International organizations consider prostate cancer screening low-priority and provide minimal guidance on implementation for low- and middle- income countries (LMICs).¹ While seeking strategies to increase prostate cancer screening access, LMICs may rely on recommendations that may not be transferable to their settings and seek cost-cutting strategies with suboptimal health benefits. We used Mexico’s prostate cancer screening efforts to illustrate the challenges LMICs face and, although not completely transferable, provide considerations to be made by policymakers.

PSA-based early detection for prostate cancer is the subject of an intense debate. Implementation of organized prostate cancer screening has been challenging, in part because the PSA test is so amenable to opportunistic screening. In the US, younger men (i.e. 50-54 years) have been under-screened while older men have been screened without considering life-expectancy. The widespread adoption of the threshold of a 4 ng/mL PSA independent of age or other risk factors led to clinically significant tumors being missed, while also prompting substantial follow-up testing for clinically irrelevant disease or benign conditions.² The “normal” PSA level is much <4 ng/mL. Robust prospective data show that median PSA levels in men in their 40s and 50s are below 0.9 ng/mL and that a threshold ≥1.0 ng/mL in men aged 40-54 years would identify a large majority of aggressive cancers.^3,4Thus, men aged 40-49 years with PSA levels below 0.68 ng/mL could safely forgo repeated screening for a decade. There is growing agreement that PSA-based early detection of high-risk disease reduces prostate cancer mortality and with a smarter PSA-based screening approach the potential harms of screening could be avoided.

The Global Burden of Disease study ranks prostate cancer as the leading cause of cancer mortality in Mexican men (age standardized mortality=19 per 100 000), while increased public awareness and the ease of PSA testing have placed prostate cancer as a public health priority. Currently, the major publicly funded insurance schemes (covering 85% of the population) offers full treatment coverage for prostate cancer. Late in 2017, health authorities in Mexico published a legally binding national prostate cancer screening guideline stating that all Mexican men ≥45 years should be screened using digital rectal examination and PSA (men with a family history of prostate cancer should begin at age 40).⁵ Implementation of this recommendation would require regular screening of more than 15 million Mexican men in an already under-resourced healthcare system. The controversial feature of this guideline is underscoring ≥4 ng/mL PSA as the threshold for early detection of prostate cancer, with the additional endorsement of capillary blood qualitative PSA test based on this threshold.⁶ Only when PSA is ≥4 ng/mL will the qualitative test read “positive,” a result that, according to the guideline, should indicate a subsequent confirmatory quantitative PSA test. The use of this qualitative test may appear to be of lower cost and increase access to screening. However, as noted above the qualitative test ignores our current knowledge of prostate biology. Clearly a one-size-fits-

all construction of PSA as a binary variable is suboptimal for a population with mixed age and genetic risk, and use of a qualitative test may result in high proportion of false negatives in men with high-risk disease and increase health costs rather than lower them.