Abstract
Purpose
To evaluate the preoperative and pathological gleason score (GS) concordance rates and biopsy, pathological and clinical parameters that may cause discordance in patients who underwent radical prostatectomy (RP) for prostate cancer (PCa) in a single tertiary referral center.
Patients and methods
The data for patients who underwent RP due to PCa were retrospectively scanned after obtaining approval from the local ethics committee. Preoperative age, total PSA value, prostate volume, PSA density, PI-RADS score, digital rectal examination findings, biopsy type and pathological parameters after RP were evaluated in terms of GS concordance. Upgrading or downgrading was defined as an increase or decrease from one GS group to another.
Results
While preoperative and pathological GS were concordant in 151 patients (56.1%), values in 118 patients (43.9%) were found to be discordant. Of the 118 patients with preoperative and pathological discordance, 41 patients (34.7%) were downgraded, and 77 patients (65.3%) were upgraded. When preoperative and pathological GS concordance is compared, International Society of Urological Pathology grade group, D’Amico risk classification and clinical stage affected downgrading or upgrading of patients. In the presence of perineural, lymphovascular, seminal vesicle invasion and positive surgical margins in pathological examinations, GS discordance increased (p = 0.020, p = 0.003, p = 0.006 and p = 0.003, respectively).
Conclusions
According to the results of our study, one out of every two patients who underwent RP due to PCa had preoperative and pathological GS discordance.
Keywords: Gleason, Prostat cancer, Upgrading, Downgrade, Discordance
Background
Prostate cancer (PCa) is the second most common cancer in men worldwide [1]. With the widespread use of prostate-specific antigen (PSA) screening, incidence has gradually increased and it has begun to be detected at low clinical stages. Although there are some markers that measure the probable progression and aggressiveness of PCa, Gleason score (GS) is the most commonly used and the most important one in clinical practice [2]. While GS together with some additional parameters affects treatment decisions, it also shapes combinations such as pelvic lymph node (LN) dissection during radical prostatectomy (RP), nerve-sparing surgery or androgen deprivation treatment time during radiotherapy [3].
Although preoperative GS provides the diagnosis and treatment decision for the patient, the main tumor characteristic is determined by pathological GS [4]. When the literature is examined, there may be occasional discordance between preoperative and pathological GS values [5]. While any upgrading to a pathologic GS creates the need for additional treatment, preoperative and pathological discordance can lead to overtreatment. While the final GS can be determined correctly in patients who undergo RP, this situation can create more problems especially in patients who undergo active surveillance and radiotherapy [6–8]. Several models were developed over the past 10 years to avoid discordance between preoperative and pathological GS [9]. However, these models did not go beyond community-based studies and have not entered routine practical use. By combining imaging methods with biopsy methods, the aim is to increase detection rates for clinically important cancer while increasing the concordance of preoperative and pathological GS at the same time. The combination of magnetic resonance imaging (MRI) with biopsy has become popular in recent years. While some studies show that MRI target biopsy (MRI-TBx) is more compatible with preoperative and pathological GS, in others, selective sampling from high-grade areas may cause pathological downgrade [10, 11]. Even MRI-TBx significantly underestimates tumor grade and this situation may cause inadequate treatment [12]. In this context, although PCa diagnosis with MRI-TBx is superior to systematic biopsy, its contribution to pathological and preoperative GS concordance is limited.
It is obvious that preoperative GS fully reflecting pathological GS is the most desirable situation for the correct management of treatment for patients. Although the developed models, imaging methods and biopsy methods have been applied to increase the concordance of preoperative and pathological GS, we do not have a method to increase this concordance yet with a high level of evidence and applied in practice. With our study, the aim was to evaluate preoperative, pathological and clinical parameters that may cause discordance, and assess preoperative and pathological GS concordance rates in patients who underwent RP in a single tertiary referral center.
Patients and methods
The data for patients who underwent RP due to PCa in Health Sciences University, Adana Training and Research Hospital between January 2017 and January 2023 were retrospectively scanned after obtaining approval from the local ethics committee. All patients were diagnosed by systematic prostate needle biopsy (10–12 core) guided by transrectal ultrasonography (TRUS) or systematic + MRI cognitive target biopsy (MRI COG-TBx) of patients with PI-RADS 3 or higher lesions in multiparametric MRI (mpMRI) (according to PI-RADS-v2 classification) [11]. Pathological evaluation was performed in the pathology department of the same center.
All biopsies were performed under local anesthesia. All mpMRI images were interpreted in the radiology department of the same center. While systematic biopsies were performed by senior fellows accompanied by a urologist, cognitive fusion biopsies were performed by experienced urologists and 2 or 3 pieces were taken from the lesion in addition to the systematic biopsy (EA, UU). Preoperative and pathological GS were reported by examining highest GS and secondary GS in at least one core and using the ISUP Consensus Conference 2014 grading system [13]. Tertiary GS was not used. As a standard, the RP specimen was evaluated with total embedding. Specimens were sliced serially and their integrity preserved for histological examination. Clinical staging was done by a urologist in accordance with the 2017 TNM classification [14]. All patients’ pathological evaluations were conducted in the pathology department of the same center.
