Re: Karim A. Touijer, James A. Eastham. The Sentinel Lymph Node Concept and Novel Approaches in Detecting Lymph Node Metastasis in Prostate Cancer. Eur Urol 2016;70:738–9: Sentinel Lymph Nodes in Adipose Tissue Surrounding the Prostate Gland and Seminal Vesicles as Observed in Virtual Whole-mount Histologic Slides
Rodolfo Montironi, Silvia Gasparrini, Roberta Mazzucchelli, Francesco Massari, Liang Cheng, Antonio Lopez-Beltran, Francesco Montorsi and Marina Scarpelli
Re: Rodolfo Montironi, Silvia Gasparrini, Roberta Mazzucchelli, et al's Letter to the Editor re: Karim A. Touijer, James A. Eastham. The Sentinel Lymph Node Concept and Novel Approaches in Detecting Lymph Node Metastasis in Prostate Cancer. Eur Urol 2016;70:738-9: Sentinel Lymph Nodes in Adipose Tissue Surrounding the Prostate Gland and Seminal Vesicles as Observed in Virtual Whole-mount Histologic Slides. Eur Urol 2017;71:e73–5
a
Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals, Ancona, Italy
b
Pathology Service, Champalimaud Clinical Center, Lisbon, Portugal
c
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
d
Department of Mechanical and Aerospace Engineering, University of California, Davis, CA, USA
e
Division of Oncology, S. Orsola-Malpighi Hospital, Bologna, Italy
f
Unit of Urology/Division of Oncology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
⁎
Corresponding author. Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals, Via Conca 71, I-60126 Ancona, Italy. Tel. +39 071 5964830; Fax: +39 071 889985.
Blockade of inhibitory receptors (IRs) overexpressed by T cells can activate antitumor immune responses, resulting in the most promising therapeutic approaches, particularly in bladder cancer, currently able to extend patient survival. Thanks to their ability to cross-present antigens to T cells, dendritic cells (DCs) are an immune cell population that plays a central role in the generation of effective antitumor T-cell responses. While IR function and expression have been investigated in T cells, very few data are available for DCs. Therefore, we analyzed whether DCs express IRs that can decrease their functions. To this end, we investigated several IRs (PD-1, CTLA-4, BTLA, TIM-3, and CD160) in circulating CD1c+ DCs, CD141+ DCs, and plasmacytoid DCs from healthy donors and patients with urothelial cancer (UCa). Different DC subsets expressed BTLA and TIM-3 but not other IRs. More importantly, BTLA and TIM-3 were significantly upregulated in DCs from blood of UCa patients. Locally, bladder tumor–infiltrating DCs also overexpressed BTLA and TIM-3 compared to DCs from paired nontumoral tissue. Finally, in vitro functional experiments showed that ligand-mediated engagement of BTLA and TIM-3 receptors significantly reduced the secretion of effector cytokines by DC subpopulations. Our findings demonstrate that UCa induces local and systemic overexpression of BTLA and TIM-3 by DCs that may result in their functional inhibition, highlighting these receptors as potential targets for UCa treatment.
Patient summary
We investigated the expression and function of a panel of inhibitory receptors in dendritic cells (DCs), an immune cell subpopulation critical in initiation of protective immune responses, among patients with urothelial carcinoma. We found high expression of BTLA and TIM-3 by blood and tumor DCs, which could potentially mediate decreased DC function. The results suggest that BTLA and TIM-3 might be new targets for urothelial carcinoma treatment.
Take Home Message
The inhibitory receptors BTLA and TIM-3 are overexpressed on circulating and intratumoral dendritic cells in urothelial cancer, mediating reduction of dendritic cell function.
KIUrologyX is a massive open online course in clinical urology that allows a broad range of people access to important clinical knowledge. It is a course that can be made available to an unlimited number of students, professionals, patients, and their kin.
