Introduction

As the global population ages, interest in urological conditions has grown, leading to an increased utilization of transrectal ultrasonography (TRUS) in health promotion centers and urology departments. This rise in the application of TRUS has correspondingly increased the diagnosis of prostate calcifications, which are reported in 7.4–76.6% of cases, depending on the patient’s age1,2,3. Prostate calcifications are commonly associated with benign prostatic hyperplasia (BPH) and prostate cancer, although their precise etiology remains unclear4,5. Chemical analyses of prostatic calcifications have identified calcium phosphate—distinct from the calcium oxalate typically found in urinary stones—as the predominant component6,7. This finding supports hypotheses suggesting that stasis of prostatic secretions or dilation of prostatic ducts are key mechanisms in the formation of prostatic calcifications. Most calcifications are localized at the junction where the urethra meets the ejaculatory duct2,8,9.

Despite advancements in imaging techniques, most studies on prostate calcifications have been limited by technical challenges. Small calcifications often become indistinguishable within ultrasound noise, and accurate measurements are hindered by acoustic shadows cast behind the calcifications. Furthermore, prior research has analyzed prostate calcifications without precise classification methods, leading to inaccuracies. The assessment of calcification burden has also been insufficient, as many studies only documented the presence or absence of calcifications without quantifying their extent. In studies that attempted to evaluate the calcification burden using transrectal ultrasound, reliance on the longest axis of the calcifications introduced significant limitations. This method often failed to provide an accurate representation of the true burden, further complicating efforts to establish reliable quantitative measurements.

Unlike ultrasound, computed tomography (CT) is unaffected by ultrasound noise and provides imaging quality comparable to magnetic resonance imaging (MRI), the gold standard for prostate imaging in the diagnosis of prostatic calcifications10. CT not only allows precise identification of the calcification’s location within the prostate but also facilitates accurate measurement of its size. This study aims to leverage the advantages of CT imaging to determine the exact location and size of prostatic calcifications. Additionally, it seeks to assess the clinical significance of various factors associated with prostate calcifications, offering insights into their diagnostic and prognostic implications.

Methods

Study participants

This retrospective study analyzed data from 5,492 male patients aged ≥ 18 years (range: 18–93 years) who underwent both enhanced and non-enhanced abdominal pelvic computed tomography (APCT) at the Department of Urology in our hospital between January 2010 and December 2020. Patients were excluded if they had a history of prostate cancer, previous prostatectomy, indwelling urethral catheter, severe imaging artifacts, or errors in imaging software. After applying these exclusion criteria, a total of 4,805 patients were included in the final analysis (Fig. 1).

Fig. 1
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Overview of patients.

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Protocol for assessment of prostate calcification on APCT

Prostate calcifications were evaluated using multiple CT scanners (Brilliance iCT 256, Somatom Definition AS+, Somatom Definition Flash, and Somatom Force) with imaging parameters set to 100–120 kVp and slice thicknesses ranging from 2 to 3 mm. Calcifications were identified and measured in non-contrast abdominal pelvic computed tomography (APCT) axial images using a threshold value of ≥ 100 Hounsfield units (HU) through three-dimensional reconstruction with imaging software (SyngoVia, Siemens Healthineers, Germany)11,12. Only highlighted pixels within the prostate boundary were selected for analysis. Lesions with HU values < 100 were not classified as calcifications; however, these lesions were identified and classified separately if their boundaries were distinct from surrounding tissues. The locations of prostate calcifications were categorized into periurethral, central, transitional, and peripheral zones. Non-contrast APCT was utilized to determine the presence and volume of calcifications, while contrast-enhanced APCT was used to differentiate the transitional and peripheral zones for precise localization. To ensure diagnostic accuracy, two experienced specialists—a urologist (S. C. Kim) and a radiologist (T. Y. Lee)—independently reviewed the images. Diagnoses were made through cross-reading of another observer’s interpretations and double-reading of their own, performed under strict blinding to prior results. In cases of discrepancies, reexaminations were conducted to achieve consensus. The prostate calcification locations are illustrated in Fig. 2.

Fig. 2
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Zone classification for prostatic calcifications.