Age of patients when first diagnosed with PCa, total PSA value, prostate volume measured by TRUS, PSA density, mpMRI PI-RADS score, digital rectal examination (DRE) findings, biopsy type, preoperative GS, positive core count, D’Amico risk classification, clinical stage, surgical method and perioperative complications were evaluated. Pathological GS, pathological stage, surgical margin (SM) status, seminal vesicle invasion (SVI), extracapsular invasion, lymphovascular invasion (LVI), perineural invasion (PNI) and LN involvement were evaluated after RP. The effects of all these parameters on GS consistency were compared. Grading of prognostic GS was determined for each GS individually. Upgrading or downgrading was defined as an increase or decrease from one GS group to another, respectively.
The inclusion and exclusion criteria
All patients who had not previously received adjuvant or neoadjuvant treatment for Pca, who had not undergone surgeries such as transurethral prostate resection and open prostatectomy, whose pathology was evaluated only in our clinic, and who underwent open, laparoscopic or robotic RP regardless of surgical technique were included in the study. Patients who received neoadjuvant therapy, used 5 alpha reductase inhibitors, were not biopsy-naive, and were diagnosed with transurethral resection or open prostatectomy were excluded from the study.
Surgical procedure
RP was performed with the retropubic approach as described by Walsh and Donker. Robot-assisted and/or laparoscopic RP was performed as previously described in the literature. Extended lymphadenectomy was performed for patients with a risk ratio of more than 5% for nodal involvement according to the D’Amico nomogram [15].
Statistical analysis
Categorical measurements are summarized as numbers and percentages, and numerical measurements as mean and standard deviation (median and minimum-maximum where appropriate). Chi-square test statistics or Fisher Exact test were used to compare categorical measures between groups. Whether numerical measurements abided by the assumption of normal distribution was tested with the Shapiro Wilk test. In the comparison of numerical measurements between groups with and without concordance, T test was used for independent groups if the assumptions were met, and Mann Whitney U test was used if the assumptions were not met. Where there is concordance or discordance with upgrade or downgrade, one way analysis of variance was used if the assumptions were met, Kruskal Wallis test was used if the assumptions were not met. Tukey and Games-Howell tests were used according to whether in-group variances were homogeneous or not, if the assumptions were met for pairwise comparisons of the groups for cases that were significant in these comparisons. If the assumptions were not met in pairwise comparisons of the groups, the Mann Whitney U test with Bonferroni correction was used. Logistic regression was used to obtain the most effective measures for discordance for all discordance types. IBM SPSS Statistics Version 20.0 package program (SPSS 20) (IBM Corp., Armonk, NY, USA) was used for statistical analysis of the data. Statistical significance level was taken as p < 0.05 in all tests.
Results
A total of 321 patient files were reviewed retrospectively. There were 269 patients who met the inclusion criteria. The mean time between biopsy and surgery was 58.8 ± 7.95 (42–80) days (. While preoperative and pathological GS were concordant in 151 patients (56.1%), values for 118 patients (43.9%) were found to be discordant. Standard biopsy was performed on 194 patients (72.1%), while saturation biopsy was conducted on 75 patients (27.9%). GS discordance was observed in 92 patients (47.4%) who underwent standard biopsy and in 26 patients (34.7%) who underwent saturation biopsy. The mean age, PSA value, prostate volume and PSA density were similar in both groups. There was no difference in the rates of concordance (60 − 52%, respectively) and discordance (40–48%, respectively) between preoperative and pathological GS of patients who underwent systematic and systematic + MRI COG-TBx (p = 0.174). Preoperative ISUP grade group, D’Amico risk classification and clinical stage were found to affect preoperative and pathological GS concordance. Except for ISUP grade 5, as ISUP grade increased, concordance decreased (p < 0.001). As the D’Amico risk group increased, concordance decreased (p = 0.002). A multiple logistic regression analysis revealed that age and ISUP score were the most effective features associated with Gleason discordance. Accordingly, an increase of one year in age is associated with a 1.05-fold increase in the risk of a patient having a GS discordance (95% CI: 1.01–1.10). In the ISUP score, a score of 3 or above is associated with a 3.25-fold increase in the risk of a discordance (95% CI: 1.78–5.93) compared to a score of 2 or below. According to clinical staging, GS concordance was high for T1C, T2A and T2C, while it was the lowest for T2B (p = 0.002). Comparison of clinical and bioptic variables according to preoperative and pathological GS concordance is given in Table 1.
Table 1.