Footnotes
a
Division of Urology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Huddinge, Sweden
b
Department of Learning, Informatics, Management and Ethics, Karolinska Institutet, Stockholm, Sweden
⁎
Corresponding author. Department of Learning, Informatics, Management and Ethics, Karolinska Institutet, Tomtebodavägen 18A, Stockholm 17177, Sweden. Tel. +46 73 7121366.
Re: Karim A. Touijer, James A. Eastham. The Sentinel Lymph Node Concept and Novel Approaches in Detecting Lymph Node Metastasis in Prostate Cancer. Eur Urol 2016;70:738–9: Sentinel Lymph Nodes in Adipose Tissue Surrounding the Prostate Gland and Seminal Vesicles as Observed in Virtual Whole-mount Histologic Slides
Rodolfo Montironi, Silvia Gasparrini, Roberta Mazzucchelli, Francesco Massari, Liang Cheng, Antonio Lopez-Beltran, Francesco Montorsi and Marina Scarpelli
Literature on conventional and minimally invasive operative techniques has not been systematically reviewed for kidney transplant recipients.
Objective
To systematically evaluate, summarize, and review evidence supporting operating technique and postoperative outcome for kidney transplant recipients.
Evidence acquisition
A systematic review was conducted in PubMed–Medline, Embase, and Cochrane Library between 1966 up to September 1, 2016, according to Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. Articles were included and scored by two independent reviewers using Group Reading Assessment and Diagnostic Evaluation (GRADE), Newcastle–Ottawa Quality Assessment Scale (NOS), and Oxford guidelines for level of evidence. Main outcomes were graft survival, surgical site infection, incisional hernia, and cosmetic result. In total, 18 out of 1954 identified publications were included in this analysis.
Evidence synthesis
Included reports described conventional open, minimally invasive open, laparoscopic, and robotic-assisted techniques. General level of evidence of included studies was low (GRADE: 1–3; NOS: 0–4; and Oxford level of evidence: 4–2). No differences in graft or patient survival were found. For open techniques, Gibson incision showed better results than the hockey-stick incision for incisional hernia (4% vs 16%), abdominal wall relaxation (8% vs 24%), and cosmesis. Minimally invasive operative recipient techniques showed lowest surgical site infection (range 0–8%) and incisional hernia rates (range 0–6%) with improved cosmetic result and postoperative recovery. Disadvantages included prolonged cold ischemia time, warm ischemia time, and total operation time.
Conclusions
Although the level of evidence was generally low, minimally invasive techniques showed promising results with regard to complications and recovery, and could be considered for use. For open surgery, the smallest possible Gibson incision appeared to yield favorable results.
Patient summary
In this paper, the available evidence for minimally invasive operation techniques for kidney transplantation was reviewed. The quality of the reviewed research was generally low but suggested possible advantages for minimally invasive, laparoscopic, and robot-assisted techniques.
Take Home Message
The general level of evidence of articles included in this systematic review was low. Minimally invasive techniques showed promising results with regard to complications and recovery. For open surgery, the smallest possible Gibson incision appeared to yield favorable results.
a
Department of Surgery, VU Medical Center, Amsterdam, The Netherlands
b
Department of Urology, Meander Medical Centre, Amersfoort, The Netherlands
c
Department of Surgery, Dutch Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
⁎
Corresponding author. Department of Surgery, VU Medical Center, Boelelaan 1118, 1081 HZ Amsterdam, The Netherlands. Tel. +31 20 4444444/+31 6 51919735.
Pharmacological thromboprophylaxis involves a trade-off between a reduction in venous thromboembolism (VTE) and increased bleeding. No guidance specific for procedure and patient factors exists in urology.
Objective
To inform estimates of absolute risk of symptomatic VTE and bleeding requiring reoperation in urological non-cancer surgery.
Evidence acquisition
We searched for contemporary observational studies and estimated the risk of symptomatic VTE or bleeding requiring reoperation in the 4 wk after urological surgery. We used the GRADE approach to assess the quality of the evidence.