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Clinical and laboratory measurements

Patient demographics, including age, medical history, and laboratory findings, were recorded. Urinary symptoms were assessed using the International Prostate Symptom Score (IPSS), which incorporates a quality-of-life (QoL) component to evaluate the impact of symptoms on patients’ daily lives. Prostate size was measured using TRUS. Prostatic calcifications were measured using a Picture Archiving and Communication System (PACS) measurement tool. Dimensions were reported in millimeters to one decimal place. The maximum anteroposterior diameter was measured on axial images, while the length and width were obtained from midsagittal images. Stone volume was calculated using the prolate ellipsoid formula (0.524 × height × width × length).13

Statistical analysis

Nominal variables were summarized as frequencies and percentages, while continuous variables were presented as mean values and interquartile ranges. The frequency of calcifications by location was illustrated using a Venn diagram. Differences based on calcification location and number were analyzed using either analysis of variance (ANOVA) or the Kruskal–Wallis test for continuous variables, depending on data distribution. Predictors of the IPSS were evaluated using linear regression analysis. Variables with a p-value < 0.2 in univariate analysis were included in the multivariate analysis to adjust for potential confounders. Statistical significance was set at p < 0.05. All statistical analyses were performed using SPSS software (version 25.0; IBM Corp., Armonk, NY, USA).

Ethics statement

This retrospective observational study was approved by the Institutional Review Board (IRB) of Ulsan University Hospital (approval number: 2021-07-0732) and adhered to the principles outlined in the Declaration of Helsinki. Due to the retrospective nature of the study and the anonymization of included data, the IRB waived the requirement for informed consent.

Results

Participants

Among the 4,805 patients included in the analysis, 1,525 had no calcifications, 285 had calcifications with a Hounsfield unit (HU) < 100, and 2,995 had calcifications with HU ≥ 100. Table 1 presents the differences in age and clinical characteristics based on the presence or absence of prostate calcifications as observed on CT imaging. Patients with calcifications were, on average, older than those without calcifications. Notably, the group with calcifications of HU ≥ 100 had the highest mean age at 60.5 years (p < 0.001). No significant differences were observed in prostate-specific antigen (PSA) levels or prostate size among the groups. However, total, storage, and voiding scores on the International Prostate Symptom Score (IPSS) were significantly higher in patients with calcifications, with the highest scores recorded in the HU ≥ 100 group.

Table 1 Patients characteristics.
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Characteristics of prostate calcification

The majority of calcifications, including duplicates, were located in the central zone (N = 2,375; 79.3%). The periurethral (N = 1,475; 48.6%) and transitional zones (N = 1,257; 42.0%) followed as the most frequently observed sites, while a small number were found in the peripheral zone (N = 28; 0.9%) (Fig. 3). One calcification was the most common, observed in 1,366 patients (45.6%), followed by two calcifications in 1,137 patients (38.0%), and three calcifications in 491 patients (16.4%). The average HU for calcifications was 172 ± 75.7, and the average calcification size was 187.6 mm2 (Table 2).

Fig. 3
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Venn diagram showing proportions by location of calcifications.

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Table 2 The description of prostate calcification.
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When calcifications were located in the peripheral zone, the mean age of patients was the highest, but the HU value was the lowest. Additionally, while calcifications in the peripheral zone had the largest size, there was no significant difference in the International Prostate Symptom Score (IPSS), suggesting that urinary symptoms are not influenced by the calcification location. As the number of calcifications increased, the mean age, HU, and calcification size showed a significant increase. However, there was no corresponding change in IPSS scores (Table 3).

Table 3 Clinical features according to prostate calcification.
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Clinical significance of prostate calcification

Total International Prostate Symptom Score (IPSS) was significantly higher with increasing age and the presence of prostate calcifications. In the univariate analysis, Storage lower urinary tract symptoms (LUTS) also showed a significant increase with both age and calcifications. However, in the multivariate analysis, only age emerged as a significant factor influencing Storage LUTS. Voiding LUTS, on the other hand, significantly increased with both age and calcification in both the univariate and multivariate analyses. Therefore, both age and prostate calcification were identified as significant factors influencing urinary symptoms (Table 4).

