The dysfunctional immune response in renal cell carcinoma correlates with changes in the metabolic landscape of ccRCC during disease progression.

Renal cell carcinoma is an immunogenic tumour with a prominent dysfunctional immune cell infiltrate, unable to control tumour growth. Although tyrosine kinase inhibitors and immunotherapy have improved the outlook for some patients, many individuals are non-responders or relapse despite treatment. The hostile metabolic environment in RCC affects the ability of T-cells to maintain their own metabolic programme constraining T-cell immunity in RCC. We investigated the phenotype, function and metabolic capability of RCC TILs correlating this with clinicopathological features of the tumour and metabolic environment at the different disease stages. Flow cytometric analysis of freshly isolated TILs showed the emergence of exhausted T-cells in advanced disease based on their PD-1high and CD39 expression and reduced production of inflammatory cytokines upon in vitro stimulation. Exhausted T-cells from advanced stage disease also displayed an overall phenotype of metabolic insufficiency, characterized by mitochondrial alterations and defects in glucose uptake. Nanostring nCounter cancer metabolism assay on RNA obtained from 30 ccRCC cases revealed significant over-expression of metabolic genes even at early stage disease (pT1-2), while at pT3-4 and the locally advanced thrombi stages, there was an overall decrease in differentially expressed metabolic genes. Notably, the gene PPARGC1A was the most significantly down-regulated gene from pT1-2 to pT3-4 RCC which correlated with loss of mitochondrial function in tumour-infiltrating T-cells evident at this tumour stage. Down-regulation of PPARGC1A into stage pT3-4 may be the 'tipping-point' in RCC disease progression, modulating immune activity in ccRCC and potentially reducing the efficacy of immunotherapies in RCC and poorer patient outcomes.

Oncological outcomes and stoma-free survival following TaTME, a prospective cohort study.

BACKGROUND: Transanal TME (TaTME) was introduced to improve access to the pelvis in difficult cases (male sex, obesity and mid to low rectal cancers) and reduce the risk of anastomotic leak by avoiding cross stapling. In April 2018 the Norwegian hospital to whom all local; recurrences for rectal cancer are referred reported an unexpected rise in early multifocal local recurrences of 9.5% following TaTME compared with 3.4% following conventional TME leading to a nationwide moratorium on the procedure and ending, in an editorial published on the British Journal of Surgery in August 2020, by saying that other countries should consider the issue in the context of local practices and results. There are limited data concerning oncological outcomes of TaTME compared to conventional TME. The aim of this study was to report perioperative and oncological outcomes for patients with rectal cancer treated with TaTME in a high-volume, experienced UK centre. METHODS: From January 2015 to January 2020 consecutive patients with histologically confirmed rectal cancer having TaTME at Worcestershire Royal Hospital NHS were prospectively entered into an online international registry. Patients were followed according to local protocol with clinical examination, tumour markers, endoscopy and radiology. RESULTS: Seventy patients underwent TaTME for rectal cancer. The median distance of the tumour from the anorectal junction was 4 cm (IQR 2-5). The mesorectal margin was involved in 20 (1%) patients, all of whom received neoadjuvant chemoradiotherapy. Overall survival was 94% at a median follow-up of 15 months (IQR 9-31 months). Distant recurrence occurred in 12 (17%) of patients at a median of 14 months (IQR 10-17 months). The 18-month stoma-free survival rate was 66%. CONCLUSIONS: A local recurrence rate of 5.7% supports the oncological safety of TaTME for rectal cancer.

Collateral damage: the impact on outcomes from cancer surgery of the COVID-19 pandemic.

