In the ProtecT trial, over 1600 men with PSA-detected localized prostate cancer were assigned to active monitoring, prostatectomy, or radiotherapy. Although more patients assigned to active ...monitoring had disease progression, overall survival was similar in the three groups.
The management of clinically localized prostate cancer that is detected on the basis of prostate-specific antigen (PSA) levels remains controversial. In the United States alone, an estimated 180,890 cases will be diagnosed in 2016, and 26,120 men will die from the disease.
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The widespread use of PSA testing has resulted in a dramatic increase in the diagnosis and treatment of prostate cancer, but many men do not benefit from intervention because the disease is either indolent or disseminated at diagnosis. Prostate cancer often progresses slowly, and many men die of competing causes. In addition, interventions for prostate cancer can have . . .
Abstract Context Prostate biopsy is commonly performed for cancer detection and management. The benefits and risks of prostate biopsy are germane to ongoing debates about prostate cancer screening ...and treatment. Objective To perform a systematic review of complications from prostate biopsy. Evidence acquisition A literature search was performed using PubMed and Embase, supplemented with additional references. Articles were reviewed for data on the following complications: hematuria, rectal bleeding, hematospermia, infection, pain, lower urinary tract symptoms (LUTS), urinary retention, erectile dysfunction, and mortality. Evidence synthesis After biopsy, hematuria and hematospermia are common but typically mild and self-limiting. Severe rectal bleeding is uncommon. Despite antimicrobial prophylaxis, infectious complications are increasing over time and are the most common reason for hospitalization after biopsy. Pain may occur at several stages of prostate biopsy and can be mitigated by anesthetic agents and anxiety-reduction techniques. Up to 25% of men have transient LUTS after biopsy, and <2% have frank urinary retention, with slightly higher rates reported after transperineal template biopsy. Biopsy-related mortality is rare. Conclusions Preparation for biopsy should include antimicrobial prophylaxis and pain management. Prostate biopsy is frequently associated with minor bleeding and urinary symptoms that usually do not require intervention. Infectious complications can be serious, requiring prompt management and continued work into preventative strategies.
In men with prostate cancer on PSA screening, radical treatments led to half the incidence of metastasis and local progression as active monitoring without affecting disease-specific or overall ...survival.
The choice of treatment for PSA-detected, localized prostate cancer is influenced by effects of the interventions on quality of life. In the ProtecT trial, patterns of side-effect severity, ...improvement, and decline in urinary, sexual, and bowel function differed among the treatments.
As reported in a companion article in the
Journal,
the U.K. National Institute for Health Research–supported Prostate Testing for Cancer and Treatment (ProtecT) trial has shown no significant difference in prostate-cancer–specific mortality or all-cause mortality among men with prostate cancer detected by prostate-specific antigen (PSA) testing who were randomly assigned to radical prostatectomy, active monitoring (a surveillance strategy), or radical conformal radiotherapy with neoadjuvant hormonal therapy, at a median of 10 years of follow-up; however, the ProtecT trial has shown higher rates of metastases and disease progression among men in the active-monitoring group than among men in the radical-treatment groups. . . .
Abstract Context Exercise could be beneficial for prostate cancer survivors. However, no systematic review across cancer stages and treatment types addressing potential benefits and harms exists to ...date. Objective To assess the effects of exercise on cancer-specific quality of life and adverse events in prostate cancer trials. Evidence acquisition We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, AMED, CINAHL, PsycINFO, SPORTDiscus, and PEDro. We also searched grey literature databases, including trial registers. Searches were from database inception to March 2015. Standardised mean differences (SMDs) were calculated for meta-analysis. Evidence synthesis We included 16 randomised controlled trials (RCTs) involving 1574 men with prostate cancer. Follow-up varied from 8 wk to 12 mo. RCTs involved men with stage I–IV cancers. A high risk of bias was frequently due to problematic intervention adherence. Seven trials involving 912 men measured cancer-specific quality of life. Pooling of the data from these seven trials revealed no significant effect on this outcome (SMD 0.13, 95% confidence interval CI –0.08 to 0.34, median follow-up 12 wk). Sensitivity analysis of studies that were judged to be of high quality indicated a moderate positive effect estimate (SMD 0.33, 95% CI 0.08–0.58; median follow-up 12 wk). Similar beneficial effects were seen for cancer-specific fatigue, submaximal fitness, and lower body strength. We found no evidence of benefit for disease progression, cardiovascular health, or sexual function. There were no deaths attributable to exercise interventions. Other serious adverse events (eg, myocardial infarction) were equivalent to those seen in controls. Conclusions These results support the hypothesis that exercise interventions improve cancer-specific quality of life, cancer-specific fatigue, submaximal fitness, and lower body strength. Patient summary This review shows that exercise/physical activity interventions can improve quality of life, fatigue, fitness, and function for men with prostate cancer.
