Neil Eric Fleshner

Despite the considerable number of studies investigating the Mediterranean diet in prostate cancer (PCa) etiology, very few focused on cancer survival. We assessed the pre-diagnostic diet and physical activity in a cohort of 777 men with PCa diagnosed between 1995 and 2002 in north-eastern Italy; adherence to the Mediterranean diet was evaluated through the Mediterranean Diet Score (MDS). Hazard ratios (HR) of death with confidence intervals (CI) were estimated using the Cox model, adjusting for potential confounders. During 10 years of follow-up, 208 patients (26.8%) died, 75 (9.7%) due to PCa. Patients reporting MDS ≥ 5 showed a higher overall survival than those with MDS < 5 (HR = 0.74; 95% CI: 0.56–0.99). Although high physical activity was not significantly associated with overall survival (HR = 0.79; 95% CI: 0.59–1.07), the HR for all-cause death was the lowest (HR = 0.58; 95% CI: 0.38–0.90) for men reporting MDS ≥ 5 and high physical activity compared to those reporting MDS < 5 and low/moderate physical activity. No association emerged for PCa specific survival. Study findings support the beneficial impact of pre-diagnostic adherence to the Mediterranean diet and physical activity on overall survival; they are mainly driven by risk reduction in non-prostate cancer mortality, which however accounts for about 80% of death in men with PCa.

Objectives: To investigate whether methylphenidate can alleviate fatigue, as measured by the F unctional A ssessment of C ancer T herapy: Fatigue subscale, in men with prostate cancer ( PCa ) treated with a luteinizing hormone‐releasing hormone ( LHRH ) for a minimum of 6 months, and to assess changes in global fatigue and quality of life ( QoL ) as measured by the B ruera G lobal F atigue S everity S cale ( BFS ) and the M edical O utcomes S tudy 36‐ I tem S hort‐ F orm H ealth S urvey ( SF ‐36), respectively. Participants and Methods: We performed a single‐centre, randomised, double‐blind, placebo‐controlled trial with the aim of recruiting 128 participants. Men treated with a LHRH agonist for PCa were screened between F ebruary 2008 and J une 2012 for fatigue at our outpatient clinics using the BFS . Participants were randomised to receive either 10 mg daily of methylphenidate or placebo. Change in fatigue levels and in SF ‐36 scores between both groups were compared using linear regression, adjusted for baseline scores. Results: The study was closed prematurely because of poor accrual. Of the 790 subjects screened, 24 men were randomised to methylphenidate or placebo (12 per group). After 10 weeks, the improvement in mean [ sd ] fatigue score was greater in the methylphenidate than in the placebo arm (+7.7 [7.7] vs +1.4 [7.6]; P = 0.022). The within‐group analysis showed a significant improvement in fatigue scores in the methylphenidate arm ( P = 0.008) but not in the placebo arm ( P = 0.82). The use of methylphenidate also resulted in a significantly greater improvement in QoL as measured by the physical and mental component summary scores than did the use of placebo ( P = 0.04 for both component scores). Conclusions: Our findings support the beneficial effect of methylphenidate on fatigue and QoL among men with LHRH ‐induced fatigue. Clinicians should be aware of these benefits and should consider discussing these findings with patients who have high levels of fatigue.

Introduction: Results from randomized trials are least prone tosystematic bias and represent the highest level of evidence in medicalpractice. We carried out a demographic analysis examiningrandomized controlled trials (RCTs) in prostate cancer. Particularemphasis was placed on newly conducted phase II/III RCTsbetween January 1997 and March 2006.Methods: We searched the MEDLINE database using the heading“prostate neoplasms” between January 1997 and March 2006. Theresults were then crossed with the MeSHs “Clinical trial.mp. ORclinical trial.pt. OR random:.mp. OR tu.xs;” this cross-checkingis considered an optimal search strategy for detecting RCTs inMEDLINE® literature. The search yielded 7831 articles in totalfor the defined period. Of this total number, 7314 articles weremanually analyzed and excluded as they did not represent RCTs.The qualifying 517 articles were then analyzed with emphasis onmodality of therapy, cohort size, principal author, participatingcountry and journal type.Results: Among the 517 randomized trials, most trials investigatedmedical therapies (42.7%). This was followed by diagnostic studies(13.2%), while the remaining categories made up 44.1%. A trendtowards more completed RCTs is noted in the later years of thecohort. Cohort sizes were generally greater than 100 participants(63.1%). Urologists were the lead investigators in 48.2% of thetrials. Trials were largely conducted in Europe and the United States(43.1% and 38.3%, respectively). About 7% of studies were basedin Canada. Articles were generally published in surgical journals(48.4%), followed by medical journals (36.9%).Conclusions: Given that initial searches yielded nearly 8000 articleslisted as RCTs in prostatic oncology, only a small percentage(5.4% to 8.6%) of these were actually RCTs which reported novelresults. Most of the published data were either review articles orcommentaries. It is abundantly clear that new recruitment strategiesneed to be developed to encourage patients to enrol in RCTs andthat such studies need to be undertaken in urologic oncology toprovide definitive answers to the abundant and unanswered questionsin urologic oncology.Introduction : Les résultats d’essais randomisés sont les moinssujets à une partialité d’emblée et représentent le plus haut niveaude données probantes en médecine. Nous avons mené une analysedémographique des essais contrôlés et randomisés (ECR) sur lecancer de la prostate, en portant attention plus particulièrementaux plus récents essais de phase II/III, menés entre janvier 1997et mars 2006.Méthodologie : Nous avons interrogé la base de données MEDLINEavec le titre « prostate neoplasms » pour la période entre janvier1997 et mars 2006. Les résultats ont ensuite été recoupés avec unerecherche dans la base de données MeSH avec les clés « Clinicaltrial.mp. OU clinical trial.pt. OU random:.mp. OU tu.xs »; cerecoupement est vu comme une stratégie optimale de recherchepour cerner les ECR dans les articles classés dans MEDLINE. Larecherche a produit un total de 7 831 articles pour la périodedéfinie. De ce nombre, 7 314 articles ont été analysés manuellementet exclus puisqu’ils ne traitaient pas d’ECR. Les 517 articlesadmissibles ont ensuite été analysés, avec une attention particulièreaux modalités de traitement, à la taille de la cohorte, à l’auteurprincipal, au pays participant et au type de périodique.Résultats : Sur les 517 essais randomisés, la plupart examinaient destraitements médicamenteux (42,7 %). Venaient ensuite les étudesdiagnostiques (13,2 %), alors que le reste (44,1 %) entrait dansles autres catégories. On a noté une tendance vers une complétudeplus élevée des ECR dans les dernières années de la période.Les cohortes comptaient habituellement plus de 100 participants(63,1 %). Les chercheurs principaux étaient des urologues dans48,2 % des essais. La grande majorité des essais ont été menésen Europe et aux États-Unis (43,1 % et 38,3 %, respectivement).Environ 7 % des études étaient menées au Canada. Règle générale,les articles étaient publiés dans des revues en chirurgie (48,4 %),suivies des revues médicales (36,9 %).Conclusions : Comme les recherches initiales ont généré près de8 000 articles classés comme des ECR en oncologie prostatique,seul un petit pourcentage (5,4 % à 8,6 %) de ces articles était enfait des ECR signalant des résultats inédits. La majorité des donnéesétaient publiées sous forme d’articles de synthèse ou de commentaires.Il est très clair que de nouvelles stratégies de recrutement doivent être établies pour encourager les patients à s’inscrire aux ECR et que de tels essais doivent être entrepris en oncologie urologique afin de fournir des réponses claires aux nombreusesquestions qui restent à élucider dans le domaine.