Table 4 Factors predictive of IPSS.
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Discussion

Prostate calcification is a common finding in middle-aged and older men, with incidence rates ranging from 7 to 70%, largely depending on the age of the study population3,14,15. In our study, the mean age of participants was 59 years, and approximately two-thirds of the cohort exhibited prostate calcifications. Notably, both the size and number of calcifications increased with age, which aligns with findings from previous studies9,16,17. Prostate calcification is most commonly associated with benign prostatic hyperplasia or chronic inflammation. The relationship between calcification and LUTS has been well-documented, though the underlying mechanism remains incompletely understood. One possible explanation is an inflammatory response. Histopathological studies often reveal lymphocytic and histiocytic infiltration of the prostate acinar glands in areas of calcification, which may create a microenvironment that perpetuates further inflammatory changes18,19. Prostate calcification causes inflammation by blocking the intraprostatic ducts, and this chronic inflammation is ultimately associated with calcification in the surrounding tissues. This can cause fibrosis, leading to tissue stiffness and LUTS19,20. In the multivariate analysis, age and calcification were significant factors affecting urinary symptoms.

Numerous studies have reported that the presence of prostate calcifications and their characteristics can influence urinary symptoms. In particular, calcifications located around the prostatic urethra can cause tissue stiffness, which exacerbates urinary symptoms8. Additionally, increasing calcification size has been shown to correlate with worsening urinary symptoms5. In our analysis, both the HU value and size of the calcifications varied according to their location within the prostate. However, no significant correlation was found between these characteristics and the IPSS. As age increased, there was a higher incidence of multiple calcifications, and the size of the calcifications also increased. Despite this, no correlation between the number or size of the calcifications and urinary symptoms was observed. This lack of correlation is likely due to the fact that not all participants in the study presented with urinary symptoms, leading to a smaller variation in IPSS scores, which made it difficult to detect significant differences. Similarly, it was difficult to identify a relationship between prostate volume and IPSS, likely because not all participants had benign prostatic hyperplasia or LUTS, resulting in minimal differences in prostate volume.

To date, most studies on prostate calcification have relied on TRUS for diagnosis8,9,16,21. However, TRUS is operator-dependent and may be limited in its ability to accurately diagnose and localize calcifications due to the noise generated behind them. In contrast, this study employed CT, which offers a standardized imaging modality that is independent of the operator. CT enables precise evaluation of not only the location, size, and number of calcifications but also the HU, which provides valuable information regarding the density of the lesions. MRI has limitations in detecting intraprostatic calcifications due to its sensitivity to variations in signal intensity and the small size of the lesions. Given these constraints, CT may offer a distinct advantage over MRI in identifying prostate calcifications, providing clearer, more accurate imaging for both diagnostic and clinical purposes10,22.

This study has several limitations. First, it was retrospective in nature, which inherently restricts the ability to establish causality and may introduce selection bias. Second, while we used the IPSS to assess the clinical significance of prostate calcification, it is important to note that calcifications can have varying clinical implications. LUTS can be caused by factors other than calcifications, which may have confounded our findings. Third, the study exclusively included patients who underwent CT scans in the urology department, regardless of their reason for seeking care. This limited our ability to detect significant differences in urinary symptoms, as the patient population may not have been fully representative of the broader group with prostate calcifications. Finally, we were unable to perform pathological evaluations to assess fibrosis or tissue stiffness surrounding the calcifications, which we hypothesize to be a major contributor to the worsening of LUTS in our study participants. Despite these limitations, our study provides valuable insights as one of the few to use CT for the assessment of prostate calcification. It represents a significant advancement in the accurate evaluation of prostate calcifications. Future large-scale, prospective studies are essential to further investigate the potential for preventing calcification by controlling the underlying inflammation, as well as to assess the efficacy of treatments aimed at removing calcifications.

Conclusions

CT can be effectively utilized to accurately assess the exact location, size, and number of prostate calcifications. Our findings indicate that the prevalence of prostate calcifications increases with age and that these calcifications are associated with worsening LUTS. However, further prospective studies are needed to validate the effectiveness of preventive strategies and treatment options for prostate calcification, particularly in alleviating associated symptoms.