Summary of Harms from Screening and Treatment for Prostate Cancer

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1 DRAFT: Advice from Dr John Childs MoH advisor Summary of Harms from Screening and Treatment for Prostate Cancer There are minimal risks directly attributable to PSA testing or transrectal ultrasound (TRUS) biopsy. The significant harms are those from prostate cancer treatment and are particularly of concern when treatment complications are a consequence of over diagnosis and treatment. Reports on the psychological impacts of prostate cancer diagnosis and treatment are limited. Studies reporting complications from TRUS biopsy show that it is a safe procedure with the common complications of rectal pain, rectal bleeding, urinary bleeding and infection being transient and self limiting. The risk of serious complications such as severe infection, major bleeding or urinary retention from TRUS biopsy requiring hospital admission occur in less than 2% of men. Deleted: The limited studies reporting Surgical prostatectomy and radiotherapy techniques can all cause complications however recent data suggests that newer techniques may reduce the risk of some complications. Prostatectomy has higher risks than radiation therapy of causing short-term urinary incontinence and sexual dysfunction; however the longer-term sexual dysfunction may be similar. Radiation treatment has a higher risk of short and long-term bowel side effects than surgery. Among the radiation options, conventional external beam radiotherapy such as 3D conformal Radiotherapy (3D CRT) and intensity modulated radiation treatment (IMRT) have a higher risk for bowel complications compared to brachytherapy. The data on newer techniques such as IMRT and robotic-assisted prostatectomy are too preliminary to make definitive conclusions about whether the overall complication risks are less. The main complications of surgical prostatectomy are: Perioperative mortality Major and minor procedure-related complications (e.g., bowel injury) Urethral stricture Acute (3 mo) and late (12 mo or more) urinary incontinence Acute and late erectile dysfunction There are many case series and reviews published since 2003 on the short and long term risks associated with radical prostatectomy, however good quality studies on comparison of harms across the different surgical approaches are limited. Most of the comparison can only be made indirectly across studies of different patient groups with differing clinical characteristics and approaches to measurement of the complications. The recent studies continue to give rise to a wide range of estimates with a significant degree of overlap between surgical approaches. A summary of data is presented in table

2 Table B Estimates of short and long term complications from surgery Complication Risk estimate Comment Urethral stricture 0% to 15% Evidence show rates have declined over time with evolving surgical techniques Pooled rate early studies 5.3% Pooled rate since % Urinary Incontinence Urinary incontinence longer term Erectile dysfunction Erectile dysfunction long term 8% to 65% There is wide variation across studies Comparisons across surgical approaches are difficult to evaluate For most men this resolves within 12 months 5% to 15% Variable rates and severity of incontinence at 12 to 24 months Longer term difficult to evaluate 50% to 90% First 3 months after surgery 50% to 80% Wide range data supports that long term rates are lower following nerve sparing procedure Nerve sparing estimate 30% to 50% Results often complicated by use of hormone therapy Note: Adapted from Ollendorf et al. (2009) Deleted: This is a pooled rate from various studies W Mortality from prostatectomy is rare reported at less than 1 percent and major post operative procedure complications such as haemorrhage, deep venous thrombosis and cardiovascular events are uncommon are estimated to occur in 3 to 4 percent of men. Minor complications such as infection, transient bowel problems and blood loss have been estimated to occur in up to 8 or 9 percent of men. Reported post operative complications vary widely and are dependent on surgeon experience, patient factors, the extent of cancer and the type of prostatectomy procedure. There is a wide range of risk reported for short and longer term complications from prostatectomy. Rates of urethral stricture vary from less than 1% to 15% however more recent studies suggest that the risk of stricture has declined over time with improved prostatectomy procedures. Short-term urinary incontinence remains a significant problem following radical prostatectomy, regardless of surgical approach. Up to 40% of patients are reported to have incontinence at 3 months post-surgery, however for many men this will be minor and it resolves for most men twelve or more months after surgery. Reports show that that 5 to 15 percent of men will require occasional or consistent use of a pad longer term. Deleted: which Short- and long-term erectile dysfunction (impotence) remains a significant concern among men undergoing radical prostatectomy, regardless of approach. Up to 80% of men may experience erectile dysfunction in the first three months following surgery however this improves over the first 12 months. 30 to 50 percent of men who were potent prior to bilateral nerve-sparing surgery will have - 2 -

