Prostate Cancer Unit Initiative in Europe: A position paper by the European School of Oncology.

The Prostate Cancer Programme of the European School of Oncology developed the concept of specialised interdisciplinary and multiprofessional prostate cancer care to be formalized in Prostate Cancer Units (PCU). After the publication in 2011 of the collaborative article "The Requirements of a Specialist Prostate Cancer Unit: A Discussion Paper from the European School of Oncology", in 2012 the PCU Initiative in Europe was launched. A multiprofessional Task Force of internationally recognized opinion leaders, among whom representatives of scientific societies, and patient advocates gathered to set standards for quality comprehensive prostate cancer care and designate care pathways in PCUs. The result was a consensus on 40 mandatory and recommended standards and items, covering several macro-areas, from general requirements to personnel to organization and case management. This position paper describes the relevant, feasible and applicable core criteria for defining PCUs in most European countries delivered by PCU Initiative in Europe Task Force.

Could machine learning improve the prediction of pelvic nodal status of prostate cancer patients? Preliminary results of a pilot study.

We tested and compared performances of Roach formula, Partin tables and of three Machine Learning (ML) based algorithms based on decision trees in identifying N+ prostate cancer (PC). 1,555 cN0 and 50 cN+ PC were analyzed. Results were also verified on an independent population of 204 operated cN0 patients, with a known pN status (187 pN0, 17 pN1 patients). ML performed better, also when tested on the surgical population, with accuracy, specificity, and sensitivity ranging between 48-86%, 35-91%, and 17-79%, respectively. ML potentially allows better prediction of the nodal status of PC, potentially allowing a better tailoring of pelvic irradiation.

Dépistage du cancer de la prostate: partager avec le patient les incertitudes [Sharing uncertainties of prostate cancer screening].

The decision of whether our patients should undergo prostate cancer screening with the prostate specifc antigen (PSA) test remains daunting. The role of the primary care doctor is to help men decide between a potential decrease in mortality from a slow evolving but sometimes lethal cancer, and the risk of diagnosing and treating cancers that would have otherwise been indolent and asymptomatic. We can structure our discussions with three steps: choice, option, and decision making. A decision aid, such as the one that we have adapted and simplifed from the Collège des médecins du Québec, can help with this complex decision.

Calidad de vida y cáncer de próstata: un programa progresivo de fuerza-resistencia = Quality of life and prostate cancer: a progressive resistance strength program

This article presents the design and implementation of a progressive resistance strength program adapted to prostate cancer. The initial model corresponds to the guide of the American College Sports Medicine Position Stand (ACSM, 2009). This program includes the most habitual symptoms related to the illness and its treatments. The study design is quasi-experimental. The sample is 33 subjects in treatment phase. Study variables are tumour classification TNM, anthropometric measures, resistance strength, hypertension, fatigue, incontinence, pain and quality of life. After 24 weeks a significant improvement on resistance strength capacity is observed. This result is more consistent in lower extremities. Also improves hypertension, urinary incontinence, pain and quality of life. As conclusion, the improvement of the quality of life is mediated by the functional and physical capacity of the ill person

Accuracy of cognitive MRI-targeted biopsy in hitting prostate cancer-positive regions of interest.

PURPOSE: Prostate cancer (PCa) diagnosis relies on clinical suspicion leading to systematic transrectal ultrasound-guided biopsy (TRUSGB). Multiparametric magnetic resonance imaging (mpMRI) allows for targeted biopsy of suspicious areas of the prostate instead of random 12-core biopsy. This method has been shown to be more accurate in detecting significant PCa. However, the precise spatial accuracy of cognitive targeting is unknown. METHODS: Consecutive patients undergoing mpMRI-targeted TRUSGB with cognitive registration (MRTB-COG) followed by robot-assisted radical prostatectomy were included in the present analysis. The regions of interest (ROIs) involved by the index lesion reported on mpMRI were subsequently targeted by two experienced urologists using the cognitive approach. The 27 ROIs were used as spatial reference. Mapping on radical prostatectomy specimen was used as reference to determine true-positive mpMRI findings. Per core correlation analysis was performed. RESULTS: Forty patients were included. Overall, 40 index lesions involving 137 ROIs (mean ROIs per index lesion 3.43) were identified on MRI. After correlating these findings with final pathology, 117 ROIs (85 %) were considered as true-positive lesions. A total of 102 biopsy cores directed toward such true-positive ROIs were available for final analysis. Cognitive targeted biopsy hit the target in 82 % of the cases (84/102). The only identified risk factor for missing the target was an anterior situated ROI (p = 0.01). CONCLUSION: In experienced hands, cognitive MRTB-COG allows for an accuracy of 82 % in hitting the correct target, given that it is a true-positive lesion. Anterior tumors are less likely to be successfully targeted.

