Prostate Cancer
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Prostate cancer accounts for over a quarter of all cancers in men. The prostate is a small male sex gland located below the bladder, it produces fluid that becomes semen. Prostate cancer occurs mostly in older men, it is rare before the age of 50, and the risk increases with age. There has been an increase in the incidence of prostate cancer since the early 1980's, most likely due to an increased use of screening using the prostate-specific antigen (PSA) test. However, the role as screening for prostate cancer remains controversial. World-wide about 395,000 men are diagnosed with prostate cancer each year.

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Information for Patients and the Public
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Latest Research Publications
Screening for Prostate Cancer

Information Patients and the Public (31 links)

Information for Health Professionals / Researchers (10 links)

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Balbontin FG, Moreno SA, Bley E, et al.
Long-acting testosterone injections for treatment of testosterone deficiency after brachytherapy for prostate cancer.
BJU Int. 2014; 114(1):125-30 [PubMed] Related Publications
OBJECTIVE: To evaluate the clinical and biochemical effects of long-acting testosterone undecanoate injections in men with prostate cancer treated with brachytherapy, as the use of testosterone therapy (TTh) in men with prostate cancer is highly controversial, with limited published safety data, particularly after brachytherapy treatment.
PATIENTS AND METHODS: In all, 20 men treated with brachytherapy for prostate cancer received TTh for symptoms of testosterone deficiency from February 2005 to August 2013. Symptoms of testosterone deficiency included low libido, erectile dysfunction, and fatigue. The mode of TTh was long-acting testosterone undecanoate injections in all cases. Sexual function was assessed by Sexual Health Inventory for Men (SHIM) questionnaire. Serum PSA and testosterone concentrations were recorded monthly for 3 months, then every 3 months for the first year, every 6 months for the second year, and annually then after.
RESULTS: The mean (range) age was 62 (49-74) years and the mean (range) serum PSA level at the time of prostate cancer diagnosis was 6.2 (2-11.5) ng/mL. The Gleason score was 2 + 3 in one patient, 3 + 3 in 15 patients, 3 + 4 in three patients and 4 + 4 in one patient. In all, 15 men were stage T1c and five were T2a. The mean (range) baseline total testosterone concentration was 343 (200-592) ng/dL, and 6.9 (2.1-9.7) ng/dL for free testosterone. The mean SHIM scores improved with treatment from 16.1 at baseline to 22.1 with TTh (P = 0.002). There was a decrease in mean PSA level from baseline of 0.7 ng/mL before initiation of TTh to 0.1 ng/mL at last follow-up (P < 0.001), with a median (range) follow-up of 31 (12-48) months. There were no cases of prostate cancer progression or recurrence.
CONCLUSIONS: With a median of 31-months follow-up, long-acting testosterone injections in men with prostate cancer treated with brachytherapy produced significant clinical benefits. There were no cases of rising serum PSA, prostate cancer progression or recurrence.

Related: Brachytherapy

Santotoribio JD, Cañavate-Solano C, Garcia-de la Torre A, et al.
Serum lactate dehydrogenase in combination with free-to-total serum prostate specific antigen ratio for diagnosis of prostate cancer.
Clin Lab. 2014; 60(6):1055-8 [PubMed] Related Publications
BACKGROUND: Evaluate the utility of serum lactate dehydrogenase (LDH) in combination with free-to-total serum prostate specific antigen ratio (%fPSA), for diagnosis of prostate cancer (PC) with serum total prostate specific antigen (PSA) levels in the intermediate range of 4 to 10 ng/mL.
METHODS: The following variables were analysed: PSA, %fPSA, and LDH. Two categories of patients were included in the analysis: NOT PC and PC.
RESULTS: We studied 134 patients, 112 had NOT PC and 22 had PC. We defined the following multivariable score (S): S = A + B, where A and B are coefficients of LDH and %fPSA, respectively. AUC values were 0.719 (p = 0.0036), 0.749 (p = 0.0082), and 0.816 (p = 0.0001) for %fPSA, LDH, and S, respectively. Using the proposed S increases by 18% specificity compared to only using the %fPSA parameter.
CONCLUSIONS: LDH in combination with %fPSA improves diagnostic performance for detection of PC compared to using only %fPSA.

Chen RC, Chang P, Vetter RJ, et al.
Recommended patient-reported core set of symptoms to measure in prostate cancer treatment trials.
J Natl Cancer Inst. 2014; 106(7) [PubMed] Related Publications
The National Cancer Institute (NCI) Symptom Management and Health-Related Quality of Life Steering Committee convened four working groups to recommend core sets of patient-reported outcomes to be routinely incorporated in clinical trials. The Prostate Cancer Working Group included physicians, researchers, and a patient advocate. The group's process included 1) a systematic literature review to determine the prevalence and severity of symptoms, 2) a multistakeholder meeting sponsored by the NCI to review the evidence and build consensus, and 3) a postmeeting expert panel synthesis of findings to finalize recommendations. Five domains were recommended for localized prostate cancer: urinary incontinence, urinary obstruction and irritation, bowel-related symptoms, sexual dysfunction, and hormonal symptoms. Four domains were recommended for advanced prostate cancer: pain, fatigue, mental well-being, and physical well-being. Additional domains for consideration include decisional regret, satisfaction with care, and anxiety related to prostate cancer. These recommendations have been endorsed by the NCI for implementation.

Related: USA

Mathew P
The bifunctional role of steroid hormones: implications for therapy in prostate cancer.
Oncology (Williston Park). 2014; 28(5):397-404 [PubMed] Related Publications
Ablation of the androgen-signaling axis is currently a dominant theme in developmental therapeutics in prostate cancer. Highly potent inhibitors of androgen biosynthesis and androgen receptor (AR) function have formally improved survival in castration-resistant metastatic disease. Resistance to androgen-ablative strategies arises through diverse mechanisms. Strategies to preserve and extend the success of hormonal therapy while mitigating the emergence of resistance have long been of interest. In preclinical models, intermittent hormonal ablative strategies delay the emergence of resistant stem-cell-driven phenotypes, but clinical studies in hormone-naive disease have not observed more than noninferiority over continual androgen ablation. In castration-resistant disease, response and improvement in subjective quality of life with therapeutic testosterone has been observed, but so too has symptomatic and life-threatening disease acceleration. The multifunctional and paradoxical role of steroid hormones in regulating proliferation and differentiation, as well as cell death, requires deeper understanding. The lack of molecular biomarkers that predict the outcome of hormone supplementation in a particular clinical context remains an obstacle to individualized therapy. Biphasic patterns of response to hormones are identifiable in vitro, and endocrine-regulated neoplasms that proliferate after prolonged periods of hormone deprivation appear preferentially sex steroid-suppressible. This review examines the relevance of a translational framework for studying therapeutic androgens in prostate cancer.

