Cell-by-cell quantification of the androgen receptor in benign and malignant prostate leads to a better understanding of changes linked to cancer initiation and progression.

The androgen receptor (AR) plays a crucial role in the development and homeostasis of the prostate and is a key therapeutic target in prostate cancer (PCa). The gold standard therapy for advanced PCa is androgen deprivation therapy (ADT), which targets androgen production and AR signaling. However, resistance to ADT develops via AR-dependent and AR-independent mechanisms. As reports on AR expression patterns in PCa have been conflicting, we performed cell-by-cell AR quantification by immunohistochemistry in the benign and malignant prostate to monitor changes with disease development, progression, and hormonal treatment. Prostates from radical prostatectomy (RP) cases, both hormone-naïve and hormone-treated, prostate tissues from patients on palliative ADT, and bone metastases were included. In the normal prostate, AR is expressed in >99% of luminal cells, 51% of basal cells, and 61% of fibroblasts. An increase in the percentage of AR negative (%AR-) cancer cells along with a gradual loss of fibroblastic AR were observed with increasing Gleason grade and hormonal treatment. This was accompanied by a parallel increase in staining intensity of AR positive (AR+) cells under ADT. Staining AR with N- and C-terminal antibodies yielded similar results. The combination of %AR- cancer cells, %AR- fibroblasts, and AR intensity score led to the definition of an AR index, which was predictive of biochemical recurrence in the RP cohort and further stratified patients of intermediate risk. Lastly, androgen receptor variant 7 (ARV7)+ cells and AR- cells expressing neuroendocrine and stem markers were interspersed among a majority of AR+ cells in ADT cases. Altogether, the comprehensive quantification of AR expression in the prostate reveals concomitant changes in tumor cell subtypes and fibroblasts, emphasizing the significance of AR- cells with disease progression and palliative ADT.

Robot-Assisted Laparoscopic Prostatectomy Experience and Pathological Quality: Are They Always Linked?

Objective: We investigated whether pathological outcomes improved with experience and surgeon generation after robot-assisted laparoscopic prostatectomy (RALP). Materials and Methods: The study included 1338 patients who underwent RALP between February 2010 and April 2020. We created learning curves for pelvic lymph node dissection (PLND), number of lymph nodes (LNs) removed, and positive surgical margin (PSM) after adjustment for confounders. We compared the outcomes between the first and second generation of surgeons in regression models. Results: The learning curve regarding PLND indications showed a significant increase with experience for the first generation, whereas the second generation had a learning curve that remained flat at a higher level (92.3%) and significantly better than the first generation (p < 0.001). Similarly, the number of LN removed showed a significant increase with experience in both generations, but the overall median number of LN removed was significantly higher in the second generation compared with the first generation (12 vs 10, p < 0.001). However, the learning curve for PSM remained flat at ∼20% after adjustment and did not show improvement with experience in both generations of surgeons (p = 0.794). Conclusions: Surgeons showed improvement with experience and education with RALP with respect to the indications for PLND and number of LNs removed. However, there was no improvement over time and generations for PSM. Experience based solely on the number of patients operated on is not an intrinsic factor in the pathological quality of RALP. Factors other than experience may also play a role in oncologic improvement.