A cast of shadow on adjuvant radiotherapy for prostate cancer: A critical review based on a methodological perspective.

OBJECTIVE: To perform a critical review focusing on the applicability in clinical daily practice of data from three randomized controlled trials (RCTs): SWOG 8794, EORTC 22911, and ARO/AUO 96-02. METHODS AND MATERIALS: An analytical framework, based on the identified population, interventions, comparators, and outcomes (PICO) was used to refine the search of the evidence from the three large randomized trials regarding the use of radiation therapy after prostatectomy as adjuvant therapy (ART). RESULTS: With regard to the inclusion criteria: (1) POPULATION: in the time since they were designed, in two among three trial (SWOG 8794 and EORTC 22911) patients had a detectable PSA at the time of randomization, thus representing de facto a substantial proportion of patients who eventually received salvage RT (SRT) at non-normalised PSA levels rather than ART. (2) INTERVENTIONS: although all the trials showed the benefit of postoperative ART compared to a wait-and-see approach, the dose herein employed would be now considered inadequate; (3) COMPARATORS: the comparison arm in all the 3 RCTs was an uncontrolled observation arm, where patients who subsequently developed biochemical failure were treated in various ways, with up to half of them receiving SRT at PSA well above 1ng/mL, a level that would be now deemed inappropriate; (4) OUTCOMES: only in one trial (SWOG 8794) ART was found to significantly improve overall survival compared to observation, with a ten-year overall survival rate of 74% vs. 66%, although this might be partly the result of imbalanced risk factors due to competing event risk stratification. CONCLUSIONS: ART has a high level of evidence due to three RCTs with at least 10-year follow-up recording a benefit in biochemical PFS, but its penetrance in present daily clinics should be reconsidered. While the benefit of ART or SRT is eagerly expected from ongoing randomized trials, a dynamic risk-stratified approach should drive the decisions making process.

"Hit the primary": A paradigm shift in the treatment of metastatic prostate cancer?

Patients with metastatic prostate cancer (PC) represent a heterogeneous group with survival rates varying between 13 and 75 months. The current standard treatment in this setting is hormonal therapy, with or without docetaxel-based chemotherapy. In the era of individualized medicine, however, maximizing treatment options, especially in long-term surviving patients with limited disease burden, is of capital importance. Emerging data, mainly from retrospective surgical series, show survival benefits in men diagnosed with metastatic PC following definitive therapy for the prostate. Whether the irradiation of primary tumor in a metastatic disease might improve the therapeutic ratio in association with systemic treatments remains investigational. In this scenario, modern radiation therapy (RT) can play a significant role owing to its intrinsic capability to act as a more general immune response modifier, as well as to the potentially better toxicity profile compared to surgery. Preclinical data, clinical experience, and challenges in local treatment in de novo metastatic PC are reviewed and discussed.

Prostate cancer screening in Switzerland: 20-year trends and socioeconomic disparities.

BACKGROUND: Despite important controversy in its efficacy, prostate cancer (PCa) screening has become widespread. Important socioeconomic screening disparities have been reported. However, trends in PCa screening and social disparities have not been investigated in Switzerland, a high risk country for PCa. We used data from five waves (from 1992-2012) of the population-based Swiss Health Interview Survey to evaluate trends in PCa screening and its association with socioeconomic indicators. METHODS: We used multivariable Poisson regression to estimate prevalence ratios (PR) and 95% Confidence Intervals (CI) adjusting for demographics, health status, and use of healthcare. RESULTS: The study included 12,034 men aged ≥50 years (mean age: 63.9). Between 1992 and 2012, ever use of PCa screening increased from 55.3% to 70.0% and its use within the last two years from 32.6% to 42.4% (p-value <0.05). Income, education, and occupational class were independently associated with PCa screening. PCa screening within the last two years was greater in men with the highest (>$6,000/month) vs. lowest income (≤$2,000) (46.5% vs. 38.7% in 2012, PR for overall period =1.29, 95%CI: 1.13-1.48). These socioeconomic disparities did not significantly change over time. CONCLUSIONS: This study shows that about half of Swiss men had performed at least one PCa screening. Men belonging to high socioeconomic status are clearly more frequently screened than those less favored. Given the uncertainty of the usefulness of PCa screening, men, including those with high socioeconomic status, should be clearly informed about benefits and harms of PCa screening, in particular, the adverse effect of over-diagnosis and of associated over-treatment.