Comparison of clinical and bioptical variables according to Gleason score concordance
| Gleason Score | p | ||
|---|---|---|---|
| Concordant | Discordant | ||
| n = 151 | n = 118 | ||
| Age, Mean ± SD | 62 ± 6.4 | 63.3 ± 5.9 | 0.083a |
| PSA (ng/mL), Mean ± SD | 11.7 ± 11.1 | 13.4 ± 14.1 | 0.197b |
| Median (IQR) | 9 (6–13) | 10 (7–16) | |
| Prostat volume (ml), Mean ± SD | 47.3 ± 21 | 48.4 ± 19.9 | 0.637a |
| PSA density (ng/mL), Mean ± SD | 0.27 ± 0.24 | 0.30 ± 0.25 | 0.498b |
| Median (IQR) | 0.2 (0.14–0.3) | 0.2 (0.13–0.36) | |
| Mp MR-I, n (%) | 0.360c | ||
| PI-RADS 1 | 33 (60) | 22 (40) | |
| PI-RADS 2 | 30 (59) | 21 (41) | |
| PI-RADS 3 | 28 (65) | 15 (35) | |
| PI-RADS 4 | 30 (54) | 26 (46) | |
| PI-RADS 5 | 30 (47) | 34 (53) | |
| DRE findings, n (%) | 0.051c | ||
| Absent | 91 (62) | 57 (38) | |
| Available | 60 (50) | 61 (50) | |
| Biopsy method, n (%) | 0.174c | ||
| TRUS Bx | 83 (60) | 55 (40) | |
| Combined Bx | 68 (52) | 63 (47) | |
| ISUP GG, n (%) | < 0.001 c | ||
| 1 | 107 (67) | 53 (33) | |
| 2 | 25 (52) | 23 (48) | |
| 3 | 11 (39) | 17 (61) | |
| 4 | 2 (10) | 19 (90) | |
| 5 | 6 (50) | 6 (50) | |
| D’Amico risk group, n (%) | 0.002 c | ||
| Low-risk | 76 (68) | 36 (32) | |
| Intermadiate-risk | 50 (52) | 46 (48) | |
| High-risk | 25 (41) | 36 (59) | |
| Clinical T Stage, n (%) | 0.002 c | ||
| T1c | 87 (67) | 43 (33) | |
| T2a | 39 (51) | 37 (49) | |
| T2b | 17 (35) | 31 (65) | |
| T2c | 8 (53) | 7 (47) | |
| Bioptical GS, n (%) | < 0.001 c | ||
| 3 + 3 | 107 (71) | 54 (46) | |
| 3 + 4 | 25 (17) | 23 (19) | |
| 4 + 3 | 11 (7) | 17 (14) | |
| 4 + 4 | 1 (1) | 16 (14) | |
| 3 + 5 | 1 (1) | 2 (2) | |
| 5 + 3 | 0 (0) | 1 (1) | |
| 4 + 5 | 1 (1) | 3 (3) | |
| 5 + 4 | 2 (1) | 1 (1) | |
| 5 + 5 | 3 (2) | 1 (1) | |
PSA: Prostate-specific antigen, Mp MR-I: Multiparametric Magnetic Resonance Imaging, PI-RADS: Prostate Imaging-Reporting and Data System, DRE: Digital Rectal Examination, TRUS Bx: Transrectal Ultrasound Biopsy, ISUP GG: International Society of Urological Pathology Gleason Grade, GS: Gleason Score
a T test, b Mann Whitney U test, c Chi Square test
Among patients, 41 patients (34.7%) were downgraded and 77 patients (65.3%) were upgraded for the 118 patients with preoperative and pathological discordance. The mean age, PSA, prostate volume and PSA density were similar according to GS downgrade, concordance and upgrade status. In patients with downgrade or upgrade, ISUP grade group, D’Amico risk classification and clinical stage seem to affect preoperative and pathological GS. Except for the ISUP grade 5 group, as the ISUP grade group increased, downgrade was more common (p < 0.001). Likewise, as the D’Amico risk group increased, downgrade increased (p < 0.001). While downgrade increased as the clinical stage increased, upgrade increased partially except for T2C (p = 0.005). Comparison of clinical and bioptic variables according to preoperative and pathological GS downgrade, concordance and upgrade is given in Table 2.
Table 2.
Comparison of clinical and bioptical variables according to Gleason score downgrade, concordance and upgrade
| Gleason Score | p | |||
|---|---|---|---|---|
| Downgrade | Concordant | Upgrade | ||
| n = 41 | n = 151 | n = 77 | ||
| Age, mean ± SD | 63.1 ± 5.8 | 62 ± 6.4 | 63.4 ± 6.1 | 0.115 |
| PSA density (ng/mL), mean ± SD | 0.29 ± 0.23 | 0.27 ± 0.24 | 0.31 ± 0.28 | 0.351 |
| Mp MR-I, n (%) | ||||
| PI-RADS 1 | 7 (13) | 33 (60) | 15 (27) | |
| PI-RADS 2 | 10 (19) | 30 (59) | 11 (22) | 0.273 |
| PI-RADS 3 | 5 (12) | 28 (65) | 10 (23) | |
| PI-RADS 4 | 10 (18) | 30 (54) | 16 (28) | |
| PI-RADS 5 | 9 (14) | 30 (47) | 25 (39) | |
| Size of dominant/index lesion in MR-I, mean ± SD (mm) | 9.8 ± 3.7 | 11.4 ± 4.9 | 12.8 ± 5.3 | 0.179 |
| ISUP GG, n (%) | < 0.001 c | |||
| 1 | 0 (0) | 107 (67) | 53 (33) | |
| 2 | 11 (23) | 25 (52) | 12 (25) | |
| 3 | 11 (39) | 11 (39) | 6 (22) | |
| 4 | 14 (67) | 2 (9) | 5 (24) | |
| 5 | 5 (42) | 6 (50) | 1 (8) | |
| Clinical T Stage, n (%) | 0.005 c | |||
| T1c | 12 (9) | 87 (67) | 31 (24) | |
| T2a | 12 (16) | 39 (51) | 25 (33) | |
| T2b | 13 (27) | 17 (35) | 18 (38) | |
| T2c | 4 (27) | 8 (53) | 3 (20) | |
| Number of involved biopsy cores, mean ± SD | 3.3 ± 2.6 | 3.7 ± 2.8 | 4.5 ± 3.1 | 0.004 |
| Percentage of involved cores, mean ± SD | 35.2 ± 26.7 | 39.3 ± 28.5 | 52.4 ± 33.1 | < 0.001 |
| Bioptical GS, n (%) | < 0.001 c | |||
| 3 + 3 | 0 (0) | 107 (71) | 53 (69) | |
| 3 + 4 | 11 (27) | 25 (17) | 12 (16) | |
| 4 + 3 | 11 (27) | 11 (7) | 6 (8) | |
| 4 + 4 | 12 (29) | 1 (1) | 4 (5) | |
| 3 + 5 | 1 (2) | 1 (1) | 1 (1) | |
| 5 + 3 | 1 (2) | 0 (0) | 0 (0) | |
| 4 + 5 | 3 (7) | 1 (1) | 0 (0) | |
| 5 + 4 | 1 (2) | 2 (1) | 1 (1) | |
| 5 + 5 | 1 (2) | 3 (2) | 0 (0) | |
ISUP GG: International Society of Urological Pathology Gleason Grade, GS: Gleason Score
a T test, b Mann Whitney U test, c Chi Square test
In the presence of PNI, LVI, SVI and positive SM’s in pathological examinations, GS discordance increased (p = 0.020, p = 0.003, p = 0.006 and p = 0.003, respectively). According to the pathological results of the patients, the GS concordance status is given in Tables 3 and 4.
