical studies with immune checkpoint inhibitors have shown limited benefits in prostate cancer and more trials are needed to demonstrate efficacy. The identification of improved, personalized treatments will be much supported by the major progress recently made in the molecular characterization of early- and late-stage prostate cancer using “omics” technologies. This has already led to novel classifications of prostate tumors based on gene expression profiles and mutation status, and should greatly help in the choice of novel targeted therapies best tailored to the needs of patients.

Incremental value of 68-gallium-prostate-specific membrane antigen positron emission tomography/computed tomography in patients with abnormal prostate-specific antigen and benign transrectal ultrasound biopsy.

Introduction:Bladder outlet obstruction due to prostate enlargement is a common health problem in male and frequently investigated with prostate-specific antigen (PSA) and transrectal ultrasound (TRUS). TRUS-guided biopsy is critical to differentiate benign prostatic hyperplasia (BPH) or prostate cancer (PCa) even though it has been associated with false negative with reported 3%–16% incidence of PCa in BPH specimens. Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT), a targeted molecular imaging for PCa, has showed promising results in recurrence and staging. We analyzed its role in patients with abnormal PSA and benign TRUS biopsy.Material and Methods:Of 558 68Ga-PSMA PET/CT performed from July 2014 to February 2017, we found six patients with abnormal PSA (range 8.2–24.2 ng/ml, median: 13.3 ng/ml) with benign 12 cores TRUS biopsy as indication. These cases were reanalyzed in detail. Spearman's rank test was used entire correlation using SPSS version 21.Results:68Ga-PSMA PET/CT showed mild diffuse tracer uptake in prostate in all patients with no focality and maximum standard uptake value normalized to body weight (SUVmax) range was 3.2-5.8 (median: 3.9). Two patients with PSA <10 ng/ml had normal 68Ga-PSMA PET/CT and underwent medical management. In other four patients with PSA >10 ng/ml, two showed metastatic disease in pelvic lymph node in both and in lung in one; hence, 68Ga-PSMA PET/CT changed these patients' management. Spearman's rank test showed no correlation with baseline PSA and SUVmax of prostate (rs −0.0287, P = 0.9571) while strong positive correlation was seen with baseline PSA and 68Ga-PSMA PET/CT scan positivity for extraprostatic disease (rs = 0.828, P = 0.042).Conclusions:68Ga-PSMA whole-body PET/CT can provide useful incremental information in patient with high PSA and negative TRUS biopsy and has a potential to guide management in this subgroup of PCa patients.

Mutational Analysis of Gene Fusions Predicts Novel MHC Class I-Restricted T-Cell Epitopes and Immune Signatures in a Subset of Prostate Cancer.

Purpose: Gene fusions are frequently found in prostate cancer and may result in the formation of unique chimeric amino acid sequences (CASQ) that span the breakpoint of two fused gene products. This study evaluated the potential for fusion-derived CASQs to be a source of tumor neoepitopes, and determined their relationship to patterns of immune signatures in prostate cancer patients.Experimental Design: A computational strategy was used to identify CASQs and their corresponding predicted MHC class I epitopes using RNA-Seq data from The Cancer Genome Atlas of prostate tumors. In vitro peptide-specific T-cell expansion was performed to identify CASQ-reactive T cells. A multivariate analysis was used to relate patterns of in silico-predicted tumor-infiltrating immune cells with prostate tumors harboring these mutational events.Results: Eighty-seven percent of tumors contained gene fusions with a mean of 12 per tumor. In total, 41% of fusion-positive tumors were found to encode CASQs. Within these tumors, 87% gave rise to predicted MHC class I-binding epitopes. This observation was more prominent when patients were stratified into low- and intermediate/high-risk categories. One of the identified CASQ from the recurrent TMPRSS2:ERG type VI fusion contained several high-affinity HLA-restricted epitopes. These peptides bound HLA-A*02:01 in vitro and were recognized by CD8+ T cells. Finally, the presence of fusions and CASQs were associated with expression of immune cell infiltration.Conclusions: Mutanome analysis of gene fusion-derived CASQs can give rise to patient-specific predicted neoepitopes. Moreover, these fusions predicted patterns of immune cell infiltration within a subgroup of prostate cancer patients. Clin Cancer Res; 23(24); 7596-607. ©2017 AACR.

