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).

Venkatasubramanian PN, Brendler CB, Plunkett BA, et al.
Periprostatic adipose tissue from obese prostate cancer patients promotes tumor and endothelial cell proliferation: a functional and MR imaging pilot study.
Prostate. 2014; 74(3):326-35 [PubMed] Related Publications
BACKGROUND: Obesity, particularly visceral adiposity, confers a worse prognosis for prostate cancer (PCa) patients, and increasing periprostatic adipose (PPA) tissue thickness or density is positively associated with more aggressive disease. However, the cellular mechanism of this activity remains unclear. Therefore, in this pilot study, we assessed the functional activity of PPA tissue secretions and established a biochemical profile of PPA as compared to subcutaneous adipose (SQA) tissues from lean, overweight and obese PCa patients.
METHODS: Adipose tissues were collected from PCa patients undergoing surgical prostate removal. Tissues were analyzed by histologic and magnetic resonance (MR) techniques. Explant tissue culture secretions were used in proliferation assays on PCa and endothelial cells.
RESULTS: PPA secretions obtained from obese patients were significantly more pro-proliferative in both PCa and endothelial cells as compared to PPA obtained from lean or overweight men and SQA tissues. Consistent with this, PPA microvessel density was increased, and the T2 relaxation time was decreased, compared to SQA tissues, and we observed a modest, inverse correlation between the T2 and tumor stage. Moreover, the ratio of unsaturated to saturated fatty acids, obtained using MR spectroscopy, showed a modest, inverse correlation with Gleason score.
CONCLUSIONS: These pilot data show that PPA stimulates PCa cell proliferation and angiogenesis and that obesity intensifies this activity, thus generating a mechanistic hypothesis to explain the worse prognosis observed in obese PCa patients. Our pilot study also shows that MR technology may be useful in further elucidating the relationship between obesity and PCa progression.

Rashid S, Fazli L, Boag A, et al.
Separation of benign and malignant glands in prostatic adenocarcinoma.
Med Image Comput Comput Assist Interv. 2013; 16(Pt 3):461-8 [PubMed] Related Publications
This paper presents an analysis of the high resolution histopathology images of the prostate with a focus on the evolution of morphological gland features in prostatic adenocarcinoma. Here we propose a novel technique of labeling individual glands as malignant or benign. In the first step, the gland and nuclei objects of the images are automatically segmented. Individual gland units are segmented out by consolidating their lumina with the surrounding layers of epithelium and nuclei. The nuclei objects are segmented by using a marker controlled watershed algorithm. Two new features, Number of Nuclei Layer (N(NL)) and Ratio of Epithelial layer area to Lumen area (R(EL)) have been extracted from the segmented units. The main advantage of this approach is that it can detect individual malignant gland units, irrespective of neighboring histology and/or the spatial extent of the cancer. The proposed algorithm has been tested on 40 histopathology scenes taken from 10 high resolution whole mount images and achieved a sensitivity of 0.83 and specificity of 0.81 in a leave-75%-out cross-validation.

Lee G, Ali S, Veltri R, et al.
Cell orientation entropy (COrE): predicting biochemical recurrence from prostate cancer tissue microarrays.
Med Image Comput Comput Assist Interv. 2013; 16(Pt 3):396-403 [PubMed] Related Publications
We introduce a novel feature descriptor to describe cancer cells called Cell Orientation Entropy (COrE). The main objective of this work is to employ COrE to quantitatively model disorder of cell/nuclear orientation within local neighborhoods and evaluate whether these measurements of directional disorder are correlated with biochemical recurrence (BCR) in prostate cancer (CaP) patients. COrE has a number of novel attributes that are unique to digital pathology image analysis. Firstly, it is the first rigorous attempt to quantitatively model cell/nuclear orientation. Secondly, it provides for modeling of local cell networks via construction of subgraphs. Thirdly, it allows for quantifying the disorder in local cell orientation via second order statistical features. We evaluated the ability of 39 COrE features to capture the characteristics of cell orientation in CaP tissue microarray (TMA) images in order to predict 10 year BCR in men with CaP following radical prostatectomy. Randomized 3-fold cross-validation via a random forest classifier evaluated on a combination of COrE and other nuclear features achieved an accuracy of 82.7 +/- 3.1% on a dataset of 19 BCR and 20 non-recurrence patients. Our results suggest that COrE features could be extended to characterize disease states in other histological cancer images in addition to prostate cancer.

Sun Y, Yuan J, Rajchl M, et al.
Efficient convex optimization approach to 3D non-rigid MR-TRUS registration.
Med Image Comput Comput Assist Interv. 2013; 16(Pt 1):195-202 [PubMed] Related Publications
In this study, we propose an efficient non-rigid MR-TRUS deformable registration method to improve the accuracy of targeting suspicious locations during a 3D ultrasound (US) guided prostate biopsy. The proposed deformable registration approach employs the multi-channel modality independent neighbourhood descriptor (MIND) as the local similarity feature across the two modalities of MR and TRUS, and a novel and efficient duality-based convex optimization based algorithmic scheme is introduced to extract the deformations which align the two MIND descriptors. The registration accuracy was evaluated using 10 patient images by measuring the TRE of manually identified corresponding intrinsic fiducials in the whole gland and peripheral zone, and performance metrics (DSC, MAD and MAXD) for the apex, mid-gland and base of the prostate were also calculated by comparing two manually segmented prostate surfaces in the registered 3D MR and TRUS images. Experimental results show that the proposed method yielded an overall mean TRE of 1.74 mm, which is favorably comparable to a clinical requirement for an error of less than 2.5 mm.