Table 3.
Comparison of Gleason score compliance according to the pathological Gleason score results of the patients
| Concordant | Discordant | p | |
|---|---|---|---|
| n = 151 | n = 118 | ||
| Pathological ISUP grade group, n (%) | < 0.001 c | ||
| 1 | 107 (71) | 22 (19) | |
| 2 | 25 (17) | 46 (39) | |
| 3 | 11 (7) | 23 (19) | |
| 4 | 2 (1) | 12 (10) | |
| 5 | 6 (4) | 15 (13) | |
| Perineural invasion, n (%) | 0.020 c | ||
| Absent | 44 (29) | 20 (17) | |
| Available | 107 (71) | 98 (83) | |
| Lymphovascular invasion, n (%) | 0.003 c | ||
| Absent | 129 (85) | 83 (70) | |
| Available | 22 (15) | 35 (30) | |
| Surgical margin, n (%) | 0.003 c | ||
| Negative | 122 (81) | 76 (65.4) | |
| Positive | 29 (19) | 42 (35.6) | |
| Seminale vesicle invasion, n (%) | 0.006 c | ||
| Absent | 136 (90) | 92 (78) | |
| Available | 15 (10) | 26 (22) | |
| Lymph node involvement, n (%) | 0.462c | ||
| Absent | 139 (92) | 105 (89) | |
| Available | 12 (8) | 13 (11) | |
| Periprostatic capsule invasion, n (%) | < 0.001 c | ||
| Absent | 122 (81) | 71 (60) | |
| Available | 29 (19) | 47 (40) | |
| Percentage of pathology quadrant involvement, Median (IQR) | 20 (10–30) | 20 (10–35) | 0.349b |
| Pathological GS, n (%) | < 0.001 c | ||
| 3 + 3 | 27 (18) | 20 (17) | |
| 3 + 4 | 56 (37) | 49 (42) | |
| 4 + 3 | 32 (21) | 21 (18) | |
| 4 + 4 | 11 (7) | 10 (8) | |
| 3 + 5 | 4 (3) | 3 (2) | |
| 5 + 3 | 2 (1) | 2 (2) | |
| 4 + 5 | 10 (7) | 9 (8) | |
| 5 + 4 | 5 (3) | 3 (2) | |
| 5 + 5 | 4 (2) | 1 (1) | |
| Pathological T stage, n (%) | 0.003 c | ||
| T2 | 112 (74) | 65 (55) | |
| T3a | 24 (16) | 27 (23) | |
| T3b | 15 (10) | 26 (22) |
ISUP: International Society of Urological Pathology, GS: Gleason Score
a T test, b Mann Whitney U test, c Chi Square test
Table 4.
