Editing AUA: Prostate Cancer Screening (2018) (section)

== Evidence base ==

* In a 2013 systematic review, 6 well known randomized trials addressed the question of mortality benefit of prostate cancer screening. 
* 3 trials (PLCO, ERSPC, Goteborg) are considered relevant due to limitations of the Stockholm, Quebec, and Norrkoping trials ('''See [[Prostate Cancer: Screening|Prostate Cancer Screening Chapter Notes]]''').
** The PLCO and ERSPC randomized trials ultimately addressed different questions: screening versus no or little screening in ERSPC as compared to annual screening versus usual care in the PLCO trial. A modest effect of PSA screening versus none in PLCO implies that a substantially larger study than PLCO is needed to meaningfully test more versus less frequent screening. Thus, PLCO was underpowered to address the question of organized versus opportunistic screening. The Panel interprets the randomized evidence to indicate that the ERSPC trial reflects the effect of PSA screening in a situation with low background screening and the estimate for the effect of screening (versus no screening) on prostate cancer-specific mortality was obtained from the ERSPC trial.
* '''Benefits of PSA screening (3)'''
*# '''Reduced prostate-cancer specific mortality'''
*#* Risk of dying of prostate cancer is about 3% over a lifetime on average
*#* Numbers needed to invite to screen and additional number needed to diagnose to avoid one prostate cancer death in the ERSPC (11 years of follow-up) and the Goteborg (14 years of follow-up) studies are as follows: 1,055 to invite and 37 to diagnose, 293 to invite and 12 to diagnose, respectively. However, these estimates are extremely sensitive to follow-up duration and are likely to be much lower over the long term
*#* Several studies have revealed a significant reduction in prostate cancer specific mortality rates attributable to PSA-based screening for prostate cancer.
*#* Population-based studies have found that the introduction of PSA-based prostate cancer screening was followed by subsequent dramatic reductions in prostate cancer mortality.
*# '''Reduced risk of metastatic disease'''
*#* In ERSPC, the cumulative risk of metastatic disease at 9 to 11 years of follow-up was 31-33% lower in the screened arm compared to the control arm. The Goteborg arm of the trial demonstrated a 56% reduction in risk of metastatic disease
*# '''Lower stage and grade of cancer at diagnosis'''
*#* Almost all of the randomized studies that have evaluated PSA-based screening for prostate cancer have demonstrated a benefit in terms of lower stage and grade of cancer at diagnosis
* '''Potential harms of screening'''
** '''Risks of biopsy'''
***The transrectal or transperineal prostate biopsy has risks of hematuria, hematochezia, hematospermia, dysuria and retention, pain and infection. 
****Hematuria and hematospermia are the most frequently observed side effects with wide variation in observed rates. 
*****Hematospermia after biopsy occurs in 10-70% of patients while hematuria is seen 14-50% of the time.
****Risk of hospitalization due to bleeding complications remains low
**** Infectious complications
*****Increasing steadily over time, possibly due to fluoroquinolone resistance. 
******'''The 30-day risk of hospitalization after biopsy for any cause has been estimated to be approximately 4%''', of which 3/4 are for infections. 
******The use of routine fecal culture and sensitivity tailored antibiotic prophylaxis may be one approach to reduce infection rates.
* Modeling studies have yielded the following inferences that are particularly pertinent for screening policy development. 
**First, PSA screening yields survival benefits that have contributed, to some extent, to the dramatic and sustained drop in prostate cancer death rates in this country. 
**Second, PSA screening advances prostate cancer diagnosis by five to six years on average. 
**Approximately one in four screen-detected cases reflects overdiagnosis. 
**Strategies that screen less frequently than every year, and even less frequently for men with low PSA levels, are likely to be of value in reducing costs and harms while preserving most of the potential benefit of PSA-based screening.
* '''In 2018, USPSTF used modeling studies in the development of the most recent grade C recommendation for PSA-based prostate cancer screening'''
** '''Grade C: selectively offering or providing this service to individual patients based on professional judgment and patient preferences'''
* '''Biopsy trigger'''
** Multiple approaches subsequent to a PSA test (urinary and serum biomarkers, imaging) are available for identifying men more likely to harbor a prostate cancer and/or one with an aggressive phenotype
** The use of novel markers, imaging, and/or risk calculators can be considered for prostate biopsy decisions in men with a suspicious PSA level to inform biopsy decisions.
***At this point, the use of DRE, PSA derivatives (PSA density and age specific reference ranges) and PSA kinetics (velocity and doubling time), PSA molecular forms (percent free PSA and proPSA), novel urinary markers (PCA3), and prostate imaging should be considered secondary tests (not primary screening tests) with potential utility for determining the need for a prostate biopsy, but with unproven benefit as primary screening tests.
****The Panel recognizes that these tests can be used as adjuncts for informing decisions about the need for a prostate biopsy –or repeat biopsy- after PSA screening, but emphasizes the lack of evidence that these tests will increase the ratio of benefit to harm.
** Risk calculators that include multiple variables (in addition to PSA) as an aid to predicting the risk of prostate cancer have not been proven to increase the benefit to harm ratio, and their value in predicting cancer on biopsy is not necessarily generalizable to a population that differs from that in which the tool was developed. 
***No defined threshold based on calculator as to when to biopsy