Evidence synthesis
The 37 eligible studies reported on 11 urological non-cancer procedures. The duration of prophylaxis varied widely both within and between procedures; for example, the median was 12.3 d (interquartile range [IQR] 3.1–55) for open recipient nephrectomy (kidney transplantation) studies and 1 d (IQR 0–1.3) for percutaneous nephrolithotomy, open prolapse surgery, and reconstructive pelvic surgery studies. Studies of open recipient nephrectomy reported the highest risks of VTE and bleeding (1.8–7.4% depending on patient characteristics and 2.4% for bleeding). The risk of VTE was low for 8/11 procedures (0.2–0.7% for patients with low/medium risk; 0.8–1.4% for high risk) and the risk of bleeding was low for 6/7 procedures (≤0.5%; no bleeding estimates for 4 procedures). The quality of the evidence supporting these estimates was low or very low.
Conclusions
Although inferences are limited owing to low-quality evidence, our results suggest that extended prophylaxis is warranted for some procedures (eg, kidney transplantation procedures in high-risk patients) but not others (transurethral resection of the prostate and reconstructive female pelvic surgery in low-risk patients).
Patient summary
The best evidence suggests that the benefits of blood-thinning drugs to prevent clots after surgery outweigh the risks of bleeding in some procedures (such as kidney transplantation procedures in patients at high risk of clots) but not others (such as prostate surgery in patients at low risk of clots).
Take Home Message
Although inferences are limited owing to low-quality evidence, our results suggest that extended prophylaxis is likely to be warranted for some procedures (eg, kidney transplantation procedures in high-risk patients) but not others (transurethral resection of the prostate and reconstructive female pelvic surgery in low-risk patients).
a
Departments of Urology and Public Health, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
b
Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada
c
Michael G. DeGroote National Pain Centre, McMaster University, Hamilton, ON, Canada
d
School of Medicine, University of Toronto, Toronto, ON, Canada
e
Department of Medicine, University of Toronto, Toronto, ON, Canada
f
Department of Epidemiology and Biostatistics, Imperial College London, London, UK
g
Department of Urogynaecology, St Mary's Hospital, London, UK
h
Department of Surgery, Division of Urology, Woodstock General Hospital, Woodstock, ON, Canada
i
Department of Surgical, Oncological, and Gastroenterological Sciences, Urology Clinic, University of Padua, Padua, Italy
j
Department of Urology, ASST Papa Giovanni XXIII, Bergamo, Italy
k
Department of Oncology, McMaster University, Hamilton, ON, Canada
l
Faculty of Pharmacy, University of Waterloo, Kitchener, ON, Canada
m
Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA, USA
n
Institute of Clinical Medicine, University of Oslo, Oslo, Norway
o
Department of Haematology, Oslo University Hospital, Oslo, Norway
p
Department of Medicine, McMaster University, Hamilton, ON, Canada
q
McMaster Department of Surgery Division of Urology, Hamilton, ON, Canada
⁎
Corresponding author. Department of Urology, University of Helsinki and Helsinki University Hospital, Haartmaninkatu 4, Helsinki 00029, Finland. Tel. +358 50 5393222.
Metastasis-directed therapy is of interest for the management of oligometastatic prostate cancer. Improved imaging may help with patient selection, but the approach to metastatic prostate cancer of “catching 'em all”, or “Pokemet”, must be considered experimental.
Footnotes
a
Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Australia
b
Australian Prostate Cancer Research Centre, Epworth Healthcare, Richmond, Australia
c
The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia
d
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
e
Institut de Recherche Clinique, Cliniques Universitaires Saint-Luc, Brussels, Belgium
⁎
Corresponding author. Division of Cancer Surgery, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, Victoria 3000, Australia. Tel. +61 399368032; Fax: +61 39429 4683.
