- Email: [email protected]
Validation of 2001 Partin Tables in Turkey: A Multicenter Study
European Urology
European Urology 47 (2005) 185–189
Validation of 2001 PartinTables inTurkey: A Multicenter Study Saadettin Yilmaz Eskicorapci*, Erdem Karabulut, Levent Tu¨rkeri, Su¨mer Baltacı, Cag Cal, Gokhan Toktas, Haluk Akpınar, Gokhan Ozer, Sinan Sozen, Resit Tokuc, Murat Lekili, Ahmet Soylu, Selami Albayrak, Hayrettin Sahin, Reha Alpar, Haluk Ozen Hacettepe Universitesi, Uroloji ABD, Sihhiye, 06120 Ankara, Turkey Accepted 3 August 2004 Available online 25 August 2004
Abstract Objective: Although Partin tables were developed in United States to predict the stage of prostate cancer preoperatively, they are used by many clinics throughout the world assuming that these figures apply to their population as well. However the predictive value of current Partin tables, which was updated in 2001, has not been validated in most of the countries as well as in Turkey. Therefore, we evaluated the validity of 2001 Partin tables, for the ability to predict the pathological stage in Turkish patients. Patients and Methods: The clinical and pathological findings of 1043 patients who have had radical prostatectomy were assessed. Serum PSA values, clinical stage, biopsy Gleason score and the pathological features of the radical prostatectomy specimens were collected from each clinic and evaluated. The predictive value of Partin nomogram and pathological findings of prostatectomy specimens were compared and analyzed according to Receiver Operating Characteristics (ROC) analysis. Results: Median age of the patients was 60 (45–74). In the presented study, percentage of patients with clinical stage T1c was 43%. Patients with Gleason score of 2–4 in biopsy constituted 23.4% of the study group. In the present study, the ratio of the patients with serum PSA higher than 10 ng/ml was 39.6%. Organ confined disease, seminal vesicle involvement, lymph node metastases ratios were 64.7%, 10.3%, 1.8% respectively. Area Under Curve (AUC) values for organ confined disease, seminal vesicle involvement and lymph node involvement were calculated as 0.665, 0.733 and 0.759 respectively. Conclusion: It appears that Partin tables have a reasonable predictive value for the final pathological features like organ confined disease, seminal vesicle and lymph node involvement in Turkish patients. This multicenter study showed that current Partin tables could also be used in Turkish patients with comparable accuracy. # 2004 Elsevier B.V. All rights reserved. Keywords: Prostate cancer; Partin tables; Radical prostatectomy; Validation
1. Introduction Radical prostatectomy is known to be the most effective when the disease is organ or specimen confined [1–3]. Thus one of the critical issues in the decision for radical prostatectomy would be the prediction of the final pathological state from preoperative parameters. In recent years multiple investigators have * Corresponding author. Tel. +90 3123051969; Fax: +90 3123112262. E-mail address: [email protected] (S.Y. Eskicorapci).
published numerous nomograms about the prediction of radical prostatectomy findings by the aid of preoperative variables such as serum prostate specific antigen (PSA), Gleason score, clinical stage, cancer volume and PSA density [4–9]. Clinical predictive capacity of a nomogram must be validated by other clinics before it is recommended for clinical application. Most nomograms have not been validated widely in different settings and thus, clinical usefulness of them is controversial. Partin et al. combined preoperative serum PSA, Gleason score and clinical stage to
0302-2838/$ – see front matter # 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.eururo.2004.08.002
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predict the radical prostatectomy pathology and created a well-known nomogram called ‘‘Partin tables’’ [4]. They updated the model in 1997 on a multiinstitutional series of 4133 men who were treated at three major clinics of the United States [5]. They renewed the nomogram at 2001 with 5079 patients with their data at Johns Hopkins Hospital [10]. The validation studies of former Partin tables confirmed its clinical accuracy not only for the United States, but also for Europe [11–14]. Augustin et al. recently published the first validation study of 2001 Partin tables in a patient group of a single tertiary referral center [15]. Partin tables are usually used in the United States and elsewhere to predict the pathological stage of prostate cancer. They are frequently used in many clinics in Turkey as well. However the predictive value of the Partin tables for our country is not well known. Therefore, we evaluated the validity of current Partin tables, which was updated in 2001, for the ability to predict the pathological stage in Turkish patients.