Summary Background Vascular-targeted photodynamic therapy, a novel tissue-preserving treatment for low-risk prostate cancer, has shown favourable safety and efficacy results in single-arm phase 1 and ...2 studies. We compared this treatment with the standard of care, active surveillance, in men with low-risk prostate cancer in a phase 3 trial. Methods This randomised controlled trial was done in 47 European university centres and community hospitals. Men with low-risk, localised prostate cancer (Gleason pattern 3) who had received no previous treatment were randomly assigned (1:1) to vascular-targeted photodynamic therapy (4 mg/kg padeliporfin intravenously over 10 min and optical fibres inserted into the prostate to cover the desired treatment zone and subsequent activation by laser light 753 nm with a fixed power of 150 mW/cm for 22 min 15 s) or active surveillance. Randomisation was done by a web-based allocation system stratified by centre with balanced blocks of two or four patients. Best practice for active surveillance at the time of study design was followed (ie, biopsy at 12-month intervals and prostate-specific antigen measurement and digital rectal examination at 3-month intervals). The co-primary endpoints were treatment failure (histological progression of cancer from low to moderate or high risk or death during 24 months' follow-up) and absence of definite cancer (absence of any histology result definitely positive for cancer at month 24). Analysis was by intention to treat. Treatment was open-label, but investigators assessing primary efficacy outcomes were masked to treatment allocation. This trial is registered with ClinicalTrials.gov , number NCT01310894. Findings Between March 8, 2011, and April 30, 2013, we randomly assigned 206 patients to vascular-targeted photodynamic therapy and 207 patients to active surveillance. Median follow-up was 24 months (IQR 24–25). The proportion of participants who had disease progression at month 24 was 58 (28%) of 206 in the vascular-targeted photodynamic therapy group compared with 120 (58%) of 207 in the active surveillance group (adjusted hazard ratio 0·34, 95% CI 0·24–0·46; p<0·0001). 101 (49%) men in the vascular-targeted photodynamic therapy group had a negative prostate biopsy result at 24 months post treatment compared with 28 (14%) men in the active surveillance group (adjusted risk ratio 3·67, 95% CI 2·53–5·33; p<0·0001). Vascular-targeted photodynamic therapy was well tolerated. The most common grade 3–4 adverse events were prostatitis (three 2% in the vascular-targeted photodynamic therapy group vs one <1% in the active surveillance group), acute urinary retention (three 2% vs one <1%) and erectile dysfunction (two 1% vs three 1%). The most common serious adverse event in the vascular-targeted photodynamic therapy group was retention of urine (15 patients; severe in three); this event resolved within 2 months in all patients. The most common serious adverse event in the active surveillance group was myocardial infarction (three patients). Interpretation Padeliporfin vascular-targeted photodynamic therapy is a safe, effective treatment for low-risk, localised prostate cancer. This treatment might allow more men to consider a tissue-preserving approach and defer or avoid radical therapy. Funding Steba Biotech.
Abstract Context Androgen-deprivation therapy (ADT) is a key component of treatment for aggressive and advanced prostate cancer, but it has also been associated with adverse effects on bone, ...metabolic, cardiovascular, sexual, and cognitive health as well as body composition. Objective To review the current literature on the adverse effects of ADT and strategies for ameliorating harm from ADT. Evidence acquisition The Medline database (through PubMed) was searched from inception to August 1, 2013, for studies documenting the side effects of ADT and for randomized and prospective trials of interventions to mitigate those side effects. Evidence synthesis Adverse effects of ADT include decreases in bone mineral density; metabolic changes such as weight gain, decreased muscle mass, and increased insulin resistance; decreased libido and sexual dysfunction; hot flashes; gynecomastia; reduced testicle size; anemia; and fatigue. Several observational studies suggest an increased risk of diabetes and cardiovascular events, although most published studies report that ADT is not linked to greater cardiovascular mortality. Randomized trials have found value in treatments for some adverse effects including bone loss (bisphosphonates, denosumab, selective estrogen receptor modulators), markers of metabolic syndrome (exercise, diet, metformin), gynecomastia (tamoxifen, prophylactic radiation), muscle loss (resistance and aerobic exercise), and hot flashes (venlafaxine, medroxyprogesterone, cyproterone acetate, gabapentin). Conclusions ADT is often a necessary component of the treatment of aggressive prostate cancer, yet it has known harms that can impair health and quality of life. Clinicians should be aware of interventions that can help mitigate these adverse effects. Patient summary Androgen deprivation therapy is a critical component of the management of aggressive and advanced prostate cancer, but it causes adverse effects including bone loss, metabolic changes, gynecomastia, muscle loss, hot flashes, and possibly increased cardiovascular events. Clinicians should be aware of interventions that can help mitigate these adverse effects.