Updated 2016 EAU Guidelines on Muscle-invasive and Metastatic Bladder Cancer
J. Alfred Witjes, Thierry Lebret, Eva M. Compérat, Nigel C. Cowan, Maria De Santis, Harman Maxim Bruins, Virginia Hernández, Estefania Linares Espinós, James Dunn, Mathieu Rouanne, Yann Neuzillet, Erik Veskimäe, Antoine G. van der Heijden, Georgios Gakis and Maria J. Ribal
Department of Urology, Clinical Hospital Sveti Duh, Zagreb, Croatia
⁎
Corresponding author. Department of Urology, Clinical Hospital Sveti Duh, Sveti Duh 64, 10000 Zagreb, Croatia. Tel. +385 1 3712147; Fax: +385 1 3712027.
Tract Sizes in Miniaturized Percutaneous Nephrolithotomy: A Systematic Review from the European Association of Urology Urolithiasis Guidelines Panel
Yasir Ruhayel, Abdulkadir Tepeler, Saeed Dabestani, Steven MacLennan, Aleš Petřík, Kemal Sarica, Christian Seitz, Andreas Skolarikos, Michael Straub, Christian Türk, Yuhong Yuan and Thomas Knoll
The randomized, phase 3 CheckMate 025 study of nivolumab (n = 410) versus everolimus (n = 411) in previously treated adults (75% male; 88% white) with advanced renal cell carcinoma (aRCC) demonstrated significantly improved overall survival (OS) and objective response rate (ORR).
Objective
To investigate which baseline factors were associated with OS and ORR benefit with nivolumab versus everolimus.
Design, setting, and participants
Subgroup OS analyses were performed using Kaplan-Meier methodology. Hazard ratios were estimated using the Cox proportional hazards model.
Intervention
Nivolumab 3 mg/kg every 2 wk or everolimus 10 mg once daily.
Results and limitations
The minimum follow-up was 14 mo. Baseline subgroup distributions were balanced between nivolumab and everolimus arms. Nivolumab demonstrated an OS improvement versus everolimus across subgroups, including Memorial Sloan Kettering Cancer Center (MSKCC) and International Metastatic Renal Cell Carcinoma Database Consortium risk groups; age <65 and ≥65 yr; one and two or more sites of metastases; bone, liver, and lung metastases; number of prior therapies; duration of prior therapy; and prior sunitinib, pazopanib, or interleukin-2 therapy. The benefit with nivolumab versus everolimus was noteworthy for patients with poor MSKCC risk (hazard ratio 0.48, 95% confidence interval 0.32–0.70). The mortality rate at 12 mo for all subgroups was lower with nivolumab compared with everolimus. ORR also favored nivolumab. The incidence of grade 3 or 4 treatment-related adverse events across subgroups was lower with nivolumab. Limitations include the post hoc analysis and differing sample sizes between groups.
Conclusion
The trend for OS and ORR benefit with nivolumab for multiple subgroups, without notable safety concerns, may help to guide treatment decisions, and further supports nivolumab as the standard of care in previously treated patients with aRCC.
Patient summary
We investigated the impact of demographic and pretreatment features on survival benefit and tumor response with nivolumab versus everolimus in advanced renal cell carcinoma (aRCC). Survival benefit and response were observed for multiple subgroups, supporting the use of nivolumab as a new standard of care across a broad range of patients with previously treated aRCC.
The trial is registered on ClinicalTrials.gov as NCT01668784.
Take Home Message
Consistent with the benefit demonstrated in previously treated patients with advanced renal cell carcinoma from CheckMate 025, an overall survival and objective response rate benefit with nivolumab versus everolimus was observed for multiple subgroups, including prognostic risk categories, age, number and sites of metastases, and prior therapies.
Diagnostic Performance of Prostate Imaging Reporting and Data System Version 2 for Detection of Prostate Cancer: A Systematic Review and Diagnostic Meta-analysis
Sungmin Woo, Chong Hyun Suh, Sang Youn Kim, Jeong Yeon Cho and Seung Hyup Kim
a
Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
b
Division of Genitourinary Radiology, Ghent University Hospital, Ghent, Belgium
c
Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA
⁎
Corresponding author. Department of Radiology and Nuclear Medicine, Radboud University Medical Center, P.O. Box 9101, Nijmegen, The Netherlands. Tel. +31 24 3619196.
