Long-term follow-up results of multiparametric prostate MRI and the prognostic value of PI-RADS: a single-center retrospective cohort study

Abstract

Purpose: We aim to examine the long-term outcomes of patients who underwent multiparametric prostate magnetic resonance imaging (mp-MRI) for suspected prostate cancer (PCa), specifically based on their initial Prostate Imaging Reporting and Data System (PI-RADS) categories and various clinical factors. Our secondary aim is to evaluate the prognostic value of the PI-RADS through the National Comprehensive Cancer Network (NCCN) risk group distribution.

Methods: This research was conducted as a single-center retrospective cohort study in a tertiary care hospital. A total of 1,359 cases having at least one histopathological examination after the initial mp-MRI and/or adequate clinical/radiological follow-up data were included in the clinically significant PCa (cs-PCa) diagnosis-free survival analysis. Initial mp-MRI dates were accepted as the start of follow-up for the time-to-event analysis. The event was defined as cs-PCa diagnosis (International Society of Urological Pathology ≥2). Patients who were not diagnosed with cs-PCa during follow-up were censored according to predefined literature-based criteria at the end of the maximum follow-up duration with no reasonable suspicion of PCa and no biopsy indication. The impact of various factors on survival was assessed using a log-rank test and multivariable Cox regression. Subsequently, 394 cases diagnosed with PCa during follow-up were evaluated, based on initial PI-RADS categories and NCCN risk groups.

Results: Three main risk factors for cs-PCa diagnosis during follow-up were an initial PI-RADS 5 category, initial PI-RADS 4 category, and high MRI-defined PSA density (mPSAD), with average hazard ratios of 29.52, 14.46, and 3.12, respectively. The PI-RADS 3 category, advanced age group, and biopsy-naïve status were identified as additional risk factors (hazard ratios: 2.03, 1.54-1.98, and 1.79, respectively). In the PI-RADS 1-2 cohort, 1, 3, and 5-year cs-PCa diagnosis-free survival rates were 99.1%, 96.5%, and 93.8%, respectively. For the PI-RADS 3 cohort, 1, 3, and 5-year cs-PCa diagnosis-free survival rates were 94.9%, 90.9%, and 89.1%, respectively. For the PI-RADS 4 cohort, 1, 3, and 5-year cs-PCa diagnosis-free survival rates were 56.6%, 55.1%, and 55.1%, respectively. These rates were found to all be 24.2% in the PI-RADS 5 cohort. Considering the 394 cases diagnosed with PCa during follow-up, PI-RADS ≥4 cases were more likely to harbor unfavorable PCa compared to PI-RADS ≤3 cases (P < 0.001). In the PI-RADS 3 subgroup analysis, a low mPSAD (<0.15 ng/mL²) was found to be a protective prognostic factor against unfavorable PCa (P = 0.005).

Conclusion: The PI-RADS category has a significant impact on patient management and provides important diagnostic and prognostic information. Higher initial PI-RADS categories are associated with decreased follow-up losses, a shorter time to PCa diagnosis, increased biopsy rates, a higher likelihood of developing cs-PCa during follow-up, and a worse PCa prognosis. Combining mPSAD with PI-RADS categories could enhance diagnostic stratification in the identification of cs-PCa.

Keywords: Prostatic neoplasm; biopsy; diagnosis; follow-up studies; multiparametric magnetic resonance imaging; prognosis.

Figure 1

Workflow of the study. PCa, prostate cancer; PSA, prostate-specific antigen; mp-MRI, multiparametric prostate magnetic resonance imaging; PI-RADS, Prostate Imaging Reporting and Data System; cs-PCa, clinically significant prostate cancer; NCCN, National Comprehensive Cancer Network.

Figure 2

In the main dataset, the rates of follow-up loss for Prostate Imaging Reporting and Data System (PI-RADS) 1–2, PI-RADS 3, and PI-RADS 4–5 subgroups are 59%, 46%, and 20%, respectively. Meanwhile, the rates of undergoing at least one biopsy during follow-up are 11%, 27%, and 76% for these categories, in the order given. Consequently, as the initial PI-RADS category increases, follow-up losses decrease, and the probability of undergoing biopsy during follow-up increases. Each distinct PI-RADS subgroup within the main dataset exhibits similar characteristics concerning age, baseline prostate-specific antigen (PSA) levels, magnetic resonance imaging-defined PSA density, and prior biopsy status, with corresponding PI-RADS cohorts included in the survival analysis.

Figure 3

(a) The clinically significant prostate cancer (cs-PCa) diagnosis-free survival curves of all cases included in the survival analysis, stratified by the initial Prostate Imaging Reporting and Data System (PI-RADS) category. Among all PI-RADS cohorts, a statistically significant inverse correlation was identified between the initial PI-RADS category and cs-PCa diagnosis-free survival (P < 0.001). (b) The cs-PCa diagnosis-free survival curves of the PI-RADS 3 cohort, stratified by initial magnetic resonance imaging-defined prostate-specific antigen density (mPSAD) range. A higher probability of survival was observed in the low mPSAD (<0.15 ng/mL²) subgroup (P < 0.001). (c) The cs-PCa diagnosis-free survival curves of the PI-RADS 3 cohort, stratified by prior biopsy status. Biopsy-naïve cases exhibited a lower probability of cs-PCa diagnosis-free survival (P = 0.018). (d) The cs-PCa diagnosis-free survival curves of the PI-RADS 4–5 cohort, stratified by initial mPSAD range. The subgroup with a high mPSAD (≥0.15 ng/mL²) demonstrated a lower probability of cs-PCa diagnosis-free survival (P < 0.001). (e) The cs-PCa diagnosis-free survival curves of the PI-RADS 4–5 cohort, stratified by prior biopsy status. Cases with a history of prior negative biopsy displayed a higher probability of survival without a cs-PCa diagnosis (P < 0.001). (f) The cs-PCa diagnosis-free survival curves of the PI-RADS 4–5 cohort, stratified by age group. A negative correlation was observed between the age range and the probability of a cs-PCa diagnosis-free survival (P < 0.001).