Using cluster analysis of anxiety-depression to identify subgroups of prostate cancer patients for targeted treatment planning.

To explore any possible subgroupings of prostate cancer (PCa) patients based upon their combined anxiety-depression symptoms for the purposes of informing targeted treatments. A sample of 119 PCa patients completed the GAD7 (anxiety) and PHQ9 (depression), plus a background questionnaire, by mail survey. Data on the GAD7 and PHQ9 were used in a cluster analysis procedure to identify and define any cohesive subgroupings of patients within the sample. Three distinct clusters of patients were identified and were found to be significantly different in the severity of their GAD7 and PHQ9 responses, and also by the profile of symptoms that they exhibited. The presence of these 3 clusters of PCa patients indicates that there is a need to extend assessment of anxiety and depression in these men beyond simple total score results. By applying the clustering profiles to samples of PCa patients, more focussed treatment might be provided to them, hopefully improving outcome efficacy.

Early dynamic imaging in 68Ga- PSMA-11 PET/CT allows discrimination of urinary bladder activity and prostate cancer lesions.

PET/CT with 68Ga-labelled prostate-specific membrane antigen (PSMA)-ligands has been proven to establish a promising imaging modality in the work-up of prostate cancer (PC) patients with biochemical relapse. Despite a high overall detection rate, the visualisation of local recurrence may be hampered by high physiologic tracer accumulation in the urinary bladder on whole body imaging, usually starting 60min after injection. This study sought to verify whether early dynamic 68Ga-PSMA-11 (HBED-CC)PET/CT can differentiate pathologic PC-related tracer uptake from physiologic tracer accumulation in the urinary bladder. Eighty consecutive PC patients referred to 68Ga -PSMA-11 PET/CT were included in this retrospective analysis (biochemical relapse: n = 64; primary staging: n = 8; evaluation of therapy response/restaging: n = 8). In addition to whole-body PET/CT acquisition 60min post injection early dynamic imaging of the pelvis in the first 8min after tracer injection was performed. SUVmax of pathologic lesions was calculated and time-activity curves were generated and compared to those of urinary bladder and areas of physiologic tracer uptake. A total of 55 lesions consistent with malignancy on 60min whole body imaging exhibited also pathologic 68Ga-PSMA-11 uptake during early dynamic imaging (prostatic bed/prostate gland: n = 27; lymph nodes: n = 12; bone: n = 16). All pathologic lesions showed tracer uptake within the first 3min, whereas urinary bladder activity was absent within the first 3min of dynamic imaging in all patients. Suvmax was significantly higher in PC lesions in the first 6min compared to urinary bladder accumulation (p < 0.001). In the subgroup of PC patients with biochemical relapse the detection rate of local recurrence could be increased from 20.3 to 29.7%. Early dynamic imaging in 68Ga-PSMA-11 PET/CT reliably enables the differentiation of pathologic tracer uptake in PC lesions from physiologic bladder accumulation. Performance of early dynamic imaging in addition to whole body imaging 60min after tracer injection might improve the detection rate of local recurrence in PC patients with biochemical relapse referred for 68Ga-PSMA-11 PET/CT.

Brachytherapy boost and cancer-specific mortality in favorable high-risk and other high-risk prostate cancer.