BACKGROUND: Cancer diagnostics and surgery have been disrupted by the response of health care services to the coronavirus disease 2019 (COVID-19) pandemic. Progression of cancers during delay will impact on patients' long-term survival. PATIENTS AND METHODS: We generated per-day hazard ratios of cancer progression from observational studies and applied these to age-specific, stage-specific cancer survival for England 2013-2017. We modelled per-patient delay of 3 and 6 months and periods of disruption of 1 and 2 years. Using health care resource costing, we contextualise attributable lives saved and life-years gained (LYGs) from cancer surgery to equivalent volumes of COVID-19 hospitalisations. RESULTS: Per year, 94 912 resections for major cancers result in 80 406 long-term survivors and 1 717 051 LYGs. Per-patient delay of 3/6 months would cause attributable death of 4755/10 760 of these individuals with loss of 92 214/208 275 life-years, respectively. For cancer surgery, average LYGs per patient are 18.1 under standard conditions and 17.1/15.9 with a delay of 3/6 months (an average loss of 0.97/2.19 LYGs per patient), respectively. Taking into account health care resource units (HCRUs), surgery results on average per patient in 2.25 resource-adjusted life-years gained (RALYGs) under standard conditions and 2.12/1.97 RALYGs following delay of 3/6 months. For 94 912 hospital COVID-19 admissions, there are 482 022 LYGs requiring 1 052 949 HCRUs. Hospitalisation of community-acquired COVID-19 patients yields on average per patient 5.08 LYG and 0.46 RALYGs. CONCLUSIONS: Modest delays in surgery for cancer incur significant impact on survival. Delay of 3/6 months in surgery for incident cancers would mitigate 19%/43% of LYGs, respectively, by hospitalisation of an equivalent volume of admissions for community-acquired COVID-19. This rises to 26%/59%, respectively, when considering RALYGs. To avoid a downstream public health crisis of avoidable cancer deaths, cancer diagnostic and surgical pathways must be maintained at normal throughput, with rapid attention to any backlog already accrued.

Meta-analysis of the prevalence of renal cancer detected by abdominal ultrasonography.

BACKGROUND: The potential for an ultrasound-based screening programme for renal cell carcinoma (RCC) to improve survival through early detection has been the subject of much debate. The prevalence of ultrasound-detected asymptomatic RCC is an important first step to establishing whether a screening programme may be feasible. METHODS: A systematic search of MEDLINE and Embase was performed up to March 2016 to identify studies reporting the prevalence of renal masses and RCC. Two populations of patients were chosen: asymptomatic individuals undergoing screening ultrasonography and patients undergoing ultrasonography for abdominal symptoms not related to RCC. A random-effects meta-analysis was performed. Study quality was evaluated using a validated eight-point checklist. RESULTS: Sixteen studies (413 551 patients) were included in the final analysis. The pooled prevalence of renal mass was 0·36 (95 per cent c.i. 0·23 to 0·52) per cent and the prevalence of histologically proven RCC was 0·10 (0·06 to 0·15) per cent. The prevalence of RCC was more than double in studies from Europe and North America than in those from Asia: 0·17 (0·09 to 0·27) versus 0·06 (0·03 to 0·09) per cent respectively. Data on 205 screen-detected RCCs showed that 84·4 per cent of tumours were stage T1-T2 N0, 13·7 per cent were T3-T4 N0, and only 2·0 per cent had positive nodes or metastases at diagnosis. CONCLUSION: At least one RCC would be detected per 1000 individuals screened. The majority of tumours identified are early stage (T1-T2).

Genomic analyses of tropical beef cattle fertility based on genotyping pools of Brahman cows with unknown pedigree.

We introduce an innovative approach to lowering the overall cost of obtaining genomic EBV (GEBV) and encourage their use in commercial extensive herds of Brahman beef cattle. In our approach, the DNA genotyping of cow herds from 2 independent properties was performed using a high-density bovine SNP chip on DNA from pooled blood samples, grouped according to the result of a pregnancy test following their first and second joining opportunities. For the DNA pooling strategy, 15 to 28 blood samples from the same phenotype and contemporary group were allocated to pools. Across the 2 properties, a total of 183 pools were created representing 4,164 cows. In addition, blood samples from 309 bulls from the same properties were also taken. After genotyping and quality control, 74,584 remaining SNP were used for analyses. Pools and individual DNA samples were related by means of a "hybrid" genomic relationship matrix. The pooled genotyping analysis of 2 large and independent commercial populations of tropical beef cattle was able to recover significant and plausible associations between SNP and pregnancy test outcome. We discuss 24 SNP with significant association ( < 1.0 × 10) and mapped within 40 kb of an annotated gene. We have established a method to estimate the GEBV in young herd bulls for a trait that is currently unable to be predicted at all. In summary, our novel approach allowed us to conduct genomic analyses of fertility in 2 large commercial Brahman herds managed under extensive pastoral conditions.

Using CRP to predict anastomotic leakage after open and laparoscopic colorectal surgery: is there a difference?

