2. UroToday Home
  3. Recent Abstracts
  4. Urologic Oncology
  5. Prostate Cancer

Infiltrative Growth Pattern of Prostate Cancer Is Associated with Lower Uptake on PSMA PET and Reduced Diffusion Restriction on mpMRI - Beyond the Abstract

For the detection and staging of prostate cancer (PCa), attention has focused on the prostate-specifc membrane antigen (PSMA) targeting PET tracer. It is well established that the PSMA uptake of the primary tumor is related to a higher Gleason Score and a worse prognosis. However, preliminary results also showed the presence of clinically significant PCa without PSMA uptake. Further histopathological analysis of PSMA-negative PCa showed that these tumors have a predominantly infiltrative (INF) rather than expansive (EXP) growth pattern.1 This observation induced the hypothesis that growth patterns might also affect mpMRI diffusion sequences and could cause false-negative results and indeed, a few publications already suggested a correlation between morphological patterns and ADC values in the past.2-4


Therefore, we aimed to test the new proposed definition of infiltrative and expansive growth, regarding the reproducibility with an interrater agreement for the new growth patterns on histopathology, and the correlation between them and ADC values, PSMA uptake, and ISUP grades.

In this retrospective analysis, we included all PCa patients who, between July 2016 and February 2020, consecutively underwent a staging or prospectively biopsy guidance [68GaPSMA simultaneous PET/MRI (n = 62).The histopathological 2-µm hematoxylin and eosin (H&E) slides with the dominant tumor lesion were subjected to established WHO2016/International Society of Urological Pathology (ISUP) prognostic grade group grading by two experienced genito-urinary pathologists, in a multidisciplinary meeting (including pathologist, radiologist, and nuclear medicine physicians) with direct comparison of imaging and histopathology we ensured that quantitative MRI and PET metrics were taken from the selected lesion area, excluding lesions smaller than 4 mm to reduce the risk of partial volume effects on imaging data.

In analogy to our first study we defined an INF growth pattern for entrapped benign glands or stroma within the carcinoma complexes, whereas an EXP growth in case of pure carcinoma glands within an area of at least 3x5 mm2 (circle with a radius 1.26 mm, Fig. 1).1 With this simple and easy to implement definition, two experienced pathologist reached an almost perfect, classification between EXP and INF growth (κ = 0.81).

A region of interest (ROI) was inserted over the area selected on pathology on both PSMA images and ADC maps (mm2/1000 s) (Fig. 1). Semi-quantitative image parameters were obtained for both modalities, including ADCmean and the corresponding [68Ga]PSMA-11 SUVmax. We observed significantly higher uptake on PSMA PET in lesions with EXP growth (SUVmax 19.2 ± 10.9) versus INF-growth (SUVmax 9.3 ± 6.2, p<0.001). In analogy, we observed significantly more diffusion restriction in lesions with EXP growth (ADCmean 0.777 ± 0.109) versus INF growth (ADCmean 1.079± 0.262, p<0.001). Interestingly the well-established correlation between ADCmean and ISUP grades was lost if the analysis was performed for both growth patterns separately (EXP growth: r = −0.004, p = 0.986; INF growth: r = 0.034, p = 0.844).

Burger_BTA.png

Fig 1) Upper row: an example of an expansive growing ISUP 3 tumor in the posterior right peripheral zone with a diameter of 13 mm. 3 circles of 1.26 mm diameter could be placed within the tumor, without any benign tissue within the circle. The lesion had a high 68Ga-PSMA-11 uptake and showed diffusion restriction on the ADC map. Lower row: example of an infiltrative growing ISUP 3 tumor in the posterior left peripheral zone, of 15 mm diameter, note the dilated benign prostatic glands (arrow heads) within the cancerous tissue. There was only mild 68Ga-PSMA-11 uptake and no evidence for diffusion restriction on ADC map.

The strong correlation between growth pattern and imaging parameters confirms that morphology characteristics of PCa on histopathology have an impact on the visibility of prostate cancer on imaging Further investigations are needed to improve our understanding of different PCa characteristics and How this should impact our interpretation of molecular imaging.

Written by: Riccardo Laudicella, Jan H. Rüschoff, Niels J. Rupp, & Irene A. Burger, University Hospital Zurich, University of Zurich, Zurich, Switzerland

References:

  1. Ruschoff JH, Ferraro DA, Muehlematter UJ, Laudicella R, Hermanns T, Rodewald AK, et al. What's behind (68)Ga-PSMA-11 uptake in primary prostate cancer PET? Investigation of histopathological parameters and immunohistochemical PSMA expression patterns. Eur J Nucl Med Mol Imaging. 2021;48(12):4042-53.
  2. Langer DL, van der Kwast TH, Evans AJ, Plotkin A, Trachtenberg J, Wilson BC, et al. Prostate tissue composition and MR measurements: investigating the relationships between ADC, T2, K(trans), v(e), and corresponding histologic features. Radiology. 2010;255(2):485-94.
  3. Langer DL, van der Kwast TH, Evans AJ, Sun L, Yaffe MJ, Trachtenberg J, et al. Intermixed normal tissue within prostate cancer: effect on MR imaging measurements of apparent diffusion coefficient and T2--sparse versus dense cancers. Radiology. 2008;249(3):900-8.
  4. Rosenkrantz AB, Mendrinos S, Babb JS, Taneja SS. Prostate cancer foci detected on multiparametric magnetic resonance imaging are histologically distinct from those not detected. J Urol. 2012;187(6):2032-8.

Read the Abstract