Related: Signal Transduction

Gidron Y, De Couck M, De Greve J
If you have an active vagus nerve, cancer stage may no longer be important.
J Biol Regul Homeost Agents. 2014 Apr-Jun; 28(2):195-201 [PubMed] Related Publications
The parasympathetic system, and primarily the vagus nerve, informs the brain about multiple signals and returns the body to homeostasis. Recent studies have shown that vagal nerve activity independently predicts prognosis in cancer. Here, we take this one step further and show that when vagal nerve activity is high, cancer stage no longer predicts tumor burden. We examined whether vagal nerve activity, indexed by Heart Rate Variability (HRV), moderated the effects of initial tumor stage on tumor burden at followup. Patients' HRVs were derived from ECGs near diagnosis in colorectal cancer (CRC) and in prostate cancer (PC) patients. Outcomes included the tumor markers carcinoembryonic antigen (CEA) at 12 months for CRC and prostate-specific antigen (PSA) at 6 months for PC. As would be expected, initially advanced tumor stages of CRC or PC predicted higher tumor marker levels at follow-up than did early stages. However, this occurred only in patients with low, not high, vagal activity (HRV). Furthermore, in patients with advanced tumor stage at diagnosis, high HRV predicted lower tumor marker levels than did low HRV, in both cancers. Estimating a cancer patient's prognosis by determining his tumor stage needs to also consider the vagal nerve activity. This activity is easily measurable, and it determines in which subjects the tumor stage is prognostic. Importantly, higher vagal activity may even protect against the adverse effects of advanced cancer stage. These findings, observed in two distinct cancers, support the hypothesized neuroimmunomodulatory effects of vagal nerve activity on tumors.

Related: Colorectal (Bowel) Cancer

De Felice F, Musio D, Caiazzo R, et al.
Two different intensity-modulated radiotherapy strategies for patients with high-risk prostate cancer.
Anticancer Res. 2014; 34(7):3747-51 [PubMed] Related Publications
AIM: To compare toxicity profiles of two different intensity-modulated radiation therapy (IMRT) strategies in patients with high-risk prostate cancer.
PATIENTS AND METHODS: From May 2010 to September 2012, 43 patients with high-risk prostate cancer were treated with IMRT and concurrent hormone therapy; 23 patients were treated by conventional fractionation (IMRT/C) and 20 patients by simultaneous integrated boost (IMRT/SIB). Acute and late toxicities were compared for each group.
RESULTS: Severe acute genitourinary toxicity was recorded in 8.6% and 2% of patients in the IMRT/C and IMRT/SIB group, respectively. Genitourinary toxicity G2 was observed in 39.1% (IMRT/C group) and 25% (IMRT/SIB group) of patients. Severe acute gastrointestinal toxicity was not observed; Grade 2 acute gastrointestinal toxicity was recorded in 21.7% (IMRT/C group) and 10% (IMRT/SIB group). Grade 2 late genitourinary toxicity was observed in 26% (IMRT/C group) and 15% (IMRT/SIB group), whereas G2 late gastrointestinal toxicity in 34.5% and 30% of patients, respectively. No significant differences in incidence and severity of genitourinary and gastrointestinal toxicity were detected between the two IMRT treatment strategies.
CONCLUSION: IMRT/SIB was well-tolerated with favorable rates of acute and late toxicity, both genitourinary and gastrointestinal. Compared to IMRT/C, IMRT/SIB maintained the same efficacy and reduced the overall treatment time.

Kolostova K, Broul M, Schraml J, et al.
Circulating tumor cells in localized prostate cancer: isolation, cultivation in vitro and relationship to T-stage and Gleason score.
Anticancer Res. 2014; 34(7):3641-6 [PubMed] Related Publications
The most promising near-term application of circulating tumor cells (CTCs) monitoring relates to the development of targeted cancer therapies, and the need to tailor such treatments to individual tumor characteristics. A high number of new innovative technologies to improve methods for detecting CTCs, with extraordinarily high sensitivity, have recently been presented. The identification and characterization of CTCs require extremely sensitive and specific methods that are able to isolate CTCs with the possibility of cultivation and downstream analysis of in vitro culture of separated CTCs. In this original research paper, we demonstrate that it is possible to isolate human CTCs from a patient with prostate cancer, with subsequent cultivation and proliferation in vitro. We show that the use of a filtration device implemented by MetaCell® can fulfil all the requirements mentioned above. Fifty-five patients with localized prostate cancer have so far been enrolled into the study. CTCs were detected in the blood samples of 28 (52%) out of the 55 patients. We report successful isolation of CTCs from patients with prostate cancer, capturing cells with a proliferative capacity in 18 (64.3%) out of the 28 CTC-positive patients. Direct correlation with Gleason score and T stage was not proven. The cells, captured by a size-based filtration approach, remain in a good state, unaffected by any antibodies or lysing solutions. During the filtration process, no interactions occurred between antibodies and antigens on the surface of CTCs. This biological interaction is specific for immunomagnetic methods. The MetaCell device provides the possibility of reaching virgin CTCs suitable for subsequent cultivation or single-cell analysis. This aspect will have an important impact on the future design of clinical trials testing new drugs against targets expressed on metastatic cancer cells. In addition to measurement of CTC counts, future trials with targeted therapies should also include the assessment of the specific therapeutic target on CTCs.