Renal function after partial nephrectomy (PN) may depend on modifiable factors including ischemia time, excision of healthy parenchyma (excisional volume loss, EVL), and reconstructive methods. We retrospectively reviewed our institutional robotic PN database to identify the predictors of glomerular filtration rate (GFR) preservation (GFR-P) at 3–12 mo postoperatively, during which GFR decline plateaus. Baseline clinical, sociodemographic, and radiologic characteristics were captured. Univariate and multivariate (MV) linear regression analyses were performed and marginal effects were employed to examine the relative effect of EVL on renal function. A total of 647 patients who underwent robotic PN had GFR data at a median follow-up of 6 mo. On MV models, EVL was significantly correlated with GFR-P following log transformation (p = 0.001). Each doubling of EVL caused a 1.5% decrease in GFR-P. Ischemia time and tumor complexity were not significantly associated with GFR-P. In summary, GFR-P after PN appears to be significantly associated with the excised volume of benign parenchyma.
Patient summary
At a high-volume tertiary care center, we investigated the impact of surgical factors on kidney function after kidney cancer surgery. We found that the surgical precision with which the tumor is excised significantly impacts kidney function at 3–12 mo after surgery.
Take Home Message
We reviewed a 10-yr database of over 600 patients with glomerular filtration rate data at 3–12 mo after robotic partial nephrectomy. We found that excisional precision significantly mitigates the iatrogenic effects of tumor excision on renal function on multivariate models.
[18F]-Fluorodeoxyglucose Positron Emission Tomography in the Diagnosis, Treatment Stratification, and Monitoring of Patients with Retroperitoneal Fibrosis: A Prospective Clinical Study
Archie Fernando, James Pattison, Catherine Horsfield, David D’Cruz, Gary Cook and Tim O’Brien
Germline mutations in DNA repair genes were recently reported in 8–12% of patients with metastatic castration-resistant prostate cancer (mCRPC). It is unknown whether these mutations associate with differential response to androgen receptor (AR)-directed therapy.
Objective
To determine the clinical response of mCRPC patients with germline DNA repair defects to AR-directed therapies and to establish whether biallelic DNA repair gene loss is detectable in matched circulating tumor DNA (ctDNA).
Design, setting, and participants
We recruited 319 mCRPC patients and performed targeted germline sequencing of 22 DNA repair genes. In patients with deleterious germline mutations, plasma cell-free DNA was also sequenced.
Outcome measurements and statistical analysis
Prostate-specific antigen response and progression were assessed in relation to initial androgen deprivation therapy (ADT) and subsequent therapy for mCRPC using Kaplan–Meier analysis.
Results and limitations
Of the 319 patients, 24 (7.5%) had deleterious germline mutations, with BRCA2 (n = 16) being the most frequent. Patients (n = 22) with mutations in genes linked to homologous recombination were heterogeneous at initial presentation but, after starting ADT, progressed to mCRPC with a median time of 11.8 mo (95% confidence interval [CI] 5.1–18.4). The median time to prostate-specific antigen progression on first-line AR-targeted therapy in the mCRPC setting was 3.3 mo (95% CI 2.7-3.9). Ten out of 11 evaluable patients with germline BRCA2 mutations had somatic deletion of the intact allele in ctDNA. A limitation of this study is absence of a formal control cohort for comparison of clinical outcomes.
Conclusions
Patients with mCRPC who have germline DNA repair defects exhibit attenuated responses to AR-targeted therapy. Biallelic gene loss was robustly detected in ctDNA, suggesting that this patient subset could be prioritized for therapies exploiting defective DNA repair using a liquid biopsy.
Patient summary
Patients with metastatic prostate cancer and germline DNA repair defects exhibit a poor response to standard hormonal therapies, but may be prioritized for potentially more effective therapies using a blood test.