AIM: C-reactive protein (CRP) has proven to be a useful adjunct in early diagnosis of anastomotic leak (AL) after colorectal surgery. It would be of considerable value to examine whether modality of surgery has influence upon postoperative CRP serum levels and their predictive value in the diagnosis of AL. METHODS: All patients undergoing elective colorectal surgery with anastomosis were enrolled into a prospective database between 2011 and 2014. AL was defined with strict operative and radiological criteria. Outcomes between open and laparoscopic resections were assessed statistically and Receiver Operating Characteristic (ROC) curve analysis performed. RESULTS: Seven hundred twenty-seven patients with an intestinal anastomosis were identified including 468 laparoscopic procedures (468/727; 64 %). There were 58 anastomotic leaks (58/727; 7.9 %) of which 29 (6.2 %) were laparoscopic and 29 (11.2 %) were open. Mean CRP levels were significantly higher in patients after open surgery compared with laparoscopic both with AL (p = 0.013), and without (p = 0.02). ROC curve analysis revealed postoperative day 3 (cut-off CRP 209) and day 4 (cut-off CRP 123.5) to be most predictive of leak in the open group with an area under the curve (AUC) 0.794 (sensitivity 80 %, specificity 80 %) and AUC 0.806 (sensitivity 94 %, specificity 60 %), respectively. In the laparoscopic group, day 2 proved to be the most accurate day for detection of leak with a cut-off CRP of 146.5 showing 75 % sensitivity and a 70 % specificity (AUC 0.766). CONCLUSION: CRP levels are higher after open surgery compared with laparoscopic surgery, both with and without AL. AL generates a significant detectable increase in CRP within 2-4 days after surgery.

PITX2 and non-canonical Wnt pathway interaction in metastatic prostate cancer.

The non-canonical Wnt pathway, a regulator of cellular motility and morphology, is increasingly implicated in cancer metastasis. In a quantitative PCR array analysis of 84 Wnt pathway associated genes, both non-canonical and canonical pathways were activated in primary and metastatic tumors relative to normal prostate. Expression of the Wnt target gene PITX2 in a prostate cancer (PCa) bone metastasis was strikingly elevated over normal prostate (over 2,000-fold) and primary prostate cancer (over 200-fold). The elevation of PITX2 protein was also evident on tissue microarrays, with strong PITX2 immunostaining in PCa skeletal and, to a lesser degree, soft tissue metastases. PITX2 is associated with cell migration during normal tissue morphogenesis. In our studies, overexpression of individual PITX2A/B/C isoforms stimulated PC-3 PCa cell motility, with the PITX2A isoform imparting a specific motility advantage in the presence of non-canonical Wnt5a stimulation. Furthermore, PITX2 specific shRNA inhibited PC-3 cell migration toward bone cell derived chemoattractant. These experimental results support a pivotal role of PITX2A and non-canonical Wnt signaling in enhancement of PCa cell motility, suggest PITX2 involvement in homing of PCa to the skeleton, and are consistent with a role for PITX2 in PCa metastasis to soft and bone tissues. Our findings, which significantly expand previous evidence that PITX2 is associated with risk of PCa biochemical recurrence, indicate that variation in PITX2 expression accompanies and may promote prostate tumor progression and metastasis.

Kallikrein 4 (hK4) and prostate-specific antigen (PSA) are associated with the loss of E-cadherin and an epithelial-mesenchymal transition (EMT)-like effect in prostate cancer cells.