52 Background: A randomized trial has recently reported improved 5-year biochemical recurrence-free survival with brachytherapy (BT) boost compared with external beam radiation therapy (EBRT) boost in intermediate- to high-risk prostate cancer. Recent retrospective data suggest that BT boost may also confer a cancer-specific survival benefit in the high-risk subgroup. We sought to determine whether this survival benefit would extend to the recently defined favorable high-risk subgroup of prostate cancer patients (T1c, Gleason 4+4 = 8, PSA &lt; 10 ng/mL or T1c, Gleason 6, PSA &gt; 20 ng/mL). Methods: We identified 45,078 patients in the Surveillance, Epidemiology, and End Results database with cT1c-T3aN0M0 intermediate- to high-risk prostate cancer diagnosed 2004-2011 treated with EBRT or EBRT plus BT. We used multivariable competing risks regression to determine differences in the rate of prostate cancer-specific mortality (PCSM) after EBRT+BT or EBRT alone in patients with intermediate-risk, favorable high-risk, or other high-risk disease after adjusting for demographic and clinical factors. Results: BT boost was not associated with an improvement in 5-year PCSM compared with EBRT alone among patients with favorable high-risk disease (1.6% vs 1.9%; adjusted hazard ratio [AHR] 0.56; 95% confidence interval [CI], 0.21 to 1.52, P = 0.258) and intermediate-risk disease (0.7% vs 0.9%; AHR 0.83; 95% CI, 0.59 to 1.16; P = 0.270). Others with high-risk disease had significantly lower 5-year PCSM when treated with BT boost compared with EBRT alone (3.9% vs 5.0%; AHR 0.73; 95% CI, 0.55 to 0.95; P = 0.022). Conclusions: Brachytherapy boost is associated with a decreased rate of PCSM in men with high-risk prostate cancer, but this benefit was not seen among patients with favorable high-risk disease. This suggests that the recently-defined “favorable high-risk” category may be used to personalize therapy for men with high risk disease.

Brachytherapy boost and cancer-specific mortality in favorable high-risk versus other high-risk prostate cancer.

PurposeRecent retrospective data suggest that brachytherapy (BT) boost may confer a cancer-specific survival benefit in radiation-managed high-risk prostate cancer. We sought to determine whether this survival benefit would extend to the recently defined favorable high-risk subgroup of prostate cancer patients (T1c, Gleason 4 + 4 = 8, PSA < 10 ng/ml or T1c, Gleason 6, PSA > 20 ng/ml).Material and methodsWe identified 45,078 patients in the Surveillance, Epidemiology, and End Results database with cT1c-T3aN0M0 intermediate- to high-risk prostate cancer diagnosed 2004-2011 treated with external beam radiation therapy (EBRT) only or EBRT plus BT. We used multivariable competing risks regression to determine differences in the rate of prostate cancer-specific mortality (PCSM) after EBRT + BT or EBRT alone in patients with intermediate-risk, favorable high-risk, or other high-risk disease after adjusting for demographic and clinical factors.ResultsEBRT + BT was not associated with an improvement in 5-year PCSM compared to EBRT alone among patients with favorable high-risk disease (1.6% vs. 1.8%; adjusted hazard ratio [AHR]: 0.56; 95% confidence interval [CI]: 0.21-1.52, p = 0.258), and intermediate-risk disease (0.8% vs. 1.0%, AHR: 0.83, 95% CI: 0.59-1.16, p = 0.270). Others with high-risk disease had significantly lower 5-year PCSM when treated with EBRT + BT compared with EBRT alone (3.9% vs. 5.3%; AHR: 0.73; 95% CI: 0.55-0.95; p = 0.022).ConclusionsBrachytherapy boost is associated with a decreased rate of PCSM in some men with high-risk prostate cancer but not among patients with favorable high-risk disease. Our results suggest that the recently-defined “favorable high-risk” category may be used to personalize therapy for men with high-risk disease.

Secondary Cancers After Radiation Therapy for Primary Prostate or Rectal Cancer.

