Gleason score 3+3=6 prostatic adenocarcinoma is not benign and the current debate is unhelpful to clinicians and patients.

Prostate adenocarcinoma is a common malignancy associated with a significant morbidity and mortality. In both prostate biopsies and radical prostatectomy specimens Gleason scoring informs both treatment and outcome prediction. The current convention is that in needle biopsies, Gleason patterns 3, 4 and 5 are considered to be malignant. Despite this there is debate as to whether or not Gleason score (GS) 3+3=6 should be diagnosed as cancer due to potential over-treatment and the psychological impact on patients. It is apparent that GS 3+3=6 is indolent disease with a low risk of metastasis. However, it does have the histological features of malignancy and is capable of infiltrating the prostate gland, extraprostatic extension, and metastatic spread. Furthermore GS 3+3=6 carcinoma has immunohistochemical and molecular genetic features similar to those of higher grade prostatic carcinoma. If GS 3+3=6 tumour is considered benign, the question arises should a benign label be given to the Gleason pattern 3 component of tumour that includes Gleason patterns of higher grade? This would seem a logical step as GS 3+3=6 cancers and the pattern 3 component in cancers with multiple patterns are morphologically identical. If pattern 3 is considered to be benign, then Gleason scoring would be limited to 4+4=8, 4+5=9, 5+4=9 and 5+5=10 which is clearly inappropriate. The correct strategy to address potential over-treatment of patients with low-grade cancer is clinician and patient education, not the recalibration of Gleason grading to reclassify malignant tumours as benign.

Clinicopathologic Significance of Anterior Prostate Cancer: Comparison With Posterior Prostate Cancer in the Era of Multiparametric Magnetic Resonance Imaging.

Anterior prostate cancer (APC) has been considered an indolent tumor, most commonly arising in the transition zone (TZ). More recently, detection of APC has been facilitated through multiparametric magnetic resonance imaging and improved biopsy techniques, enabling earlier detection. The pathologic features and clinical significance of pure APC in a large contemporary series of well-characterized tumors have, to date, not been elucidated. Cases with APC defined as cancer present anterior to the urethra only were identified from 1761 consecutive radical prostatectomy specimens accessioned between January 2015 and August 2016. The clinicopathologic features of these cases were compared with those of pure posterior prostate cancer (PPC) and the features of anterior peripheral zone (APZ) cancers were compared with those of TZ cancers. In addition, the tumor series from 2015 to 2016 was compared with a cohort of 1054 patients accessioned before the utilization of multiparametric magnetic resonance imaging in the routine workup of patients with prostate cancer. In the 2015-2016 series, there were 188 (10.7%) patients with APC compared with 5.4% in the series from the pre-multiparametric magnetic resonance imaging era. No difference was observed between APC and PPC with regards to patient age or mean serum prostate-specific antigen at presentation. Mean tumor volume and positive surgical margin (PSM) rates were significantly higher in APC. In contrast, PPC was more commonly high grade with more frequent extraprostatic extension (EPE). None of the cases of APC had infiltration of the seminal vesicle or lymph node involvement, in contrast to PPC, with almost 14% of cases in each category. The 3- and 5-year biochemical recurrence-free survival was significantly higher in APC when compared with PPC, although this was not retained on multivariable analysis which included tumor location. On division of APCs according to anatomic zone of origin, 45% were APZ cancer and 37% TZ cancer. On comparison of APZ and TZ cancers, there were no significant differences in mean age and serum prostate-specific antigen at presentation as well as tumor volume, Gleason score, and PSM rate. High-grade malignancy (Gleason score >3 + 4=7) was seen in 26% of TZ cancers which compared with 44% of APZ cancers and 56% of PPC cancers. The rate of EPE was significantly higher in APZ when compared with TZ cancer ( P< 0.0005); however, the biochemical recurrence rate was not significantly different between the groups. The prevalence of APC in radical prostatectomy specimens has increased in recent times, in association with earlier detection at a stage amenable to curative surgical treatment. APC, when compared with PPC, is less commonly high grade with less frequent EPE, despite the APC group having larger tumors and a higher PSM rate at presentation. However, not all anterior cancers are indolent. Anterior cancers are more commonly seen in the APZ than the TZ and APZ cancers appear more locally aggressive than TZ cancers.