Prostate-specific antigen (PSA) and the related kallikrein family of serine proteases are current or emerging biomarkers for prostate cancer detection and progression. Kallikrein 4 (KLK4/hK4) is of particular interest, as KLK4 mRNA has been shown to be elevated in prostate cancer. In this study, we now show that the comparative expression of hK4 protein in prostate cancer tissues, compared with benign glands, is greater than that of PSA and kallikrein 2 (KLK2/hK2), suggesting that hK4 may play an important functional role in prostate cancer progression in addition to its biomarker potential. To examine the roles that hK4, as well as PSA and hK2, play in processes associated with progression, these kallikreins were separately transfected into the PC-3 prostate cancer cell line, and the consequence of their stable transfection was investigated. PC-3 cells expressing hK4 had a decreased growth rate, but no changes in cell proliferation were observed in the cells expressing PSA or hK2. hK4 and PSA, but not hK2, induced a 2.4-fold and 1.7-fold respective increase, in cellular migration, but not invasion, through Matrigel, a synthetic extracellular matrix. We hypothesised that this increase in motility displayed by the hK4 and PSA-expressing PC-3 cells may be related to the observed change in structure in these cells from a typical rounded epithelial-like cell to a spindle-shaped, more mesenchymal-like cell, with compromised adhesion to the culture surface. Thus, the expression of E-cadherin and vimentin, both associated with an epithelial-mesenchymal transition (EMT), was investigated. E-cadherin protein was lost and mRNA levels were significantly decreased in PC-3 cells expressing hK4 and PSA (10-fold and 7-fold respectively), suggesting transcriptional repression of E-cadherin, while the expression of vimentin was increased in these cells. The loss of E-cadherin and associated increase in vimentin are indicative of EMT and provides compelling evidence that hK4, in particular, and PSA have a functional role in the progression of prostate cancer through their promotion of tumour cell migration.

Hypermethylation of the 5' CpG island of the gene encoding the serine protease Testisin promotes its loss in testicular tumorigenesis.

The Testisin gene (PRSS21) encodes a glycosylphosphatidylinositol (GPI)-linked serine protease that exhibits testis tissue-specific expression. Loss of Testisin has been implicated in testicular tumorigenesis, but its role in testis biology and tumorigenesis is not known. Here we have investigated the role of CpG methylation in Testisin gene inactivation and tested the hypothesis that Testisin may act as a tumour suppressor for testicular tumorigenesis. Using sequence analysis of bisulphite-treated genomic DNA, we find a strong relationship between hypermethylation of a 385 bp 5' CpG rich island of the Testisin gene, and silencing of the Testisin gene in a range of human tumour cell lines and in 100% (eight/eight) of testicular germ cell tumours. We show that treatment of Testisin-negative cell lines with demethylating agents and/or a histone deacetylase inhibitor results in reactivation of Testisin gene expression, implicating hypermethylation in Testisin gene silencing. Stable expression of Testisin in the Testisin-negative Tera-2 testicular cancer line suppressed tumorigenicity as revealed by inhibition of both anchorage-dependent cell growth and tumour formation in an SCID mouse model of testicular tumorigenesis. Together, these data show that loss of Testisin is caused, at least in part, by DNA hypermethylation and histone deacetylation, and suggest a tumour suppressor role for Testisin in testicular tumorigenesis.

Are patents for methods of medical treatment contrary to the ordre public and morality or "generally inconvenient"?

"No one has advanced a just and logical reason why reward for service to the public should be extended to the inventor of a mechanical toy and denied to the genius whose patience, foresight, and effort have given a valuable new [discovery] to mankind" (Katopis CJ. Patents v patents: policy implications of recent patent legislation. St John's Law Review 1997;71:329). The law around the world permits the granting of patents for drugs, medical devices, and cosmetic treatment of the human body. At the same time, patentability for a method of treatment of the same body is denied in some countries on various public policy grounds. Is there any logical justification for this distinction? Are methods of medical treatment not as vital to the health or even to the life of a patient as drugs or medical devices? Why is a cosmetic result patentable and a curative result not?

Papillary urothelial neoplasm of low malignant potential: reliability of diagnosis and outcome.

OBJECTIVE: To determine the ability of pathologists to reproducibly diagnose a newly defined lesion, i.e. the papillary urothelial neoplasm of low malignant potential (PUNLMP) using the published criteria, defined by the 1998 World Health Organisation/International Society of Urological Pathology (WHO/ISUP) classification system; in addition, debate remains about the clinical behaviour of these lesions, thus the rates of recurrence and progression of PUNLMP lesions were assessed and compared with low-grade papillary urothelial carcinomas (LG-PUC) and high-grade (HG-PUC) over a 10-year follow-up. PATIENTS AND METHODS: Forty-nine cases of superficial bladder cancer (G1-3 pTa) representing an initial diagnosis of transitional cell carcinoma made in 1990 were identified and re-graded using the 1998 WHO/ISUP classification by two pathologists. Inter-observer agreement was assessed using Cohen weighted kappa statistics. After re-classification the clinical follow-up was reviewed retrospectively, and episodes of recurrence and progression recorded. RESULTS: The inter-observer agreement was moderate, regardless of whether one (kappa 0.45) or two (kappa 0.60) pathologists were used to grade these lesions. Re-classification identified 12 PUNLMP, 28 LG-PUC and nine HG-PUC. PUNLMP lesions recurred in 25% (3/12) of cases; no progression was documented. Recurrence rates were 75% (21/28) and 67% (6/9) for LG- and HG-PUC, respectively, and progression rates were 4% (1/28) and 22% (2/9). CONCLUSION: The 1998 WHO/ISUP classification of urothelial neoplasms can be reproducibly applied by pathologists, with a moderate level of agreement. There is evidence that PUNLMP lesions have a more indolent clinical behaviour than urothelial carcinomas. However, the risk of recurrence and progression remains, and clinical monitoring of these patients is important.