Background
This is an updated version of the original Cochrane Review published in the Cochrane Library 2013, Issue 9. Despite good evidence for the health benefits of regular exercise for people ...living with or beyond cancer, understanding how to promote sustainable exercise behaviour change in sedentary cancer survivors, particularly over the long term, is not as well understood. A large majority of people living with or recovering from cancer do not meet current exercise recommendations. Hence, reviewing the evidence on how to promote and sustain exercise behaviour is important for understanding the most effective strategies to ensure benefit in the patient population and identify research gaps.
Objectives
To assess the effects of interventions designed to promote exercise behaviour in sedentary people living with and beyond cancer and to address the following secondary questions: Which interventions are most effective in improving aerobic fitness and skeletal muscle strength and endurance? Which interventions are most effective in improving exercise behaviour amongst patients with different cancers? Which interventions are most likely to promote long‐term (12 months or longer) exercise behaviour? What frequency of contact with exercise professionals and/or healthcare professionals is associated with increased exercise behaviour? What theoretical basis is most often associated with better behavioural outcomes? What behaviour change techniques (BCTs) are most often associated with increased exercise behaviour? What adverse effects are attributed to different exercise interventions?
Search methods
We used standard methodological procedures expected by Cochrane. We updated our 2013 Cochrane systematic review by updating the searches of the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, Embase, AMED, CINAHL, PsycLIT/PsycINFO, SportDiscus and PEDro up to May 2018. We also searched the grey literature, trial registries, wrote to leading experts in the field and searched reference lists of included studies and other related recent systematic reviews.
Selection criteria
We included only randomised controlled trials (RCTs) that compared an exercise intervention with usual care or 'waiting list' control in sedentary people over the age of 18 with a homogenous primary cancer diagnosis.
Data collection and analysis
In the update, review authors independently screened all titles and s to identify studies that might meet the inclusion criteria, or that could not be safely excluded without assessment of the full text (e.g. when no is available). We extracted data from all eligible papers with at least two members of the author team working independently (RT, LS and RG). We coded BCTs according to the CALO‐RE taxonomy. Risk of bias was assessed using the Cochrane's tool for assessing risk of bias. When possible, and if appropriate, we performed a fixed‐effect meta‐analysis of study outcomes. If statistical heterogeneity was noted, a meta‐analysis was performed using a random‐effects model. For continuous outcomes (e.g. cardiorespiratory fitness), we extracted the final value, the standard deviation (SD) of the outcome of interest and the number of participants assessed at follow‐up in each treatment arm, to estimate the standardised mean difference (SMD) between treatment arms. SMD was used, as investigators used heterogeneous methods to assess individual outcomes. If a meta‐analysis was not possible or was not appropriate, we narratively synthesised studies. The quality of the evidence was assessed using the GRADE approach with the GRADE profiler.
Main results
We included 23 studies in this review, involving a total of 1372 participants (an addition of 10 studies, 724 participants from the original review); 227 full texts were screened in the update and 377 full texts were screened in the original review leaving 35 publications from a total of 23 unique studies included in the review. We planned to include all cancers, but only studies involving breast, prostate, colorectal and lung cancer met the inclusion criteria. Thirteen studies incorporated a target level of exercise that could meet current recommendations for moderate‐intensity aerobic exercise (i.e.150 minutes per week); or resistance exercise (i.e. strength training exercises at least two days per week).
Adherence to exercise interventions, which is crucial for understanding treatment dose, is still reported inconsistently. Eight studies reported intervention adherence of 75% or greater to an exercise prescription that met current guidelines. These studies all included a component of supervision: in our analysis of BCTs we designated these studies as 'Tier 1 trials'. Six studies reported intervention adherence of 75% or greater to an aerobic exercise goal that was less than the current guideline recommendations: in our analysis of BCTs we designated these studies as 'Tier 2 trials.' A hierarchy of BCTs was developed for Tier 1 and Tier 2 trials, with programme goal setting, setting of graded tasks and instruction of how to perform behaviour being amongst the most frequent BCTs. Despite the uncertainty surrounding adherence in some of the included studies, interventions resulted in improvements in aerobic exercise tolerance at eight to 12 weeks (SMD 0.54, 95% CI 0.37 to 0.70; 604 participants, 10 studies; low‐quality evidence) versus usual care. At six months, aerobic exercise tolerance was also improved (SMD 0.56, 95% CI 0.39 to 0.72; 591 participants; 7 studies; low‐quality evidence).
