Evolution of Bosniak IIF Renal Cysts and Impact of the 2019 Bosniak Classification.

PURPOSE: The follow-up of Bosniak IIF renal cysts is associated with significant costs, radiation, and anxiety. Recent studies have suggested a risk of malignancy and upgrading lower than previously reported. We aimed to determine their clinical outcomes and to evaluate the impact of the 2019 Bosniak classification on the diagnosis of such lesions. MATERIALS AND METHODS: We identified all radiology reports with the diagnosis of a Bosniak IIF cyst at our institution between January 2000 and December 2018. Imaging was reviewed to confirm the diagnosis and determine progression based on the 2005 Bosniak classification. Radiological and clinical characteristics were established, and the 2019 Bosniak criteria were retrospectively applied. RESULTS: Out of 252 cysts reviewed, 55 (22%) were reclassified as Bosniak II upon revision using the 2005 Bosniak classification. A total of 181 Bosniak IIF cysts were included for final analysis. The median imaging follow-up was 50 months. Four (2.2%) cysts progressed to Bosniak III or IV. Five (2.8%) patients underwent surgical interventions, with only 1 malignant pathology being reported. No malignant progression was observed after 36 months. When applied to our cohort, the 2019 Bosniak classification would have led to a 76% decrease in Bosniak IIF diagnoses, with no increase in Bosniak III or IV diagnoses, and identical classification of the confirmed malignant pathology. CONCLUSIONS: Upgrading and malignancy rates among Bosniak IIF cysts was markedly lower than traditionally reported. No patient had a significant progression beyond 36 months. More than 20% of Bosniak IIF cysts were initially overdiagnosed. The 2019 Bosniak classification may help to reduce the overdiagnosis of Bosniak IIF lesions requiring follow-up.

The Triple-Tracer strategy against Metastatic PrOstate cancer (3TMPO) study protocol.

OBJECTIVE: To determine the prevalence of intra-patient inter-metastatic heterogeneity based on positron emission tomography (PET)/computed tomography (CT) in patients with metastatic castration-resistant prostate cancer (mCRPC) and to determine the prevalence of neuroendocrine disease in these patients and their eligibility for radioligand therapies (RLTs). PATIENTS AND METHODS: This multicentre observational prospective clinical study will include 100 patients with mCRPC from five Canadian academic centres. Patients with radiological or biochemical progression and harbouring at least three metastases by conventional imaging will be accrued. Intra-patient inter-metastatic heterogeneity will be determined with triple-tracer imaging using fluorine-18 fluorodeoxyglucose (18 F-FDG), gallium-68-(68 Ga)-prostate-specific membrane antigen (PSMA)-617 and 68 Ga-DOTATATE, which are a glucose analogue, a PSMA receptor ligand and a somatostatin receptor ligand, respectively. The 68 Ga-PSMA-617 and 18 F-FDG PET/CT scans will be performed first. If at least one PSMA-negative/FDG-positive lesion is observed, an additional PET/CT scan with 68 Ga-DOTATATE will be performed. The tracer uptake of individual lesions will be assessed for each PET tracer and patients with lesions presenting discordant uptake profiles will be considered as having inter-metastatic heterogeneous disease and may be offered a biopsy. EXPECTED RESULTS: The proposed triple-tracer approach will allow whole-body mCRPC characterisation, investigating the inter-metastatic heterogeneity in order to better understand the phenotypic plasticity of prostate cancer, including the neuroendocrine transdifferentiation that occurs during mCRPC progression. Based on 68 Ga-PSMA-617 or 68 Ga-DOTATATE PET positivity, the potential eligibility of patients for PSMA and DOTATATE-based RLT will be assessed. Non-invasive whole-body determination of mCRPC heterogeneity and transdifferentiation is highly innovative and might establish the basis for new therapeutic strategies. Comparison of molecular imaging findings with biopsies will also link metastasis biology to radiomic features. CONCLUSION: This study will add novel, biologically relevant dimensions to molecular imaging: the non-invasive detection of inter-metastatic heterogeneity and transdifferentiation to neuroendocrine prostate cancer by using a multi-tracer PET/CT strategy to further personalise the care of patients with mCRPC.

Does Time Spent on Active Surveillance Adversely Affect the Pathological and Oncologic Outcomes in Patients Undergoing Delayed Radical Prostatectomy?