Comparison of Gleason score downgrade, concordance and upgrade status according to the pathological results of the patients
| Downgrade | Concordant | Upgrade | p | |
|---|---|---|---|---|
| n = 41 | n = 151 | n = 77 | ||
| Pathological ISUP GG, n (%) | < 0.001 c | |||
| 1 | 18 (44) | 107 (71) | 4 (5) | |
| 2 | 13 (32) | 25 (17) | 33 (43) | |
| 3 | 9 (22) | 11 (7) | 14 (18) | |
| 4 | 0 (0) | 2 (1) | 12 (16) | |
| 5 | 1 (2) | 6 (4) | 14 (18) | |
| Perineural invasion, n (%) | 0.043 c | |||
| Absent | 9 (22) | 44 (29) | 11 (14) | |
| Available | 32 (78) | 107 (71) | 66 (86) | |
| Lymphovascular invasion, n (%) | 0.001 c | |||
| Absent | 34 (83) | 129 (85) | 49 (64) | |
| Available | 7 (17) | 22 (15) | 28 (36) | |
| Surgical margin, n (%) | 0.001 c | |||
| Negative | 32 (78) | 122 (81) | 45 (58) | |
| Positive | 9 (22) | 29 (19) | 32 (42) | |
| Seminale vesicle invasion, n (%) | < 0.001 c | |||
| Absent | 39 (95) | 136 (90) | 53 (69) | |
| Available | 2 (5) | 15 (10) | 24 (31) | |
| Periprostatic capsule invasion, n (%) | < 0.001 c | |||
| Absent | 31 (76) | 122 (81) | 40 (52) | |
| Available | 10 (24) | 29 (19) | 37 (48) | |
| Pathological GS, n (%) | < 0.001 c | |||
| 3 + 3 | 18 (44) | 107 (71) | 2 (3) | |
| 3 + 4 | 14 (34) | 25 (17) | 35 (45) | |
| 4 + 3 | 8 (20) | 11 (7) | 13 (17) | |
| 4 + 4 | 0 (0) | 1 (1) | 10 (13) | |
| 3 + 5 | 0 (0) | 1 (1) | 3 (4) | |
| 5 + 3 | 0 (0) | 0 (0) | 2 (3) | |
| 4 + 5 | 1 (2) | 1 (1) | 8 (10) | |
| 5 + 4 | 0 (0) | 2 (1) | 3 (4) | |
| 5 + 5 | 0 (0) | 3 (2) | 1 (1) | |
| Pathological T stage, n (%) | < 0.001 c | |||
| T2 | 30 (73) | 112 (74) | 35 (46) | |
| T3a | 9 (22) | 24 (16) | 18 (23) | |
| T3b | 2 (5) | 15 (10) | 24 (31) |
ISUP GG: International Society of Urological Pathology Gleason Grade, GS: Gleason Score
a T test, b Mann Whitney U test, c Chi Square test
Discussion
Considering that PCa is a heterogeneous tumor, from time to time 10–12 core biopsies do not represent the whole organ. Difference between preoperative and pathological GS is expected but not desirable. When the results of our study are examined, approximately one out of every two patients had GS discordance, in line with the literature [5, 9]. GS discordance may cause overtreatment sometimes, and incomplete treatment sometimes. For this reason, it is very important to predict and even prevent this discordance for management of the disease.
Advanced age, elevated PSA levels, family history, abnormal digital rectal examination findings, and high PI-RADS scores on multiparametric MRI are significant risk factors for prostate cancer. Particularly in patients with PSA levels between 4 and 10 ng/ml, PSA density can be used as a more predictive parameter. A study reported that patients with PSA density < 0.165 and PI-RADS 1–3 lesions had lower rates of clinically significant cancer detection [16]. There are various risk classification systems for determining the prognosis of prostate cancer. In the D’Amico risk classification, patients are divided into low-, intermediate-, and high-risk groups based on clinical stage, biopsy Gleason score, and PSA levels [17]. In the NCCN risk classification, additional parameters such as the number of positive cores and the percentage of cancer involvement per core are used, allowing for the identification of intermediate-risk patients with a high risk of recurrence [18]. The Cambridge Prognostic Group classification has been reported to better predict prostate cancer-related mortality compared to other classification systems [19].
The effect of preoperative PSA on GS discordance has been questioned by many studies in the literature before, and a clear consensus was not reached yet. In our study, there was no relationship between PSA and GS concordance. Xu et al. [9] and Wang et al. [15] reported that there was an interaction between PSA increase and GS upgrade in their studies. The PSA averages in these studies were higher than our study (19.23 ng/m L and 19.7 ng/mL, respectively). Imamoto et al. [20] and Chun et al. [21] had similar mean PSA levels to ours in their studies and they could not detect a relationship between PSA and GS concordance as in our study.
In the literature, the relationship of many preoperative variables such as DRE, age, PSA density, prostate volume, and time between biopsy and RP with GS compliance was evaluated. Xu et al. [9] did not find one of these, DRE, a significant predictor for GS discordance, consistent with the results of our study. According to the results of our study, as the clinical stage based on DRE findings increased, agreement decreased in line with the literature, except for T2c [5, 22–24]. Although samples taken from larger volume prostate tissue compared to the small volume prostate tissue represent proportionally less of the prostate theoretically, there are studies in the literature that do not support this [25]. Epstein et al. [26] found that upgrade was decreased with prostate weight > 75 g. However, there are studies in the literature showing that prostate volume does not affect discordance, similar to our results [26]. Age and PSA density are among the variables for which no consensus can be reached in the literature. When the literature was examined, some studies found an association with upgrade, while others could not detect a relationship, as in our study [25, 27, 28]. Contrary to our study, many studies in the literature showed that the time elapsed between biopsy and operation affects GS discordance [5, 29]. Of these, Kvale et al. [5] had longer intervals in their study compared to our study. Our concordance rates in the first 60 days, which fit the mean interval of our study (58.8 days), were similar (66.7% and 56.1%, respectively). Although our results could not detect a relationship between this time interval and concordance, the rate of concordance for our mean time was consistent with the literature.