Take Home Message
Metastatic castration-resistant prostate cancer patients with germline DNA repair defects respond poorly to androgen receptor-targeted therapy. However, biallelic gene loss was robustly detected in circulating tumor DNA, suggesting that this patient subset could be prioritized for therapies exploiting defective DNA repair using a liquid biopsy.
a
Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, British Columbia, Canada
b
Institute of Biosciences and Medical Technology, University of Tampere, Tampere, Finland
c
Department of Medical Oncology, British Columbia Cancer Agency, British Columbia, Canada
d
RSM Durham Regional Cancer Centre, Oshawa, Ontario, Canada
e
University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California, USA
⁎
Corresponding author. Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada. Tel. +1 604 875 4818; Fax: +1 604 875 5654.
a
Translational Genomics and Targeted Therapeutics in Solid Tumours Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
b
Medical Oncology Department, Hospital Clínic, Barcelona, Spain
c
Fundació Clínic per a la Recerca Biomèdica, Barcelona, Spain
d
Medical Oncology Department, Hospital Plató, Barcelona, Spain
e
Department of Pathology, Hospital Clónic, Barcelona, Spain
The Prostate Imaging Reporting and Data System (PI-RADS) is the most commonly used scoring system in prostate magnetic resonance imaging (MRI). One of the available techniques to target suspicious lesions is direct in-bore MRI-guided biopsy (MRGB).
Objective
To report on the experience and results of MRGB in a large cohort of patients with lesions classified as equivocal (PI-RADS 3), likely (PI-RADS 4), or highly likely (PI-RADS 5) to be clinically significant (cs) prostate cancer (PCa).
Design, setting, and participants
We retrospectively included 1057 patients having MRGB, between January 2012 and September 2016, of lesions classified as PI-RADS ≥ 3 on multiparametric MRI. Biopsy-naïve patients, patients with prior negative systematic transrectal ultrasound-guided biopsy, and patients in active surveillance were included.
Outcome measurements and statistical analysis
The primary outcome measurement is the detection rate of csPCa. Descriptive statistics and chi-square tests were used to calculate the differences in proportions. We considered a Gleason score of ≥3 + 4 as csPCa.
Results and limitations
PCa was diagnosed in 35% (55/156), 60% (223/373), and 91% (479/528), and csPCa in 17% (26/156), 34% (128/373), and 67% (352/528) of patients with PI-RADS 3, 4, and 5 lesions, respectively. Follow-up of patients with negative biopsy findings resulted in csPCa in 1.7% (5/300) after a median period of 41 (interquartile range 25–50) mo. The evaluation of prostate-specific antigen density (PSAD) to predict csPCa resulted in 42% of patients with a PI-RADS 3 lesion who could avoid biopsy in case a PSAD of ≥ 0.15 ng/ml/ml would be used. In 6% (95% confidence interval, 2–15), csPCa would then be missed. The study is limited because of its retrospective character.
Conclusions
MRGB in lesions scored PI-RADS ≥ 3 yields high detection rates of csPCa in daily clinical practice in cases with previous negative biopsy.
Patient summary
In daily clinical practice, direct in-bore magnetic resonance imaging-guided biopsy of suspicious lesions reported according to the Prostate Imaging Reporting and Data System yields high detection rates of clinically significant prostate cancer.
Take Home Message
Prostate Imaging Reporting and Data System (PI-RADS) is an accurate tool to predict clinically significant prostate cancer in daily clinical practice. Using prostate-specific antigen density in patients with a PI-RADS 3 level of suspicion allows patients to avoid unnecessary biopsy.
Keywords:Prostate cancer, Magnetic resonance imaging, In-bore biopsy, Prostate Imaging Reporting and Data System.
Footnotes
a
Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
b
Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands
c
Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands
⁎
Corresponding author. Department of Radiology and Nuclear Medicine, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. Tel.: +31 0 24 361 8766; fax: +31 0 24 354 0866.
Physical exercise mitigates fatigue during androgen deprivation therapy (ADT); however, the effects of different exercise prescriptions are unknown.