Prostate cancer (PCa) is the most common internal malignancy and the third most frequent cause of cancer death in men. It is estimated that in each week of 2009 over 490 Canadian men were diagnosed with PCa, and 85 will have died from the disease. The introduction of PSA (prostate-specific antigen) screening tests has contributed in part, to men being diagnosed and treated at an early stage. Chemoprevention is a strategy whereby patients are administered drugs, vitamins, or other agents to prevent/reduce the risk of cancer progression and/ or delay the development of its recurrence thereby decreasing patient morbidity and mortality. PCa has a long latency period, thereby offering plenty of opportunity to intervene through the implementation of chemopreventive therapies. A large body of epidemiologic evidence, together with published data from in vivo and in vitro studies, strongly supports relationships between dietary constituents and the risk of prostate cancer. This article aims to review the diverse aspects of chemoprevention including the benefit of both macro- and micronutrients that have been implicated in prostate cancer prevention. In addition we discuss perspectives on the putative mechanisms of selected chemopreventive agents and highlight several clinical studies using specific chemopreventive interventions.

Stage I seminoma represents the paradigm of a curable malignancy, with survival of 100% an expected outcome no matter what treatment option is chosen. However, consensus has not been reached among urologists and oncologists regarding the optimal postoperative management in men with clinical stage I testicular seminoma. Currently, men are offered active surveillance, adjuvant radiation therapy, or single-agent chemotherapy. Active surveillance is associated with an 80% chance of no relapse, with all such events salvageable. Radiotherapy has an almost universal cure rate but has the potential for long-term toxicities and an overtreatment rate of about 80%. Chemotherapy efficacy and toxicity data are still immature. Recent guidelines recognize that the options of surveillance, chemotherapy, and radiotherapy are appropriate in the treatment of patients with clinical stage I seminoma. We believe active surveillance to be the best option, then radiotherapy (considering the efficacy and safety data), with single-agent chemotherapy emerging as a possible alternative.

Prostate cancer is the most common male malignancy and the second or third leading cause of cancer death among men in the West. The descriptive epidemiology of prostate cancer suggests that it is a preventable disease. Prevention has the theoretical advantage of not only saving lives, but also reduce the morbidity of radical prostate cancer therapy. This article reviews the past, present, and future of prostate cancer prevention. In particular, the evidence and scientific data of a variety of prevention strategies are reviewed. Strategies reviewed include dietary fat reduction and supplementation with vitamins D and E, and selenium. Dietary intake of soy, green tea, and tomato‐rich products (lycopene) are also reviewed. Data regarding pharmacological intervention with cyclo‐oxygenease inhibitors, antiestrogens, and in particular 5‐alpha reductase inhibitors are reviewed. The results of the Prostate Cancer Prevention Trial including the controversy surrounding higher‐grade cancers among men randomized to finasteride are also summarized. Finally, a variety of trial designs as well as a roster of current phase 2 trials are presented. Probably no cancer is being investigated more thoroughly in the context of prevention as prostate cancer in 2007. Definitive answers to pivotal phase 3 trials will be available in the coming 2 to 7 years. Cancer 2007. © 2007 American Cancer Society.

The role of hormonal therapy in the management of prostate cancer has been known for almost half a century. However, many controversies exist regarding the place and timing of androgen deprivation therapy. An increasing spectrum for the use of androgen deprivation therapy has been assessed, including multimodal treatment with radiation therapy. New approaches to androgen deprivation have been explored, including LHRH (luteinizing hormone-releasing hormone) antagonists and improved depot formulations. Recent evidence about the chemo-sensitivity of prostate cancer has opened avenues for treatment of hormone refractory disease and the combination of hormonal and chemotherapy is being studied at various stages of the disease. We explore the evidence, controversies and future of androgen deprivation therapy and critically reexamine the dogmas surrounding hormone therapy for prostate cancer.