- Email: [email protected]
The Significance of Primary Biopsy Gleason 5 in Patients with Grade Group 5 Prostate Cancer
EUF-865; No. of Pages 4 E U RO P E A N U R O L O GY F O C U S X X X ( 2 019 ) X X X– X X X
available at www.sciencedirect.com journal homepage: www.europeanurology.com/eufocus
Brief Correspondence
The Significance of Primary Biopsy Gleason 5 in Patients with Grade Group 5 Prostate Cancer Derya Tilki a,b,*, Christoph Wu¨rnschimmel a, Felix Preisser a,c, Markus Graefen a, Hartwig Huland a, Philipp Mandel a,c, Pierre Tennstedt a a
Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany;
b
Department of Urology, University Hospital
c
Hamburg-Eppendorf, Hamburg, Germany; Department of Urology, University Hospital Frankfurt, Frankfurt, Germany
Article info
Abstract
Article history: Accepted January 16, 2020
The five-tier grade group (GG) classification for prostate cancer (PCa) does not differentiate between primary (5 + 4) or secondary (4 + 5) histological Gleason 5 pattern in GG 5. We addressed the prognostic value of primary versus secondary biopsy Gleason 5 for GG 5 among 18 555 PCa patients treated with radical prostatectomy (RP) between 1992 and 2014. Of these, 922 patients had GG 5 PCa with primary (n = 295) or secondary (n = 627) Gleason 5 on biopsy. Prediction of biochemical recurrence (BCR), metastasis, and cancer-specific mortality (CSM) was assessed using Kaplan-Meier curves and univariable/multivariable Cox regression controlling for known prognosticators. Median follow-up was 74.8 mo (interquartile range [IQR] 49.2–120.2). BCR developed in 24.3% of patients (n = 4508) at a median of 23.6 mo (IQR 7.1–48.6). Metastasis developed in 4.5% (n = 827) and 2.0% (n = 370) died of PCa. When stratifying GG 5 by primary versus secondary Gleason 5, the estimated 5-yr metastasis-free survival was 80.4% (95% confidence interval [CI] 76.1–85.0%) versus 86.9% (95% CI 84.2–89.7%; p = 0.002) and cancer-specific survival was 90.9% (95% CI 87.5–94.4%) versus 96.3% (95% CI 94.7–98.0%; p < 0.001). On multivariable analysis, the negative impact of primary biopsy Gleason 5 among GG 5 patients remained significant for metastasis (hazard ratio [HR] 1.58; p < 0.001) and CSM (HR 2.44; p < 0.001). Therefore, stratifying GG 5 into primary (5 + 4, 5 + 5) and secondary (4 + 5) Gleason 5 may be warranted. Patient summary: We recorded worse oncological outcomes for patients with a primary histological Gleason 5 pattern on prostate biopsy compared to patients with a secondary biopsy Gleason 5 pattern. © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.
Associate Editor: Christian Gratzke Keywords: Prostate cancer grading system Gleason grade group Prostate cancer Gleason score High-risk prostate cancer
* Corresponding author at: Martini-Klinik Prostate Cancer Center, University Hospital HamburgEppendorf, Martinistrasse 52, Hamburg, 20246, Germany. E-mail address: [email protected] (D. Tilki).
During the International Society of Urological Pathology Consensus Conference on Gleason Grading of Prostatic Carcinoma (PCa) in 2014, Epstein and colleagues [1] proposed an improved and simplified five-tiered grading system that has been implemented by the World Health Organization.
Owing to significant disadvantages of the 2005 Gleason grading system that can affect patient care, the working group proposed the 2014 grade group (GG) system, which divides histopathological Gleason scores into the following groups: GG 1 (Gleason score 6), GG 2 (Gleason score 3 + 4),
https://doi.org/10.1016/j.euf.2020.01.008 2405-4569/© 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.