Gottlieb BH, Maitland SB, Brown J
Social support and adjustment among wives of men with prostate cancer.
J Psychosoc Oncol. 2014; 32(1):16-36 [PubMed] Related Publications
This study aims to understand how wives' mental health and life enjoyment are affected by their perceptions of the sufficiency of the support they render to their husbands who have prostate cancer. Its specific purpose is to determine whether these outcomes accrue more strongly to wives who perceive their husbands coping in avoidant ways. Drawing on data from an interview study of 51 wives of men diagnosed with prostate cancer, the authors employ heiarchical regression analysis to examine the wives' adjustment in relation to their provision of support to their husbands. Our findings reveal a significant moderating effect of the husbands' avoidant coping; consistent with cognitive dissonance theory, wives who provided sufficient support to more avoidant husbands demonstrated better mental health and life enjoyment than wives of men who were less avoidant. In addition, the perceived sufficiency of the support provided by the wives' social networks had a stronger bearing on their adjustment than the support provided by their husbands. These findings add to our understanding of the psychological benefits that support providers derive when they communicate support in ways that suit the recipient's style of managing threat.

Ost P, Decaestecker K, Lambert B, et al.
Prognostic factors influencing prostate cancer-specific survival in non-castrate patients with metastatic prostate cancer.
Prostate. 2014; 74(3):297-305 [PubMed] Related Publications
BACKGROUND: In non-castrate prostate cancer (PCa), the prognostic value of the number of metastases on prostate cancer-specific survival (PCSS) is not well studied.
METHODS: We retrospectively analyzed the medical records of 1,206 patients, referred for radiotherapy of the prostate (bed) following diagnosis of PCa. Distant metastases (nodal, skeletal, and/or visceral) developed in 121 patients following curative treatment, of which 80 with complete records were not castrated at time of metastasis. The treatment at time of metastases was androgen deprivation therapy (ADT; n = 22), active surveillance (n = 10) or metastasis-directed therapy (MDT; n = 48). Cox-regression analyses were used to examine the influence of different variables on PCSS.
RESULTS: The median follow-up from primary PCa treatment was 6.9 years with a median interval from diagnosis to first metastatic event of 4.1 year (range: 0.2-15 years). The primary site of metastases was limited to lymph nodes (48%), bone (39%), and viscera (1%) or a combination (12%). Median PCSS from diagnosis of noncastrate metastases was 6.6 years (95% confidence interval [CI], 5.6-7.7 years). A longer premetastatic PSA doubling time (DT) (hazard ratio [HR] 0.73; 95% CI: 0.57-0.92), a lower number of metastases at first presentation (HR 1.07; 95% CI: 1.02-1.12) and pattern of metastatic spread (HR 3.6; 95% CI: 1.13-11.8 for extensive vs. minimal) were associated with improved PCSS.
CONCLUSION: A longer PSA DT, involvement of nodes or axial skeleton and a lower number of metastases are associated with an improved PCSS in non-castrated patients developing metastases.

Mooney D, Paluri R, Mehta A, et al.
Update in systemic therapy of urologic malignancies.
Postgrad Med. 2014; 126(1):44-54 [PubMed] Related Publications
Systemic therapy of advanced prostate and renal cancers has gained several recent additions to the therapeutic armamentarium. Treatment of patients with castration-resistant prostate cancer now includes additional immunotherapy (sipuleucel-T), chemotherapy (cabazitaxel), androgen-signaling inhibitors (abiraterone acetate, enzalutamide), and a radiopharmaceutical (alpharadin), based on extension of patient survival. Similarly, therapy for patients with renal cell carcinoma, a chemoresistant malignancy, has undergone dramatic changes based on an understanding of the role of angiogenesis. Multiple vascular endothelial growth factor inhibitors (sorafenib, sunitinib, pazopanib, axitinib, bevacizumab) and mammalian target of rapamycin inhibitors (temsirolimus, everolimus) have been added to the therapeutic arsenal. Additionally, immunotherapy retains an important treatment role, with a continuing application of high-dose interleukin-2 in select patients and the emergence of novel immunotherapeutic agents that may have significant benefit. Other major urologic malignancies, including urothelial, testicular, and penile cancers, have witnessed relatively few or no recent advances in therapy, although testicular germ cell tumors are one of the most curable malignancies. An agent for treatment of advanced urothelial cancer now has commercial approval, the chemotherapeutic agent, vinflunine, as second-line therapy in multiple countries-but not in the United States. Our review summarizes and updates the field of systemic therapy for advanced urologic malignancies, with a focus on castration-resistant prostate cancer and renal cell carcinoma.

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Westphalen AC, Rosenkrantz AB
Prostate imaging reporting and data system (PI-RADS): reflections on early experience with a standardized interpretation scheme for multiparametric prostate MRI.
AJR Am J Roentgenol. 2014; 202(1):121-3 [PubMed] Related Publications
OBJECTIVE: In this article, we provide our perspective on current multiinstitutional efforts to improve standardization of interpretation and reporting of multiparametric prostate MRI, emphasizing their strengths and limitations based on our experiences, and provide several suggestions for guiding continued initiatives for standardizing multiparametric prostate MRI reporting.
CONCLUSION: Significant steps are being taken to facilitate the adoption of prostate MRI by urologists and other physicians in the community. Ultimately, however, prospective multicenter validation studies assessing the various aspects of a diagnostic test will be required.

Rosenkrantz AB, Taneja SS
Radiologist, be aware: ten pitfalls that confound the interpretation of multiparametric prostate MRI.
AJR Am J Roentgenol. 2014; 202(1):109-20 [PubMed] Related Publications
OBJECTIVE: In this article, we describe 10 diagnostic challenges that may confound the interpretation of multiparametric prostate MRI for tumor, grouped into three categories on the basis of our experience: normal anatomic structures that may be misinterpreted as suspicious lesions if their normal appearance is not recognized, benign processes that may mimic tumor, and technical issues relating to acquisition and interpretation of diffusion-weighted imaging that may decrease sensitivity for tumor. Strategies for addressing these challenges are suggested.
CONCLUSION: It is important that the radiologist involved in the interpretation of prostate MRI be aware of these pitfalls that will be encountered during routine clinical practice. This awareness can contribute to improved diagnostic performance in MRI interpretation.