PURPOSE: Pathological and oncologic outcomes of delayed radical prostatectomy following prostate cancer active surveillance are not well established. We determined the pathological and oncologic outcomes of favorable risk, Grade Group 1, prostate cancer managed with active surveillance and progressing to radical prostatectomy for clinically significant prostate cancer (Grade Group 2 or greater). MATERIALS AND METHODS: Between 1992 and 2015, 170 men with favorable risk prostate cancer underwent delayed radical prostatectomy for clinically significant prostate cancer (ASRP) at the Princess Margaret Cancer Centre. Pathological and oncologic outcomes of the ASRP cohort were compared with a matched cohort treated with up-front radical prostatectomy (405) immediately before surgery. Biochemical recurrence-free survival, overall survival and cancer specific survival were compared. We examined the association between delayed radical prostatectomy and adverse pathology at radical prostatectomy and biochemical recurrence using logistic and Cox regression analyses, respectively. RESULTS: Median time spent on active surveillance before radical prostatectomy was 31.0 months. At radical prostatectomy pT3 (extraprostatic extension, seminal vesicle invasion), positive surgical margin and pN1 rates were comparable between the 2 cohorts. Median followup after radical prostatectomy was 5.6 years. The 5-year biochemical recurrence-free survival rate in the ASRP cohort and up-front radical prostatectomy cohort were 85.8% and 82.4%, respectively (p=0.38). Overall survival and cancer specific survival were comparable between the 2 groups. Delayed radical prostatectomy was not associated with adverse pathological outcomes and biochemical recurrence on regression analyses. CONCLUSIONS: Curative intent radical prostatectomy after a period of active surveillance results in excellent pathological and oncologic outcomes at 5 years. A period of active surveillance does not result in inferior outcomes compared to patients with similar risk characteristics undergoing up-front radical prostatectomy.

Management of complex renal cysts in Canada: results of a survey study.

BACKGROUND: Bosniak III and IV cysts have a high risk of malignancy and have traditionally been managed surgically. However, growing evidence suggests that many can be managed by active surveillance. The main objective of this study was to characterize the use of surveillance in the management of complex renal cysts. METHODS: A web-based survey was sent to all registered, active members of the Canadian Urological Association (N = 583) in October 2018. RESULTS: The survey response rate was 24.7%. Management of Bosniak III cysts varied considerably. A large proportion of respondents (33.1%) offered active surveillance in > 50% of cases. Only 13.7% of respondents reported never or rarely (< 5% of cases) offering surveillance. In contrast, for Bosniak IV cysts, 60.1% of urologists never or rarely offered surveillance, while only 10.1% offer it in > 50% of cases. A significantly greater proportion of academic urologists, compared to non-academic urologists, viewed surveillance as a management option for patients with a Bosniak III or IV cyst. The most commonly reported barriers to a greater adoption of surveillance were concerns regarding its oncologic safety, the lack of data to support surveillance in this population, and the lack of triggers for discontinuation of active surveillance and intervention. CONCLUSIONS: Despite active surveillance being included as a management option in guidelines, many Canadian urologists are reluctant to offer surveillance to patients with Bosniak III or IV cysts. Practice patterns are heterogeneous among those offering surveillance. High-quality studies are required to better define the benefits and risks of cystic renal mass surveillance.

Combined genetic and epigenetic alterations of the TERT promoter affect clinical and biological behavior of bladder cancer.

In urothelial bladder cancer (UBC), risk stratification remains an important unmet need. Limitless self-renewal, governed by TERT expression and telomerase activation, is crucial for cancer progression. Thus, telomerase activation through the interplay of mutations (TERTpMut ) and epigenetic alterations in the TERT promoter may provide further insight into UBC behavior. Here, we investigated the combined effect of TERTpMut and the TERT Hypermethylated Oncological Region (THOR) status on telomerase activation and patient outcome in a UBC international cohort (n = 237). We verified that TERTpMut were frequent (76.8%) and present in all stages and grades of UBC. Hypermethylation of THOR was associated with higher TERT expression and higher-risk disease in nonmuscle invasive bladder cancers (NMIBC). TERTpMut alone predicted disease recurrence (HR: 3.18, 95%CI 1.84 to 5.51, p < 0.0001) but not progression in NMIBC. Combined THORhigh /TERTpMut increased the risk of disease recurrence (HR 5.12, p < 0.0001) and progression (HR 3.92, p = 0.025). Increased THOR hypermethylation doubled the risk of stage progression of both TERTpwt and TERTpMut NMIBC. These results highlight that both mechanisms are common and coexist in bladder cancer and while TERTpMut is an early event in bladder carcinogenesis THOR hypermethylation is a dynamic process that contributes to disease progression. While the absence of alterations comprises an extremely indolent phenotype, the combined genetic and epigenetic alterations of TERT bring additional prognostic value in NMIBC and provide a novel insight into telomere biology in cancer.