Stope MB, Stender C, Schubert T, et al.
Heat-shock protein HSPB1 attenuates microRNA miR-1 expression thereby restoring oncogenic pathways in prostate cancer cells.
Anticancer Res. 2014; 34(7):3475-80 [PubMed] Related Publications
BACKGROUND: Heat-shock proteins (HSPs) as well as microRNAs have been identified to orchestrate crucial mechanisms in prostate cancer (PCa) progression and treatment resistance. Due to cytoprotective properties of HSPB1 we analyzed molecular mechanisms of drug resistance in PCa cell culture systems, and notably found HSPB1 functionality linked to microRNA miR-1 activities.
MATERIALS AND METHODS: HSPB1 and miR-1 levels were genetically modified in PCa cell lines and alterations in molecular and cellular responses were assessed by quantitative reverse transcription/polymerase chain reaction, western blotting, and proliferation assays.
RESULTS: Our data provided for the first time evidence that HSPB1 regulates miR-1 expression, and subsequently restores oncogenic signaling pathways of androgen receptor (AR) and transforming growth factor β1 (TGFB1).
CONCLUSION: Our data point towards HSPB1 and miR-1 involvement in development of castration-resistant PCa and therefore represent promising targets for anticancer therapy of advanced PCa.

Related: Signal Transduction TGFB1

Park HS, Hong SK, Oh MM, et al.
Synergistic antitumor effect of NVP-BEZ235 and sunitinib on docetaxel-resistant human castration-resistant prostate cancer cells.
Anticancer Res. 2014; 34(7):3457-68 [PubMed] Related Publications
According to recent studies, mTOR (mammalian target of rapamycin) inhibitor and tyrosine kinase inhibitor (TKI) can be used as combinational agents to enhance the antitumor effect or overcome resistance to one of the agents. In the present study, we investigated the synergistic interaction between NVP-BEZ235, a PI3K (phosphoinositide 3-kinase)/mTOR dual inhibitor, and sunitinib, a TKI, in castration-resistant prostate cancer (CRPC) cells with docetaxel resistance. Prostate cancer cells with different sensitivities to hormones and docetaxel levels were exposed to escalating doses of NVP-BEZ235 alone and in combination with sunitinib. The synergy between NVP-BEZ235 and sunitinib was determined by the combination index, three-dimensional model, and clonogenic assays. Flow cytometry and western blot analysis of proteins related to apoptosis and cell survival axis were performed. The combination of NVP-BEZ235 and sunitinib caused a significant synergistic antitumor effect over a wide range of doses in docetaxel-resistant CRPC cells. Furthermore, the IC50 (half-maximal inhibitory concentration) of NVP-BEZ235 and sunitinib was reduced by 7.8-fold and 6.6-fold, respectively. The three-dimensional synergy analysis resulted in a synergy volume of 182.47 μM/ml2%, indicating a strong synergistic effect of combination therapy. Combination therapy caused an induction of caspase-dependent apoptosis in docetaxel-resistant CRPC cells. Adding sunitinib did not produce any additional effect on the NVP-BEZ235-mediated inhibition of PI3K/AKT/mTOR phosphorylation. In conclusion, combining NVP-BEZ235, a dual PI3K/mTOR inhibitor, with sunitinib can synergistically potentiate the antitumor effect in CRPC cells after docetaxel failure though induction of caspase-dependent apoptosis.

Related: Apoptosis AKT1 Sunitinib (Sutent) Docetaxel

Mizutani K, Terazawa R, Kameyama K, et al.
Isolation of prostate cancer-related exosomes.
Anticancer Res. 2014; 34(7):3419-23 [PubMed] Related Publications
BACKGROUND/AIM: Exosomes have been demonstrated to be useful non-invasive biomarkers for several cancers including prostate cancer. Since normal cells also secrete exosomes, isolation of cancer-derived exosomes from blood is a prerequisite for their better understanding. The aim of this study is to establish the method for isolation of prostate cancer-related exosomes from blood.
MATERIALS AND METHODS: Exosomes were collected from prostate cancer LNCaP and PC-3 cell lines by ultracentrifugation and by using magnetic beads conjugated with anti-CD9 antibody and anti-prostate-specific membrane antigen (PSMA) antibody. Prostate cancer-related exosomes were also isolated from the plasma of prostate cancer patients by anti-PSMA beads. Isolated exosomes were analyzed by western blotting.
RESULTS: Exosomes were isolated from LNCaP cells by ultracentrifugation, contained PSMA and androgen receptor (AR). AR was also detected in exosomes isolated from LNCaP cells by anti-PSMA and anti-CD9 beads, showing that AR is present in prostate cancer-related exosomes. The amount of CD9 in isolated exosomes was much higher in advanced and chemo-resistant prostate cancer patients than in prostate cancer patients without metastasis and healthy volunteers, indicating that patients with aggressive prostate cancer exhibit higher levels of prostate cancer-related exosomes in blood.
CONCLUSION: The immunoaffinity-based method we developed is capable of isolating prostate cancer-related exosomes from blood, the use of which will enhance investigation processes on exosomes in prostate cancer.

Huang H, Cui XX, Chen S, et al.
Combination of Lipitor and Celebrex inhibits prostate cancer VCaP cells in vitro and in vivo.
Anticancer Res. 2014; 34(7):3357-63 [PubMed] Related Publications
BACKGROUND/AIM: Lipitor is a cholesterol-lowering drug and Celebrex is a Cyclooxygenase-2 inhibitor. We investigated the effects of Lipitor and Celebrex on human prostate cancer VCaP cells cultured in vitro and grown as orthotopic xenograft tumors in SCID mice.
MATERIALS AND METHODS: Apoptosis was measured by morphological assessment and caspase-3 assay. Nuclear factor-kappa B (NF-κB) activation was determined by luciferase reporter assay. B-cell lymphoma-2 (Bcl2) was measured by western blotting and immunohistochemistry. Orthotopic prostate tumors were monitored by the IVIS imaging system.
RESULTS: the combination of Lipitor and Celebrex had stronger effects on the growth and apoptosis of VCaP cells than did either drug alone. The combination more potently inhibited activation of NFκB and expression of Bcl2 than either drug alone. The growth of orthotopic VCaP prostate tumors was strongly inhibited by treatment with the drug combination.
CONCLUSION: Administration of Lipitor and Celebrex in combination may be an effective strategy for inhibiting the growth of prostate cancer.

