Oncologic Outcomes of Total Length Gleason Pattern 4 on Biopsy in Men with Grade Group 2 Prostate Cancer

Abstract

Purpose: Gleason Score 7 prostate cancer comprises a wide spectrum of disease risk, and precise substratification is paramount. Our group previously demonstrated that the total length of Gleason pattern (GP) 4 is a better predictor than %GP4 for adverse pathological outcomes at radical prostatectomy. We aimed to determine the association of GP4 length on prostate biopsy with post-prostatectomy oncologic outcomes. Materials and Methods: We compared 4 GP4 quantification methodsdincluding maximum %GP4 in any single core, overall %GP4, total length GP4 (mm) across all cores and length GP4 (mm) in the highest volume coredfor prediction of biochemical recurrence-free survival after radical prostatectomy using multivariable Cox proportional hazards regression. Results: A total of 457 men with grade group 2 prostate cancer on biopsy subsequently underwent radical prostatectomy. The 3-year biochemical recurrence-free survival probability was 85% (95% CI 81e88). On multivariable analysis, all 4 GP4 quantification methods were associated with biochemical recurrencedmaximum % GP4 (HR[1.30; 95% CI 1.07e1.59; p[0.009), overall %GP4 (HR[1.61; 95% CI 1.21e2.15; p[0.001), total length GP4 (HR[2.48; 95% CI 1.36e4.52; p[0.003) and length GP4 in highest core (HR[1.32; 95% CI 1.11e1.57; p[0.001). However, we were unable to identify differences between methods of quantification with a relatively low event rate. Conclusions: These findings support further studies on GP4 quantification in addition to the ratio of GP3 and GP4 to classify prostate cancer risk. Research should also be conducted on whether GP4 quantification could provide a surrogate endpoint for disease progression for trials in active surveillance.

The oncologic risk of magnetic resonance imaging‐targeted and systematic cores in patients treated with radical prostatectomy

“…Regardless, the current study was not designed to further interrogate this phenomenon. Future studies may also benefit from incorporating additional imaging parameters, such as lesion size, and biopsy parameters, such as including an assessment of the length of pattern 4 or higher GG cancer 19,20 …”

Interobserver Reproducibility of Quantifying Gleason Pattern 4 Cancer in Prostate Biopsy: Implications for Clinical Practice

“…The overall percentage of GP4 (GP4 mm/total cancer mm) and total length of GP4 in mm in all cores were significantly associated with an increased risk of adverse pathology in RP and biochemical recurrence risk. 3,7 Cole et al also reported that the incremental percentage of GP4 in the biopsies was an important predictor of adverse pathology and PSA recurrence across the entire range of GS 7-8 PCa. 2 The quantity of GP4 has been used in determining the candidacy for active surveillance, which has been increasingly used for patients with the National Comprehensive Cancer Network (NCCN) very low-risk/low-risk PCa.…”

“…Studies have shown that the quantity of GP4 in Grade Groups 2 and 3 PCa in prostate biopsies, measured in a percentage or linear length, correlates with adverse pathological findings in radical prostatectomies (RP), including extraprostatic extension, seminal vesicle invasion, lymph node metastases, positive surgical margins, and oncological outcomes (postsurgical biochemical progression). [1][2][3][4][5][6][7][8][9] For these reasons, reporting the quantity of GP4 in a needle biopsy has been recommended by the World Health Organization (WHO), 10 Genitourinary Pathology Society (GUPS), 11 International Society of Urological Pathology (ISUP), 12 and College of American Pathologists (CAP). 13 For the GP4 quantity to be impactful for patient prognosis and management, quantification should be done in a uniform and reproducible way.…”

Active surveillance should not be routinely considered in ISUP grade group 2 prostate cancer

“…The 18% cut-off was proposed to increase the proportion of potentially eligible patients without compromising oncologic control and, therefore, the presence of GG 2 disease alone potentially excluded patients from being considered for AS. Recently, efforts in estimating the added prognostic value of length of Gleason pattern 4, rather than its ratio compared to pattern 3 have been undertaken [ 33 , 34 ]. Albeit a signal towards an increased clinical utility of measuring total length of pattern 4 was observed, no significant differences in terms of net benefits were demonstrated.…”

“…Albeit a signal towards an increased clinical utility of measuring total length of pattern 4 was observed, no significant differences in terms of net benefits were demonstrated. Perera et al, however, concluded that in terms of risk-stratification for patients with GG 2 disease on AS, length of pattern 4, rather than its proportion, may be of added clinical utility to establish cut-offs for inclusion of those patients [ 34 ].…”