Risk of Bone Fractures Following Urinary Intestinal Diversion: A Population Based Study.

PURPOSE: Patients with bladder cancer who undergo intestinal urinary diversion may be at increased risk for bone fractures thought to be secondary to chronic metabolic acidosis and ensuing bone loss. Our main objective was to assess whether patients who undergo intestinal urinary diversion are at increased risk for fracture. MATERIALS AND METHODS: Patients who underwent intestinal urinary diversion between 1994 and 2014 in Ontario, Canada were identified using linked administrative databases. Patients were categorized as undergoing diversion for bladder cancer or nonbladder cancer causes and matched 4:1 to a healthy cohort. We determined incidence rates of the incidence of fractures per 100 person-years. Multivariable Cox proportional hazards models were used to evaluate the impact of intestinal urinary diversion on the risk of fracture. RESULTS: Overall 4,301 patients with and 907 without bladder cancer underwent intestinal urinary diversion. The fracture incidence rate was significantly greater in the bladder cancer and nonbladder cancer cohorts compared to respective matched controls. In the bladder cancer cohort vs matched controls there were 4.41 vs 2.63 fractures per 100 person-years and in the nonbladder cancer cohort vs matched controls there were 5.67 vs 3.51 fractures per 100 person-years (each p <0.001). On multivariable analysis patients who underwent intestinal urinary diversion for bladder cancer or nonbladder cancer reasons had significantly shorter fracture-free survival compared to the respective matched cohorts (HR 1.48, IQR 1.35-1.63, and HR 1.48, IQR 1.31-1.69, respectively). CONCLUSIONS: Our results demonstrated that regardless of age patients with intestinal urinary diversion are at increased risk for bone fractures compared to the general population. Our findings are in line with previous reports and support the need for bone health monitoring.

Is Routine Renal Tumor Biopsy Associated with Lower Rates of Benign Histology following Nephrectomy for Small Renal Masses?

PURPOSE: Renal tumor biopsies have been proposed as a management alternative to avoid treatment of benign or low risk small renal masses. However, many urologists are reluctant to recommend renal tumor biopsy because they feel its result frequently will not impact management. Our primary objective was to evaluate if centers that routinely favor renal tumor biopsy have lower rates of benign histology after surgery than centers where a selective renal tumor biopsy approach is used. MATERIALS AND METHODS: This was a retrospective multicenter study of patients who underwent partial or radical nephrectomy for a lesion suspicious for localized renal cell carcinoma which measured 4 cm or less (cT1a and pT1a or pT3a) between 2013 and 2015. A logistic regression model was used to examine whether the odds of obtaining a benign tumor following surgery differed between centers that routinely favor renal tumor biopsy and centers where a selective renal tumor biopsy approach is used. RESULTS: A total of 542 small renal masses in 516 patients were included in study. The rate of histologically benign tumors after surgery was 11%. This rate was significantly lower at centers that routinely favor renal tumor biopsy than at centers where a selective renal tumor biopsy approach is used (5% vs 16%, p <0.001). On multivariable analysis older age, smaller tumors and centers where a selective renal tumor biopsy approach is used were significantly associated with greater odds of finding a histologically benign tumor postoperatively. Compared to centers that routinely favor renal tumor biopsy the odds of finding a benign tumor at surgery was 4 times more likely at centers where a selective renal tumor biopsy approach is used (OR 4.1, 95% CI 1.9-8.3). CONCLUSIONS: Routine renal tumor biopsy reduces surgery for benign tumors and the potential for short-term and long-term morbidity associated with these procedures. This study suggests that routine renal tumor biopsy may be a valuable tool to decrease overtreatment of small renal masses.