Related: Apoptosis

Bienz M, Hueber PA, Al-Hathal N, et al.
Accuracy of transrectal ultrasonography to evaluate pathologic prostate weight: correlation with various prostate size groups.
Urology. 2014; 84(1):169-74 [PubMed] Related Publications
OBJECTIVE: To report the accuracy of transrectal ultrasonography (TRUS) to measure prostate size before robotic-assisted radical prostatectomy using the prolate ellipsoid formula and its correlation to the weight of the postoperative prostate specimen, for different prostate size groups.
METHODS: Preoperative prostate size estimated by TRUS and the weight of postoperative prostate specimens were collected from 440 men undergoing robotic-assisted radical prostatectomy. Patients were grouped according to preoperative prostate size: <30, 30-60, 60-80, and ≥80 g. To evaluate accuracy, the mean absolute percentage of error was used. The mean percentage of error was used to indicate whether the estimation of TRUS had a tendency to overestimate or underestimate prostate size. The correlation between both measurements was analyzed for each size group.
RESULTS: Accuracy of TRUS estimation was associated with increased prostate size. TRUS estimation was more accurate for larger prostates. The mean absolute percentage of error of each group was 38.64% (<30 g), 21.33% (30-60 g), 13.23% (60-80 g), and 14.96% (≥80 g). Correlation followed a similar size-dependent trend, with a stronger r coefficient for larger prostates: 0.174 (<30 g), 0.327 (30-60 g), 0.457 (60-80 g), and 0.839 (≥80 g). Interestingly, smaller prostates were underestimated, whereas larger glands (≥80 g) had a tendency to be overestimated by TRUS.
CONCLUSION: This study demonstrates that the accuracy of the prolate ellipsoid formula for TRUS varies according to prostate size. Although this formula is fairly accurate for assessing larger prostates, it shows some limitations for smaller prostates. This must be taken into account when evaluating treatment modalities such as transurethral incision of the prostate and brachytherapy.

James H, Aleksic I, Bienz MN, et al.
Comparison of fracture risk assessment tool score to bone mineral density for estimating fracture risk in patients with advanced prostate cancer on androgen deprivation therapy.
Urology. 2014; 84(1):164-8 [PubMed] Related Publications
OBJECTIVE: To estimate the risk of fracture (Fracture Risk Assessment Tool [FRAX] algorithm) because of the development of osteoporosis in prostate cancer patients undergoing androgen deprivation therapy (ADT) for patients who would otherwise not have been identified for treatment by the T score.
METHODS: This study includes men undergoing ADT for prostate cancer at our urology group. Clinical data were collected via chart review. Subjects were evaluated for fracture risk using country specific (for the United States of America) World Health Organization's FRAX. The FRAX calculations were then compared to fracture risk as determined by T score, for a subset of our cohort that received dual-energy X-ray absorptiometry.
RESULTS: Our cohort consisted of 613 patients on ADT, 94 of which had a dual-energy X-ray absorptiometry scan. The FRAX algorithm identified 61.6% patients requiring therapy without bone mass density (BMD), 46.8% with BMD, and 19.14% with T score alone. In addition, positive correlation was found between FRAX with and without BMD as well as T score and FRAX with BMD and without BMD.
CONCLUSION: Our data indicate that many patients who were not found at significant risk for fracture with T score were in fact found to be at risk with the FRAX calculation. The largest proportion of patients was found to be at risk through the FRAX calculation without BMD, followed by FRAX with BMD, followed by T score alone. The utility of FRAX is beneficial in identifying patients that may benefit from effective bone-tropic treatment modalities.

Hong SK, Poon BY, Sjoberg DD, et al.
Prostate size and adverse pathologic features in men undergoing radical prostatectomy.
Urology. 2014; 84(1):153-7 [PubMed] Article available free on PMC after 01/07/2015 Related Publications
OBJECTIVE: To investigate the relationship between prostate volume measured from preoperative imaging and adverse pathologic features at the time of radical prostatectomy and evaluate the potential effect of clinical stage on such relationship.
METHODS: In 1756 men who underwent preoperative magnetic resonance imaging and radical prostatectomy from 2000 to 2010, we examined associations of magnetic resonance imaging-measured prostate volume with pathologic outcomes using univariate logistic regression and with postoperative biochemical recurrence using Cox proportional hazards models. We also analyzed the effects of clinical stage on the relationship between prostate volume and adverse pathologic features via interaction analyses.
RESULTS: In univariate analyses, smaller prostate volume was significantly associated with high pathologic Gleason score (P<.0001), extracapsular extension (P<.0001), and positive surgical margins (P=.032). No significant interaction between clinical stage and prostate volume was observed in predicting adverse pathologic features (all P>.05). The association between prostate volume and recurrence was significant in a multivariable analysis adjusting for postoperative variables (P=.031) but missed statistical significance in the preoperative model (P=.053). Addition of prostate volume did not change C-Indices (0.78 and 0.83) of either model.
CONCLUSION: Although prostate size did not enhance the prediction of recurrence, it is associated with aggressiveness of prostate cancer. There is no evidence that this association differs depending on clinical stage. Prospective studies are warranted assessing the effect of initial method of detection on the relationship between volume and outcome.

Trpkov C, Yilmaz A, Trpkov K
Perineural invasion in prostate cancer patients who are potential candidates for active surveillance: validation study.
Urology. 2014; 84(1):149-52 [PubMed] Related Publications
OBJECTIVE: To validate whether perineural invasion (PNI) on needle biopsy should represent an exclusion criterion in patients considered for active surveillance (AS). Validation was performed in an independent cohort of patients who fulfilled the Epstein AS criteria, but proceeded to surgery, as recent study showed that PNI in this scenario was not associated with adverse findings on radical prostatectomy.
METHODS: Biopsy, prostatectomy, and clinical data of 845 patients who met the Epstein AS criteria were retrieved from the institutional prostate cancer database. We compared the clinical, biopsy, and prostatectomy findings in patients with and without PNI. All patients had a 10-core biopsy and a radical prostatectomy performed between July 2000 and June 2010.
RESULTS: PNI was present in 63 of 845 (7.4%) patients. Clinical findings were not significantly different between patients with and without PNI. PNI vs no PNI patients demonstrated slightly larger cancer volume on biopsy (2.5% vs 1.8%; P<.001) and greater proportion of 2-core positive biopsies (57.1% vs 36.8%; P=.001). No significant differences were found between the patients with and without PNI regarding the organ-confined disease (95.2% vs 96.4%; P=.5), positive margins (20.6% vs 16.4%; P=.39), tumor volume (8.2% vs 7.3%; P=.36), and prostatectomy Gleason score (≤6 vs >6; P=.13).
CONCLUSION: We confirm that finding PNI on biopsy should not influence the decision to exclude patients from AS, if Epstein criteria are met. Although patients with biopsy PNI demonstrated greater volume of cancer and rate of 2-positive cores, PNI on biopsy was not associated with worse prostatectomy findings.