Table 1 Clinical and pathological characteristics of our study population and Partin cohort in 2001 % Turkey (n = 1043)
% Partin 2001 (n = 5079)
Clinical stage T1c T2a T2b T2c
43 38.6 14.5 3.9
63 32 11 3
PSA(ng/ml) 0–2.5 2.6–4 4.1–6 6.1–10 More than 10
2.5 6.2 14.8 36.9 39.6
7 10 27 35 21
Biopsy Gleason sum 2–4 5–6 7 8–10
23.4 54.1 16.0 6.5
0.6 79 17.4 3
Pathological stage Organ confined Extraprostatic extension Seminal vesicle involvement Lymph node metastases
63.7 24.2 10.3 1.8
64 30 4 2
2. Materials and methods
3. Results
The clinical and pathological findings of 1043 patients who have had radical prostatectomy in 13 clinics in Turkey between January 1992 and May 2003 were assessed. All of the patients had clinically localized disease and thus were candidates for radical prostatectomy. Serum PSA values, clinical stage, biopsy Gleason score and the pathological features of the radical prostatectomy specimens were collected from each clinic and evaluated. Those with missing information of the preoperative serum PSA, Gleason score, clinical stage and patients who had neoadjuvant endocrine treatment were excluded. The names of the clinics are depicted in the appendix. Serum PSA values, clinical staging, biopsy Gleason scores and pathological evaluations of the radical prostatectomy specimens were done by different physicians in each clinic. All biopsy specimens were graded histologically using the Gleason scoring system [16]. Capsular penetration, surgical margin invasion, seminal vesicle invasion and lymph node status of the patients were determined in each clinic staging was done by using the 1992 TNM staging system [17]. Cancer was considered as organ confined if the capsule was not penetrated. The clinical staging was also done by the aid of the same staging system. Preoperative characteristics and the pathological findings in our patients, Johns’ Hopkins group and other validation study groups were compared. All statistical evaluations were 2-sided and done by SPSS 10.0 package program. Partin tables, which were published in 2001, were applied to Turkish patients and the prediction of organ confinement, seminal vesicle and lymph node invasion was calculated. Receiver Operating Characteristics (ROC) analysis was done to assess the discriminative ability of the Partin tables in our patient group. Power value of ROC curves was calculated by using NCSSPASS program.
Median age of the patients was 60 (45–74). The clinical and pathological characteristics such as clinical stage, serum PSA, Gleason score and final pathological result of the prostate of the patients were compared to Partin tables updated in 2001 (Table 1).
Fig. 1. ROC curve analysis comparing predicted probabilities of organ confinement from Partin tables and actual incidence of organ confined prostate cancers in Turkish patients.
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value of 14 ng/ml. For the whole group organ confined disease, seminal vesicle involvement and lymph node metastases ratios were 64.7%, 10.3% and 1.8% respectively (Table 1). The predictive value of Partin tables was evaluated with ROC curve analyses. Area Under Curve (AUC) values for organ confined disease, seminal vesicle involvement and lymph node involvement were 0.665 ( p < 0.0001), 0.733 ( p < 0.0001) and 0.759 ( p < 0.0001), respectively (Figs. 1–3). One-sided ROC curve power analysis for organ confined disease revealed 1.00 power value.
4. Discussion
Fig. 2. ROC curve analysis comparing predicted probabilities of seminal vesicle involvement from Partin tables and actual incidence of seminal vesicle involvement in Turkish patients.
In our study group, percentage of patients with clinical stage T1c was 43%. Patients with Gleason score of 2–4 in biopsy constituted 23,4% of the study group (Table 1). In the present study, the ratio of the patients with serum PSA higher than 10 ng/ml was 39.6% (Table 1). Patients who had PSA over 10 ng/ml had a median PSA
Fig. 3. ROC curve analysis comparing predicted probabilities of lymph node involvement from Partin tables and actual incidence of lymph node involvement in Turkish patients.
