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Prostate cancer is the most common noncutaneous malignancy in men and the second leading cause of cancer death in men. Screening offers the ability to detect prostate cancer before it becomes symptomatic. Until the late 1980’s, men were usually diagnosed at a late stage when it had already spread to the bones and caused pain. At this stage, treatment options are limited, and the prognosis is poor. However, since the FDA approved the use of prostate-specific antigen (PSA) in screening for prostate cancer in 1994, most cancers are diagnosed when they are still confined to the prostate.
Despite this achievement, current screening recommendations from the US Preventative Services Task Force (USPSTF) are quite weak. For men aged 55-69, the recommendation reads “the decision to undergo periodic prostate-specific antigen (PSA)-based screening for prostate cancer should be an individual one.” And for men 70 years and older, they actually recommend AGAINST screening (Grossman). Without strong guidance from the medical community, many men are left feeling unsure about what to do. To help you make the best decision for your own health, we are breaking down the arguments against and for screening, supported by the literature.
The arguments against screening
PSA is far from a perfect test for prostate cancer (digital rectal exam is even worse and won’t be discussed at all here). It is a protein made by both cancerous and noncancerous tissue in the prostate. Elevated PSA can mean cancer, but it is also seen with enlarged or inflamed prostates. It has also been found to temporarily go up after sex and COVID-19 infection. On the other hand, a “normal” PSA (historically considered as ≤4 ng/mL) is no guarantee of being cancer-free. A 2004 study of 2950 men with PSA ≤4 ng/mL who underwent prostate biopsy found prostate cancer in 15.2% of patients, 14.9% of which was clinically-significant (Gleason 7 or greater)(Thompson).
Let’s say that a patient’s elevated PSA prompts a biopsy. The most common next step would be a transrectal ultrasound-guided (TRUS) biopsy. TRUS biopsies do not specifically target any prostate masses. Rather, the ultrasound imaging is used to help the urologist biopsy 12 scattered areas throughout the prostate with the goal of sampling any cancer present. Unfortunately, this method is far from perfect. A large, multicenter trial found the sensitivity of the traditional TRUS biopsy was only 48% (Ahmed). That means that fewer than half of prostate cancers would be detected by TRUS. There is a type of biopsy called a saturation biopsy which obtains 20-50 samples throughout the prostate in an effort to improve sensitivity, however this increases patient discomfort and complications, and is not commonly performed.
Even if an elevated PSA leads to a biopsy which leads to the diagnosis of cancer, treatment may not extend the patient’s life. In many cases, a small, low-grade cancer is discovered which would likely never spread or metastasize. The patient may choose active surveillance or watchful waiting rather than treatment, but they will be burdened with the knowledge that they have cancer, which has been shown to have a negative impact on the quality of life (Arredondo and Pickles).
If the patient decides to undergo radical prostatectomy or radiation therapy, he may experience a number of debilitating side effects such as erectile dysfunction or urinary incontinence. While some men may consider this a small price to pay for a “cure” (recurrences occur in 20-30%), many end up regretting their decision (Slomski). For this reason, only the subset of clinically-significant cancers are worth finding and treating.
The arguments for screening
The whole goal of screening is to detect cancer when it is confined to the prostate and when treatment can extend a patient’s life. A new study presented at the annual meeting of the American Society for Radiation Oncology (ASTRO) demonstrated this in action. More than 5 million men older than 40 years at 128 VA facilities were studied, and researchers found that when screening was not encouraged, the diagnosis of advanced cancers were more frequent. Between 2005 and 2019, the overall rates of screening with PSA dropped from 47.2% to 37%, and over the same period the rate of metastatic prostate cancer diagnoses rose from 5.2 to 7.9 per 100,000 men. In individual facilities, every 10% decrease in screening was associated with a corresponding 10% increase in the incidence of metastatic prostate cancer five years later. On the other hand, higher screening rates at individual facilities were associated with lower rates of subsequent diagnoses of metastatic cancers (Lapid).
That’s great, but what about the pathetically low sensitivity of TRUS biopsies? And what about overdiagnosing clinically-insignificant cancers that would probably never kill the patient, but would stress patients out after being discovered? Enter multiparametric MRI (mpMRI). mpMRI utilizes a specific protocol of sequences designed to evaluate the prostate for clinically-significant cancer. The negative predictive value of mpMRI has been reported to be 91-100% (Martins). That means that if there is no suspicious lesion on mpMRI, you can be 91-100% sure there are no clinically-significant cancers (not bad!) Improved visualization of prostate cancer on MRI has also allowed targeted biopsies of tumors, rather than the random sampling with traditional TRUS biopsies.
A groundbreaking multicenter randomized controlled trial published in the New England Journal of Medicine in 2018 sought to determine if these new techniques could improve detection of clinically-significant cancers while minimizing detection of clinically-insignificant cancers. They randomly assigned patients with elevated PSA to either have a standard TRUS biopsy or MRI-targeted biopsy. In the latter group, a mpMRI was performed first and if there were no suspicious findings, no biopsy was performed. If a suspicious lesion was found, biopsy was performed using MRI guidance. They found that clinically-significant cancer was diagnosed in 38% in the MRI-targeted biopsy group, compared with 26% of the TRUS biopsy group. They also found that there were 13% fewer clinically-insignificant prostate cancers diagnosed in the MRI-targeted biopsy group than the TRUS biopsy group (Kasivisvanathan). So PSA + MRI-targeted biopsies found more clinically-significant cancers and fewer clinically-insignificant cancers than traditional biopsies.
Conclusion
PSA alone is not nearly a perfect test for prostate cancer. However, when combined with mpMRI, it has been shown to detect more clinically-significant cancers and fewer clinically-insignificant cancers. And increased rates of screening have been shown to decrease rates of metastatic disease by finding cancers at an earlier stage. As of right now, the USPSTF has not updated its guidelines to reflect the findings of these newer studies. Until that happens, patients should do their own research and make their own choices based on the most current information available.
References
Grossman DC, Curry SJ, et al. US Preventive Services Task Force, Screening for Prostate Cancer: US Preventive Services Task Force Recommendation Statement. JAMA 2018; 319(18):1901–1913.
Thompson et al. Prevalence of Prostate Cancer among Men with a Prostate-Specific Antigen Level ≤4.0 ng per Milliliter. NEJM 2004; 350:2239-46.
Barry MJ. Clinical practice. Prostate-specific-antigen testing for early diagnosis of prostate cancer. New England Journal of Medicine 2001; 344(18):1373–1377.
Ahmed HU et al. Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study. Lancet 2017; 389: 815–822
Arredondo SA et al. Watchful waiting and health related quality of life for patients with localized prostate cancer: Data from CaPSURE, J. Urol. 172 (2004) 1830–1834
Pickles T et al. Psychosocial barriers to active surveillance for the management of early prostate cancer and a strategy for increased acceptance, BJU Int 100 (2007) Slomski A. Some Men With Localized Prostate Cancer Regret Surgery. JAMA 2022;327(1):26.
Martins M et al. The diagnostic accuracy of multiparametric MRI for detection and localization of prostate cancer depends on the affected region. BJUI 2021;2:178-187.
Kasivisvanathan V et al. MRI-targeted or standard biopsy for prostate-cancer diagnosis. New England Journal of Medicine 2018;