Please cite this article in press as: Tilki D, et al. The Significance of Primary Biopsy Gleason 5 in Patients with Grade Group 5 Prostate Cancer. Eur Urol Focus (2020), https://doi.org/10.1016/j.euf.2020.01.008
EUF-865; No. of Pages 4 2
E U RO P E A N U RO L O GY F O C U S X X X ( 2 019 ) X X X– X X X
GG 3 (Gleason score 4 + 3), GG 4 (Gleason score 8), and GG 5 (Gleason scores 9–10) [1]. GG 5 includes Gleason 4 + 5, Gleason 5 + 4, and Gleason 5 + 5, which may mask differences in aggressive potential among these three scores. Several validation studies proving the ability of GG to predict oncological outcomes after treatment have been performed [2–8]. However, most of these validation studies had distinct limitations, such as the use of biochemical recurrence (BCR) as a surrogate for cancerspecific-mortality (CSM) and lacking sufficient follow-up. Furthermore, the amount of high-risk PCa was generally low (10%) in most of the cohorts [2,4,6,7]. Still, the issue of combining both primary and secondary Gleason 5 patterns in GG 5 raises concern, as recent literature suggests that oncological outcomes between primary and secondary Gleason 5 might differ significantly, which raises the necessity to further investigate this topic [9]. The aim of our study was to analyze the impact of primary and secondary biopsy Gleason 5 pattern in GG 5 on oncological outcomes. After approval of the study by the institutional review board we retrospectively analyzed 18 555 PCa patients from our institutional database who underwent open retropubic or robot-assisted radical prostatectomy (RP) at the Martini-Klinik Prostate Cancer Center between 1992 and 2014 (Table 1). Patients with metastatic disease or those who did not consent to research were excluded from the study. Neoadjuvant and adjuvant therapy routines were administered according to the treating physician’s discretion. For the final analysis, 295 patients with a primary biopsy Gleason 5 pattern and 627 patients with a secondary biopsy Gleason 5 pattern within GG 5 were identified. Prediction of BCR, metastasis, and cancer-specific mortality (CSM) according to primary biopsy Gleason 5 pattern among GG 5 patients was assessed using Kaplan-Meier curves and univariable/multivariable Cox regression analysis controlling for known prognosticators (prostate-specific antigen, clinical stage, age at RP, year of RP). All statistical tests were two-sided and p < 0.05 was considered statistically significant. Statistical analyses were performed using R (www.R-project.org/).
Table 1 – Descriptive characteristics for 18 555 patients. Parameter
Result
Median age at diagnosis (yr) Median prostate-specific antigen (ng/ml)
64.4 6.88
Grade group at biopsy, n (%) 1 (Gleason score 6) 2 (Gleason score 3 + 4) 3 (Gleason score 4 + 3) 4 (Gleason score 8) 5 (Gleason score 9–10)
8818 (47.5) 5419 (29.2) 2208 (11.9) 1188 (6.4) 922 (5.0)
cT stage, n (%) T1 T2 T3
14483 (78.1) 3941 (21.2) 131 (0.7)
Median follow-up was 74.8 mo (interquartile range [IQR] 49.2–120.2). BCR developed in 24.3% of men (n = 4508) at a median of 23.6 mo (IQR 7.1–48.6). Metastasis developed in 827 men (4.5%) and 370 men (2.0%) died of PCa. Overall, as expected, GG was a significant factor influencing oncological outcomes in the whole patient group. When stratifying GG 5 by primary versus secondary biopsy Gleason 5 pattern, the estimated 5-yr metastasis-free survival was 80.4% (95% confidence interval [CI] 76.1–85.0%) versus 86.9% (95% CI 84.2–89.7%; p = 0.002) and cancer-specific survival (CSS) was 90.9% (95% CI 87.5–94.4%) versus 96.3% (95% CI 94.7–98.0%; p < 0.001; Fig. 1). On multivariable analyses (Supplementary Tables 1 and 2), the negative impact of primary biopsy Gleason 5 pattern (compared to secondary Gleason 5) in GG 5 remained significant for metastasis (hazard ratio [HR] 1.58; p < 0.001) and CSM (HR 2.44; p < 0.001). Our data confirm and validate the performance of Gleason GG in terms of oncological outcomes. While the focus of this study was patients with GG 5, we carried out a supplementary analysis for patients with primary Gleason 5 within GG 4, namely patients with biopsy Gleason 5 + 3 (n = 35), which showed that oncological outcomes for these patients were not significantly different