Repeat urethrotomy and dilation for the treatment of urethral stricture are neither clinically effective nor cost-effective.

PURPOSE: We developed an algorithm for the management of urethral stricture based on cost-effectiveness. MATERIALS AND METHODS: United Kingdom medical and hospital costs associated with the current management of urethral stricture were calculated using private medical insurance schedules of reimbursement and clean intermittent self-catheterization supply costs. These costs were applied to 126 new patients treated endoscopically for urethral stricture in a general urological setting between January 1, 1991 and December 31, 1999. Treatment failure was defined as recurrent symptomatic stricture requiring further operative intervention following initial intervention. Mean followup available was 25 months (range 1 to 132). RESULTS: The costs were urethrotomy/urethral dilation 2,250.00 pounds sterling (3,375.00 dollars, ratio 1.00), simple 1-stage urethroplasty 5,015.00 pounds sterling (7,522.50 dollars, ratio 2.23), complex 1-stage urethroplasty 5,335.00 pounds sterling (8,002.50 dollars, ratio 2.37) and 2-stage urethroplasty 10,370 pounds sterling (15,555.00 dollars, ratio 4.61). Of the 126 patients assessed 60 (47.6%) required more than 1 endoscopic retreatments (mean 3.13 each), 50 performed biweekly clean intermittent self-catheterization and 7 underwent urethroplasty during followup. The total cost per patient for all 126 patients for stricture treatment during followup was 6,113 pounds sterling (9,170 dollars). This cost was calculated by multiplying procedure cost by the number of procedures performed. A strategy of urethrotomy or urethral dilation as first line treatment, followed by urethroplasty for recurrence yielded a total cost per patient of 5,866 pounds sterling (8,799 dollars). CONCLUSIONS: A strategy of initial urethrotomy or urethral dilation followed by urethroplasty in patients with recurrent stricture proves to be the most cost-effective strategy. This financially based strategy concurs with evidence based best practice for urethral stricture management.

Quality of life compared during pharmacological treatments and clinical monitoring for non-localized prostate cancer: a randomized controlled trial.

OBJECTIVES: To investigate the effects of different management strategies for non-localized prostate cancer on men's quality of life and cognitive functioning. PATIENTS, SUBJECTS AND METHODS: Men with prostate cancer were randomly assigned to one of four treatment arms: leuprorelin, goserelin, cyproterone acetate (CPA), or close clinical monitoring. In a repeated-measures design, men were assessed before treatment (baseline) and after 6 and 12 months of treatment. A community comparison group of men of the same age with no prostate cancer participated for the same length of time. The men were recruited from public and private urology departments from university teaching hospitals. All those with prostate cancer who were eligible for hormonal therapy had no symptoms requiring immediate therapy. In all, 82 patients were randomized and 62 completed the 1-year study, and of the 20 community participants, 15 completed the study. The main outcome measures were obtained from questionnaires on emotional distress, existential satisfaction, physical function and symptoms, social and role function, subjective cognitive function, and sexual function, combined with standard neuropsychological tests of memory, attention, and executive functions. RESULTS: Sexual dysfunction increased for patients on androgen-suppressing therapies, and emotional distress increased in those assigned to CPA or close clinical monitoring. Compared with before treatment there was evidence of an adverse effect of leuprorelin, goserelin, and CPA on cognitive function. CONCLUSIONS: In deciding the timing of androgen suppression therapy for prostate cancer, consideration should be given to potential adverse effects on quality of life and cognitive function.

Red cell N5-methyltetrahydrofolate concentrations and C677T methylenetetrahydrofolate reductase genotype in patients with stroke.