Relationship between two year PSA nadir and biochemical recurrence in prostate cancer patients treated with iodine-125 brachytherapy

Objective To evaluate the relationship between two year PSA nadir (PSAn) after brachytherapy and biochemical recurrence rates in prostate cancer patients. Materials and Methods In the period from January 1998 to August 2007, 120 patients were treated with iodine-125 brachytherapy alone. The results analysis was based on the definition of biochemical recurrence according to the Phoenix Consensus. Results Biochemical control was observed in 86 patients (71.7%), and biochemical recurrence, in 34 (28.3%). Mean PSAn was 0.53 ng/ml. The mean follow-up was 98 months. The patients were divided into two groups: group 1, with two year PSAn < 0.5 ng/ml after brachytherapy (74 patients; 61.7%), and group 2, with two year PSAn ≥ 0.5 ng/ml after brachytherapy (46 patients; 38.3%). Group 1 presented biochemical recurrence in 15 patients (20.3%), and group 2, in 19 patients (43.2%) (p < 0.02). The analysis of biochemical disease-free survival at seven years, stratified by the two groups, showed values of 80% and 64% (p < 0.02), respectively. Conclusion Levels of two year PSAn ≥ 0.5 ng/ml after brachytherapy are strongly correlated with a poor prognosis. This fact may help to identify patients at risk for disease recurrence.

The role of transrectal ultrasound in the diagnosis of prostate cancer: new contributions

Objective: The present study was aimed at evaluating the contribution of transrectal prostate ultrasound in the screening for prostate neoplasias and in the guidance of prostate biopsies. Materials and Methods: Prospective study developed over a one-year period. All the patients with indication for prostate biopsy were evaluated. Regardless of PSA values, the patients underwent ultrasound in order to identify suspicious nodules (confirmed by two observers). Sextant biopsy was subsequently performed. In cases of finding suspicious nodules, an additional puncture directed to such nodules was done. Results: In a total of 155 cases the prevalence of malignancy was of 53%. Suspicious nodules were detected in 34 patients, and 25 where malignant (positive predictive value of 74%). The specificity and sensitivity for suspicious nodules were 88% and 31% respectively. Comparatively with the randomly obtained sextant specimens, the rate of findings of neoplasia was higher in the specimens obtained with puncture directed to the nodule (p = 0.032). No statistically significant difference was observed in the Gleason score for both types of specimens (p = 0.172). Conclusion: The high positive predictive value and the high rate of findings of neoplasia in specimens of suspicious nodules should be taken into consideration in the future. The authors suggest a biopsy technique similar to the one described in the present study (sextant biopsy plus puncture directed to the suspicious nodule).

Strategies to evaluate the impact of rectal volume on prostate motion during three-dimensional conformal radiotherapy for prostate cancer

Abstract Objective: To evaluate the rectal volume influence on prostate motion during three-dimensional conformal radiotherapy (3D-CRT) for prostate cancer. Materials and Methods: Fifty-one patients with prostate cancer underwent a series of three computed tomography scans including an initial planning scan and two subsequent scans during 3D-CRT. The organs of interest were outlined. The prostate contour was compared with the initial CT images considering the anterior, posterior, superior, inferior and lateral edges of the organ. Variations in the anterior limits and volume of the rectum were assessed and correlated with prostate motion in the anteroposterior direction. Results: The maximum range of prostate motion was observed in the superoinferior direction, followed by the anteroposterior direction. A significant correlation was observed between prostate motion and rectal volume variation ( p = 0.037). A baseline rectal volume superior to 70 cm3 had a significant influence on the prostate motion in the anteroposterior direction ( p = 0.045). Conclusion: The present study showed a significant interfraction motion of the prostate during 3D-CRT with greatest variations in the superoinferior and anteroposterior directions, and that a large rectal volume influences the prostate motion with a cutoff value of 70 cm3. Therefore, the treatment of patients with a rectal volume > 70 cm3 should be re-planned with appropriate rectal preparation.