to those for patients with biopsy Gleason 4 + 4. Baras et al [10] examined the occurrence of limited Gleason 5 pattern (<5%) among prostatectomy specimens with predominantly lower GG. They concluded that the presence of limited Gleason 5 pattern significantly worsens the oncological outcome and has the most distinct effect in GG 4, which led to the consideration to re-group those patients to GG 5. This work implies the importance to recognize Gleason 5 pattern as one of the most significant factors influencing the oncological outcome. A study by Moschini et al [9] supported these findings using data for 1080 patients from a high-volume database. The authors compared oncological outcomes for biopsy Gleason scores 4 + 4, 4 + 5, and 5 + 4. They concluded that both biopsy Gleason 4 + 5 and 5 + 4 were associated with significantly higher CSM compared to Gleason 4 + 4. On the basis of our data presented here, differentiation between primary and secondary Gleason 5 for GG 5 patients (eg, using six Gleason grade groups) deserves consideration. This stratification might help in allocating patients to the correct prognostic group more precisely, improve patient counselling based on individual risk, and help in identifying those who could benefit from multimodal therapies. Several limitations of our study must be mentioned. First, we analyzed retrospective data derived from a single surgical database. Furthermore, routines for neoadjuvant, adjuvant, or salvage therapies were not standardized and were determined at the discretion of the treating physician. In conclusion, we were able to further validate the Gleason GGs with our data and found a significant correlation between biopsy-based Gleason GG and oncological outcomes. However, it seems to be important to differentiate between primary and secondary Gleason 5 patterns in GG 5 to adequately anticipate oncological outcomes and treatment options and improve patient care. Further studies are needed to confirm our results.
Please cite this article in press as: Tilki D, et al. The Significance of Primary Biopsy Gleason 5 in Patients with Grade Group 5 Prostate Cancer. Eur Urol Focus (2020), https://doi.org/10.1016/j.euf.2020.01.008
EUF-865; No. of Pages 4 E U R O P E A N U R O L O GY F O C U S X X X ( 2 019 ) X X X– X X X
Fig. 1 – Survival outcomes. Biochemical-free survival according to (A) grade groups 1–5 and (B) grade groups 1–4, Gleason 4 + 5, and Gleason 5 + 4/5 + 5. Metastasis-free survival according to (C) grade groups 1–5 and (D) grade groups 1–4, Gleason 4 + 5, and Gleason 5 + 4/5 + 5. Cancer-specific survival according to (E) grade groups 1–5 and (F) grade groups 1–4, Gleason 4 + 5, and Gleason 5 + 4/5 + 5. RP = radical prostatectomy.
Please cite this article in press as: Tilki D, et al. The Significance of Primary Biopsy Gleason 5 in Patients with Grade Group 5 Prostate Cancer. Eur Urol Focus (2020), https://doi.org/10.1016/j.euf.2020.01.008
3
EUF-865; No. of Pages 4 4
E U RO P E A N U RO L O GY F O C U S X X X ( 2 019 ) X X X– X X X
Author contributions: Derya Tilki had full access to all the data in the
References
study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Tilki.
[1] Epstein JI, Egevad L, Amin MB, et al. The 2014 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grad-
Acquisition of data: Tilki, Würnschimmel, Preisser, Graefen, Huland,
ing of Prostatic Carcinoma: definition of grading patterns and pro-
Mandel, Tennstedt.
posal for a new grading system. Am J Surg Pathol 2016;40:244–52.
Analysis and interpretation of data: Tilki, Würnschimmel, Mandel. Drafting of the manuscript: Tilki, Würnschimmel. Critical revision of the manuscript for important intellectual content: Tilki, Würnschimmel, Preisser, Graefen, Huland, Mandel, Tennstedt.
[2] Epstein JI, Zelefsky MJ, Sjoberg DD, et al. A contemporary prostate cancer grading system: a validated alternative to the Gleason score. Eur Urol 2016;69:428–35. [3] Leapman MS, Cowan JE, Simko J, et al. Application of a prognostic
Statistical analysis: Tennstedt, Tilki.
Gleason grade grouping system to assess distant prostate cancer
Obtaining funding: None.
outcomes. Eur Urol 2017;71:750–9.
Administrative, technical, or material support: None. Supervision: Tilki. Other: None.