Literature about the risk of secondary cancer after radiation therapy (RT) of prostate and rectal cancer reveals contradictory results. We conducted a meta-analysis to examine whether the RT induces secondary rectal or prostate cancer in patients, respectively, with prostate or rectal cancer. All studies published in Medline or Pubmed up to March 3, 2015, containing RT of primary rectal or prostate cancer, and providing risk estimates of secondary prostate or rectal cancer were considered as eligible. Relative risk (RR) and standardized incidence ratios (SIR) were calculated using the random-effects model. Twenty studies met the inclusion criteria. 12 of them were from the Surveillance, Epidemiology, and End Results (SEER) database. For prostate cancer patients, pooled adjusted RRs or SIRs did not show an effect on the risk of secondary rectal cancer. However, notwithstanding the limitations of SEER-based studies, the subgroup of prostate cancer patients receiving external beam radiation therapy (EBRT) showed an increased risk of rectal cancer. For rectal cancer patients, pooled adjusted RR of prostate cancer was 1.12 (95 % CI, 0.44-2.8) and SIR was 0.40 (95 % CI, 0.29-0.55). All studies included in the SIR analysis of rectal cancer were derived from the SEER data source. Based on current evidence, RT for prostate cancer patients had no effect on rectal cancer incidence, except for patients who received EBRT therapy. However, compared with the general population, RT for rectal cancer is associated with a decreased prostate cancer risk as found in SEER-based studies.

Statin use and risk of disease recurrence and death after radical prostatectomy.

Statins have been linked with improved prostate cancer survival and lower risk of recurrence in men treated with radiation therapy. However, the association is unclear for surgically-treated men. We studied the risk of prostate cancer recurrence and death by statin usage after radical prostatectomy in a cohort of prostate cancer patients treated with radical prostatectomy. A cohort of 1,314 men who underwent curative-intent radical prostatectomy at the Tampere University Hospital, Tampere, Finland during 1995-2009 were linked to national prescription database to obtain detailed information on statin purchases. The risk of PSA recurrence and death (overall and prostate cancer-specific) by statin use before and after the surgery were evaluated using Cox regression with model adjustment for tumor characteristics, total cholesterol and simultaneous use of antidiabetic and antihypertensive drugs. Tissue expression of putative prognostic markers were measured from a subgroup of 323 men. During the median follow-up of 8.6 years after surgery 484 men recurred, while 244 men died (32 due to prostate cancer). In general statin use before or after prostatectomy was not associated with risk of disease recurrence or death. Tissue expression of Ki-67 and ERG modified the association between statin use and risk of disease recurrence; the risk estimates were lower in men with Ki-67 expression above the median (P for interaction 0.001 and 0.004 for statin use before and after prostatectomy, respectively) and no ERG expression in the tumor tissue (P for interaction 0.006 and 0.011). Statin use generally did not affect prostate cancer prognosis after prostatectomy. The effect on disease recurrence may depend on tumor properties, such as proliferation activity. Thus possible future prospective studies should recognize and enroll subgroups of prostate cancer patients most likely to benefit from statins.

Immunosuppression via Tenascin-C.

Immunosuppression via Tenascin-C.

Importance of complementary medicine approaches for patients with prostate cancer

In Germany, many prostate cancer patients use complementary medicine (CM) or have an interest in these treatment approaches; however, the information and consultation situation of cancer patients is insufficient and therefore the Competence Network Complementary Medicine in Oncology (COCON) was launched by the German Cancer Aid Society. One of the projects of the COCON examines the use of CM and the information and counseling needs regarding these topics in various groups of cancer patients. The focus of this article is on the qualitative study reporting selected results for the subgroup of prostate cancer patients. A total of 19 semi-structured qualitative interviews with prostate cancer patients were conducted regarding the use of CM as well as their information and consultation needs. It was found that the patients interviewed discussed various issues surrounding nutrition, particularly a healthy diet, the selective use of certain foods and the use of dietary supplements. Additional themes mentioned by interviewees were physical exercise, psychological well-being, mistletoe therapy, homeopathy and traditional Chinese medicine. Patients indicated that they wanted more information and counseling opportunities with regards to CM. They also expressed a desire for more holistic care. The results show that prostate cancer patients use a range of CM and have a need for information about CM. Prostate cancer patients are in a special situation because of a regular feedback on the prostate-specific antigen (PSA) value. This should be taken into consideration in consultation with prostate cancer patients regarding CM.