The validation studies of the former Partin tables (1997) confirmed its accuracy not only for the United States, but also for Europe [11–14]. Only one validation study of the 2001 Partin tables revealed acceptable accuracy in a patient population of a single tertiary referral center [15]. Our aim was to carry out a multicenter validation study of current Partin tables in Turkish patients. Our study population was heterogeneous including patients from 13 clinics, which varied from tertiary referral academic centers to community hospitals. Thus there was no bias in recruitment of the patients. Area under curve (AUC) values had been previously assessed for the validation studies evaluating the predictive capacity of the former 1997 Partin tables [12– 14]. AUC values for the organ-confined disease were 0.727, 0.757, 0.684 and 0.817 for the 1997 Partin cohort, Mayo cohort, CaPSURE cohort and Hamburg study group, respectively [5,12–14]. The area under curve (AUC) values for the lymph node involvement were 0.818, 0.837, 0.766 and 0.807 for Partin cohort (1997), Mayo cohort, CaPSURE cohort and Hamburg study group, respectively [5,12–14]. Although the values were lower for the CaPSURE study, all studies concluded that Partin tables (1997) could be used effectively to predict the final pathological outcome. The validation study of 2001 Partin tables also found AUC values as 0.787, 0.775 and 0.790 for organconfined disease, seminal vesicle and lymph node involvement respectively [15]. Likewise we performed ROC analysis to determine the predictive capacity of the 2001 Partin tables. Our area under curve values for organ-confined disease, seminal vesicle and lymph node involvement were 0.665, 0.733 and 0.759 respectively and all ROC analyses were statistically significant. AUC values were not as high as the previous studies validating the 1997 and 2001 Partin tables. In
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ROC curve analysis AUC values less than 0.700 may be considered as a poor result. In this respect, we performed power analysis for the AUC value (0.665) of organ-confined disease and found 1.00 value, which was highly acceptable. So we can clearly say that we can use Partin tables for the prediction of organ confined disease in Turkish patients. Our findings demonstrate that the current Partin tables have a reasonable predictive value for organ-confined disease, seminal vesicle and lymph node involvement in patients who undergo radical prostatectomy in Turkish patients. Since Partin tables do not provide information beyond pathological outcome, they cannot predict clinical outcome and also they are not ideal tools for further treatment planning. However, prediction of organ-confined disease may be useful to select the patients for nerve sparing surgery. Different nomograms to predict the recurrence probability for individual patients were also developed and were thought to be more useful for both patients and physicians [8]. The dataset of our study population appeared to be similar to Partin cohort in many aspects. In Turkish study, two major differences from Partin series were observed. The clinical stage T1c ratio was 43% in our study and 63% in Partin series. This ratio was 33% for the former Partin cohort in 1997 [5]. In recent years the number of localized prostate cancer increased with increasing usage of serum PSA throughout the world and in our country. Our ratio of 43% is in somewhere between the two Partin cohorts of 1997 and 2001. Organ confinement ratios of the present study and that of current Partin tables were similar albeit the relatively high percentage of patients with serum PSA levels >10 ng/ml in the present study. Although this seems to be a conflicting result, same trend was also observed in Hamburg validation study [14]. In the Hamburg study although overall 41% had high serum PSA levels (>10 ng/ml) compared to 29% in 1997 Partin tables they have reported a surprisingly high organ confined ratio of 56% compared to 48% in the former Partin study. Interestingly, similar to our results they had higher seminal vesicle involvement compared to Partin cohort. It is not clear whether this is a European phenomenon or that PSA to a certain level is not the main predictor of organ confinement. It must be emphasized that although almost 40% of our patients had serum PSA levels >10 ng/ml with the median value of 14 ng/ml. The second difference in our series was a 23.4% ratio of biopsy Gleason score 2–4 in our study while it was 0.6% in Partin series. The number of Gleason scores lower than 5 is extremely low such as 0–1% in the modern series [10,14]. But in former series the ratios of
biopsy Gleason of 2–4 were 5%, 17%, and 19% for Partin cohort 1997, Mayo cohort and CaPSURE cohorts, respectively. Epstein offered to improve the Gleason score by not assigning Gleason scores 2 to 4 for adenocarcinoma of prostate on needle biopsy [18]. There were three reasons for such approach: First, the vast majority of the tumors with Gleason score 2 to 4 were graded as Gleason score 5 to 6 by experts in urologic pathology. Second the reproducibility of Gleason score 2 to 4 is low and third assigning Gleason score 2 to 4 can adversely affect the patient care because clinicians may assume low-grade cancers do not need definitive therapy. Epstein stated that 55% of the patients with Gleason score 2 to 4 diagnosed outside clinics other than Johns Hopkins Hospital had extraprostatic extension. In order to overcome this low reproducibility education of the pathologists is of paramount importance. The help of these educational efforts will achieve standardization of grading in the coming years. Our study is limited by the lack of central pathological review. There may be considerable variations in the interpretation of the radical prostatectomy specimens [19]. Although some studies reported acceptable interobserver reliability among pathologists when reporting biopsy results [20], there could be some variability for the interpretation of the pathological results. Thus one can prefer a single pathologist to review each pathological specimen. However this will not reflect the real world practice [21]. Despite those differences with two study groups in pretreatment variables, Partin tables were adequate in predicting the final pathological features in Turkish patients as well. The differences in some of the preoperative parameters reflect the differences of the patient’s attitude to screening and the availability of serum PSA testing in two countries.