Messina M, Ricci F, Spina B, Boccardo F
Single skull metastasis 15 years after primary treatment of prostate cancer and with undetectable PSA levels: a case report and review of the literature.
Tumori. 2013 Sep-Oct; 99(5):e220-4 [PubMed] Related Publications
Prostate cancer is the first cause of skull metastases in men, accounting for 12-18% of all cases. This condition is generally a late event in the course of the disease, involving patients with disseminated lesions. Quite rarely is skull involvement the first and single site of distant recurrence. We report the case of a patient who developed a single skull lesion 15 years after primary treatment of prostate cancer, in the presence of undetectable PSA levels. Pathological assessment performed after resection of the lesion revealed a metastasis from prostate carcinoma. Basing on this experience the appearance of craniofacial pain or a nerve deficit in patients with a history of prostate cancer should alert the clinician to exclude distant recurrence of disease, even in the presence of undetectable PSA levels and even if many years have elapsed since the treatment of the primary tumor. Knowledge of these manifestations will reduce any diagnostic delay and lead to the effective delivery of appropriate treatment.

Torelli T, Lughezzani G, Catanzaro M, et al.
Prostatic metastases from testicular nonseminomatous germ cell cancer: two case reports and a review of the literature.
Tumori. 2013 Sep-Oct; 99(5):e203-7 [PubMed] Related Publications
BACKGROUND: Prostatic metastases from testicular germ cell tumors (TGCTs) are extremely uncommon. To the best of our knowledge, only five cases of prostatic metastases from seminoma have been reported in the literature. Conversely, no cases of metastases to the prostate from nonseminomatous germ cell tumors (NSGCT) have been previously reported.
CASE PRESENTATION: We present two patients who developed prostatic metastases 5 and 21 years after the initial diagnosis. The first case concerned a 28-year-old Caucasian man who underwent a right orchiectomy and right retroperitoneal lymph node dissection (RPLND) for a stage I NSGCT in 1999 and five years later was diagnosed with prostatic metastases. The second case concerned a 30-year-old man treated with a right orchiectomy and right RPLND for stage I NSGCT in 1985 who was diagnosed with prostatic metastases in 2006, 21 years after primary surgery. We reviewed the available literature on the topic.
CONCLUSION: Prostatic metastases from TCGTs are highly unusual. Lower urinary tract symptoms in patients treated for previous testicular cancer require immediate clinical attention. However, because of their extreme rarity, specific clinical investigations to screen for possible prostatic involvement from TGCT should not be recommended.

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Shore ND, Sieber P, Schimke L, et al.
Comparison of tolerability and adverse events following treatment with two GnRH agonists in patients with advanced prostate cancer.
Urol Nurs. 2013 Sep-Oct; 33(5):236-44, 248 [PubMed] Related Publications
This multicenter, randomized, crossover, open-label study ( identifier: NCT01161563) assessed patients'and clinicians'perceptions of injection site tolerability and adverse events following the intramuscular injection of triptorelin pamoate or subcutaneous injection of leuprolide acetate in 107 male, patients with advanced prostate cancer.

Briganti A, Joniau S, Gandaglia G, et al.
Patterns and predictors of early biochemical recurrence after radical prostatectomy and adjuvant radiation therapy in men with pT3N0 prostate cancer: implications for multimodal therapies.
Int J Radiat Oncol Biol Phys. 2013; 87(5):960-7 [PubMed] Related Publications
PURPOSE: The aim of our study was to evaluate patterns and predictors of early biochemical recurrence (eBCR) after radical prostatectomy (RP) and adjuvant radiation therapy (aRT) in order to identify which individuals might benefit from additional treatments.
METHODS AND MATERIALS: We evaluated 390 patients with pT3N0 prostate cancer (PCa) receiving RP and aRT at 6 European centers between 1993 and 2006. Patients who were free from BCR at <2 years' follow-up were excluded. This resulted in 374 assessable patients. Early BCR was defined as 2 consecutive prostate-specific antigen (PSA) test values >0.2 ng/mL within 2 or 3 years after aRT. Uni- and multivariable Cox regression analyses predicting overall and eBCR after aRT were fitted. Covariates consisted of preoperative PSA results, surgical margins, pathological stage, Gleason score, and aRT dose.
RESULTS: Overall, 5- and 8-year BCR-free survival rates were 77.1% and 70.8%, respectively. At a median follow-up of 86 months after aRT, 33 (8.8%) and 55 (14.6%) men experienced BCR within 2 or 3 years after aRT, respectively. In multivariable analyses, Gleason scores of 8 to 10 represented the only independent predictor of eBCR after aRT (all, P≤.01). The risk of BCR was significantly higher in patients with a Gleason score of 8 to 10 disease than in those with Gleason 2 to 6 within 24 months after treatment, after adjusting for all covariates (all, P≤.04). However, given a 24-month BCR free period, the risk of subsequent BCR for men with poorly differentiated disease was equal to that of men with less aggressive disease (all, P≥.3).
CONCLUSIONS: High Gleason score represents the only predictor of eBCR after RP and aRT in patients affected by pT3N0 PCa. Given the association between early PSA recurrence, clinical progression, and mortality, these patients might be considered candidates for adjuvant medical therapy and/or prophylactic whole-pelvis radiation therapy in addition to aRT, delivered to the prostatic bed.

Foster R, Meyer J, Iyengar P, et al.
Localization accuracy and immobilization effectiveness of a stereotactic body frame for a variety of treatment sites.
Int J Radiat Oncol Biol Phys. 2013; 87(5):911-6 [PubMed] Related Publications
PURPOSE: The purpose of this study was to analyze the pretreatment setup errors and intrafraction motion using cone beam computed tomography (CBCT) for stereotactic body radiation therapy patients immobilized and localized with a stereotactic body frame for a variety of treatment sites.
METHODS AND MATERIALS: Localization errors were recorded for patients receiving SBRT for 141 lung, 29 liver, 48 prostate, and 45 spine tumors representing 1005 total localization sessions. All patients were treated in a stereotactic body frame with a large custom-molded vacuum pillow. Patients were first localized to the frame using tattoos placed during simulation. Subsequently, the frame was aligned to the room lasers according to the stereotactic coordinates determined from the treatment plan. Every patient received a pretreatment and an intrafraction CBCT. Abdominal compression was used for all liver patients and for approximately 40% of the lung patients to reduce tumor motion due to respiration.
RESULTS: The mean ± standard deviation pretreatment setup errors from all localizations were -2.44 ± 3.85, 1.31 ± 5.84, and 0.11 ± 3.76 mm in the anteroposterior, superoinferior, and lateral directions, respectively. The mean pretreatment localization results among all treatment sites were not significantly different (F test, P<.05). For all treatment sites, the mean ± standard deviation intrafraction shifts were 0.33 ± 1.34, 0.15 ± 1.45, and -0.02 ± 1.17 mm in the anteroposterior, superoinferior, and lateral directions, respectively. The mean unidimensional intrafraction shifts were statistically different for several of the comparisons (P<.05) as assessed by the Tukey-Kramer test.
CONCLUSIONS: Despite the varied tumor locations, the pretreatment mean localization errors for all sites were found to be consistent among the treatment sites and not significantly different, indicating that the body frame is a suitable immobilization and localization device for a variety of tumor sites. Our pretreatment localization errors and intrafraction shifts compare favorably with those reported in other studies using different types of immobilization devices.