Novel approaches in the high-risk prostate cancer patient: Summary of key research presented at AUA 2014.

Another topic of focus at AUA 2014 was the subgroup of prostate cancer patients deemed to be at high risk.

S206 Radiation therapy for high risk subgroup of prostate cancer patients

S206 Radiation therapy for high risk subgroup of prostate cancer patients

Pushing the Limits of Radiation Therapy for Prostate Cancer: Where Do We Go Next?

There have been significant advancements in the quality and precision of radiation therapy (RT) for prostate cancer over the past two decades. The development and implementation of intensity-modulated radiation therapy has allowed for RT dose-escalation without parallel increases in treatment morbidity. Moreover, integration of androgen deprivation therapy with definitive RT has led to improvements in outcomes for certain subgroups of prostate cancer patients. In this review, we highlight several ongoing and developing technical advances that hold promise for further optimizing RT care, including proton beam therapy, inter- and intra-fractional image-guided dose-delivery, methods for improved target volume definition, and development of techniques for safely performing hypofractionation and stereotactic body radiotherapy. We also discuss the importance of investigating the potential benefit of integrating novel systemic therapies with prostate RT to further improve outcomes for patients with locally advanced prostate cancer.

A functional polymorphism in the CYR61 (IGFBP10) gene is associated with prostate cancer risk

CYR61 (cysteine-rich protein 61, also named IGFBP10) is a secreted signaling molecule that promotes angiogenesis and tumor growth. The goal of this study is to determine whether a functional polymorphism in the promoter region of the CYR61 gene (rs3753793) is associated with prostate cancer (PCa) risk and gene expression in Chinese patients. A total of 665 patients diagnosed with PCa and 703 cancer-free controls were genotyped in this hospital-based case-control study, and 26 PCa tissue samples were evaluated for mRNA expression of CYR61 by real-time quantitative reverse-transcription PCR. Men carrying the G allele of rs3753793 (TG+GG) had significantly lower risk of PCa when compared with the TT genotype (odds ratio (OR) = 0.76, 95% confidence interval (CI) = 0.61-0.95). The association was generally more pronounced among subgroups of PCa patients with advanced stage (OR = 0.70, 95% CI = 0.53-0.94), Gleason score >7 (OR = 0.63, 95% CI = 0.46-0.86) and PSA>20 ng ml(-1) (OR = 0.68, 95% CI = 0.53-0.88). Prostate tumors derived from cases with the GT/GG genotypes had significantly lower levels of CYR61 mRNA when compared with cases with the TT genotypes (P = 0.02). Our results indicate that the genetic variation of rs3753793 in the CYR61 promoter may contribute to genetic predisposition to PCa and intra-tumor expression gene expression.

Results of combined radiotherapy and hormonal treatment of prostate cancer patients with initial PSA value >40 ng/ml

AimTo evaluate the outcome of prostate cancer patients with initial PSA value >40ng/ml. BackgroundThe outcome of prostate cancer patients with very high initial PSA value is not known and patients are frequently treated with palliative intent. We analyzed the outcome of radical combined hormonal treatment and radiotherapy in prostate cancer patients with initial PSA value >40ng/ml. MethodsBetween January 2003 and December 2007 we treated, with curative intent, 56 patients with non-metastatic prostate cancer and initial PSA value >40ng/ml. The treatment consisted of two months of neoadjuvant hormonal treatment (LHRH analog), radical radiotherapy (68–78Gy, conformal technique) and an optional two-year adjuvant hormonal treatment. ResultsThe median time of follow up was 61 months. 5-Year overall survival was 90%. 5-Year biochemical disease free survival was 62%. T stage, Gleason score, PSA value, and radiotherapy dose did not significantly influence the outcome. Late genitourinal and gastrointestinal toxicity was acceptable. ConclusionRadical treatment in combination with hormonal treatment and radiotherapy can be recommended for this subgroup of prostate cancer patients with good performance status and life expectancy.