5. Conclusions It appears that Partin tables have a reasonable predict value for the final pathological features like organ confined disease, seminal vesicle and lymph node involvement in Turkish patients. This multicenter study showed that current Partin tables could also be used in Turkish patients with comparable accuracy.
Appendix A The list of the centers and the investigators included in the study: From the departments of Urology:
S.Y. Eskicorapci et al. / European Urology 47 (2005) 185–189
1. Hacettepe University Hospital: Saadettin Eskicorapci, MD and Haluk Ozen, MD. 2. Marmara University Hospital: Levent Tu¨ rkeri MD. 3. Ankara University Hospital: Sumer Baltacı MD. 4. Ege University Hospital: Cag Cal MD. 5. SSK Istanbul Egitim Hospital: Gokhan Toktas MD. 6. Florans Nightingale Hospital: Haluk Akpınar MD. 7. Yuksek Ihtisas Hospital: Gokhan Ozer MD. 8. Gazi University Hospital: Sinan Sozen MD. 9. Goztepe SSK Egitim Hospital: Resit Tokuc MD.
189
10. Manisa Celal Bayar University Hospital: Murat Lekili MD. 11. Inonu University Hospital: Ahmet Soylu MD. 12. Dr. L. Kirdar Kartal Egitim ve Arastirma Hospital: Selami Albayrak MD. 13. Dicle University Hospital: Hayrettin Sahin MD. From the department of Biostatistics of Hacettepe University Hospital: Erdem Karabulut MD, Reha Alpar MD.
References [1] Walsh PC, Partin AW, Epstein JI. Cancer control and quality of life following anatomical radical retropubic prostatectomy: results at 10 years. J Urol 1994;152(Pt 2):1831. [2] Epstein JI, Pizov G, Walsh PC. Correlation of pathologic findings with progression following radical retropubic prostatectomy. Cancer 1993;71:3582. [3] Epstein JI, Walsh PC, Carmichael M, et al. Pathologic and clinical findings to predict tumor extent of nonpalpable (stage 1c) prostate cancer. JAMA 1994;271:368. [4] Partin AW, Yoo J, Carter HB, et al. The use of prostate specific antigen, clinical stage and Gleason score to predict pathological stage in men with localized prostate cancer. J Urol 1993;150:110. [5] Partin AW, Kattan MW, Subong EN, et al. Combination of prostatespecific antigen, clinical stage and Gleason score to predict pathological stage of localized prostate cancer. A multiinstutional update. JAMA 1997;277:1445. [6] Narayan P, Gajendran V, Taylor SP, et al. The role of transrectal ultrasound-guided biopsy-based staging, preoperative serum prostatespecific antigen and biopsy Gleason score in prediction of final pathological diagnosis in prostate cancer. Urology 1995;46:205. [7] Graefen M, Noldus J, Pichleimer U, Haese A, Hammerer P, Fernandez S, et al. Early prostate-specific antigen relapse after radical retropubic prostatectomy: prediction on the basis of preoperative and postoperative tumor characteristics. Eur Urol 1999;36:21. [8] Kattan MW, Eastham JA, Stapleton AM, Wheeler TM, Scardino PT. A preoperative nomogram for disease recurrence following radical prostatectomy for prostate cancer. J Natl Cancer Inst 1998;90:776. [9] Bauer JJ, Connely RR, Seterhenn IA, Deausen J, Srivastava S, McLeod DG, et al. Biostatistical modeling using traditional preoperative and pathological prognostic variables in the selection of men at high risk for disease recurrence after radical prostatectomy for prostate cancer. J Urol 1998;159:929. [10] Partin AW, Mangold LA, Lamm DM, Walsh PC, Epstein JI, Pearson JD. Contemporary update of prostate cancer staging nomograms(Partin tables) for the new millennium. Urology 2001;58:843.