Arsov et al. [30] compared MRI-TBx + systematic Bx and TRUS-Bx and found GS concordance rates (44.2% vs. 34.6%, respectively) were lower than concordance rates (52% vs. 60%, respectively) in our study. However, there was no difference in GS concordance between the two Bx methods in both studies. Similarly, Aslan et al. [31] found the concordance results were compatible with our study (50% and 57.5%, respectively). Although our consistency rates are similar, in their study, there were higher upgrade and lower downgrade rates in the group with systematic Bx compared to our study (43.3% vs. 6.7 and 31% vs. 22%, respectively). In many studies in the literature, MRI-assisted TBx, using different methods, was compared in terms of cancer detection or GS concordance. However, since the size, location and number of lesions in the targeted prostate are not clearly defined in most of these compared studies, uncertainty still exists in this regard.
Ryan et al. [32] compared MRI COG-TBx and TRUS-Bx and they found a concordance rate of 50.4% and 28.7%, respectively. While the concordance rates in the MR COG-TBx group were compatible with our study, the TRUS-Bx group had lower concordance than our study. While both studies were retrospective and single-centered, the number of patients in our study was more than the study by Ryan et al. Despite better detection of clinically significant cancers with MRI-TBx, uncertainty remains about the final detection of pathological GS, especially in biopsy-naive patients like our study [30]. In addition to studies showing that fusion biopsies are more compatible with RP specimens than TRUS-guided biopsies, there are also studies indicating that they have similar results [33]. According to the results of our study, there was no difference in concordance between systematic and systematic + MRI COG-TBx patient groups.
A nomogram has been developed to predict upgrading in low- and intermediate-risk prostate cancer patients, incorporating such as age, race, digital rectal examination findings, PSA level, number and percentage of positive cores, prostate volume, clinical stage, prostatic intraepithelial neoplasia, and presence of perineural invasion [34]. Another nomogram utilizes PSMA PET/CT data (SUVmax and prostate volume) along with clinical parameters (BMI, biopsy ISUP grade, and number of positive biopsy cores) for predicting upgrading [35]. In our study, the highest upgrade rates were found in ISUP group 1, where active monitoring may be an option [30]. The high rate of upgrading in this group after RP shows again that we should be very careful in selecting and monitoring patients who will be recommended for active follow-up. ISUP grade group 4 theoretically consists of three separate GS (4 + 4, 3 + 5 and 5 + 3). The pathological GS of patients with preoperative GS 3 + 5 or 5 + 3 can theoretically result in 3 + 3 or 5 + 5. While two GS are completely different from each other in terms of tumor characteristics, they are bioptically evaluated in the same ISUP grade group. In our study, the lowest concordance was in ISUP grade 4 in accordance with the literature [30]. The reason why lowest concordance was found in this group is due to the heterogeneity of the group.
During RP, PSM can occur either due to incomplete tumor removal or surgical failure [36]. Therefore, PSM is known to be associated with tumor stage and surgical technique. The GS serves as an indicator of the biological aggressiveness of the tumor. In some cases, the GS at PSM may be higher than that of the primary tumor, potentially increasing the risk of biochemical recurrence [37]. Previous studies showed that positive SM, capsule invasion, SVI and increased T stage were significantly associated with GS upgrades during examination of the specimen after RP [24]. Although these pathological markers indicate poor prognosis, upgrade will cause poor prognosis. Being able to predict upgrade may benefit prognosis or affect our choice of treatment. In our study, it was observed that while PNI, LVI, SM positivity, SVI, capsule invasion and increased pathological T stage decreased GS concordance, LN positivity did not affect GS concordance.
The limitations of our study are that it was retrospective, non-randomized, the number of patients in the study group was small, and pathological evaluation was not performed by a single specialist uropathologist.
Conclusions
According to the results of our study, there was no relationship between PSA and GS concordance. Prostate volume does not affect discordance. Age and PSA density not found an association with upgrade. Approximately one out of every two patients diagnosed with PCa and undergoing surgery has preoperative and pathological GS discordance. Variables affecting preoperative and pathological GS concordance were preoperative ISUP grade group, D’Amico risk classification, and clinical stage. GS discordance increases in the presence of PNI, LVI, SVI and positive SM’s in pathological examinations. Some precautions should be taken in order to increase the concordance of preoperative and pathological GS. Additional tools are needed for good prediction of concordance because the standard clinical and pathological variables currently available are not sufficiently predictive.
Acknowledgements
Not applicable.
Abbreviations
- DRE
Digital Rectal Examination
- GS
Gleason Score
- ISUP
International Society of Urological Pathology
- MRI
Magnetic Resonance Imaging
- MRI COG-TBx
MRI Cognitive Target Biopsy
- MRI-TBx
MRI Target Biopsy
- mpMRI
Multiparametric MRI
- PCa
Prostate Cancer
- PI-RADS
Prostate Imaging Reporting and Data System
- PSA
Prostate-Specific Antigen
- RP
Radical Prostatectomy
- TRUS
Transrectal Ultrasonography
Author contributions
Z.G.G. and U.U. proposed the concepts related to this paper and designed the scheme. E.V. capture and integrate data. M.A. analyzed and interpreted the data. K.K. drafted the manuscript. All authors reviewed the manuscript. Z.G.G completed critical revision of the manuscript.