Related: Watchful Waiting - Prostate Cancer

Kadono Y, Ueno S, Yaegashi H, et al.
Urodynamic evaluation before and immediately after robot-assisted radical prostatectomy.
Urology. 2014; 84(1):106-11 [PubMed] Related Publications
OBJECTIVE: To evaluate continence status and mechanism of urinary incontinence immediately after robot-assisted radical prostatectomy (RARP) by performing urodynamic evaluation.
METHODS: A total of 87 patients with localized prostate cancer who underwent RARP were included. Filling cystometry, urethral pressure profilometry, and abdominal leak point pressure (ALPP) tests were performed before and immediately after RARP.
RESULTS: The mean urine loss ratio (ULR), calculated by dividing the total urine volume by the weight of urine loss after RARP, was 17.8%. Nerve-sparing (NS) surgery significantly affected ULR compared with non-NS surgery. In the comparison between preoperative and postoperative results, the mean maximal cystometric capacity (MCC) and maximal closure urethral pressure (MUCP) decreased from 341 mL and 84.6 cm H2O to 250 mL and 35.6 cm H2O, respectively. No urine leakage was observed in ALPP test preoperatively; however, urine leakage was observed postoperatively in 75 patients (86%), with a mean ALPP of 47.7 cm H2O. Multivariate analysis revealed that MCC, MUCP, and ALPP after RARP were predictive factors for ULR. Linear correlations were found between ULR and MUCP and between ULR and ALPP after RARP. NS status and MUCP after RARP (r=0.247; P=.021) and the ALPP (r=0.254; P=.018) were significantly correlated.
CONCLUSION: In urodynamic evaluation immediately after RARP, MCC, MUCP, and ALPP were found to predictive factors for urinary incontinence. The NS procedure contributed to continence status after RARP.

Aronowitz JN
Introduction of transperineal image-guided prostate brachytherapy.
Int J Radiat Oncol Biol Phys. 2014; 89(4):907-15 [PubMed] Related Publications
The modern prostate brachytherapy procedure is characterized by ultrasound guidance, template assistance, and a return to a "closed" transperineal approach. This review traces the introduction and evolution of these elements and charts the development of the procedure from the ashes of previous, failed efforts.

Related: Brachytherapy USA

Asawabharuj K, Ramart P, Nualyong C, et al.
Comparison of urinary continence outcome between robotic assisted laparoscopic prostatectomy versus laparoscopic radical prostatectomy.
J Med Assoc Thai. 2014; 97(4):393-8 [PubMed] Related Publications
OBJECTIVE: To compare urinary continent rate at six and 12-month postoperative period, and perioperative outcome between robotic-assisted laparoscopic radical prostatectomy (RALP) and laparoscopic radical prostatectomy (LRP) at Siriraj Hospital.
MATERIAL AND METHOD: All medical records of patients performed RALP and LRP between 2005 and 2010 were reviewed. Data composed of demographic information, perioperative outcome, and oncologic outcome. Moreover, the urinary continence rate was also collected at six and 12-month postoperative period by questionnaires based research design.
RESULTS: Between 2005 and 2010, we performed 548 cases of RALP and 613 cases of LRP. Only 486 cases of RALP (88.6%) and 561 cases of LRP (91.5%) had been followed-up more than 12 months. All demographic data including age, biopsy Gleason score, and preoperative PSA level in both groups were comparably. On the other hand, the perioperative outcome in RALP differed from LRP group significantly, including operative time (210 min vs. 255 min), blood loss (449 ml vs. 766 ml), blood transfusion rate (7.6% vs. 25.2%), and length of hospital stay (7 days vs. 8.6 days) (p < 0.001). The oncological outcome including pathologic tumor staging and Gleason score were comparably. Late complication such as anastamosis stricture was not different between the two groups (3.1% in RALP vs. 2.4% in LRP, p = 0.584). The continence rate of RALP and LRP groups at 6-month was 67.8% and 39% and at 12-month was 80% and 63.7%, respectively. The continence rate of RALP was better than LRP significantly.
CONCLUSION: From our experience, perioperative outcome and continence rate at six and 12-month of RALP group was significantly better than LRP group. The demographic data, oncological outcome, and anastamosis stricture rate were comparably in both groups. The most relevant preoperative predictors of urinary continence were patient's age and prostatic weight.

Medved M, Soylu-Boy FN, Karademir I, et al.
High-resolution diffusion-weighted imaging of the prostate.
AJR Am J Roentgenol. 2014; 203(1):85-90 [PubMed] Related Publications
OBJECTIVE: The purpose of this study was to evaluate the effect of increasing the spatial resolution of the prostate DWI protocol on image quality and lesion conspicuity.
SUBJECTS AND METHODS: Twenty-nine patients with biopsy-proven prostate cancer undergoing MRI examinations were imaged with two diffusion-weighted imaging (DWI) protocols: current standard clinical protocol (6.7 mm(3) voxels) and a new high-resolution protocol (3.1 mm(3) voxels). Diffusion-weighted images were independently and subjectively scored on lesion conspicuity, internal architecture definition, and overall image quality by two radiologists. Average apparent diffusion coefficient (ADC) values were measured in normal tissue and cancerous lesions on both sequences. Reader scores and ADC and contrast values were compared between the two protocols. Cancer ADC values were correlated with Gleason scores.
RESULTS: The signal-to-noise ratio of the new high-resolution DWI protocol was 40% lower than that of the standard protocol. The reader scores were higher by 0.73 (range, 0.29-1.16) grades, or 19% (range, 7-32%), on average, for the new protocol, indicating better image quality. The average ADC values were 8% higher with the new protocol, with ADC contrast values between cancer and normal prostate unchanged. There was marginally significant correlation of cancer ADC values with Gleason scores (p = 0.05, r ≈ -0.36).
CONCLUSION: We showed that for DWI of the prostate at 3-7 mm(3) voxel sizes the benefits of higher spatial resolution outweigh the effects of reduced signal-to-noise and contrast-to-noise ratios, potentially improving the sensitivity to small or sparse prostate cancers. Radiologists can consider using higher-spatial-resolution DWI sequences in their practices.