Safety, reliability and accuracy of small renal tumour biopsies: results from a multi-institution registry.

OBJECTIVE: To validate, in a multi-institution review, the safety, accuracy and reliability of renal tumour biopsy (RTB) and its role in decreasing unnecessary treatment. MATERIALS AND METHODS: We conducted a multi-institution retrospective study of patients who underwent RTB to characterize a small renal mass (SRM) between 2011 and May 2015. Patients were identified using the prospectively maintained Canadian Kidney Cancer information system. Diagnostic and concordance rates were presented using proportions, whereas factors associated with a diagnostic RTB were identified using a logistic regression model. RESULTS: Of the 373 biopsied SRMs, the initial biopsy was diagnostic in 87% of cases. Of the 47 non-diagnostic biopsies, 15 had a repeat biopsy of which, 80% were diagnostic. When both were combined, therefore, a diagnosis was obtained in 91% of SRMs. Of these, 18% were benign. Size was the only factor found to be associated with achieving a diagnostic biopsy. RTB histology and nuclear grade (high or low) were found to be highly concordant with surgical pathology (86 and 81%, respectively). Of the discordant tumours (n = 16), all were upgraded from low to high grade on surgical pathology. Adverse events were rare (<1% of cases). CONCLUSION: The present multi-institution study confirms that RTB of SRMs is safe, accurate and reliable across institutions, while decreasing unnecessary treatment. Given our findings, RTBs may be a helpful tool with which to triage SRMs and guide appropriate management.

Should Small Renal Masses Be Biopsied?

Over the last few decades, the incidence of renal cell carcinomas (RCCs) has been steadily increasing. This is primarily due to an increase in detection of small renal masses (SRMs) as a result of widespread utilization of abdominal imaging. Interestingly, up to 30% of incidentally discovered SRMs (solid lesions measuring ≤4 cm) are benign, and consequently, the definitive treatment of all SRMs is associated with a considerable risk of overtreatment. To decrease the overtreatment rate, renal tumour biopsy (RTB) has been advocated as a safe alternative to identify the pretreatment histology of these SRMs. Although initially fraught with high non-diagnostic rates, more recent series from centres of experience have demonstrated that RTB is safe, reliable and accurate. The future of SRM management will combine pathological, molecular and genetic information to improve our ability to predict the behaviour of these lesions and herald risk-adapted personalized treatment.

Identification of the best complete blood count-based predictors for bladder cancer outcomes in patients undergoing radical cystectomy.

BACKGROUND: We sought to determine which parsimonious combination of complete blood count (CBC)-based biomarkers most efficiently predicts oncologic outcomes in patients undergoing radical cystectomy (RC) for bladder cancer (BC). METHODS: Using our institutional RC database (1992-2012), nine CBC-based markers (including both absolute cell counts and ratios) were evaluated based on pre-treatment measurements. The outcome measures were recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). Time-dependent receiver-operating characteristics curves were used to characterise each biomarker. The CBC-based biomarkers, along with several clinical predictors, were then considered for inclusion in predictive multivariable Cox models based on the Akaike Information Criterion. RESULTS: Our cohort included 418 patients. Neutrophil-lymphocyte ratio (NLR) was the only biomarker satisfying criteria for inclusion into all models, independently predicting RFS (HR per 1-log unit=1.52, 95% CI=1.17-1.98, P=0.002), CSS (HR=1.47, 95% CI=1.20-1.80, P<0.001), and OS (HR=1.56, 95% CI=1.16-2.10, P=0.004). Haemoglobin was also independently predictive of CSS (HR per 1 g/dl=0.91, 95% CI=0.86-0.95, P<0.001) and OS (HR=0.90, 95% CI=0.88-0.93, P<0.001), but not RFS. CONCLUSIONS: Among CBC biomarkers studied, NLR was the most efficient marker for predicting RFS, whereas NLR and haemoglobin were most efficient in predicting CSS and OS. NLR and haemoglobin are promising, cost-effective, independent biomarkers for predicting oncologic BC outcomes following RC. CONDENSED ABSTRACT: Various CBC-based biomarkers have separately been shown to be predictive of oncologic outcomes in patients undergoing cystectomy for BC. Our study evaluated these biomarkers, and determined that NLR is the best CBC-based biomarker for predicting RFS, whereas NLR and haemoglobin are most efficient for predicting CSS and OS.