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Data availability
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
Declarations
Ethics approval and consent to participate
The Ethical Committee at Adana City Training and Research Hospital approved the study on 25 May 2023 with approval No. 127–2596. A written informed consent form was signed by each participant before completing the survey.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
References
- 1.Culp MB, Soerjomataram I, Efstathiou JA, Bray F, Jemal A. Recent global patterns in prostate cancer incidence and mortality rates. Eur Urol. 2020;77:38–52. [DOI] [PubMed] [Google Scholar]
- 2.van den Cornford P, Van den Briers E, Cumberbatch MG, De Santis M, et al. EAU-EANM-ESTRO-ESUR-SIOG guidelines on prostate cancer. Eur Urol. 2021;79:263–82. [DOI] [PubMed] [Google Scholar]
- 3.van der Aa AA, Mannaerts CK, van der Linden H, Gayet M, Schrier BP, Mischi M, et al. Concordance of Gleason grading with three-dimensional ultrasound systematic biopsy and biopsy core pre-embedding. World J Urol. 2018;36:863–9. [DOI] [PubMed] [Google Scholar]
- 4.D’Amico AV, Whittington R, Malkowicz SB, Schultz D, Schnall M, Tomaszewski JE, et al. A multivariate analysis of clinical and pathological factors that predict for prostate specific antigen failure after radical prostatectomy for prostate cancer. J Urol. 1995;154:131–8. [PubMed] [Google Scholar]
- 5.Kvåle R, Møller B, Wahlqvist R, Fosså SD, Berner A, Busch C, et al. Concordance between Gleason scores of needle biopsies and radical prostatectomy specimens: a population-based study. BJU Int. 2009;103:1647–54. [DOI] [PubMed] [Google Scholar]
- 6.Berglund RK, Masterson TA, Vora KC, Eggener SE, Eastham JA, Guillonneau BD. Pathological upgrading and up staging with immediate repeat biopsy in patients eligible for active surveillance. J Urol. 2008;180:1964–7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Drost FJH, Rannikko A, Valdagni R, Pickles T, Kakehi Y, Remmers S, et al. PRIAS study group. Can active surveillance really reduce the harms of overdiagnosing prostate cancer? A reflection of real life clinical practice in the PRIAS study. Transl Androl Urol. 2018;7:98–105. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Tagliaferri L, Alemanno G, Fionda B, Alitto AR, Frascino V, Cellini F, et al. Multiparametric imaging guided HDR interventional radiotherapy (brachytherapy) boost in localized prostate cancer: a multidisciplinary experience. Eur Rev Med Pharmacol Sci. 2023;27(9):4175–84. [DOI] [PubMed] [Google Scholar]
- 9.Xu H, Bai PD, Hu MB, Mao SH, Zhu WH, Hu JM, et al. Gleason sum upgrading between biopsy and radical prostatectomy in Chinese population. Actas Urol Esp. 2017;41:162–71. [DOI] [PubMed] [Google Scholar]
- 10.Monda SM, Vetter JM, Andriole GL, Fowler KJ, Shetty AS, Weese JR, et al. Cognitive versus software fusion for MRI-targeted biopsy: experience before and after implementation of fusion. Urol. 2018;119:115–20. [DOI] [PubMed] [Google Scholar]
- 11.Weinreb JC, Barentsz JO, Choyke PL, Cornud F, Haider MA, Macura KJ, et al. PI-RADS prostate imaging–reporting and data system: version 2. Eur Urol. 2016;69:16–40. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Ahdoot M, Wilbur AR, Reese SE, Lebastchi AH, Mehralivand S, Gomella PT, et al. MRI-targeted, systematic, and combined biopsy for prostate cancer diagnosis. N Engl J Med. 2020;382:917–28. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Epstein JI, Egevad L, Amin MB, Delahunt B, Srigley JR, Humphrey PA, Grading Committee. The 2014 international society of urological pathology (ISUP) consensus conference on Gleason grading of prostatic carcinoma: definition of grading patterns and proposal for a new grading system. Am J Surg Pathol. 2016;40:244–52. [DOI] [PubMed] [Google Scholar]
- 14.Brierley J. TNM classification of malignant tumours. Eighth edition. West Sussex, UK; Hoboken, NJ: Wiley Blackwell/John Wiley & Sons, Inc: ed. Chichester; 2017. [Google Scholar]
- 15.Ficarra V, Novara G, Fracalanza S, D’Elia C, Secco S, Iafrate M, et al. A prospective, non-randomized trial comparing robot‐assisted laparoscopic and retropubic radical prostatectomy in one European institution. BJU Int. 2009;104:534–49. [DOI] [PubMed] [Google Scholar]
- 16.Hamidi N, Uzel T, Demirci A, Basar H. Unlocking precision enhancing prostate cancer detection and reducing unnecessary biopsies with combined prostate-specific antigen density and PI-RADS score. J Coll Physicians Surg Pak. 2024;34:1205–10. [DOI] [PubMed] [Google Scholar]
- 17.Hernandez DJ, Nielsen ME, Han M, Partin AW. Contemporary evaluation of the d’amico risk classification of prostate cancer. Urology. 2007;70:931–5. [DOI] [PubMed] [Google Scholar]
