Minimum ADC outperforms PSA and PSA density for predicting ISUP grade group in prostate cancer: a retrospective study...

Apparent diffusion coefficient (ADC) derived from diffusion-weighted imaging (DWI) has been proposed as a quantitative biomarker of prostate cancer aggressiveness, and an inverse relationship between ADC and Gleason score has been reported across numerous single-marker studies and meta-analyses. However, most prior work has compared ADC with serum PSA alone, without accounting for PSA density (PSAD) or potential confounders such as age and prostate volume, and without formally testing - using multivariable regression and receiver operating characteristic (ROC) analysis - whether ADC provides incremental diagnostic value beyond PSA-based parameters. Whether the ADC-grade relationship persists after such adjustment, and whether combining ADC with PSA and PSAD meaningfully improves discrimination, remains inconsistently characterized.

To evaluate whether minimum apparent diffusion coefficient (ADC) values are associated with pathological International Society of Urological Pathology (ISUP) Grade Group, and to compare the diagnostic performance of ADC with that of serum PSA and PSA density (PSAD), in patients with histologically confirmed prostate cancer undergoing radical prostatectomy.

A retrospective study of 192 patients undergoing multiparametric MRI (mpMRI), biopsy, and radical prostatectomy was performed. Minimum ADC values were correlated with the final pathological ISUP Grade Group, serum PSA, PSA density, age, and prostate volume.

Minimum ADC showed a significant inverse correlation with ISUP Grade Group (Spearman's ρ = -0.355; 95% CI, -0.473 to -0.218; p < 0.001), whereas neither PSA (ρ = 0.012; p = 0.864) nor PSAD (ρ = 0.040; p = 0.578) showed a significant monotonic relationship. On multivariable ordinal logistic regression, minimum ADC remained independently associated with higher ISUP Grade Group after adjustment for age, PSA or PSAD, and prostate volume (OR = 0.995 per 1 × 10^-6 mm²/s increase; p < 0.001 in both models), while age, PSA, PSAD, and prostate volume were not independently significant. Minimum ADC discriminated ISUP Grade Group 1 from ≥2 with an AUC of 0.959 (95% CI, 0.923-0.988), substantially outperforming PSA (AUC = 0.586) and PSAD (AUC = 0.562). Combined models incorporating ADC with PSA and/or PSAD did not significantly improve discrimination over ADC alone (DeLong's test, all p ≥ 0.10).

In this radical prostatectomy cohort, minimum ADC was inversely and independently associated with pathological ISUP Grade Group, whereas serum PSA and PSAD were not. ADC substantially outperformed PSA-based markers for discriminating low- from higher-grade disease, although combining ADC with PSA-based parameters provided no significant incremental benefit. These findings support ADC as a promising quantitative imaging biomarker of tumor grade; however, given the retrospective, single-center, surgically selected design and the small number of ISUP Grade Group 1 cases, prospective multicenter validation is required before ADC-based thresholds can be recommended for active surveillance or biopsy decision-making.