Active Surveillance for Renal Neoplasms with Oncocytic Features is Safe.

PURPOSE: Oncocytomas are benign tumors often diagnosed incidentally on imaging. Small case series have suggested that the growth kinetics of oncocytomas are similar to those of malignant renal tumors. Biopsy material may be insufficient to exclude a diagnosis of chromophobe renal cell carcinoma. We evaluated and compared the growth rates of oncocytoma and chromophobe renal cell carcinoma to improve our understanding of their natural history. MATERIALS AND METHODS: This was a single center, retrospective study of patients diagnosed with lesions suggestive of oncocytoma or chromophobe renal cell carcinoma between 2003 and 2014. The growth rates were estimated using a mixed effect linear model. Patient and lesion characteristics were tested using a similar model for association with growth rate. RESULTS: Of the 95 lesions (oncocytoma 81, chromophobe renal cell carcinoma 14) included in the analysis 98% were diagnosed on biopsy. The annual growth rate was 0.14 cm and 0.38 cm for oncocytoma (median followup 34 months) and chromophobe renal cell carcinoma (median followup 25 months), respectively (p=0.5). Baseline lesion size was significantly associated with growth (p <0.001). The majority of oncocytomas (74%) and chromophobe renal cell carcinomas (67%) followed up to the 3-year mark had grown. Of these, 8 underwent surgery (6 in the chromophobe renal cell carcinoma group). The initial diagnosis was confirmed in all. Overall 5 patients died, all of nonrenal related causes. CONCLUSIONS: Although the majority of oncocytic renal neoplasms will grow with time, surveillance appears to remain safe. Patients opting for this strategy should be made aware that a diagnosis of oncocytoma following biopsy is associated with some degree of uncertainty due to the difficulty of differentiating them from other oncocytic renal neoplasms.

Stricter Active Surveillance Criteria for Prostate Cancer do Not Result in Significantly Better Outcomes: A Comparison of Contemporary Protocols.

PURPOSE: We reviewed various existing active surveillance criteria and determined the competing trade-offs of the stricter vs more inclusive active surveillance criteria. MATERIALS AND METHODS: Men enrolled in an active surveillance program at Princess Margaret Cancer Centre between 1998 and 2014 were identified through a prospectively maintained database. All patients were assessed for entry eligibility into the Prostate Cancer Research International: Active Surveillance, Johns Hopkins, University of Miami, University of California San Francisco, Memorial Sloan Kettering Cancer Center, University of Toronto-Sunnybrook and Royal Marsden protocols. The 2-sided t-test, ANOVA, Wilcoxon rank sum or chi-square tests were used for comparison as appropriate. RESULTS: Of the 1,365 men identified 1,085 met the Princess Margaret Cancer Centre inclusion criteria. When the Johns Hopkins, Prostate Cancer Research International: Active Surveillance and University of Miami criteria were applied 15.2%, 11.5% and 11.3% of these patients were excluded from active surveillance, respectively. No significant differences were noted between men who met the Princess Margaret Cancer Centre criteria and those who were excluded based on more stringent criteria when grade or volume reclassification was compared. No significant differences in prostate specific antigen velocity or the number of patients who proceeded to seek treatment were noted (p >0.1). Rates of biochemical recurrence among patients who chose to undergo radical prostatectomy after initial active surveillance were not different between men who met the more inclusive vs more exclusive active surveillance protocols. CONCLUSIONS: More selective criteria do not significantly improve short-term outcomes when considering the relative risk of grade reclassification or biochemical failure after treatment. In an era of increased awareness regarding the over diagnosis and overtreatment of prostate cancer, we believe that stricter entry criteria should be reconsidered.

Multilocular Cystic Renal Cell Carcinoma: Pathological T Staging Makes No Difference to Favorable Outcomes and Should be Reclassified.