Investigation of CCL18 and A1AT as potential urinary biomarkers for bladder cancer detection

BACKGROUND: In this study, we further investigated the association of two biomarkers, CCL18 and A1AT, with bladder cancer (BCa) and evaluated the influence of potentially confounding factors in an experimental model. METHODS: In a cohort of 308 subjects (102 with BCa), urinary concentrations of CCL18 and A1AT were assessed by enzyme-linked immunosorbent assay (ELISA). In an experimental model, benign or cancerous cells, in addition to blood, were added to urines from healthy controls and analyzed by ELISA. Lastly, immunohistochemical staining for CCL18 and A1AT in human bladder tumors was performed. RESULTS: Median urinary protein concentrations of CCL18 (52.84 pg/ml vs. 11.13 pg/ml, p < 0.0001) and A1AT (606.4 ng/ml vs. 120.0 ng/ml, p < 0.0001) were significantly elevated in BCa subjects compared to controls. Furthermore, the addition of whole blood to pooled normal urine resulted in a significant increase in both CCL18 and A1AT. IHC staining of bladder tumors revealed CCL18 immunoreactivity in inflammatory cells only, and there was no significant increase in these immunoreactive cells within benign and cancerous tissue and no association with BCa grade nor stage was noted. A1AT immunoreactivity was observed in the cytoplasm of epithelia cells and intensity of immunostaining increased with tumor grade, but not tumor stage. CONCLUSIONS: Further development of A1AT as a diagnostic biomarker for BCa is warranted.

Multidrug resistance protein 1 localization in lipid raft domains and prostasomes in prostate cancer cell lines

Background: One of the problems in prostate cancer (CaP) treatment is the appearance of the multidrug resistance phenotype, in which ATP-binding cassette transporters such as multidrug resistance protein 1 (MRP1) play a role. Different localizations of the transporter have been reported, some of them related to the chemoresistant phenotype. Aim: This study aimed to compare the localization of MRP1 in three prostate cell lines (normal, androgen-sensitive, and androgen-independent) in order to understand its possible role in CaP chemoresistance. Methods: MRP1 and caveolae protein markers were detected using confocal microscopy, performing colocalization techniques. Lipid raft isolation made it possible to detect these proteins by Western blot analysis. Caveolae and prostasomes were identified by electron microscopy. Results: We show that MRP1 is found in lipid raft fractions of tumor cells and that the number of caveolae increases with malignancy acquisition. MRP1 is found not only in the plasma membrane associated with lipid rafts but also in cytoplasmic accumulations colocalizing with the prostasome markers Caveolin-1 and CD59, suggesting that in CaP cells, MRP1 is localized in prostasomes. Conclusion: We hypothesize that the presence of MRP1 in prostasomes could serve as a reservoir of MRP1; thus, taking advantage of the release of their content, MRP1 could be translocated to the plasma membrane contributing to the chemoresistant phenotype. The presence of MRP1 in prostasomes could serve as a predictor of malignancy in CaP

Multidrug resistance protein 1 localization in lipid raft domains and prostasomes in prostate cancer cell lines

Background: One of the problems in prostate cancer (CaP) treatment is the appearance of the multidrug resistance phenotype, in which ATP-binding cassette transporters such as multidrug resistance protein 1 (MRP1) play a role. Different localizations of the transporter have been reported, some of them related to the chemoresistant phenotype. Aim: This study aimed to compare the localization of MRP1 in three prostate cell lines (normal, androgen-sensitive, and androgen-independent) in order to understand its possible role in CaP chemoresistance. Methods: MRP1 and caveolae protein markers were detected using confocal microscopy, performing colocalization techniques. Lipid raft isolation made it possible to detect these proteins by Western blot analysis. Caveolae and prostasomes were identified by electron microscopy. Results: We show that MRP1 is found in lipid raft fractions of tumor cells and that the number of caveolae increases with malignancy acquisition. MRP1 is found not only in the plasma membrane associated with lipid rafts but also in cytoplasmic accumulations colocalizing with the prostasome markers Caveolin-1 and CD59, suggesting that in CaP cells, MRP1 is localized in prostasomes. Conclusion: We hypothesize that the presence of MRP1 in prostasomes could serve as a reservoir of MRP1; thus, taking advantage of the release of their content, MRP1 could be translocated to the plasma membrane contributing to the chemoresistant phenotype. The presence of MRP1 in prostasomes could serve as a predictor of malignancy in CaP