Comments on “Risk factors for low‐risk prostate cancer: A retrospective cohort study within the <scp>FinRSPC</scp> trial”

We read with great interest the article by Okwor et al. entitled “Risk factors for low-risk prostate cancer: A retrospective cohort study within the FinRSPC trial”.1 The authors provide an elegant and comprehensive analysis of determinants of low-risk prostate cancer (PC), highlighting their distinction from those associated with high-risk PC. This well-designed study significantly contributes to the ongoing discussion on the balance of benefits and harms of prostate-specific antigen (PSA) screening. Nevertheless, we would like to offer some constructive perspectives that may further enrich the interpretation and future direction of this important work. The authors reported that family history and the use of 5-alpha reductase inhibitors (5-ARIs) were more strongly associated with low-risk PC than high-risk PC, whereas age demonstrated a consistent gradient only for high-risk disease.1 These findings suggest that the drivers of detection for low-risk PC are closely related to health-care utilization patterns rather than underlying tumor aggressiveness. We believe this raises an important theoretical consideration: the possibility that low-risk PC represents not merely a biological indolence but a “diagnostic entity” emergent from medical surveillance intensity. Prior literature has argued that Gleason 6 lesions, in particular, may not meet the hallmarks of malignancy and could instead be re-conceptualized as indolent neoplasms with limited malignant potential.2 Placing the present results into this conceptual framework underscores that the elevated incidence of low-risk PC in screened populations may reflect the interaction between health-care practices and tumor biology, rather than a distinct carcinogenic pathway. This deeper theoretical interpretation adds nuance to the study's conclusion that low- and high-risk PC may represent distinct disease entities, and highlights how diagnostic context shapes disease classification. Furthermore, the study convincingly demonstrated that the risk of high-risk PC increased steadily with age, while low-risk PC incidence remained stable across screening rounds.1 While the authors rightly focused on the immediate screening outcomes, we would emphasize the importance of considering potential long-term consequences of labeling men with low-risk PC. Evidence from long follow-up cohorts indicates that men diagnosed with Gleason 6 PC may experience increased anxiety, health-care dependence, and a higher probability of receiving deferred radical interventions despite initially indolent disease.3 The long-term psychosocial and iatrogenic burden associated with low-risk diagnoses may therefore amplify the harms of overdiagnosis beyond the short-term overtreatment rates captured in clinical records. Integrating this dimension would strengthen the article's call for balancing screening benefits with harms, as it highlights that the downstream effects of overdiagnosis extend beyond survival outcomes and persist over decades. Finally, we appreciate the authors' detailed discussion of family history and 5-ARI exposure, yet one important research gap remains: the absence of patient-reported outcomes in evaluating the impact of low-risk PC detection. While the clinical determinants of incidence are well characterized, patient experiences, values, and preferences are critical in shaping decision-making regarding screening and subsequent management. Studies have shown that men often weigh quality of life, treatment side effects, and the psychological burden of a cancer diagnosis as heavily as survival benefit when evaluating screening.4 Future research should therefore integrate patient perspectives into models of risk–benefit assessment, as this could refine counseling strategies and ensure that screening policies are aligned not only with epidemiological evidence but also with the lived realities of patients. Identifying this gap underscores the importance of broadening the evidence base to include outcomes most meaningful to those directly affected by overdiagnosis. In conclusion, Okwor et al. have provided an important and meticulously conducted analysis that advances our understanding of the differential determinants of low- and high-risk PC. Our comments aim to deepen the theoretical framing, extend consideration to long-term consequences, and emphasize the need for patient-centered outcomes in future research. We believe that addressing these points will make an already excellent contribution even more impactful and further facilitate the development of balanced screening strategies in prostate cancer. Jingxuan Dai: Conceptualization; investigation; validation; methodology; writing – review and editing; writing – original draft. Xuancheng Zhou: Supervision; validation; writing – review and editing; writing – original draft. The authors declare no conflict of interest.