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Henrique R, Oliveira AI, Costa VL, et al.
Epigenetic regulation of MDR1 gene through post-translational histone modifications in prostate cancer.
BMC Genomics. 2013; 14:898 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Multidrug resistance 1 (MDR1) gene encodes for an ATP binding cassette transporter--P-glycoprotein (P-gp)-- involved in chemoresistance to taxanes. MDR1 promoter methylation is frequent in prostate carcinoma (PCa), suggesting an epigenetic regulation but no functional correlation has been established. We aimed to elucidate the epigenetic mechanisms involved in MDR1 deregulation in PCa.
RESULTS: MDR1 promoter methylation and P-gp expression were assessed in 121 PCa, 39 high-grade prostatic intraepithelial neoplasia (HGPIN), 28 benign prostatic hyperplasia (BPH) and 10 morphologically normal prostate tissue (NPT) samples, using quantitative methylation specific PCR and immunohistochemistry, respectively. PCa cell lines were exposed to a DNA methyltransferases inhibitor 5-aza-2'deoxycytidine (DAC) and histone deacetylases inhibitor trichostatin A (TSA). Methylation and histone posttranscriptional modifications status were characterized and correlated with mRNA and protein expression. MDR1 promoter methylation levels and frequency significantly increased from NPTs, to HGPIN and to PCa. Conversely, decreased or absent P-gp immunoexpression was observed in HGPIN and PCa, inversely correlating with methylation levels. Exposure to DAC alone did not alter significantly methylation levels, although increased expression was apparent. However, P-gp mRNA and protein re-expression were higher in cell lines exposed to TSA alone or combined with DAC. Accordingly, histone active marks H3Ac, H3K4me2, H3K4me3, H3K9Ac, and H4Ac were increased at the MDR1 promoter after exposure to TSA alone or combined with DAC.
CONCLUSION: Our data suggests that, in prostate carcinogenesis, MDR1 downregulation is mainly due to histone post-translational modifications. This occurs concomitantly with aberrant promoter methylation, substantiating the association with P-gp decreased expression.

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Fraggetta F, Pepe P, Improta G, et al.
Prostate needle biopsy: what we do and what should be improved.
Anal Quant Cytol Histol. 2013; 35(3):130-8 [PubMed] Related Publications
Prostate cancer (PCa) is the cancer most frequently diagnosed in older men and the second most frequent for incidence of all tumors. With the widespread use of serum prostate-specific antigen (PSA), the detection rate as well as the incidence of localized tumors has been increasing, thus leading to a drop in PCa-related mortality. However, a corresponding estimated rate of overdiagnosis as high as 50% has been reported, and the adverse side effects related to unnecessary treatments make the overall benefit of PSA mass screening unclear. The lower PSA threshold and extended prostate biopsy protocols have led to a marked increase of small, low-grade tumors that will never threaten a patient's survival. Sextant biopsy technique, extended biopsy protocols (12-18 cores) and saturation prostate schemes are already familiar terms, together with quantitative histology in the pathology departments. This brief review will try to focus on what usually is done and what should be improved in prostate needle biopsy in order to answer many critical points such as the clinical implication of different modalities of prostate biopsy (transrectal, transperineal or even targeted), the use of quantitative histology and the importance of the new molecular findings in addition to conventional histological parameters in the era of the active surveillance protocols.

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Lee JA, Kim CY, Park YJ, et al.
Interfractional variability in intensity-modulated radiotherapy of prostate cancer with or without thermoplastic pelvic immobilization.
Strahlenther Onkol. 2014; 190(1):94-9 [PubMed] Related Publications
PURPOSE: To determine the variability of patient positioning errors associated with intensity-modulated radiotherapy (IMRT) for prostate cancer and to assess the impact of thermoplastic pelvic immobilization on these errors using kilovoltage (kV) cone-beam computed tomography (CBCT).
MATERIALS AND METHODS: From February 2012 to June 2012, the records of 314 IMRT sessions in 19 patients with prostate cancer, performed with or without immobilization at two different facilities in the Korea University Hospital were analyzed. The kV CBCT images were matched to simulation computed tomography (CT) images to determine the simulation-to-treatment variability. The shifts along the x (lateral)-, y (longitudinal)- and z (vertical)-axes were measured, as was the shift in the three dimensional (3D) vector.
RESULTS: The measured systematic errors in the immobilized group during treatment were 0.46 ± 1.75 mm along the x-axis, - 0.35 ± 3.83 mm along the y-axis, 0.20 ± 2.75 mm along the z-axis and 4.05 ± 3.02 mm in the 3D vector. Those of nonimmobilized group were - 1.45 ± 7.50 mm along the x-axis, 1.89 ± 5.07 mm along the y-axis, 0.28 ± 3.81 mm along the z-axis and 8.90 ± 4.79 mm in the 3D vector. The group immobilized with pelvic thermoplastics showed reduced interfractional variability along the x- and y-axes and in the 3D vector compared to the nonimmobilized group (p < 0.05).
CONCLUSION: IMRT with thermoplastic pelvic immobilization in patients with prostate cancer appears to be useful in stabilizing interfractional variability during the planned treatment course.