[4] Loeb S, Folkvaljon Y, Robinson D, Lissbrant IF, Egevad L, Stattin P. Evaluation of the 2015 Gleason grade groups in a nationwide population-based cohort. Eur Urol 2016;69:1135–41. [5] Pierorazio PM, Walsh PC, Partin AW, Epstein JI. Prognostic Gleason grade grouping: data based on the modified Gleason scoring sys-
Financial disclosures: Derya Tilki certifies that all conflicts of interest,
tem. BJU Int 2013;111:753–60.
including specific financial interests and relationships and affiliations
[6] Spratt DE, Cole AI, Palapattu GS, et al. Independent surgical valida-
relevant to the subject matter or materials discussed in the manuscript
tion of the new prostate cancer grade-grouping system. BJU Int
(eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: None.
2016;118:763–9. [7] Spratt DE, Jackson WC, Abugharib A, et al. Independent validation of the prognostic capacity of the ISUP prostate cancer grade grouping system for radiation treated patients with long-term follow-up. Prostate Cancer Prostat Dis 2016;19:292–7.
Funding/Support and role of the sponsor: None.
[8] Dell’Oglio P, Karnes RJ, Gandaglia G, et al. The new prostate cancer grading system does not improve prediction of clinical recurrence after radical prostatectomy: results of a large, two-center validation
Appendix A. Supplementary data
study. Prostate 2017;77:263–73. [9] Moschini M, Sharma V, Soligo M, et al. Heterogeneity of risk within Gleason 4 + 4,4 + 5 and 5 + 4 prostate cancer. Scand J Urol 2018;52:340–8.
Supplementary material related to this article can be found, in the online version, at doi:https://doi.org/10. 1016/j.euf.2020.01.008.
[10] Baras AS, Nelson JB, Han M, Parwani AV, Epstein JI. The effect of limited (tertiary) Gleason pattern 5 on the new prostate cancer grade groups. Hum Pathol 2017;63:27–32.
Please cite this article in press as: Tilki D, et al. The Significance of Primary Biopsy Gleason 5 in Patients with Grade Group 5 Prostate Cancer. Eur Urol Focus (2020), https://doi.org/10.1016/j.euf.2020.01.008
available at www.sciencedirect.com journal homepage: www.europeanurology.com/eufocus
Brief Correspondence
The Significance of Primary Biopsy Gleason 5 in Patients with Grade Group 5 Prostate Cancer Derya Tilki a,b,*, Christoph Wu¨rnschimmel a, Felix Preisser a,c, Markus Graefen a, Hartwig Huland a, Philipp Mandel a,c, Pierre Tennstedt a a
Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany;
b
Department of Urology, University Hospital
c
Hamburg-Eppendorf, Hamburg, Germany; Department of Urology, University Hospital Frankfurt, Frankfurt, Germany
Article info
Abstract
Article history: Accepted January 16, 2020
The five-tier grade group (GG) classification for prostate cancer (PCa) does not differentiate between primary (5 + 4) or secondary (4 + 5) histological Gleason 5 pattern in GG 5. We addressed the prognostic value of primary versus secondary biopsy Gleason 5 for GG 5 among 18 555 PCa patients treated with radical prostatectomy (RP) between 1992 and 2014. Of these, 922 patients had GG 5 PCa with primary (n = 295) or secondary (n = 627) Gleason 5 on biopsy. Prediction of biochemical recurrence (BCR), metastasis, and cancer-specific mortality (CSM) was assessed using Kaplan-Meier curves and univariable/multivariable Cox regression controlling for known prognosticators. Median follow-up was 74.8 mo (interquartile range [IQR] 49.2–120.2). BCR developed in 24.3% of patients (n = 4508) at a median of 23.6 mo (IQR 7.1–48.6). Metastasis developed in 4.5% (n = 827) and 2.0% (n = 370) died of PCa. When stratifying GG 5 by primary versus secondary Gleason 5, the estimated 5-yr metastasis-free survival was 80.4% (95% confidence interval [CI] 76.1–85.0%) versus 86.9% (95% CI 84.2–89.7%; p = 0.002) and cancer-specific survival was 90.9% (95% CI 87.5–94.4%) versus 96.3% (95% CI 94.7–98.0%; p < 0.001). On multivariable analysis, the negative impact of primary biopsy Gleason 5 among GG 5 patients remained significant for metastasis (hazard ratio [HR] 1.58; p < 0.001) and CSM (HR 2.44; p < 0.001). Therefore, stratifying GG 5 into primary (5 + 4, 5 + 5) and secondary (4 + 5) Gleason 5 may be warranted. Patient summary: We recorded worse oncological outcomes for patients with a primary histological Gleason 5 pattern on prostate biopsy compared to patients with a secondary biopsy Gleason 5 pattern. © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.