[11] Kattan MW, Stapleton AM, Wheeler TM, Scardino PT. Evaluation of a nomogram used to predict the pathological stage of clinically localized prostate carcinoma. Cancer 1997;79:528. [12] Blute ML, Bergstrahl EJ, Partin AW, Walsh PC, Kattan MW, Scardino PT, et al. Validation of Partin tables for predicting pathological stage of clinically localized prostate cancer. J Urol 2000;164:1591. [13] Penson DF, Grossfeld GD, Li Y, Henning JM, Lubeck DP, Carroll PR. How well does the Partin nomogram predict pathological stage after radical prostatectomy in a community based population? Results of the cancer of the prostate strategic urological research endeavor J Urol 2002;167:1653. [14] Graefen M, Augustin H, Karakiewicz PI, Hammerer PG, Haese A, Palisaar J, et al. Can predictive models for prostate cancer patients derived in the United States of America be utilized in European patients? A validation study of the Partin tables Eur Urol 2003;43:6. [15] Augustin H, Eggert T, Wenske S, Karakiewicz PI, Palisaar J, Daghofer F, et al. Comparison of accuracy between the Partin tables of 1997 and 2001 to predict final pathological stage in clinically localized prostate cancer. J Urol 2004;171:177. [16] Gleason DF. Histologic grading and clinical stage of prostatic carcinoma. In: Tannenbaum M, editor. Urologic pathology: The prostate. Philadelphia: Lea & Ferbirger; 1997. p. 171. [17] Schroeder FH, Hermanek P, Denis L, Fair WR, Gospodarowicz MK, Pavone-Macaluso M. The TNM classification of prostate cancer. Prostate 1992;4(Suppl):129. [18] Epstein JI. Campbell’s Urology: pathology of prostatic neoplasia, 8th edition, Philadelphia: Saunders, Elsevier Science; 2002. p. 3025. [19] Bostwick DG, Montironi R. Evaluation radical prostatectomy specimens: therapeutic and prognostic importance. Wirchows Arch 1997;430:1. [20] Ross PL, Scardino PT, Kattan MW. A catalog of prostate cancer nomograms. J Urol 2001;165:1562. [21] Ekici S, Ayhan A, Erkan DT, Bakkalog˘ lu M, Ozen H. The role of the pathologist in the evaluation of radical prostatectomy specimens. Scand J Urol Nephrol 2003;37:387.
European Urology 47 (2005) 185–189
Validation of 2001 PartinTables inTurkey: A Multicenter Study Saadettin Yilmaz Eskicorapci*, Erdem Karabulut, Levent Tu¨rkeri, Su¨mer Baltacı, Cag Cal, Gokhan Toktas, Haluk Akpınar, Gokhan Ozer, Sinan Sozen, Resit Tokuc, Murat Lekili, Ahmet Soylu, Selami Albayrak, Hayrettin Sahin, Reha Alpar, Haluk Ozen Hacettepe Universitesi, Uroloji ABD, Sihhiye, 06120 Ankara, Turkey Accepted 3 August 2004 Available online 25 August 2004
Abstract Objective: Although Partin tables were developed in United States to predict the stage of prostate cancer preoperatively, they are used by many clinics throughout the world assuming that these figures apply to their population as well. However the predictive value of current Partin tables, which was updated in 2001, has not been validated in most of the countries as well as in Turkey. Therefore, we evaluated the validity of 2001 Partin tables, for the ability to predict the pathological stage in Turkish patients. Patients and Methods: The clinical and pathological findings of 1043 patients who have had radical prostatectomy were assessed. Serum PSA values, clinical stage, biopsy Gleason score and the pathological features of the radical prostatectomy specimens were collected from each clinic and evaluated. The predictive value of Partin nomogram and pathological findings of prostatectomy specimens were compared and analyzed according to Receiver Operating Characteristics (ROC) analysis. Results: Median age of the patients was 60 (45–74). In the presented study, percentage of patients with clinical stage T1c was 43%. Patients with Gleason score of 2–4 in biopsy constituted 23.4% of the study group. In the present study, the ratio of the patients with serum PSA higher than 10 ng/ml was 39.6%. Organ confined disease, seminal vesicle involvement, lymph node metastases ratios were 64.7%, 10.3%, 1.8% respectively. Area Under Curve (AUC) values for organ confined disease, seminal vesicle involvement and lymph node involvement were calculated as 0.665, 0.733 and 0.759 respectively. Conclusion: It appears that Partin tables have a reasonable predictive value for the final pathological features like organ confined disease, seminal vesicle and lymph node involvement in Turkish patients. This multicenter study showed that current Partin tables could also be used in Turkish patients with comparable accuracy. # 2004 Elsevier B.V. All rights reserved. Keywords: Prostate cancer; Partin tables; Radical prostatectomy; Validation
1. Introduction Radical prostatectomy is known to be the most effective when the disease is organ or specimen confined [1–3]. Thus one of the critical issues in the decision for radical prostatectomy would be the prediction of the final pathological state from preoperative parameters. In recent years multiple investigators have * Corresponding author. Tel. +90 3123051969; Fax: +90 3123112262. E-mail address: [email protected] (S.Y. Eskicorapci).