Zbýň Š, Krššák M, Memarsadeghi M, et al.
Technical Note: evaluation of the uncertainties in (choline + creatine)/citrate ratios measured by proton MR spectroscopic imaging in patients suspicious for prostate cancer.
Rofo. 2014; 186(7):698-702 [PubMed] Related Publications
The presented evaluation of the relative uncertainty (δ'CCC) of the (choline + creatine)/citrate (CC/C) ratios can provide objective information about the quality and diagnostic value of prostate MR spectroscopic imaging data. This information can be combined with the numeric values of CC/C ratios and provides metabolic-quality maps enabling accurate cancer detection and user-independent data evaluation. In addition, the prostate areas suffering most from the low precision of CC/C ratios (e. g., prostate base) were identified.

Andersen S, Richardsen E, Nordby Y, et al.
Disease-specific outcomes of radical prostatectomies in Northern Norway; a case for the impact of perineural infiltration and postoperative PSA-doubling time.
BMC Urol. 2014; 14:49 [PubMed] Article available free on PMC after 01/07/2015 Related Publications
BACKGROUND: Prostate cancer is the most common male malignancy and a mayor cause of mortality in the western world. The impact of clinicopathological variables on disease related outcomes have mainly been reported from a few large US series, most of them not reporting on perineural infiltration. We therefore wanted to investigate relevant cancer outcomes in patients undergoing radical prostatectomy in two Norwegian health regions with an emphasis on the impact of perineural infiltration (PNI) and prostate specific antigen- doubling time (PSA-DT).
METHODS: We conducted a retrospective analysis of 535 prostatectomy patients at three hospitals between 1995 and 2005 estimating biochemical failure- (BFFS), clinical failure- (CFFS) and prostate cancer death-free survival (PCDFS) with the Kaplan-Meier method. We investigated clinicopathological factors influencing risk of events using cox proportional hazard regression.
RESULTS: After a median follow-up of 89 months, 170 patients (32%) experienced biochemical failure (BF), 36 (7%) experienced clinical failure and 15 (3%) had died of prostate cancer. pT-Stage (p = 0.001), preoperative PSA (p = 0.047), Gleason Score (p = 0.032), non-apical positive surgical margins (PSM) (p = 0.003) and apical PSM (p = 0.031) were all independently associated to BFFS. Gleason score (p = 0.019), PNI (p = 0.012) and non-apical PSM (p = 0.002) were all independently associated to CFFS while only PNI (P = 0.047) and subgroups of Gleason score were independently associated to PCDFS. After BF, patients with a shorter PSA-DT had independent and significant worse event-free survivals than patients with PSA-DT > 15 months (PSA-DT = 3-9 months, CFFS HR = 6.44, p < 0.001, PCDFS HR = 13.7, p = 0.020; PSA-DT < 3 months, CFFS HR = 11.2, p < 0.001, PCDFS HR = 27.5, p = 0.006).
CONCLUSIONS: After prostatectomy, CFFS and PCDFS are variable, but both are strongly associated to Gleason score and PNI. In patients with BF, PSA-DT was most strongly associated to CF and PCD. Our study adds weight to the importance of PSA-DT and re-launches PNI as a strong prognosticator for clinically relevant endpoints.

Kim DW, Cho LC, Straka C, et al.
Predictors of rectal tolerance observed in a dose-escalated phase 1-2 trial of stereotactic body radiation therapy for prostate cancer.
Int J Radiat Oncol Biol Phys. 2014; 89(3):509-17 [PubMed] Related Publications
PURPOSE: To convey the occurrence of isolated cases of severe rectal toxicity at the highest dose level tested in 5-fraction stereotactic body radiation therapy (SBRT) for localized prostate cancer; and to rationally test potential causal mechanisms to guide future studies and experiments to aid in mitigating or altogether avoiding such severe bowel injury.
METHODS AND MATERIALS: Clinical and treatment planning data were analyzed from 91 patients enrolled from 2006 to 2011 on a dose-escalation (45, 47.5, and 50 Gy in 5 fractions) phase 1/2 clinical study of SBRT for localized prostate cancer.
RESULTS: At the highest dose level, 6.6% of patients treated (6 of 91) developed high-grade rectal toxicity, 5 of whom required colostomy. Grade 3+ delayed rectal toxicity was strongly correlated with volume of rectal wall receiving 50 Gy >3 cm(3) (P<.0001), and treatment of >35% circumference of rectal wall to 39 Gy (P=.003). Grade 2+ acute rectal toxicity was significantly correlated with treatment of >50% circumference of rectal wall to 24 Gy (P=.010).
CONCLUSION: Caution is advised when considering high-dose SBRT for treatment of tumors near bowel structures, including prostate cancer. Threshold dose constraints developed from physiologic principles are defined, and if respected can minimize risk of severe rectal toxicity.