López JI, Angulo JC
The ejaculatory ducts and their implications in prostate adenocarcinoma.
Anal Quant Cytol Histol. 2013; 35(4):205-9 [PubMed] Related Publications
OBJECTIVE: To describe the histological characteristics of the ejaculatory duct and their importance in prostate adenocarcinoma.
STUDY DESIGN: Anatomical dissection of the prostate and seminal vesicles was performed in 20 autopsies of males without clinical evidence of prostatic pathology. Specimens were totally sampled to study the complete route of the ejaculatory ducts within the prostate, focusing specifically on the histological characteristics of the stroma enfolding the ducts.
RESULTS: Ejaculatory ducts are covered by a distinct fibrous capsule that includes lymphatics and blood vessels with a specific spatial and architectural arrangement. Although easy to recognize in normal conditions, the positive nuclear immunostaining of epithelial cells with PAX-2 and PAX-8 may be of help to recognize the ejaculatory epithelium in problematic cases. These arteriolymphatic units made of hyalinized arteries and ectatic lymphatic vessels run parallel to the ejaculatory duct along its intraprostatic course and continue outside the prostate gland in the subadventitial tissue of seminal vesicles.
CONCLUSION: The ejaculatory ducts have a unique characteristic histology that allows its recognition in transrectal core biopsies. The issue matters in daily practice and may have prognostic implications in prostate adenocarcinoma since the invasion of this structure has been associated with a high percentage of extraprostatic disease.

Bandekar A, Zhu C, Jindal R, et al.
Anti-prostate-specific membrane antigen liposomes loaded with 225Ac for potential targeted antivascular α-particle therapy of cancer.
J Nucl Med. 2014; 55(1):107-14 [PubMed] Related Publications
UNLABELLED: This study evaluates targeted liposomes loaded with the α-particle generator (225)Ac to selectively kill prostate-specific membrane antigen (PSMA)-expressing cells with the aim to assess their potential for targeted antivascular radiotherapy.
METHODS: In this study, PEGylated liposomes were loaded with (225)Ac and labeled with the mouse antihuman PSMA J591 antibody or with the A10 PSMA aptamer. The targeting selectivity, extent of internalization, and killing efficacy of liposomes were evaluated on monolayers of prostate cancer cells intrinsically expressing PSMA (human LNCaP and rat Mat-Lu cells) and on monolayers of HUVEC induced to express PSMA (induced HUVEC).
RESULTS: The loading efficiency of (225)Ac into preformed liposomes ranged from 58.0% ± 4.6% to 85.6% ± 11.7% of introduced radioactivity. The conjugation reactions resulted in approximately 17 ± 2 J591 antibodies and 9 ± 2 A10 aptamers per liposome. The average size of liposomes, 107 ± 2 nm in diameter, was not affected by conjugation or loading. LNCaP cells exhibit 2:1:0.5 relative PSMA expression, compared with MatLu and induced HUVEC, respectively, based on flow cytometry detecting association of the J591 antibody. J591-labeled liposomes display higher levels of total specific binding to all cell lines than A10 aptamer-labeled liposomes. Specific cell association of targeted liposomes increases with incubation time. Cytotoxicity studies demonstrate that radiolabeled J591-labeled liposomes are most cytotoxic, with median lethal dose values, after 24 h of incubation, equal to 1.96 (5.3 × 10(-5)), 2.92 × 10(2) (7.9 × 10(-3)), and 2.33 × 10(1) Bq/mL (6.3 × 10(-4) μCi/mL) for LNCaP, Mat-Lu, and induced HUVEC, respectively, which are comparable to the values for the radiolabeled J591 antibody. For A10 aptamer-labeled liposomes, the corresponding values are 3.70 × 10(1) (1.0 × 10(-3)), 1.85 × 10(3) (5.0 × 10(-2)), and 4.07 × 10(3) Bq/mL (1.1 × 10(-1) μCi/mL), respectively.
CONCLUSION: Our studies demonstrate that anti-PSMA-targeted liposomes loaded with (225)Ac selectively bind, become internalized, and kill PSMA-expressing cells including endothelial cells induced to express PSMA. These findings-combined with the unique ability of liposomes to be easily tuned, in terms of size and surface modification, for optimizing biodistributions-suggest the potential of PSMA-targeting liposomes encapsulating α-particle emitters for selective antivascular α radiotherapy.

Anderson B, Marshall-Lucette S
African and Afro-Caribbean men's experiences of prostate cancer.
Br J Nurs. 2013 Dec 12-2014 Jan 8; 22(22):1296-8, 1300-2, 1304-7 [PubMed] Related Publications
It is well documented that prostate cancer presents a significant health problem for middle-aged and elderly men in the UK, with further evidence suggesting that the disease is more prevalent in men of African and Afro-Caribbean (AAC) ethnicity. There is also evidence that these men are diagnosed much later and that the disease is more aggressive than in Caucasian men. Aim: To explore AAC men's experiences of prostate cancer and their understanding of its associated risks. The purpose was to gain an insight from these men's perspectives and ascertain whether a more focused health promotion strategy, and specific UK-based research, was needed in this area. Method: A purposive sample of seven AAC men was recruited from a hospital trust's patient list after gaining approval from a research ethics committee. In-depth face-to-face interviews were carried out and the transcripts analysed thematically. Findings: The four main themes that emerged were: disease-prompted awareness, checking up as a necessary evil, defining and constructing factors influencing prostate cancer screening uptake, and appraising perceived myths about prostate cancer through personal beliefs. Conclusions: Among this group of AAC men, socioeconomic status, such as education and professional background, were factors that influenced their level of awareness of prostate cancer and prompted their decisions to seek help. However, it is evident from these men's perspectives that a more specific health education strategy that promotes early detection and management, targeting AAC men, would help in demystifying prostate cancer and encourage them to seek help earlier. Further research studies and health education in prominent social outlets are recommended in increasing AAC men's awareness of prostate cancer and its associated risks.

