Prostate cancer is among the most commonly diagnosed cancers in men worldwide, underscoring the necessity of effective screening tools for early detection and mortality prevention [1]. Risk calculators based on patient demographics, clinical parameters, and biomarker data help define individualized risk and can assist providers and patients to drive personalized screening pathways. Novel prostate cancer risk calculators should be instrumental in reducing over-diagnosis while enhancing early detection of clinical-significant cases, with the goals of decreasing mortality rates while also decreasing overtreatment of biologically indolent cancers. However, a significant concern with many of the studies reporting novel risk calculators is their lack of external validity. This raises questions about the accuracy and reliability of these tools across different populations, which could lead to missed diagnoses or over-diagnosis in certain patient groups.

We eagerly read the systematic review by Denijs et al. reporting on risk calculators for the detection of prostate cancer [2]. Recognizing that PSA-based prostate cancer screening is fraught with lack of specificity, it is commendable that so much effort has been put forth to develop risk calculators for patient-specific guidance in the diagnosis of this malignancy. The ideal goals of risk stratification would be to optimize early detection of clinically impactful prostate cancers while overcoming the historical challenges of overdiagnosis and overtreatment of biologically indolent prostate cancers, which have had a measurably significant quality-of-life burden across generations of men.

With the addition of imaging with multiparametric MRI into the diagnostic landscape, we have found high-fidelity colocalization of imaging areas of suspicion and foci of clinically-significant prostate cancer with a less common diagnosis of low-grade, low-volume disease [3]. Due to its widespread use and high fidelity, the integration of MRI findings, as a functional biomarker of risk, is critical in the current and future generations of risk calculators used for prostate cancer detection [4]. Hence, risk calculators integrating MRI findings when available, can truly derive recommendations based on readily available, pre-biopsy datapoints to help guide shared decision-making in the pre-biopsy setting, with the ultimate goals of minimizing the number and frequency of biopsies, without compromising the diagnosis of clinically-significant prostate cancers that would benefit from early diagnosis and curative treatment [5, 6].

Additionally, the importance of developing widespread applicability of risk calculators by external validation across multiple institutions, allows for broad utilization and a measurable patient impact globally [7,8,9]. Furthermore, it is imperative to ensure that diverse populations are represented in risk calculators, to be reflective of the populations they are intended to serve, particularly as there are well-recognized, multifactorial disparities in the diagnosis and care pathways for patients with prostate cancer [10].

It is also worth noting that maintaining an existing risk calculator, even if it initially performs poorly with a new patient population, could be a valuable approach. This phenomenon may partly explain why so many published risk calculators have undergone only internal validation or a limited degree of external validation. Janssen et al. suggest that building on the accumulated knowledge of existing risk calculators may be more beneficial than developing a completely new risk calculator [11]. Additionally, the integration of artificial intelligence and natural language processing into the landscape of medical decision-making will likely be transformative [12]. The use of these technologies may propose optimized workflows and use of risk calculators that have been vetted and most appropriate for a given patient based upon patient demographics, clinical criteria, and biomarker profiles available for evaluation [13]. These evolving strategies could lead to a more effective, standardized risk calculator formulation and utilization, making a more global impact over risk calculators serving a more narrow population based on limited external proven validity.

The impetus to create and validate risk calculators that use readily available clinical and biomarker datapoints, which are representative of the population, and have high validity to predict the presence of clinically-significant prostate cancer as an impactful endpoint, will hopefully shift the field toward routine adoption and use of these tools.