Associate Editor: Christian Gratzke Keywords: Prostate cancer grading system Gleason grade group Prostate cancer Gleason score High-risk prostate cancer
* Corresponding author at: Martini-Klinik Prostate Cancer Center, University Hospital HamburgEppendorf, Martinistrasse 52, Hamburg, 20246, Germany. E-mail address: [email protected] (D. Tilki).
During the International Society of Urological Pathology Consensus Conference on Gleason Grading of Prostatic Carcinoma (PCa) in 2014, Epstein and colleagues [1] proposed an improved and simplified five-tiered grading system that has been implemented by the World Health Organization.
Owing to significant disadvantages of the 2005 Gleason grading system that can affect patient care, the working group proposed the 2014 grade group (GG) system, which divides histopathological Gleason scores into the following groups: GG 1 (Gleason score 6), GG 2 (Gleason score 3 + 4),
https://doi.org/10.1016/j.euf.2020.01.008 2405-4569/© 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.
Please cite this article in press as: Tilki D, et al. The Significance of Primary Biopsy Gleason 5 in Patients with Grade Group 5 Prostate Cancer. Eur Urol Focus (2020), https://doi.org/10.1016/j.euf.2020.01.008
EUF-865; No. of Pages 4 2
E U RO P E A N U RO L O GY F O C U S X X X ( 2 019 ) X X X– X X X
GG 3 (Gleason score 4 + 3), GG 4 (Gleason score 8), and GG 5 (Gleason scores 9–10) [1]. GG 5 includes Gleason 4 + 5, Gleason 5 + 4, and Gleason 5 + 5, which may mask differences in aggressive potential among these three scores. Several validation studies proving the ability of GG to predict oncological outcomes after treatment have been performed [2–8]. However, most of these validation studies had distinct limitations, such as the use of biochemical recurrence (BCR) as a surrogate for cancerspecific-mortality (CSM) and lacking sufficient follow-up. Furthermore, the amount of high-risk PCa was generally low (10%) in most of the cohorts [2,4,6,7]. Still, the issue of combining both primary and secondary Gleason 5 patterns in GG 5 raises concern, as recent literature suggests that oncological outcomes between primary and secondary Gleason 5 might differ significantly, which raises the necessity to further investigate this topic [9]. The aim of our study was to analyze the impact of primary and secondary biopsy Gleason 5 pattern in GG 5 on oncological outcomes. After approval of the study by the institutional review board we retrospectively analyzed 18 555 PCa patients from our institutional database who underwent open retropubic or robot-assisted radical prostatectomy (RP) at the Martini-Klinik Prostate Cancer Center between 1992 and 2014 (Table 1). Patients with metastatic disease or those who did not consent to research were excluded from the study. Neoadjuvant and adjuvant therapy routines were administered according to the treating physician’s discretion. For the final analysis, 295 patients with a primary biopsy Gleason 5 pattern and 627 patients with a secondary biopsy Gleason 5 pattern within GG 5 were identified. Prediction of BCR, metastasis, and cancer-specific mortality (CSM) according to primary biopsy Gleason 5 pattern among GG 5 patients was assessed using Kaplan-Meier curves and univariable/multivariable Cox regression analysis controlling for known prognosticators (prostate-specific antigen, clinical stage, age at RP, year of RP). All statistical tests were two-sided and p < 0.05 was considered statistically significant. Statistical analyses were performed using R (www.R-project.org/).