Chyan W, Zhang DY, Lippard SJ, Radford RJ
Reaction-based fluorescent sensor for investigating mobile Zn2+ in mitochondria of healthy versus cancerous prostate cells.
Proc Natl Acad Sci U S A. 2014; 111(1):143-8 [PubMed] Article available free on PMC after 07/07/2014 Related Publications
Chelatable, mobile forms of divalent zinc, Zn(II), play essential signaling roles in mammalian biology. A complex network of zinc import and transport proteins has evolved to control zinc concentration and distribution on a subcellular level. Understanding the action of mobile zinc requires tools that can detect changes in Zn(II) concentrations at discrete cellular locales. We present here a zinc-responsive, reaction-based, targetable probe based on the diacetyled form of Zinpyr-1. The compound, (6-amidoethyl)triphenylphosphonium Zinpyr-1 diacetate (DA-ZP1-TPP), is essentially nonfluorescent in the metal-free state; however, exposure to Zn(II) triggers metal-mediated hydrolysis of the acetyl groups to afford a large, rapid, and zinc-induced fluorescence response. DA-ZP1-TPP is insensitive to intracellular esterases over a 2-h period and is impervious to proton-induced turn-on. A TPP unit is appended for targeting mitochondria, as demonstrated by live cell fluorescence imaging studies. The practical utility of DA-ZP1-TPP is demonstrated by experiments revealing that, in contrast to healthy epithelial prostate cells, tumorigenic cells are unable to accumulate mobile zinc within their mitochondria.

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Santini D, Zoccoli A, Gregorj C, et al.
Zoledronic acid induces a significant decrease of circulating endothelial cells and circulating endothelial precursor cells in the early prostate cancer neoadjuvant setting.
Oncology. 2013; 85(6):342-7 [PubMed] Related Publications
PURPOSE: Published data demonstrated that zoledronic acid (ZOL) exhibits antiangiogenetic effects. A promising tool for monitoring antiangiogenic therapies is the measurement of circulating endothelial cells (CECs) and circulating endothelial precursor cells (CEPs) in the peripheral blood of patients. Our aim was to investigate the effects of ZOL on levels of CECs and CEPs in localized prostate cancer.
METHODS: Ten consecutive patients with a histologic diagnosis of low-risk prostate adenocarcinoma were enrolled and received an intravenous infusion of ZOL at baseline (T0), 28 days (T28) and 56 days (T56). Blood samples were collected at the following times: T0 (before the first infusion of ZOL), T3 (72 h after the first dose), T28, T56 (both just before the ZOL infusion) and T84 (28 days after the last infusion of ZOL) and CEC/CEP levels were directly quantified by flow cytometry at all these time points.
RESULTS: Our analyses highlighted a significant reduction of mean percentage of CECs and CEPs after initiation of ZOL treatment [p = 0.014 (at day 3) and p = 0.012 (at day 84), respectively].
CONCLUSION: These preliminary results demonstrate that ZOL could exert an antiangiogenic effect in early prostate cancer through CEP and CEC modulation.

Related: Angiogenesis Inhibitors Bisphosphonates Zoledronic acid (Zometa)

Mavroidis P, Milickovic N, Cruz WF, et al.
Comparison of different fractionation schedules toward a single fraction in high-dose-rate brachytherapy as monotherapy for low-risk prostate cancer using 3-dimensional radiobiological models.
Int J Radiat Oncol Biol Phys. 2014; 88(1):216-23 [PubMed] Related Publications
PURPOSE: The aim of the present study was the investigation of different fractionation schemes to estimate their clinical impact. For this purpose, widely applied radiobiological models and dosimetric measures were used to associate their results with clinical findings.
METHODS AND MATERIALS: The dose distributions of 12 clinical high-dose-rate brachytherapy implants for prostate were evaluated in relation to different fractionation schemes. The fractionation schemes compared were: (1) 1 fraction of 20 Gy; (2) 2 fractions of 14 Gy; (3) 3 fractions of 11 Gy; and (4) 4 fractions of 9.5 Gy. The clinical effectiveness of the different fractionation schemes was estimated through the complication-free tumor control probability (P+), the biologically effective uniform dose, and the generalized equivalent uniform dose index.
RESULTS: For the different fractionation schemes, the tumor control probabilities were 98.5% in 1×20 Gy, 98.6% in 2×14 Gy, 97.5% in 3×11 Gy, and 97.8% in 4×9.5 Gy. The corresponding P+ values were 88.8% in 1×20 Gy, 83.9% in 2×14 Gy, 86.0% in 3×11 Gy, and 82.3% in 4×9.5 Gy. With use of the fractionation scheme 4×9.5 Gy as reference, the isoeffective schemes regarding tumor control for 1, 2, and 3 fractions were 1×19.68 Gy, 2×13.75 Gy, and 3×11.05 Gy. The optimum fractionation schemes for 1, 2, 3, and 4 fractions were 1×19.16 Gy with a P+ of 91.8%, 2×13.2 Gy with a P+ of 89.6%, 3×10.6 Gy with a P+ of 88.4%, and 4×9.02 Gy with a P+ of 86.9%.
CONCLUSIONS: Among the fractionation schemes 1×20 Gy, 2×14 Gy, 3×11 Gy, and 4×9.5 Gy, the first scheme was more effective in terms of P+. After performance of a radiobiological optimization, it was shown that a single fraction of 19.2 to 19.7 Gy (average 19.5 Gy) should produce at least the same benefit as that given by the 4×9.5 Gy scheme, and it should reduce the expected total complication probability by approximately 40% to 55%.