Objectives
To determine the long-term effects of different exercise modes on fatigue in prostate cancer patients undergoing ADT.
Design, setting, and participants
Between 2009 and 2012, 163 prostate cancer patients aged 43–90 y on ADT were randomised to exercise targeting the musculoskeletal system (impact loading + resistance training; ILRT; n = 58), the cardiovascular and muscular systems (aerobic + resistance training; ART; n = 54), or to usual care/delayed exercise (DEL; n = 51) for 12 mo across university-affiliated exercise clinics in Australia.
Intervention
Supervised ILRT for 12 mo, supervised ART for 6 mo followed by a 6-mo home program, and DEL received a printed booklet on exercise information for 6 mo followed by 6-mo stationary cycling exercise.
Outcome measurements and statistical analysis
Fatigue was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 36 and vitality using the Short Form-36. Analysis of variance was used to compare outcomes for groups at 6 mo and 12 mo.
Results and limitations
Fatigue was reduced (p = 0.005) in ILRT at 6 mo and 12 mo (∼5 points), and in ART (p = 0.005) and DEL (p = 0.022) at 12 mo. Similarly, vitality increased for all groups (p ≤ 0.001) at 12 mo (∼4 points). Those with the highest levels of fatigue and lowest vitality improved the most with exercise (ptrend < 0.001). A limitation was inclusion of mostly well-functioning individuals.
Conclusions
Different exercise modes have comparable effects on reducing fatigue and enhancing vitality during ADT. Patients with the highest levels of fatigue and lowest vitality had the greatest benefits.
Patient summary
We compared the effects of different exercise modes on fatigue in men on androgen deprivation therapy. All exercise programs reduced fatigue and enhanced vitality. We conclude that undertaking some form of exercise will help reduce fatigue, especially in those who are the most fatigued.
Take Home Message
We compared the effects of different exercise modes on fatigue in men on androgen deprivation therapy. All exercise programs reduced fatigue and enhanced vitality. We conclude that undertaking some form of exercise will help reduce fatigue, especially in those who are the most fatigued.
g
Faculty of Medicine, University of Western Australia, Nedlands, WA, Australia
h
Department of Radiation Oncology, Sir Charles Gairdner Hospital, Nedlands, WA, Australia
i
Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia
j
Centre for Research in Cancer Control, Cancer Council Queensland, Brisbane, QLD, Australia
k
Prostate Cancer Foundation of Australia, Sydney, NSW, Australia
l
Department of Urology, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia
m
School of Psychology and Exercise Science, Murdoch University, Murdoch, WA, Australia
n
Institute for Health & Ageing, Australian Catholic University, Melbourne, VIC, Australia
o
Astrand Laboratory of Work Physiology, The Swedish School of Sport and Health Sciences, Stockholm, Sweden
⁎
Corresponding author. Exercise Medicine Research Institute, School of Medical and Health Sciences, Edith Cowan University, 270 Joondalup Drive, Joondalup, WA 6027, Australia. Tel.: +61 8 63045476.
Testosterone is a crucial sex hormone important for the health and development of men of all ages. It plays a role in the integrity and maintaining the function of several systems and organs. Testosterone deficiency is linked to a number of signs and symptoms potentially affecting every man in his complexity and masculinity, and is therefore of strong urological interest. For this reason, urologists should attach importance to the need for knowledge, vocational education, and training in this specific area.
Footnotes
a
Urology Department, University of Naples Federico II, Naples, Italy
b
Urology Department, Andros Clinic, Arnhem, The Netherlands
c
Urology Department, Erasmus University Medical Center, Rotterdam, The Netherlands
d
Division of Experimental Oncology/Unit of Urology, IRCCS Ospedale San Raffaele, Milan, Italy
e
Urology Department, Medical School, University of Ioannina, Ioannina, Greece
f
Urology Department, Zealand University Hospital, Roskilde, Denmark
g
Urology Department, Herlev and Gentofte Hospital, Herlev, Denmark
⁎
Corresponding author. Urology Department, University of Naples Federico II, Via S. Pansini 5, Naples 80131, Italy. Tel. +39 081 7462611; Fax: +39 081 5452959.