Table 1 – Descriptive characteristics for 18 555 patients. Parameter
Result
Median age at diagnosis (yr) Median prostate-specific antigen (ng/ml)
64.4 6.88
Grade group at biopsy, n (%) 1 (Gleason score 6) 2 (Gleason score 3 + 4) 3 (Gleason score 4 + 3) 4 (Gleason score 8) 5 (Gleason score 9–10)
8818 (47.5) 5419 (29.2) 2208 (11.9) 1188 (6.4) 922 (5.0)
cT stage, n (%) T1 T2 T3
14483 (78.1) 3941 (21.2) 131 (0.7)
Median follow-up was 74.8 mo (interquartile range [IQR] 49.2–120.2). BCR developed in 24.3% of men (n = 4508) at a median of 23.6 mo (IQR 7.1–48.6). Metastasis developed in 827 men (4.5%) and 370 men (2.0%) died of PCa. Overall, as expected, GG was a significant factor influencing oncological outcomes in the whole patient group. When stratifying GG 5 by primary versus secondary biopsy Gleason 5 pattern, the estimated 5-yr metastasis-free survival was 80.4% (95% confidence interval [CI] 76.1–85.0%) versus 86.9% (95% CI 84.2–89.7%; p = 0.002) and cancer-specific survival (CSS) was 90.9% (95% CI 87.5–94.4%) versus 96.3% (95% CI 94.7–98.0%; p < 0.001; Fig. 1). On multivariable analyses (Supplementary Tables 1 and 2), the negative impact of primary biopsy Gleason 5 pattern (compared to secondary Gleason 5) in GG 5 remained significant for metastasis (hazard ratio [HR] 1.58; p < 0.001) and CSM (HR 2.44; p < 0.001). Our data confirm and validate the performance of Gleason GG in terms of oncological outcomes. While the focus of this study was patients with GG 5, we carried out a supplementary analysis for patients with primary Gleason 5 within GG 4, namely patients with biopsy Gleason 5 + 3 (n = 35), which showed that oncological outcomes for these patients were not significantly different to those for patients with biopsy Gleason 4 + 4. Baras et al [10] examined the occurrence of limited Gleason 5 pattern (<5%) among prostatectomy specimens with predominantly lower GG. They concluded that the presence of limited Gleason 5 pattern significantly worsens the oncological outcome and has the most distinct effect in GG 4, which led to the consideration to re-group those patients to GG 5. This work implies the importance to recognize Gleason 5 pattern as one of the most significant factors influencing the oncological outcome. A study by Moschini et al [9] supported these findings using data for 1080 patients from a high-volume database. The authors compared oncological outcomes for biopsy Gleason scores 4 + 4, 4 + 5, and 5 + 4. They concluded that both biopsy Gleason 4 + 5 and 5 + 4 were associated with significantly higher CSM compared to Gleason 4 + 4. On the basis of our data presented here, differentiation between primary and secondary Gleason 5 for GG 5 patients (eg, using six Gleason grade groups) deserves consideration. This stratification might help in allocating patients to the correct prognostic group more precisely, improve patient counselling based on individual risk, and help in identifying those who could benefit from multimodal therapies. Several limitations of our study must be mentioned. First, we analyzed retrospective data derived from a single surgical database. Furthermore, routines for neoadjuvant, adjuvant, or salvage therapies were not standardized and were determined at the discretion of the treating physician. In conclusion, we were able to further validate the Gleason GGs with our data and found a significant correlation between biopsy-based Gleason GG and oncological outcomes. However, it seems to be important to differentiate between primary and secondary Gleason 5 patterns in GG 5 to adequately anticipate oncological outcomes and treatment options and improve patient care. Further studies are needed to confirm our results.
Please cite this article in press as: Tilki D, et al. The Significance of Primary Biopsy Gleason 5 in Patients with Grade Group 5 Prostate Cancer. Eur Urol Focus (2020), https://doi.org/10.1016/j.euf.2020.01.008
EUF-865; No. of Pages 4 E U R O P E A N U R O L O GY F O C U S X X X ( 2 019 ) X X X– X X X
Fig. 1 – Survival outcomes. Biochemical-free survival according to (A) grade groups 1–5 and (B) grade groups 1–4, Gleason 4 + 5, and Gleason 5 + 4/5 + 5. Metastasis-free survival according to (C) grade groups 1–5 and (D) grade groups 1–4, Gleason 4 + 5, and Gleason 5 + 4/5 + 5. Cancer-specific survival according to (E) grade groups 1–5 and (F) grade groups 1–4, Gleason 4 + 5, and Gleason 5 + 4/5 + 5. RP = radical prostatectomy.