- 18.Xu H, Zhu Y, Dai B, Ye DW. National Comprehensive Cancer Network (NCCN) risk classification in predicting biochemical recurrence after radical prostatectomy: a retrospective cohort study in Chinese prostate cancer patients. Asian J Androl. 2018;20:551–4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Parry MG, Cowling TE, Sujenthiran A, Nossiter J, Berry B, Cathcart P, et al. Risk stratification for prostate cancer management: value of the Cambridge prognostic group classification for assessing treatment allocation. BMC Med. 2020;18:114. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Wang JY, Zhu Y, Wang CF, Zhang SL, Dai B, Ye DW. A nomogram to predict Gleason sum upgrading of clinically diagnosed localized prostate cancer among Chinese patients. Chin J Cancer. 2014;33:241–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Imamoto T, Utsumi T, Takano M, Komaru A, Fukasawa S, Suyama T et al. Development and external validation of a nomogram predicting the probability of significant Gleason sum upgrading among Japanese patients with localized prostate cancer. Prostate Cancer. 2011;754382. [DOI] [PMC free article] [PubMed]
- 22.Chun FK, Briganti A, Shariat SF, Graefen M, Montorsi F, Erbersdobler A, et al. Significant upgrading affects a third of men diagnosed with prostate cancer: predictive nomogram and internal validation. BJU Int. 2006;98:329–34. [DOI] [PubMed] [Google Scholar]
- 23.Quintana L, Ward A, Gerrin SJ, Genega EM, Rosen S, Sanda MG, et al. Gleason misclassification rate is independent of number of biopsy cores in systematic biopsy. Urology. 2016;91:143–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Jain S, Loblaw A, Vesprini D, Zhang L, Kattan MW, Mamedov A, et al. Gleason upgrading with time in a large prostate cancer active surveillance cohort. J Urol. 2015;194:79–84. [DOI] [PubMed] [Google Scholar]
- 25.Serkin FB, Soderdahl DW, Cullen J, Chen Y, Hernandez J. Patient risk stratification using Gleason score concordance and upgrading among men with prostate biopsy Gleason score 6 or 7. Urol Oncol. 2010;28:302–7. [DOI] [PubMed] [Google Scholar]
- 26.Epstein JI, Feng Z, Trock BJ, Pierorazio PM. Upgrading and downgrading of prostate cancer from biopsy to radical prostatectomy: incidence and predictive factors using the modified Gleason grading system and factoring in tertiary grades. Eur Urol. 2012;61:1019–24. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Wang X, Zhang Y, Ji Z, Yang P, Tian Y. Old men with prostate cancer have higher risk of Gleason score upgrading and pathological upstaging after initial diagnosis: a systematic review and meta-analysis. World J Surg Oncol. 2021;19:18. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Truong M, Slezak JA, Lin CP, Iremashvili V, Sado M, Razmaria AA, et al. Development and multi-institutional validation of an upgrading risk tool for Gleason 6 prostate cancer. Cancer. 2013;119:3992–4002. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Evans SM, Bandarage VP, Kronborg C, Earnest A, Millar J, Clouston D. Gleason group concordance between biopsy and radical prostatectomy specimens: a cohort study from Prostate Cancer Outcome Registry–Victoria. Prostate Int. 2016;4:145–51. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Arsov C, Becker N, Rabenalt R, Hiester A, Quentin M, Dietzel F, et al. The use of targeted MR-guided prostate biopsy reduces the risk of Gleason upgrading on radical prostatectomy. J Cancer Res Clin Oncol. 2015;141:2061–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Aslan G, Çelik S, Sözen S, Akdoğan B, İzol V, Yücel Bilen C, et al. Comparison of TRUS and combined MRI-targeted plus systematic prostate biopsy for the concordance between biopsy and radical prostatectomy pathology. Int J Clin Pract. 2021;75:e13797. [DOI] [PubMed] [Google Scholar]
- 32.Ryan J, Broe MP, Moran D, Mulvin D, Heffernan E, Swan N, et al. Prostate cancer detection with magnetic resonance imaging (MRI)/cognitive fusion biopsy: comparing standard and targeted prostate biopsy with final prostatectomy histology. Can Urol Assoc J. 2021;15:483–7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33.Kayano PP, Carneiro A, Castilho TML, Sivaraman A, Claros OR, Baroni RH, et al. Comparison of Gleason upgrading rates in transrectal ultrasound systematic random biopsies versus US-MRI fusion biopsies for prostate cancer. Int Braz J Urol. 2018;44:1106–13. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34.Moussa AS, Kattan MW, Berglund R, Yu C, Fareed K, Jones JS. A nomogram for predicting upgrading in patients with low- and intermediate-grade prostate cancer in the era of extended prostate sampling. BJU Int. 2010;105:352–8. [DOI] [PubMed] [Google Scholar]
- 35.Hu Q, Hong X, Xu L, Jia R. A nomogram for accurately predicting the pathological upgrading of prostate cancer, based on 68 Ga-PSMA PET/CT. Prostate. 2022;82:1077–87. [DOI] [PubMed] [Google Scholar]
- 36.Bolat D, Eskiçorapçı S, Karabulut E, Baltacı S, Yıldırım A, Sözen S, et al. Can we predict the surgical margin positivity in patients treated with radical prostatectomy?? A multicenter cohort of Turkish association of Uro-Oncology. J Urol Surg. 2015;2:7–12. [Google Scholar]
- 37.Kates M, Sopko NA, Han M, Partin AW, Epstein JI. Importance of reporting the Gleason score at the positive surgical margin site: analysis of 4,082 consecutive radical prostatectomy cases. J Urol. 2016;195:337–42. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.