Sex Hormones and Colorectal Cancer: What Have We Learned So Far?

Sex Hormones and Colorectal Cancer: What Have We Learned So Far?

IL15 Can Reverse the Unresponsiveness of Wilms' Tumor Antigen-Specific CTL in Patients with Prostate Cancer

The Wilms' tumor antigen 1 (WT1) is overexpressed in several leukemias and solid tumors, but there is currently limited information regarding its role in prostate cancer. This study aimed to investigate WT1 expression in prostate cancer, and to determine the number and function of WT1-specific T cells in the peripheral blood of patients. Immunohistochemistry was used to assess WT1 expression in cancer tissues. Human leukocyte antigen A2 (HLA-A2) tetramers served to detect WT1-specific T cells, and peptide-specific stimulation was used to assess T-cell function in vitro. Immunohistochemistry of tissue arrays comprising 36 cancer and 8 normal prostate samples revealed nuclear WT1 staining in 39% of cancer samples, but not in normal prostate tissues. Tetramer analysis revealed a low frequency of WT1-specific T cells in 20 of 38 HLA-A2-positive patients. In vitro stimulation with WT1 peptide plus interleukin 2(IL2) and interleukin 7 (IL7) did not lead to an accumulation of WT1-specific T cells in any of the patient samples, although all patients were able to generate T-cell responses against Melan-A/MART1 control peptide. Stimulation with WT1 peptide in the presence of interleukin 15 (IL15), a cytokine that was shown to reverse tolerance of murine tumor-specific T cells, was able to restore the expansion and IFNgamma production of WT1-specific T cells in a subgroup of prostate cancer patients. The observation that IL15 can restore the function of WT1-specific T cells that were unresponsive to IL2 has implications for vaccination and immunotherapeutic strategies that aim to enhance WT1-specific T cell immunity in patients.

TMPRSS2:ERG Fusion Identifies a Subgroup of Prostate Cancers with a Favorable Prognosis

Our aim was to assess the frequency of ERG overexpression and TMPRSS2:ERG rearrangement in prostate cancer and their association with clinicopathologic variables and outcome. The presence of the TMPRSS2:ERG rearrangement was studied by reverse transcription-PCR and fluorescence in situ hybridization in 19 prostate cancer xenografts and 7 prostate cancer cell lines. The expression of ERG was studied in the xenografts and cell lines and in 49 freshly frozen clinical prostate samples by quantitative reverse transcription-PCR. The frequency of the TMPRSS2:ERG fusion in clinical prostate cancer (n = 253) on tissue microarrays was assessed by three-color fluorescence in situ hybridization. Seven of 19 (37%) of the xenografts overexpressed ERG and had TMPRSS2:ERG rearrangement. Two xenografts, representing small cell carcinomas, also contained the fusion but did not express ERG. In clinical tumor specimens, the overexpression of ERG was associated with the rearrangement (P = 0.0019). Fifty of 150 (33%) of the prostatectomy specimens and 28 of 76 (37%) of the hormone-refractory prostate cancers on the tissue microarrays carried the TMPRSS2:ERG rearrangement. It was associated with longer progression-free survival in patients treated by prostatectomy (P = 0.019), and according to multivariate analysis, it was an independent predictor of favorable outcome (relative risk, 0.54; 95% confidence interval, 0.30-0.98). The fusion was not associated with Gleason score, pT stage, diagnostic prostate-specific antigen, or cell proliferation activity in prostatectomy specimens nor with the AR gene amplification in hormone-refractory tumors. The TMPRSS2:ERG rearrangement can be found in about one third of prostate cancers. A subgroup of prostate cancer patients with a good prognosis may be identified by the rearrangement.