Please cite this article in press as: Tilki D, et al. The Significance of Primary Biopsy Gleason 5 in Patients with Grade Group 5 Prostate Cancer. Eur Urol Focus (2020), https://doi.org/10.1016/j.euf.2020.01.008
3
EUF-865; No. of Pages 4 4
E U RO P E A N U RO L O GY F O C U S X X X ( 2 019 ) X X X– X X X
Author contributions: Derya Tilki had full access to all the data in the
References
study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Tilki.
[1] Epstein JI, Egevad L, Amin MB, et al. The 2014 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grad-
Acquisition of data: Tilki, Würnschimmel, Preisser, Graefen, Huland,
ing of Prostatic Carcinoma: definition of grading patterns and pro-
Mandel, Tennstedt.
posal for a new grading system. Am J Surg Pathol 2016;40:244–52.
Analysis and interpretation of data: Tilki, Würnschimmel, Mandel. Drafting of the manuscript: Tilki, Würnschimmel. Critical revision of the manuscript for important intellectual content: Tilki, Würnschimmel, Preisser, Graefen, Huland, Mandel, Tennstedt.
[2] Epstein JI, Zelefsky MJ, Sjoberg DD, et al. A contemporary prostate cancer grading system: a validated alternative to the Gleason score. Eur Urol 2016;69:428–35. [3] Leapman MS, Cowan JE, Simko J, et al. Application of a prognostic
Statistical analysis: Tennstedt, Tilki.
Gleason grade grouping system to assess distant prostate cancer
Obtaining funding: None.
outcomes. Eur Urol 2017;71:750–9.
Administrative, technical, or material support: None. Supervision: Tilki. Other: None.
[4] Loeb S, Folkvaljon Y, Robinson D, Lissbrant IF, Egevad L, Stattin P. Evaluation of the 2015 Gleason grade groups in a nationwide population-based cohort. Eur Urol 2016;69:1135–41. [5] Pierorazio PM, Walsh PC, Partin AW, Epstein JI. Prognostic Gleason grade grouping: data based on the modified Gleason scoring sys-
Financial disclosures: Derya Tilki certifies that all conflicts of interest,
tem. BJU Int 2013;111:753–60.
including specific financial interests and relationships and affiliations
[6] Spratt DE, Cole AI, Palapattu GS, et al. Independent surgical valida-
relevant to the subject matter or materials discussed in the manuscript
tion of the new prostate cancer grade-grouping system. BJU Int
(eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: None.
2016;118:763–9. [7] Spratt DE, Jackson WC, Abugharib A, et al. Independent validation of the prognostic capacity of the ISUP prostate cancer grade grouping system for radiation treated patients with long-term follow-up. Prostate Cancer Prostat Dis 2016;19:292–7.
Funding/Support and role of the sponsor: None.
[8] Dell’Oglio P, Karnes RJ, Gandaglia G, et al. The new prostate cancer grading system does not improve prediction of clinical recurrence after radical prostatectomy: results of a large, two-center validation
Appendix A. Supplementary data
study. Prostate 2017;77:263–73. [9] Moschini M, Sharma V, Soligo M, et al. Heterogeneity of risk within Gleason 4 + 4,4 + 5 and 5 + 4 prostate cancer. Scand J Urol 2018;52:340–8.
Supplementary material related to this article can be found, in the online version, at doi:https://doi.org/10. 1016/j.euf.2020.01.008.
[10] Baras AS, Nelson JB, Han M, Parwani AV, Epstein JI. The effect of limited (tertiary) Gleason pattern 5 on the new prostate cancer grade groups. Hum Pathol 2017;63:27–32.
Please cite this article in press as: Tilki D, et al. The Significance of Primary Biopsy Gleason 5 in Patients with Grade Group 5 Prostate Cancer. Eur Urol Focus (2020), https://doi.org/10.1016/j.euf.2020.01.008