3 erectile dysfunction 12 months following surgery however the estimated risk for erectile dysfunction following non nerve sparing surgery is 50 to 80 percent. Other aspects such as libido and orgasm are not affected by surgery and many men can be helped with the range of drugs commonly used for treatment of erectile impotence. The main complications from radiation treatment are: Acute effects (these are transient and usually resolve within 6 weeks of completing treatment) Bowel symptoms Bladder symptoms Other general effects (such as skin reaction and fatigue) Late complications (These develop after 3 months and may be progressive) Altered bowel habit including bowel incontinence Persistent urinary symptoms Erectile dysfunction (impotence) Second Malignancy A summary of radiation complications is provided in table 2. Table 2: Short and Long Term from Radiotherapy Complication Bowel Bowel Long term Urinary Short Term Urinary Long term Erectile dysfunction long term External Beam (3D CRT) IMRT Brachytherapy Not assessed 3% to 50% 0 to 10% 10% to 21% 1.6% to 24% 0 to 13% Not assessed 6.9% to 49% 10% to 5% 8% to 23% 6% to 23% 0 to 40% 28% to 39% 48 to 49% 14% to 43% Note: Adapted from Stanley Ip et al. (2010) The risk and severity of late effects from radiation treatment reported in recent studies are difficult to evaluate because of the widely varying populations and study methodologies. The acute (early) side effects from radiation are usually of - 3 -

4 minor intensity however a small proportion of men will have more significant acute complications. The long term effects from radiation treatment are of more concern. The reports on erectile dysfunction are of variable quality and may be similar to those for nerve sparing prostatectomy with estimated rate of 30 to 45 percent at 2 years following treatment. Reports suggest that brachytherapy erectile failure may respond well to drugs that are commonly used to treat erectile impotence from other causes. Significant bowel complications are reported in about 5 percent to 15 percent of men and appear to be higher following conventional external beam radiotherapy (3D CRT) and IMRT approaches compared to brachytherapy. However firm conclusions cannot be made about the advantages of IMRT or brachytherapy compared to conventional external beam radiotherapy because of limited comparative evidence Deleted: Bowel The risk of second malignancy from radiation treatment is estimated at 0.5 to 1 percent. The option for prostatectomy is relevant for younger men to reduce the risk for second malignancy. Although there have been early reports of quality of life data from the ERSPC and PLCO trials their results are consistent with more recent evidence. It is expected that further information on treatment harms and the impact on quality of life will be reported from these two studies. At present there is still insufficient evidence to assess whether the potential benefits reported in the ERSCP and Goteborg studies outweigh the harms. However many clinicians and men believe that the evidence of benefit outweighs the harms. The current evidence means that adverse effects associated with treatment options should be discussed on an individual basis with men and should be weighed alongside the risk of mortality and risk of problems from advanced disease. References Stanley Ip, Tomas Dvorak, Winifred Yu et al. Comparative evaluation Prostate of Radiation Treatments for clinically localised prostate cancer: an Update Agency for Healthcare Research and Quality (AHRQ) Technology Assessment Tufts Evidence Based Practice Centre August Ollendorf DA, Hayes J, McMahon P, Kuba M, Pearson SD. Management options for low-risk prostate cancer: a report on comparative effectiveness and value. Boston, MA: Institute for Clinical and Economic Review, December 2009: Available at: - 4 -

5 Wilt TJ, MacDonald R, Rutks I et al. Systematic review: comparative effectiveness and harms of treatments for clinically localised prostate cancer. Ann Intern Med Mar 18;148(6): Epub 2008 Feb 4. Deleted: Review of literature by Schaeffer and Walsh, Johns Hopkins, Urological Clinics of North America, 37: 49-55, Update of evidence for prostate-specific antigen (PSA) testing in asymptomatic men: Evidence report prepared for Ministry of Health, New Zealand New Zealand Guidelines Group November