Authors' conclusions
Since the last version of this review, none of the new relevant studies have provided additional information to change the conclusions. We have found some improved understanding of how to encourage previously inactive cancer survivors to achieve international physical activity guidelines. Goal setting, setting of graded tasks and instruction of how to perform behaviour, feature in interventions that meet recommendations targets and report adherence of 75% or more. However, long‐term follow‐up data are still limited, and the majority of studies are in white women with breast cancer. There are still a considerable number of published studies with numerous and varied issues related to high risk of bias and poor reporting standards. Additionally, the meta‐analyses were often graded as consisting of low‐ to very low‐certainty evidence. A very small number of serious adverse effects were reported amongst the studies, providing reassurance exercise is safe for this population.
Objectives To measure the effect of the adverse events within 35 days of transrectal ultrasound guided biopsy from the perspective of asymptomatic men having prostate specific antigen (PSA) testing; ...to assess early attitude to re-biopsy; to estimate healthcare resource use associated with adverse events due to biopsy; and to develop a classification scheme for reporting adverse events after prostate biopsy.Design Prospective cohort study (Prostate Biopsy Effects: ProBE) nested within Prostate Testing for Cancer and Treatment (ProtecT) study.Participants Between 1999 and 2008, 227 000 community dwelling men aged 5069 years were identified at 352 practices and invited to counselling about PSA testing. 111 148 attended a nurse led clinic in the community, and 10 297 with PSA concentrations of 3-20 ng/mL were offered biopsy within ProtecT. Between February 2006 and May 2008, 1147/1753 (65%) eligible men (mean age 62.1 years, mean PSA 5.4 ng/mL) having 10 core transrectal ultrasound guided biopsy under antibiotic cover in the context of ProtecT were recruited to the ProBE study.Outcome measures Purpose designed questionnaire administered at biopsy and 7 and 35 days after the procedure to measure frequency and effect of symptoms related to pain, infection, and bleeding; patients’ attitude to repeat biopsy assessed immediately after biopsy and 7 days later; participants’ healthcare resource use within 35 days of biopsy evaluated by questionnaire, telephone follow-up, and medical note review; each man’s adverse event profile graded according to symptoms and healthcare use.Results Pain was reported by 429/984 (43.6%), fever by 172/985 (17.5%), haematuria by 642/976 (65.8%), haematochezia by 356/967 (36.8%), and haemoejaculate by 605/653 (92.6%) men during the 35 days after biopsy. Fewer men rated these symptoms as a major/moderate problem—71/977 (7.3%) for pain, 54/981 (5.5%) for fever, 59/958 (6.2%) for haematuria, 24/951 (2.5%) for haematochezia, and 172/646 (26.6%) for haemoejaculate. Immediately after biopsy, 124/1142 (10.9%, 95% confidence interval 9.2 to 12.8) men reported that they would consider further biopsy a major or moderate problem: seven days after biopsy, this proportion had increased to 213/1085 (19.6%, 17.4% to 22.1%). A negative attitude to repeat biopsy was associated with unfavourable experience after the first biopsy, particularly pain at biopsy (odds ratio 8.2, P<0.001) and symptoms related to infection (7.9, P<0.001) and bleeding (4.2, P<0.001); differences were evident between centres (P<0.001). 119/1147 (10.4%, 8.7% to 12.3%) men reported consultation with a healthcare professional (usually their general practitioner), most commonly for infective symptoms. Complete data for all index symptoms at all time points were available in 851 participants. Symptoms and healthcare use could be used to grade these men as follows: grade 0 (no symptoms/contact) 18 (2.1%, 1.3% to 3.3%); grade 1 (minor problem/no contact) 550 (64.6%, 61.4% to 67.8%); grade 2 (moderate/major problem or contact) 271 (31.8%, 28.8% to 35.1%); grade 3 (hospital admission) 12 (1.4%, 0.8% to 2.4%); and grade 4 (death) 0. Grade of adverse event was associated with an unfavourable attitude to repeat biopsy (Kendall’s τ-b ordinal by ordinal 0.29, P<0.001).Conclusion This study with a high response rate of 89% at 35 days in men undergoing biopsy in the context of a randomised controlled trial has shown that although prostate biopsy is well tolerated by most men, it is associated with significant symptoms in a minority and affects attitudes to repeat biopsy and primary care resource use. These findings will inform men who seek PSA testing for detection of prostate cancer and assist their physicians during counselling about the potential risks and effect of biopsy. Variability in the adverse event profile between centres suggests that patients’ outcomes could be improved and healthcare use reduced with more effective administration of local anaesthetic and antibiotics.Trial registration Current Controlled Trials ISRCTN20141297.
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