Infiltrative growth pattern of prostate cancer is associated with lower uptake on PSMA PET and reduced diffusion restriction on mpMRI

Abstract

Purpose: Recently, a significant association was shown between novel growth patterns on histopathology of prostate cancer (PCa) and prostate-specific membrane antigen (PSMA) uptake on [⁶⁸Ga]PSMA-PET. It is the aim of this study to evaluate the association between these growth patterns and ADC (mm²/1000 s) values in comparison to [⁶⁸Ga]PSMA uptake on PET/MRI.

Methods: We retrospectively evaluated patients who underwent [⁶⁸Ga]PSMA PET/MRI for staging or biopsy guidance, followed by radical prostatectomy at our institution between 07/2016 and 01/2020. The dominant lesion per patient was selected based on histopathology and correlated to PET/MRI in a multidisciplinary meeting, and quantified using SUV_max for PSMA uptake and ADC_mean for diffusion restriction. PCa growth pattern was classified as expansive (EXP) or infiltrative (INF) according to its properties of forming a tumoral mass or infiltrating diffusely between benign glands by two independent pathologists. Furthermore, the corresponding WHO2016 ISUP tumor grade was evaluated. The t test was used to compare means, Pearson's test for categorical correlation, Cohen's kappa test for interrater agreement, and ROC curve to determine the best cutoff.

Results: Sixty-two patients were included (mean PSA 11.7 ± 12.5). The interrater agreement between both pathologists was almost perfect with κ = 0.81. While 25 lesions had an EXP-growth with an ADC_mean of 0.777 ± 0.109, 37 showed an INF-growth with a significantly higher ADC_mean of 1.079 ± 0.262 (p < 0.001). We also observed a significant difference regarding PSMA SUV_max for the EXP-growth (19.2 ± 10.9) versus the INF-growth (9.4 ± 6.2, p < 0.001). Within the lesions encompassing the EXP- or the INF-growth, no significant correlation between the ISUP groups and ADC_mean could be observed (p = 0.982 and p = 0.861, respectively).

Conclusion: PCa with INF-growth showed significantly lower SUV_max and higher ADC_mean values compared to PCa with EXP-growth. Within the growth groups, ADC_mean values were independent from ISUP grading.

Keywords: Diffusion-weighted imaging; MRI; PSMA PET/MRI; Prostate cancer; Radical prostatectomy.

Fig. 1

Patients’ selection and inclusion in the study

Fig. 2

Examples of different growth patterns. A, C Example of infiltrative growth pattern (INF) defined by prostate carcinoma (circled) growing between benign glands (arrowheads). B, D Expansive growth pattern (EXP), which homogenously comprises tumor glands containing at least 3 circles of 5 mm² (radius 1.26 mm). A, B Scale bar 1 mm. C, D Scale bar 0.5 mm

Fig. 3

Region of interest (ROI) selection. Example of a 74-year-old patient with PSA of 20 ng/ml. Subsequently, he underwent radical prostatectomy (GS = 4 + 4, ISUP 4). A Histopathology slide showing an expansive growth pattern of the “dominant lesion’’ on the left posterior part of the prostatic peripheral zone. B Corresponding axial T2-weighted MRI showing a large hypointense area. C Axial ADC MRI with low ADC_mean values = 0.540. D axial [⁶⁸Ga]PSMA PET/MRI with high PSMA-uptake (SUV_max of 32.0)

Fig. 4

A Bar graphs for patients’ distribution according to RPE ISUP grade and growth pattern and box plot illustrations. B RPE ISUP distribution and C the maximum tumor diameter on histopathology according to growth-pattern. D Illustration of the distribution of PCa subtypes divided into either acinar or mixed (including combinations of acinar, ductal, intraductal and/or cribriform) according to growth pattern and E ISUP on histopathology

Fig. 5

Box plots illustrating the relationship between imaging parameters and RPE ISUP grade. A PSMA SUV_max had a positive correlation to ISUP (r = 0.508, p < 0.001). B ADC_mean a negative trend in correlation to ISUP (r =  − 0.192, p = 0.135) for all lesions. C A significant positive correlation for SUV_max with ISUP was confirmed for EXP growth (r = 0.415, p = 0.039) but not for INF growth (r = 0.284, p = 0.088). D For subdivided growth patterns, the ADC_mean had no correlation to ISUP (p = 0.861 for EXP, and p = 0.982 for INF)

Fig. 6

Two cases without correspondence between growth pattern and imaging parameters. A–D A 62-year-old patient with PSA of 12.7 ng/ml, GS = 4 + 3 (ISUP 3). A Histopathology slide showing an infiltrative growth pattern of the “dominant lesion’’ (continuous circle, detail on the right lower right side) on the anterior left part of the prostate apex with a maximum diameter of 8.3 mm; next to the carcinomatous lesion, acute inflammation (dotted circle, detail on the upper right side) can be found. B Corresponding axial T2-weighted MRI with a hypointense area. C On ADC map, the lesion had a low ADC_mean of 0.69. D On axial [⁶⁸Ga]PSMA PET/MRI, the lesion showed high PSMA-uptake (SUV_max = 16.7). In direct correlation of imaging and histopathology, the acute inflammation was probably responsible for the low ADC value and high PSMA uptake. E–H A 60-year-old patient with PSA of 1.3 ng/ml, GS = 4 + 3 (ISUP 3). E Histopathology slide showing an expansive growth pattern of the large “dominant lesion’’ on the posterior right part of the prostate apex with a maximum diameter of 17.3 mm. F Corresponding axial T2-weighted MRI with a hypointense area. G On ADC map, the lesion had a low ADC_mean of 0.717. H On [⁶⁸Ga]PSMA PET/MRI, the lesion showed low PSMA-uptake (SUV_max = 3.1)