AIMS: To investigate the relation between total red cell folate, red cell N(5)-methyltetrahydrofolate (N(5)MTHF) concentrations, and N(5)N(10)-methylenetetrahydrofolate reductase (MTHFR) genotypes in stroke. METHODS: The study comprised 120 consecutive patients presenting to hospital with acute stroke. Multivitamin supplement use was recorded. Serum and red cell folate were measured by microbiological assays using Lactobacillus casei and Enterococcus faecalis, and by the DPC-BioMediq Immulite 2000 analyser. Total plasma homocysteine (tHcy), serum cobalamin, and serum vitamin B(6) were measured and the C677T MTHFR genotype determined. RESULTS: There were no significant differences in blood tHcy or vitamin concentrations according to MTHFR genotype in the overall patient cohort. However, when patients taking vitamins were excluded, total red cell folate and red cell N(5)MTHF were significantly lower in patients with the TT genotype compared with CT or CC genotypes. In the overall cohort, irrespective of genotype, red cell folate was significantly lower when assayed microbiologically than with the Immulite assay. This discrepancy remained after exclusion of patients taking vitamins. CONCLUSION: Total red cell folate and red cell N(5)MTHF are significantly lower in stroke patients with the TT compared with the CT and TT MTHFR genotypes, particularly those not taking vitamin supplements. Microbiological assays that measure biologically active folates provide substantially lower estimates of folate than the Immulite assay. Because folate is a key determinant of blood homocysteine values, these findings may impact on the interpretation of the strength and independence of the association between raised blood concentrations of homocysteine and atherothrombosis risk reported in most epidemiological studies.

Prostatic and peripheral blood selenium levels after oral supplementation.

PURPOSE: The dietary trace element selenium has been proposed to be a potential chemopreventive agent for prostate cancer. Epidemiological studies have suggested an inverse association between blood selenium and prostate cancer incidence. However, to our knowledge no study to date has examined selenium absorption by the prostate. Therefore, we determine whether oral selenium supplementation alters selenium levels within the prostate and/or peripheral blood. MATERIALS AND METHODS: In this prospective trial 51 men undergoing transurethral resection of the prostate for benign prostatic hyperplasia were randomly assigned to serve as controls or receive 200 microg selenium daily orally for 1 month. Sample size was calculated to detect a difference of 30 ng/gm in prostate tissue with a power of 80%. Peripheral blood was obtained at enrollment and subsequently at surgery, when prostate tissue was also sampled. Selenium levels were determined using inductively coupled plasma mass spectrometry. RESULTS: Baseline erythrocyte selenium was within the standard reference range. Supplementation increased erythrocyte (initial median 173 and final median 209 ng/ml, p = 0.008) and prostate (supplement median 241 and control median 196 ng/gm, p = 0.016) levels. Erythrocyte levels at surgery correlated poorly with prostate levels in the control (r = 0.18) and supplement (r = 0.07) groups. CONCLUSIONS: Oral selenium supplementation increases prostatic and peripheral blood levels in men in a nonselenium deficient population. Blood and prostate levels correlated poorly, suggesting that peripheral blood measurements are a poor indicator of prostatic selenium content.

Altered cognitive function in men treated for prostate cancer with luteinizing hormone-releasing hormone analogues and cyproterone acetate: a randomized controlled trial.

OBJECTIVE: To report the first systematic investigation of the cognitive effects of luteinizing hormone-releasing hormone (LHRH) analogues in male patients, as LHRH analogues have been associated with memory impairments in women using these drugs for gynaecological conditions. PATIENTS AND METHODS: Eighty-two men with extraprostatic prostate cancer were randomly assigned to receive either continuous leuprorelin, goserelin (both LHRH analogues), cyproterone acetate (a steroidal antiandrogen) or close clinical monitoring. These patients underwent cognitive assessments at baseline and before starting treatment (77), and then 6 months later (65). RESULTS: Compared with the baseline assessments, men receiving androgen suppression monotherapy performed worse in two of 12 tests of attention and memory; 24 of 50 men randomized to active treatment and assessed 6 months later had a clinically significant decline in one or more cognitive tests but not one patient randomized to close monitoring showed a decline in any test performance. CONCLUSION: Pharmacological androgen suppression monotherapy for prostate cancer may be associated with impaired memory, attention and executive functions.