Related: Brachytherapy

Lo AC, Morris WJ, Lapointe V, et al.
Prostate-specific antigen at 4 to 5 years after low-dose-rate prostate brachytherapy is a strong predictor of disease-free survival.
Int J Radiat Oncol Biol Phys. 2014; 88(1):87-93 [PubMed] Related Publications
PURPOSE: To determine (1) the prognostic utility of prostate-specific antigen (PSA) concentration at 45 to 60 months (48mPSA) after low-dose-rate prostate brachytherapy (LDR-PB); (2) the predictors of 48mPSA; and (3) the prognostic utility of directional trends between PSA levels at 24, 36, and 48 months after LDR-PB.
METHODS AND MATERIALS: Between 1998 and 2008, 2223 patients with low- and intermediate-risk prostate cancer received LDR-PB monotherapy. A cohort of 1434 of these patients was identified with a documented 48mPSA and no evidence of disease relapse prior to the 48mPSA. In addition, a subset of this cohort (n=585) was identified with ≥72 months of follow-up and documented PSA values at both 24 and 36 months after implantation.
RESULTS: Median follow-up time was 76 months. Eight-year Kaplan-Meier disease-free survival (DFS) rates were 100% vs 73.4% for patients with 48mPSA≤0.2 vs those with >0.2 ng/mL; 99.1% versus 53.8% for a 48mPSA threshold of ≤0.4 versus >0.4 ng/mL, respectively; and 97.3% versus 0% for a threshold of ≤1.0 versus >1.0 ng/mL, respectively. On multivariate analysis, the only factor predictive of DFS was 48mPSA (P<.0001). On subset analysis (n=585), 29 patients had a PSA rise (defined as >0.2 ng/mL) between 24 and 36 months, 24 patients had a rise between 36 and 48 months, and 11 patients had rises over both intervals. Failure rates in these patients were 52%, 79%, and 100%, respectively. On multivariate analysis, initial PSA, androgen deprivation therapy, and dose to 90% of the prostate significantly correlated with 48mPSA but together accounted for only ∼5% of its total variance.
CONCLUSIONS: The 48mPSA after LDR-PB is highly predictive of long-term DFS. Patients with 48mPSA≤0.4 ng/mL had a <1% risk of disease relapse at 8 years, whereas all patients with 48mPSA>1.0 ng/mL relapsed. Consecutive PSA rises of >0.2 ng/mL from 24 to 36 months and from 36 to 48 months were also highly predictive of subsequent failure.

Related: Brachytherapy

Schveigert D, Valuckas KP, Kovalcis V, et al.
Significance of MMP-9 expression and MMP-9 polymorphism in prostate cancer.
Tumori. 2013 Jul-Aug; 99(4):523-9 [PubMed] Related Publications
BACKGROUND: The aim of the study was to assess the expression of the MMP-9 gene and -1562 C/T polymorphism in MMP-9 gene promoter in relation to clinicopathological parameters in predicting the clinical outcome of prostate cancer patients.
METHODS: A total of 82 patients with histopathologically diagnosed prostate cancer were enrolled in the study. MMP-9 gene expression was assessed by reverse transcription-PCR method. MMP-9 (-1562 C/T) polymorphism variants were determined by the polymerase chain reaction-based restriction fragment length polymorphism method.
RESULTS: MMP-9 expression and MMP-9 -1562 polymorphism variants in relation to disease pathological stage (P = 0.006; P <0.0001, respectively), as well as to prognostic group (P = 0.019; P <0.0001, respectively), were statistically significant. Only MMP-9 -1562 polymorphism variants in relation to tumor differentiation grade (P = 0.044) were found to be statistically significant. Positive MMP-9 gene expression was associated with 5-year survival rate of prostate cancer patients with pathological stage III (P = 0.036) and for the patients in prognostic group III (P = 0.012). Patients with tumor differentiation grade G2 and with the identified CC variant had a significantly longer survival time than patients with the identified TT variant (P = 0.007).
CONCLUSIONS: MMP-9 gene expression and MMP-9 -1562 polymorphism variants were associated with prostate cancer pathological stage and prognostic group. MMP-9 -1562 polymorphism CC variant was associated with prostate cancer tumor differentiation grade. Five-year survival analysis showed the relationship between MMP-9 gene expression and pathological stage III, as well as prognostic group III, whereas MMP-9 -1562 polymorphism variants, with tumor differentiation grade G2.

Related: MMP9: matrix metallopeptidase 9

Valeriani M, Carnevale A, Osti MF, et al.
Hypofractionated intensity-modulated simultaneous integrated boost and image-guided radiotherapy in the treatment of high-risk prostate cancer patients: a preliminary report on acute toxicity.
Tumori. 2013 Jul-Aug; 99(4):474-9 [PubMed] Related Publications
AIMS AND BACKGROUND: To evaluate acute toxicity of hypofractionated intensity-modulated radiotherapy with simultaneous integrated boost and image-guided radiotherapy in the treatment of high-risk prostate cancer patients.
METHODS: Between November 2009 and March 2012, 59 patients with high-risk prostate cancer were enrolled. The eclipse inverse planning system (Varian) was used to calculate an IMRT plan with simultaneous integrated boost, delivering 68.75 Gy (2.75 Gy per fraction) to the prostate, 55 Gy (2.2 Gy per fraction) to the seminal vesicles and positive nodes, and 45 Gy (1.8 Gy per fraction) to the pelvis, 4 fractions per week, 25 fractions. Prior to each treatment, patients underwent a kilo-voltage cone-beam CT performing an image-guided radiation therapy (IGRT). All patients were submitted to neoadjuvant, concomitant and adjuvant hormone therapy.
RESULTS: The median follow-up for all patients was 13 months (range, 3-28). At the last follow-up, no grade 3 or 4 side effect was observed. Toxicity occurred as follows during the treatment: grade 1 and 2 gastrointestinal toxicity 5.2% and 6.9%, respectively; grade 1 and 2 genitourinary toxicity 24.1% and 1.7%, respectively. Only 1.7% of the patients developed grade 3 genitourinary toxicity. No grade 3 gastrointestinal toxicity was observed.
CONCLUSIONS: The present study demonstrated that 4/w hypofractionated intensity-modulated radiotherapy with simultaneous integrated boost and image-guided radiotherapy in patients with high-risk prostate cancer is feasible and safe. Low acute toxicity rates were verified. Longer follow-up is needed to evaluate the outcomes in terms of late toxicity and survival.