1The remaining members of the URO-TRAM working group are listed in Appendix A.
Miniaturized instruments for percutaneous nephrolithotomy (PNL), utilizing tracts sized ≤22 Fr, have been developed in an effort to reduce the morbidity and increase the efficiency of stone removal compared with standard PNL (>22 Fr).
Objective
We systematically reviewed all available evidence on the efficacy and safety of miniaturized PNL for removing renal calculi.
Evidence acquisition
The review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Since it was not possible to perform a meta-analysis, the data were summarized in a narrative synthesis.
Evidence synthesis
After screening 2945 abstracts, 18 studies were included (two randomized controlled trials [RCTs], six nonrandomized comparative studies, and 10 case series). Thirteen studies were full-text articles and five were only available as congress abstracts. The size of tracts used in miniaturized procedures ranged from 22 Fr to 4.8 Fr. The largest mean stone size treated using small instruments was 980 mm2. Stone-free rates were comparable in miniaturized and standard PNL procedures. Procedures performed with small instruments tended to be associated with significantly lower blood loss, while the procedure duration tended to be significantly longer. Other complications were not notably different between PNL types. Study designs and populations were heterogeneous. Study limitations included selection and outcome reporting bias, as well as a lack of information on relevant confounding factors.
Conclusions
The studies suggest that miniaturized PNL is at least as efficacious and safe as standard PNL for the removal of renal calculi. However, the quality of the evidence was poor, drawn mainly from small studies, the majority of which were single-arm case series, and only two of which were RCTs. Furthermore, the tract sizes used and types of stones treated were heterogeneous. Hence, the risks of bias and confounding were high, highlighting the need for more reliable data from RCTs.
Patient summary
Removing kidney stones via percutaneous nephrolithotomy (PNL) using smaller sized instruments (mini-PNL) appears to be as effective and safe as using larger (traditional) instruments, but more clinical research is needed.
Take Home Message
Percutaneous nephrolithotomy (PNL) using smaller tract sizes (<22 Fr, mini-PNL) for removal of renal calculi appears to be as efficacious and safe as standard PNL. However, the studies are heterogeneous and generally small, so well-designed and sufficiently powered randomized controlled trials are warranted.
Effective stakeholder integration for guideline development should improve outcomes and adherence to clinical practice guidelines.
Footnotes
a
Academic Urology Unit, University of Aberdeen, Aberdeen, UK
b
Urological Cancer Charity, Foresterhill Health Centre, Aberdeen, UK
c
Department of Urology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
d
Academic Urology Unit, University of Sheffield, Sheffield, UK
e
Cancer Research Centre, University of Warwick, UK
f
Leeds Institute of Cancer & Pathology, University of Leeds, Leeds, UK
g
Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden
h
European Association of Urology Guidelines Office, Arnhem, The Netherlands
i
Faculty of Economics and Social Sciences, Universitat Internacional de Catalunya, Barcelona, Spain
j
Department of Urology, University Hospitals of KU Leuven, Leuven, Belgium
k
Department of Nephrology and Hypertension, Regenerative Medicine Centre Utrecht, University Medical Centre Utrecht, Utrecht, The Netherlands
l
International Kidney Cancer Coalition, www.ikcc.org
⁎
Corresponding author. Department of Nephrology and Hypertension, Regenerative Medicine Centre Utrecht, University Medical Centre Utrecht, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands. Tel. +31 887556508.
Aviso para pacientes:
Esta página contiene información urológica dirigida a profesionales de la sanidad.
Si tiene algún problema relacionado con esta patología,
consulte con su urólogo o médico de familia.
Si desea información diseñada para pacientes y público general. puede visitar:
Portal de Información Urológica para Pacientes
Los Blogs de UroPortal:
