UROLOGICAL ONCOLOGY Does the New Proposal for Prostate Cancer Grading Correlate With CAPRA Score? Levent Isikay1 , Senol Tonyali1*, Gulden Aydog2 Purpose: To determine if there is a correlation between the newly proposed Gleason grading system by the Inter- national Society of Urological Pathology and the Cancer of the Prostate Risk Assessment (CAPRA) score. Material and Methods: The records of all patients that underwent radical prostatectomy at our hospital between 2007 and 2013 were retrospectively reviewed. The study parameters included patient demographics, the percent- age of pre-operative prostate biopsies positive for PCa, biopsy Gleason Score (GS), and pre- and post-operative PSA values. Result: The study included 146 patients with complete medical records and follow-up data. Mean age of the pa- tients was 66.6 ± 6.08 years. According to the newly proposed Gleason grading system, 97 (66.4%) patients were grade 1, 20 (13.7%) were grade 2, 8 (5.5%) were grade 3, 11 (7.5%) were grade 4, and 10 (6.8%) were grade 5. The distribution of CAPRA scores was as follows: 1: n = 43 (29.5%); 2: n = 53 (36.3%); 3: n = 22 (15.1%); 4: n = 14 (9.6%); 5: n = 8 (5.5%); 6: n = 4 (2.7%); 7: n = 1 (0.7%); 8: n = 1 (0.7%). Correlation analysis showed that the CAPRA score was significantly correlated with GS based on the newly proposed Gleason grading system (Corre- lation Coefficient=0.361, P < 0.001). Conclusion: As a strong correlation was noted between these 2 independent grading systems, we think clinicians that seek to predict the prognosis in PCa patients should take into consideration both the newly proposed ISUP grading system and the CAPRA score. Keywords: biochemical recurrence; CAPRA; Gleason pattern; pathologic examination; prostatectomy INTRODUCTION Prostate cancer (PCa) is the most common solid neo- plasm in Europe, with an incidence of 214 cases per 1000 men(1). Nowadays, patient counseling and pa- tient-oriented treatment form the core of PCa treatment, because each treatment modality can have serious ef- fects on patient quality of life;(2) as such, stratification and grading of PCa continue to increase in importance. The treatment of PCa is based on clinical stage and risk status, and treatment options for localized PCa include active surveillance, radical prostatectomy (RP), radia- tion therapy, brachytherapy, cryosurgical ablation, and high-intensity focused ultrasound (HIFU)(1). The Gleason grading system is the most common sys- tem used to grade prostate cancer aggressiveness. The system uses a scale of 1 to 5 to calculate the Gleason score (GS) (range: 2-10), which is the sum of the most common and second most common grade patterns. The most commonly reported GSs in clinical practice is ≥ 6. Many patients and clinicians consider a GS of 6 indic- ative of an intermediate prognosis and seek immediate treatment;(3,4) however, there is a lack of consensus con- cerning the cancerous pattern of PCa with a GS of 6(5). Due to deficiencies, the International Society of Uro- logical Pathology (ISUP) has updated the Gleason grading system from time to time; the latest update was 1Clinic of Urology, Turkiye Yuksek Ihtisas Training and Research Hospital, Ankara. TURKEY. 2Clinic of Pathology, Turkiye Yuksek Ihtisas Training and Research Hospital, Ankara. TURKEY. *Correspondence: Turkiye Yuksek Ihtisas Training and Research Hospital Clinic of Urology, 06230 Altindag Ankara, TURKEY Tel: +90 312 3061829. E-mail: dr.senoltonyali@gmail.com. Received May 2018& Accepted July 2018 in 2014. The newly proposed system stratifies patients into 5 distinct prognostic groups, which enables more accurate and simplified classification of tumors. More- over, the lowest grade in the newly proposed system is 1 not 6, as in the Gleason system, which might result in reducing the incidence of overtreatment of indolent cancer(3). There are several pre- and post-treatment assessment tools used to predict prognosis after definitive treat- ment of PCa, including the Kattan nomogram, D’Am- ico classification, and the Cancer of the Prostate Risk Assessment (CAPRA) score(6-8). The CAPRA score is a pre-treatment score based on patient age, preoperative prostate-specific antigen (PSA), prostate biopsy GS, clinical stage, and the percentage of positive cores in a prostate biopsy specimen. Although the CAPRA score is an externally validated and easy to use tool; biopsy GS, clinical stage, and the percentage of positive biop- sy cores are approximations by nature and, therefore, might over- or underestimate the actual grade or exten- sion of disease(8). As such, the present study aimed to determine the correlation between the newly proposed Gleason grading system and the CAPRA score. A pos- sible correlation might help clinician in patient risk stratification and treatment planning. Urological Oncology 355 Vol 15 No 06 November-December 2018 356 MATERIALS AND METHODS After the approval of the study protocol by Turkiye Yuksek Ihtisas Training and Research Hospital review board, the records of all patients that underwent radical prostatectomy at our hospital between 2007 and 2013 were retrospectively reviewed. Patients who had a bi- opsy confirmed localized PCa were treated with radi- cal prostatectomy. Patients that received neoadjuvant treatment for PCa were excluded from the study. The study parameters included patient demographics, the percentage of pre-operative prostate biopsies positive for PCa, biopsy GS, and pre- and post-operative PSA values. The CAPRA score was calculated using The University of California, San Francisco (UCSF), web- based calculator(9) by S.T.. Needle biopsies and radical prostatectomy materials were examined by the same pa- thologist (G.A.). Samples that could not be diagnosed via hematoxylin & eosin staining were studied using p63, HMWK, and AMACR immunohistochemistry. Mean ± SD was used to describe quantitative varia- bles. Quantitative measurements were compared using non-parametric Spearman’s correlation analysis. Data were analyzed using IBM SPSS Statistics for Windows v.21.0 (IBM Corp., Armonk, NY). The level of statisti- cal significance was set at P < .05. RESULTS The study included 146 patients with complete medical records and follow-up data. Mean age of the patients was 66.6 ± 6.08 years. The mean pre-operative PSA value was 9.3 ± 9.6 mg dL˗1 and the mean number of PCa-positive prostate biopsy cores was 3.1 ± 1.3 (range: 1-6). The distribution of prostate biopsy GSs was as follows: GS 6: n = 115 (78.7%); GS 7: n = 18 (12.3%); GS 8: n = 13 (8.9%). An upstaging of GS was observed via final pathologic examination of some RP specimens, as shown in Table 1. According to the new- ly proposed Gleason grading system, 97 (66.4%) pa- tients were grade 1, 20 (13.7%) were grade 2, 8 (5.5%) were grade 3, 11 (7.5%) were grade 4, and 10 (6.8%) were grade 5. The distribution of CAPRA scores was as follows: 1: n = 43 (29.5%); 2: n = 53 (36.3%); 3: n = 22 (15.1%); 4: n = 14 (9.6%); 5: n = 8 (5.5%); 6: n = 4 (2.7%); 7: n = 1 (0.7%); 8: n = 1 (0.7%). According to CAPRA risk categorization 96 patients (65.7%) had low risk, 44 patients (30.1%) had intermediate risk and 6 patients (4.4%) had high-risk disease. Among the 146 patients, 25 (17.1%) patients developed biochemical recurrence; 18 within 2 years and 7 within 5 years of treatment. Correlation analysis showed that the CAPRA score was significantly correlated with GS based on the newly proposed Gleason grading system (Correlation Coefficient=0.361, P < .001). On univariate regression analysis both CAPRA score and newly proposed Gleason grading system were found significantly predict biochemical recurrence af- ter radical prostatectomy (P < .01 for both correlations) (Table 3). DISCUSSION PCa is the most common solid malignancy diagnosed in men in Europe and the United States,(1,10) and is the sec- ond leading cause of death in the United States(10). Most patients with PCa die due to other causes; however, PCa does cause mortality in some cases. Due to the ambigu- ous behavior of the disease and the potential side effects of its treatment, risk stratification of PCa patients has become an important facet of its management(11). The Gleason grading system was developed in the 1960’s to categorize adenocarcinoma of the prostate ac- cording to 5 patterns, ranging from well differentiated (1) to poorly differentiated (5)(12). The GS is the sum of the most common (primary) and the second most com- mon (secondary) grade patterns, ranging from 2 to 10; Table 1. Upstaging between prostate biopsy and final pathology results Table 2. The Newly Proposed Grading System Groups for Prostate Cancer by ISUP Gleason Score Prostate Biopsy GS RP Specimen GS Gleason 6 (3+3) 115 (78.8 %) 97 (66.4 %) Gleason 7 (3+4) 14 (9.6 %) 20 (13.6%) Gleason 7 (4+3) 4 (2.7 %) 8 (5.4%) Gleason 8 (3+5) 12 (8.2 %) 8 (5.4%) Gleason 8 (4+4) 1 (0.7 %) 2 (1.3%) Gleason 8 (5+3) - 1 (0.6%) Gleason 9 (4+5) - 6 (4.1%) Gleason 9 (5+4) - 4 (2.7%) Prognostic Grade Group Definition Grade group 1 Gleason score ≤ 6 Grade group 2 Gleason score 3+4=7 Grade group 3 Gleason score 4+3=7 Grade group 4 Gleason score 8 (4+4, 3+5, 5+3) Grade group 5 Gleason score 9–10 (4+5,5+4,5+5) Biochemical recurrence, n (%) P value International Society of Urological Pathology (ISUP) Grade Group < 0,01 1 9/97 (9,3) 2 6/20 (30) 3 2/8 (25) 4 1/11 (9,1) 5 7/10 (70) Cancer of the Prostate Risk Assessment (CAPRA) score < 0,01 1 2/43 (4,7) 2 6/53 (11,3) 3 7/22 (31,8) 4 4/14 (28,6) 5 3/8 (37,5) 6 1/4 (25) 7 1/1 (100) 8 1/1 (100) Table 3. Association Between Different Grading Systems And Frequency Of Biochemical Recurrence (BR). New proposal for prostate cancer grading-Isikay et al. however, nowadays the most commonly reported GS in clinical practice is ≥ 6. Despite being the most popular grading system, the Gleason grading system is not per- fect(4). A rational patient could consider a GS of 6 (on a scale of 10) to indicate an intermediate prognosis or to indicate that immediate treatment is required, whereas, in fact, GS 3 + 3 = 6 is a good score indicating that treatment with active surveillance is sufficient. In addi- tion, although both are GS 7, GS 3 + 4 = 7 has a better prognosis than GS 4 + 3 = 7(4). Due to Gleason grading system deficiencies, the need for a better grading sys- tem emerged and in 2014 ISUP proposed a new grading system, as shown in Table 2(3). During the past 20 years several research groups have proposed various nomograms and statistical models for predicting recurrence-free survival following definitive treatment and for determining pre-treatment patholog- ic stage of PCa; the most well-known being the Kat- tan nomogram and D’Amico classification,(6,13) and the CAPRA score(14). Cooperberg et al.(14) developed the CAPRA score for preoperative prediction of biochem- ical recurrence-free survival after RP in patients with clinically localized PCa, as appropriate preoperative risk assessment is an integral component of counseling such patients(15). The CAPRA score is the sum of the weighted risk factors, including age and PSA value at diagnosis, biopsy GS, clinical tumor stage, and the percentage of biopsy cores positive for PCa(16). The ex- ternal validation of the CAPRA score was studied by multiple researchers,(17, 18) and was reported to accurate- ly predict recurrence-free survival and stratify patients according to their risk. In the past, PCa patients were stratified according to GS as low risk (GS < 7), intermediate risk (GS = 7), and high risk (GS = 8-10); however, now it is well known that all GS 7 and GS 8-10 PCa cannot be grouped in the same categories and treated in that manner. In the pres- ent study the CAPRA score was significantly correlated with the newly proposed ISUP grading system. Based on this finding, we think that both the newly proposed ISUP grading system and the CAPRA score can be con- sidered reliable instruments for predicting the progno- sis in PCa patients. None of the patients in the present study had a GS of 9 or 10, which might have been due the widespread use of PSA screening in Turkey, which facilitates early detection of PCa. Also patients with high GS in prostate biopsy might have chosen or been directed to alternative treatment modalities. Our study is also not without limitations. First of all, this is a retrospective study with a relatively small num- ber of patients. And as mentioned above there are not many patients with high grade/high risk PCa. CONCLUSIONS The literature includes multiple studies on the validi- ty of the CAPRA score for predicting PCa recurrence; however, to the best of our knowledge the present study is the first to determine the correlation between the new- ly proposed Gleason grading system and the CAPRA score. As a strong correlation was noted between these 2 independent grading systems, we think clinicians that seek to predict the prognosis in PCa patients should take into consideration both the newly proposed ISUP grading system and the CAPRA score. CONFLICT OF INTEREST No potential conflict of interest relevant to this article was reported. REFERENCES 1. 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