Jin C, Yang L, Xie M, et al.
Chem-seq permits identification of genomic targets of drugs against androgen receptor regulation selected by functional phenotypic screens.
Proc Natl Acad Sci U S A. 2014; 111(25):9235-40 [PubMed] Article available free on PMC after 01/07/2015 Related Publications
Understanding the mechanisms by which compounds discovered using cell-based phenotypic screening strategies might exert their effects would be highly augmented by new approaches exploring their potential interactions with the genome. For example, altered androgen receptor (AR) transcriptional programs, including castration resistance and subsequent chromosomal translocations, play key roles in prostate cancer pathological progression, making the quest for identification of new therapeutic agents and an understanding of their actions a continued priority. Here we report an approach that has permitted us to uncover the sites and mechanisms of action of a drug, referred to as "SD70," initially identified by phenotypic screening for inhibitors of ligand and genotoxic stress-induced translocations in prostate cancer cells. Based on synthesis of a derivatized form of SD70 that permits its application for a ChIP-sequencing-like approach, referred to as "Chem-seq," we were next able to efficiently map the genome-wide binding locations of this small molecule, revealing that it largely colocalized with AR on regulatory enhancers. Based on these observations, we performed the appropriate global analyses to ascertain that SD70 inhibits the androgen-dependent AR program, and prostate cancer cell growth, acting, at least in part, by functionally inhibiting the Jumonji domain-containing demethylase, KDM4C. Global location of candidate drugs represents a powerful strategy for new drug development by mapping genome-wide location of small molecules, a powerful adjunct to contemporary drug development strategies.

Tuppin P, Samson S, Fagot-Campagna A, et al.
Prostate cancer outcomes in France: treatments, adverse effects and two-year mortality.
BMC Urol. 2014; 14:48 [PubMed] Article available free on PMC after 01/07/2015 Related Publications
BACKGROUND: This very large population-based study investigated outcomes after a diagnosis of prostate cancer (PCa) in terms of mortality rates, treatments and adverse effects.
METHODS: Among the 11 million men aged 40 years and over covered by the general national health insurance scheme, those with newly managed PCa in 2009 were followed for two years based on data from the national health insurance information system (SNIIRAM). Patients were identified using hospitalisation diagnoses and specific refunds related to PCa and PCa treatments. Adverse effects of PCa treatments were identified by using hospital diagnoses, specific procedures and drug refunds.
RESULTS: The age-standardised two-year all-cause mortality rate among the 43,460 men included in the study was 8.4%, twice that of all men aged 40 years and over. Among the 36,734 two-year survivors, 38% had undergone prostatectomy, 36% had been treated by hormone therapy, 29% by radiotherapy, 3% by brachytherapy and 20% were not treated. The frequency of treatment-related adverse effects varied according to age and type of treatment. Among men between 50 and 69 years of age treated by prostatectomy alone, 61% were treated for erectile dysfunction and 24% were treated for urinary disorders. The frequency of treatment for these disorders decreased during the second year compared to the first year (erectile dysfunction: 41% vs 53%, urinary disorders: 9% vs 20%). The frequencies of these treatments among men treated by external beam radiotherapy alone were 7% and 14%, respectively. Among men between 50 and 69 years with treated PCa, 46% received treatments for erectile dysfunction and 22% for urinary disorders. For controls without PCa but treated surgically for benign prostatic hyperplasia, these frequencies were 1.5% and 6.0%, respectively.
CONCLUSIONS: We report high survival rates two years after a diagnosis of PCa, but a high frequency of PCa treatment-related adverse effects. These frequencies remain underestimated, as they are based on treatments for erectile dysfunction and urinary disorders and do not reflect all functional outcomes. These results should help urologists and general practitioners to inform their patients about outcomes at the time of screening and diagnosis, and especially about potential treatment-related adverse effects.

Related: France

Kim SP, Gross CP, Nguyen PL, et al.
Perceptions of Active Surveillance and Treatment Recommendations for Low-risk Prostate Cancer: Results from a National Survey of Radiation Oncologists and Urologists.
Med Care. 2014; 52(7):579-85 [PubMed] Related Publications
BACKGROUND: With the growing concerns about overtreatment in prostate cancer, the extent to which radiation oncologists and urologists perceive active surveillance (AS) as effective and recommend it to patients are unknown.
OBJECTIVE: To assess opinions of radiation oncologists and urologists about their perceptions of AS and treatment recommendations for low-risk prostate cancer.
RESEARCH DESIGN: National survey of specialists.
PARTICIPANTS: Radiation oncologists and urologists practicing in the United States.
MEASURES: A total of 1366 respondents were asked whether AS was effective and whether it was underused nationally, whether their patients were interested in AS, and treatment recommendations for low-risk prostate cancer. Pearson's χ test and multivariate logistic regression were used to test for differences in physician perceptions on AS and treatment recommendations.
RESULTS: Overall, 717 (52.5%) of physicians completed the survey with minimal differences between specialties (P=0.92). Although most physicians reported that AS is effective (71.9%) and underused in the United States (80.0%), 71.0% stated that their patients were not interested in AS. For low-risk prostate cancer, more physicians recommended radical prostatectomy (44.9%) or brachytherapy (35.4%); fewer endorsed AS (22.1%). On multivariable analysis, urologists were more likely to recommend surgery [odds ratio (OR): 4.19; P<0.001] and AS (OR: 2.55; P<0.001), but less likely to recommend brachytherapy (OR: 0.13; P<0.001) and external beam radiation therapy (OR: 0.11; P<0.001) compared with radiation oncologists.
CONCLUSIONS AND RELEVANCE: Most prostate cancer specialists in the United States believe AS effective and underused for low-risk prostate cancer, yet continue to recommend the primary treatments their specialties deliver.

Related: Brachytherapy USA Watchful Waiting - Prostate Cancer

Noguez JH, Fantz CR
Pathology consultation on prostate-specific antigen testing.
Am J Clin Pathol. 2014; 142(1):7-15 [PubMed] Related Publications
OBJECTIVES: To provide clarity on the pros and cons of using prostate-specific antigen (PSA) as a screening tool for prostate cancer.
METHODS: Case scenarios and a literature review of recently published clinical trial data are presented to provide evidence of the controversy.
RESULTS: PSA is a sensitive biomarker for detecting diseases of the prostate, but it is limited in its ability to distinguish cancerous from noncancerous conditions or aggressive from indolent cancers and has resulted in a considerable amount of overdiagnosis and overtreatment.
CONCLUSIONS: The analytical methodology for total PSA testing is both reliable and cost-effective, but patients should be encouraged to talk to their providers to understand the benefits and harms associated with this testing.