PURPOSE: We evaluated survival outcomes of cystic/multilocular cystic renal cell carcinomas in a long-term population based study based on size and pathological tumor stage. MATERIALS AND METHODS: We retrospectively reviewed a provincial cancer registry of all histologically proven cases of multilocular cystic renal cancers treated surgically between 1995 and 2008. All cases of cystic necrosis were excluded from study. Primary end points were overall and cancer specific survival estimated using Kaplan-Meier curves. Cox proportional hazards models of univariable and multivariable analyses were used to assess for factors associated with survival. RESULTS: Of 172 cases of cystic renal cancers 168 with complete data were analyzed, of which 98% were multilocular cystic. Median patient age at treatment was 55 years and 58% of the patients were male. More than 40% of cases were pT1b or greater, 15% were pT2 or greater and most cases were low Fuhrman grade (1-2). At a median followup of 9.75 years overall and cancer specific survival was 82.1% and 100%, respectively. No difference was noted in higher pathological T stage, size or grade. Limitations inherent in population based studies include under ascertainment of cause of death, lack of data on histologically benign cysts that are treated surgically and a lack of central pathology review. CONCLUSIONS: Multilocular cystic renal cell carcinoma has an excellent prognosis, which remains unchanged regardless of tumor size or pathological T stage. This suggests a strong case for nephron and adrenal sparing surgery when indicated, and nonsurgical management when feasible. Since postoperative followup protocols are dictated by staging, we propose that for this entity pathological T staging should be abandoned or reassigned as pT1c to guide clinicians.

An Increase in Gleason 6 Tumor Volume While on Active Surveillance Portends a Greater Risk of Grade Reclassification with Further Followup.

PURPOSE: We evaluated the relative risk of later grade reclassification and outcomes of patients in whom high volume Gleason 6 prostate cancer develops while on active surveillance. MATERIALS AND METHODS: A prospectively maintained database was used to identify patients on active surveillance between 1998 and 2013. Tumor volume was assessed based on the number of positive cores and proportion of core involvement. The chi-square and Fisher exact tests were used for analysis as appropriate. The primary end point was the development of grade reclassification, defined as grade only and/or grade and volume at the event biopsy. RESULTS: A total of 555 men met the study inclusion criteria. Mean followup was 46 months. Overall 70 patients demonstrated an increase in tumor volume at or after biopsy 2. Compared to those men never experiencing volume or grade reclassification, prostate specific antigen at diagnosis was not significantly different (p=0.95), but median prostate volume was smaller in patients who demonstrated volume reclassification (p <0.001). The incidence of pure volume reclassification was 6.8%, 6.1% and 7.8% at biopsy 2, 3 and 4, respectively. Men with volume reclassification were more likely to experience later grade reclassification than those without at 33.3% vs 9.3%, respectively (p <0.0001). CONCLUSIONS: While Gleason 6 prostate cancer has a favorable natural history, it appears that patients on active surveillance who experience volume reclassification are at substantially higher risk for grade reclassification. Thus, urologists should pay close attention to tumor core involvement, and monitoring should be adjusted accordingly for early volume reclassification in younger men and those in good health.

Phase II, randomised, double-blind, placebo-controlled trial of methylphenidate for reduction of fatigue levels in patients with prostate cancer receiving LHRH-agonist therapy.

OBJECTIVES: To investigate whether methylphenidate can alleviate fatigue, as measured by the Functional Assessment of Cancer Therapy: 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 Bruera Global Fatigue Severity Scale (BFS) and the Medical Outcomes Study 36-Item Short-Form Health Survey (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 February 2008 and June 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.

5-Alpha reductase inhibitors in active surveillance.

PURPOSE OF REVIEW: Active surveillance is now one of the recommended treatment options for low-risk prostate cancer (PCa). However, about 10-30% of men on active surveillance will progress and require definitive therapy. In this review, we examine the role of 5-alpha reductase inhibitors (5-ARIs) in secondary prevention among men with low-risk PCa who opted to be managed by active surveillance. RECENT FINDINGS: Three retrospective studies and one randomized controlled trial have evaluated the role of 5-ARIs in preventing clinical progression among men followed by active surveillance. These studies largely support the role of 5-ARIs for secondary chemoprevention, although the drugs do not have an indication for this setting. SUMMARY: 5-ARIs have been shown to play an important role in preventing clinical progression among men with low-risk PCa on active surveillance. However, in light of the US Food and Drug Administration recommendation against 5-ARIs for primary chemoprevention, these findings should be interpreted with caution. Patients should be made aware of this warning label before starting the drug.