Figure 4

(a) Unfavorable prostate cancer (PCa) percentages in Prostate Imaging Reporting and Data System (PI-RADS) 1–2, 3, 4, and 5 groups were 46%, 40%, 58%, and 88%, respectively. The PI-RADS 1–2 and 3 groups exhibited similar prognostic distribution regarding unfavorable PCa (P = 0.55). However, comparing PI-RADS ≤3, 4, and 5 subgroups revealed statistically significant differences concerning unfavorable PCa rates, which were positively correlated with the initial PI-RADS category (P < 0.001). (b, c) In subgroup analyses, the PI-RADS 3 group was evaluated in terms of magnetic resonance imaging-defined prostate-specific antigen density (mPSAD) range (b) and prior biopsy status (c) for prognostic assessment. The rate of unfavorable PCa was 28% in the low mPSAD (<0.15 ng/mL²) subgroup and increased to 60% in the high mPSAD (≥0.15 ng/mL2) subgroup (P = 0.005). Conversely, prior biopsy status had no statistically significant impact on prognostic distribution (P = 1). Very low-risk, low-risk, and intermediate risk-favorable PCa cases according to National Comprehensive Cancer Network (NCCN) classification were accepted as favorable PCa. Intermediate risk-unfavorable, high-risk, and very high-risk PCa cases according to NCCN classification were accepted as unfavorable PCa.

Supplementary Figure 1

Schematic algorithm for follow-up evaluation. ISUP, International Society of Urological Pathology; cs-PCa, clinically significant prostate cancer; mp-MRI, multiparametric prostate magnetic resonance imaging; PI-RADS, Prostate Imaging Reporting and Data System.

Supplementary Figure 2

Illustrative case examples explaining follow-up evaluation. (a, b) The time-to-event was calculated considering the first detection time of cs-PCa (ISUP ≥2). (c) Cases without cs-PCa diagnosis during follow-up were considered cs-PCa-diagnosis-free at the points where histopathological examination results indicated non-neoplastic pathology or ISUP = 1 PCa, regardless of interim clinical or radiological follow-up findings. After biopsy, the final censoring time was determined based on additional clinical and/or radiological stability, if available. In the absence of any histopathological examination during an evaluated follow-up interval or in the subsequent follow-up period after a histopathological examination confirming the absence of cs-PCa, radiological stability was examined first and then clinical stability was considered to determine the final censoring time. (d) Cases with follow-up PI-RADS category 1–2 were considered cs-PCa diagnosis-free at the time of the follow-up mp-MRI, independent of previous clinical follow-up findings. After mp-MRI, the final censoring time was determined based on additional clinical and radiological follow-up, if available. (e-i) The approach to cases with follow-up PI-RADS category 3 was determined based on the previous PI-RADS. (e) Cases with a PI-RADS downgrade from PI-RADS 4–5 to PI-RADS 3 were considered cs-PCa diagnosis-free at the time of follow-up mp-MRI. The final censoring time was determined based on additional clinical and radiological follow-up, if available. (f) Cases with a PI-RADS upgrade from PI-RADS 1–2 to PI-RADS 3 were evaluated for the presence of at least 1-year stable subsequent clinical follow-up or further radiological stability to be considered as cs-PCa diagnosis-free. (g) PI-RADS 3 cases that did not meet these criteria were considered indeterminate at the end of follow-up. Censoring was done based on the stable clinical and/or radiological follow-up interval between the first mp- MRI and the indeterminate follow-up interval. Cases without such a stable follow-up interval were excluded from survival analysis. (h) PI-RADS 3 cases that did not show any PI-RADS change and radiological progression in the follow-up mp-MRI were considered as cs-PCa-diagnosis-free at the time of follow-up mp-MRI. The final censoring time was determined based on additional clinical and radiological follow-up, if available. (i) Cases with progressive PI-RADS 3 lesion(s) or follow-up PI-RADS category of 4–5 were considered indeterminate regardless of interim clinical follow-up, unless a subsequent histopathological examination was performed. Censoring was done based on the stable clinical and/or radiological follow-up interval between the first mp-MRI and the indeterminate follow-up interval. (j) Cases without such a follow-up interval were excluded from survival analysis. (k) In the absence of histopathological or radiological examination during the evaluated follow-up interval or in the subsequent follow-up period after these examinations, clinical stability was evaluated to determine the final censoring time. Cases showing at least 1 year of clinical stability, regardless of baseline PI-RADS category, were censored as cs-PCa diagnosis-free. (l) Cases where the criteria for clinical stability were not met during a certain time interval were considered indeterminate. Censoring was done based on the stable clinical interval between the first mp- MRI and the indeterminate follow-up interval. cs-PCa, clinically significant prostate cancer; ISUP, International Society of Urological Pathology; PCa, prostate cancer; PI-RADS, Prostate Imaging Reporting and Data System; mp-MRI, multiparametric prostate magnetic resonance imaging