Related: Cancer Screening and Early Detection

Statkiewicz M, Maryan N, Lipiec A, et al.
The role of the SHH gene in prostate cancer cell resistance to paclitaxel.
Prostate. 2014; 74(11):1142-52 [PubMed] Related Publications
BACKGROUND: The increased activity of the Sonic Hedgehog (SHH) pathway has been demonstrated in many types of cancer including prostate cancer (PCa). It has been shown that SHH pathway is involved in tumor angiogenesis and in regulation of metabolism of cancer stem cells. The increased activity of the SHH pathway is responsible for generation and maintenance of the multidrug resistance in cancer cells. A key role in the development of this insensitivity to cytotoxic drugs play ATP-binding cassette (ABC) transporters.
METHODS: SHH encoding plasmid was stably transfected into PCa cell lines DU145 and LNCaP. The expression of SHH was silenced by shRNA and the level of SHH was tested by quantitative (q)PCR and western blot methods. The effect of SHH overexpression in cells after treatment with paclitaxel was measured by MTT assay, crystal violet assay and flow cytometry. The level of 44 ABC transporters was estimated by qPCR.
RESULTS: Expression of exogenous SHH protein in DU145 and LNCaP cell lines enhanced their resistance to paclitaxel along with increased expression of ABC transporters transcripts. Paclitaxel treatment further enhanced the expression of increased ABC transporters transcripts in cells overexpressing SHH.
CONCLUSIONS: Overexpression of SHH enhances PCa cell lines resistance to paclitaxel. Higher level of SHH leads to increase in ABC transporters expression in a manner dependent on paclitaxel.

Related: Paclitaxel

Yoshida K, Yamazaki H, Nakamura S, et al.
Role of novel risk classification method, Prostate Cancer Risk Index (PRIX) for clinically localized prostate cancer after high-dose-rate interstitial brachytherapy as monotherapy.
Anticancer Res. 2014; 34(6):3077-81 [PubMed] Related Publications
AIM: To examine the role of the new grading system Prostate Cancer Risk Index (PRIX) with existing risk-grouping after high-dose-rate interstitial brachytherapy (HDR-ISBT) as monotherapy for localized prostate cancer.
PATIENTS AND METHODS: We analyzed outcome in 100 patients treated by HDR-ISBT as monotherapy using PRIX and compared this with D'Amico, the National Comprehensive Cancer Network (NCCN), and Seattle classifications. The median follow-up was 74 (range=48-109) months.
RESULTS: Five-year prostate-specific antigen control and overall survival rates were 94% and 98%, respectively. PRIX separated the risks statistically significantly (p=0.004), while D'Amico (p=0.319), NCCN 2002 (p=0.126), NCCN 2012 (p=0.052) and Seattle (p=0.112) classifications failed to show a statistically significant separation.
CONCLUSION: PRIX is a more useful risk classification system in high-risk patient selection than existing risk classification system in clinically localized prostate cancer after HDR-ISBT as monotherapy.

Related: Brachytherapy

Jiao L, Shen D, Liu G, et al.
PPM1D as a novel biomarker for prostate cancer after radical prostatectomy.
Anticancer Res. 2014; 34(6):2919-25 [PubMed] Related Publications
Protein phosphatase magnesium-dependent 1 delta (PPM1D) is involved in several types of cancer. The current study examined the role of PPM1D expression in prostate cancer (PCa) tissues and in PCa cell lines. Expression of PPM1D was evaluated using immunohistochemistry in 234 PCa tissues after radical prostatectomy and 80 benign prostatic hyperplasia (BPH) tissues. The associations of PPM1D expression with clinicopathological parameters and survival were analyzed. In vitro, tumor cells were transfected with small interfering RNA targeting PPM1D (siPPM1D) or si-Scramble, and the cell proliferation, migration and invasion were determined. We found that PPM1D expression was significantly higher in PCa tissues than that in BPH tissues. PPM1D expression was positively correlated with Gleason score (p=0.022), T stage (p=0.015) and lymph node status (p=0.016). Kaplan-Meier curve analysis showed that patients with positive PPM1D expression had shorter biochemical recurrence-free survival and overall survival. Furthermore, multivariate analyses showed that PPM1D expression was an independent predictor of both biochemical recurrence-free (hazard ratio=3.437, 95% confidence interval=1.154-6.209, p=0.016) and overall survival (hazard ratio=5.026, 95% confidence interval=2.545-8.109, p=0.007). Knockdown of PPM1D inhibited the proliferation, migration and invasion capabilities of PC-3 and LNCaP cells. PPM1D expression may predict for both overall and biochemical recurrence-free survival in patients after radical prostatectomy for PCa. Elevated PPM1D expression plays a key role in progression of PCa.

Related: Apoptosis

Kim J, Mizokami A, Shin M, et al.
SOD3 acts as a tumor suppressor in PC-3 prostate cancer cells via hydrogen peroxide accumulation.
Anticancer Res. 2014; 34(6):2821-31 [PubMed] Related Publications
BACKGROUND: The functions of superoxide dismutase-3 (SOD3), which acts on the cell surface and protects cells from oxidative stress, remain uncertain in the progression of prostate cancer.
MATERIALS AND METHODS: To verify SOD3 expression in human prostate tissue, immunohistochemistry was performed using tissue microarrays. To investigate the effects of SOD3 on proliferation, migration, and invasion, SOD3 was overexpressed and recombinant SOD3 was employed in PC-3 prostate cancer cells. H2O2 levels, reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio, catalase activity, and 8-oxo-2'-deoxyguanosine (8-OHdG) were estimated in SOD3-overexpressing PC-3 cells.
RESULTS: Immunohistochemistry revealed reduced expression of SOD3 in prostate cancer tissue. SOD3 overexpression in PC-3 cells inhibited cell proliferation, migration, and invasion. Recombinant SOD3 had the same effect. H2O2 accumulation was increased by SOD3 overexpression, GSH/GSSG ratio was decreased, and catalase activity was decreased. DNA damage in SOD3-overexpressing cells was confirmed by 8-OHdG elevation.
CONCLUSION: Since SOD3 acts as a tumor suppressor, SOD3 overexpression and recombinant SOD3 might lead to treatment for prostate cancer.

Related: Apoptosis

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