Iwama K, Yamazaki H, Nishimura T, et al.
Analysis of intrafractional organ motion for patients with prostate cancer using soft tissue matching image-guided intensity-modulated radiation therapy by helical tomotherapy.
Anticancer Res. 2013; 33(12):5675-9 [PubMed] Related Publications
AIM: To analyze an intrafractional organ motion for patients with prostate cancer using soft tissue matching by megavolt computed tomography (MVCT) images during the course of image-guided intensity-modulated radiotherapy (IGRT-IMRT) using helical tomotherapy.
PATIENTS AND METHODS: Data from a total of 10 patients with prostate cancer who received IGRT-IMRT were analyzed, and MVCT images were acquired before and after radiation therapy. Intra-fractional movement and PTV margins for soft tissue matching were calculated by comparing treatment planning images with 740 MVCT images for right-left (RL), superior-inferior (SI), and anteroposterior (AP) dimensions. A total of 74 Gy/37 fractions were administered. A margin to compensate for these variations was calculated using the van Herk's equation.
RESULTS: The intrafractional motion was 0.03 (-1.3 to 1.4) ±0.39 mm in the RL dimension, 0.08 (-1.8 to 0.28) ±0.73 mm in the SI dimension, and 0.52 (-1.8 to 1.8) ±0.63 mm in the AP dimension. The required PTV margin was 0.60 mm, 1.10 mm, and 0.78 mm in the RL, SI, and AP dimensions, respectively. Only one patient exhibited a deviation greater than 5 mm only once in 37 fractions (1/370=0.2%) caused by anal contraction.
CONCLUSION: The PTV margin in soft tissue matching IGRT-IMRT by helical tomotherapy for a patient with prostate cancer was 3 mm or less, and our tentative PTV margin of 3-5 mm is sufficient for most patients, if adequate instruction for avoiding anal contraction is given.

Nishimura T, Yamazaki H, Aibe N, et al.
Exceptionally high incidence of grade 2-3 late rectal toxicity in patients with prostate cancer receiving hypofractionated (2.2 Gy) soft tissue-matched image-guided intensity-modulated radiotherapy.
Anticancer Res. 2013; 33(12):5507-10 [PubMed] Related Publications
AIM: To evaluate the incidence of rectal toxicity in patients undergoing hypofractionated (2.2 Gy) image-guided intensity-modulated radiotherapy (IG-IMRT) for prostate cancer.
PATIENTS AND METHODS: We examined 117 consecutive patients with prostate cancer who underwent IG-IMRT from June 2007 to July 2009. The median follow-up time was 32 months (range 20-42 months). The clinical target volume (CTV) consisted of the prostate and seminal vesicles, and the planning target volume (PTV) consisted of the CTV plus a 5-mm expansion, not avoiding the rectum. The PTV received a dose of 72.6-74.8 Gy in 33-34 fractions (2.2 Gy/fraction). Megavoltage computed tomographic (MVCT) scans were performed before each treatment and corrected to the registered position for planning CT scans using prostate soft tissue matching.
RESULTS: Late rectal bleeding of grades 1, 2, and 3 (Common Terminology Criteria for Adverse Events v3.0) occurred in 19 (16%), five (4%), and four (3%) patients, respectively. Late urinary toxicities of grades 1 and 2 occurred in five (4.3%) and eight (6.8%) patients, respectively. We found a paradoxically increased risk of rectal bleeding with more accurate irradiation of the rectum using soft tissue matching, whereas only a small percentage was reported in other IMRT series.
CONCLUSION: IG-IMRT using daily MVCT scans allowed for exact dose delivery, which resulted in an increased rectal dose and exceptionally high incidence of rectal toxicity. Therefore, careful PTV contouring and dose schedule settings are important for safe administration of IG-IMRT.

Moritz R, Ellinger J, Nuhn P, et al.
DNA hypermethylation as a predictor of PSA recurrence in patients with low- and intermediate-grade prostate cancer.
Anticancer Res. 2013; 33(12):5249-54 [PubMed] Related Publications
BACKGROUND: DNA CpG island hypermethylation causes gene silencing and is a common event in prostate carcinogenesis and progression. We investigated its role as a possible prognostic marker in patients with PCA Gleason score ≤7.
PATIENTS AND METHODS: We used a quantitative, methylation-specific PCR to analyze methylation patterns at five gene loci (APC, GSTP1, PTGS2, RARbeta and TIG1) in 84 prostate cancer (PCA) tissues (Gleason Score ≤7). Methylation was correlated with established clinico-pathological parameters (preoperative PSA, pathological Gleason score, extraprostatic extension, seminal vesicle penetration, lymph node involvement, surgical margins and age) and PSA recurrence.
RESULTS: DNA hypermethylation was frequently detected at APC (95.2%), GSTP1 (84.5%), PTGS2 (100%), RAR-beta (81.0%) and TIG1 (95.2%). DNA hypermethylation was correlated with Gleason Score (p=0.027; PTGS2) and lymph node involvement (p=0.024; RARbeta). High methylation levels at RARbeta (p=0.023) was a significant predictor of PSA recurrence following radical prostatectomy.
CONCLUSION: The analysis of DNA hypermethylation provides prognostic information in prognosis of low- and intermediate-grade PCA.

Tsaur I, Renninger M, Hennenlotter J, et al.
Reliable housekeeping gene combination for quantitative PCR of lymph nodes in patients with prostate cancer.
Anticancer Res. 2013; 33(12):5243-8 [PubMed] Related Publications
BACKGROUND: To reliably compare the results of gene expression studies, the expression of the target gene should be normalized to the expression of a reference gene. For lymph node metastases of prostate cancer, no data on polymerase chain reaction (PCR) normalization have yet been reported. We aimed to determine the most reliable reference gene combination for this purpose in patients with prostate cancer.
MATERIALS AND METHODS: Ten histologically- positive and ten negative lymph nodes of patients with prostate cancer were analyzed respectively. Expression of six candidate reference genes was comparatively assessed with quantitative Real-time PCR. The most stably-expressed gene combination was determined with geNorm software version 3.4.
RESULTS: Hypoxanthine phosphoribosyltransferase-1 (HPRT1) and TATA box binding protein (TPB) were found to be the most stably expressed genes, with their combination having an expression stability value of M=0.17.
CONCLUSION: Gene combination HPRT1 and TPB has the potential to be utilized for normalization in gene profiling assessment of metastatic and non-metastatic pelvic lymph node tissue from patients with prostate cancer.

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