published numerous nomograms about the prediction of radical prostatectomy findings by the aid of preoperative variables such as serum prostate specific antigen (PSA), Gleason score, clinical stage, cancer volume and PSA density [4–9]. Clinical predictive capacity of a nomogram must be validated by other clinics before it is recommended for clinical application. Most nomograms have not been validated widely in different settings and thus, clinical usefulness of them is controversial. Partin et al. combined preoperative serum PSA, Gleason score and clinical stage to
0302-2838/$ – see front matter # 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.eururo.2004.08.002
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predict the radical prostatectomy pathology and created a well-known nomogram called ‘‘Partin tables’’ [4]. They updated the model in 1997 on a multiinstitutional series of 4133 men who were treated at three major clinics of the United States [5]. They renewed the nomogram at 2001 with 5079 patients with their data at Johns Hopkins Hospital [10]. The validation studies of former Partin tables confirmed its clinical accuracy not only for the United States, but also for Europe [11–14]. Augustin et al. recently published the first validation study of 2001 Partin tables in a patient group of a single tertiary referral center [15]. Partin tables are usually used in the United States and elsewhere to predict the pathological stage of prostate cancer. They are frequently used in many clinics in Turkey as well. However the predictive value of the Partin tables for our country is not well known. Therefore, we evaluated the validity of current Partin tables, which was updated in 2001, for the ability to predict the pathological stage in Turkish patients.
Table 1 Clinical and pathological characteristics of our study population and Partin cohort in 2001 % Turkey (n = 1043)
% Partin 2001 (n = 5079)
Clinical stage T1c T2a T2b T2c
43 38.6 14.5 3.9
63 32 11 3
PSA(ng/ml) 0–2.5 2.6–4 4.1–6 6.1–10 More than 10
2.5 6.2 14.8 36.9 39.6
7 10 27 35 21
Biopsy Gleason sum 2–4 5–6 7 8–10
23.4 54.1 16.0 6.5
0.6 79 17.4 3
Pathological stage Organ confined Extraprostatic extension Seminal vesicle involvement Lymph node metastases
63.7 24.2 10.3 1.8
64 30 4 2
2. Materials and methods
3. Results
The clinical and pathological findings of 1043 patients who have had radical prostatectomy in 13 clinics in Turkey between January 1992 and May 2003 were assessed. All of the patients had clinically localized disease and thus were candidates for radical prostatectomy. Serum PSA values, clinical stage, biopsy Gleason score and the pathological features of the radical prostatectomy specimens were collected from each clinic and evaluated. Those with missing information of the preoperative serum PSA, Gleason score, clinical stage and patients who had neoadjuvant endocrine treatment were excluded. The names of the clinics are depicted in the appendix. Serum PSA values, clinical staging, biopsy Gleason scores and pathological evaluations of the radical prostatectomy specimens were done by different physicians in each clinic. All biopsy specimens were graded histologically using the Gleason scoring system [16]. Capsular penetration, surgical margin invasion, seminal vesicle invasion and lymph node status of the patients were determined in each clinic staging was done by using the 1992 TNM staging system [17]. Cancer was considered as organ confined if the capsule was not penetrated. The clinical staging was also done by the aid of the same staging system. Preoperative characteristics and the pathological findings in our patients, Johns’ Hopkins group and other validation study groups were compared. All statistical evaluations were 2-sided and done by SPSS 10.0 package program. Partin tables, which were published in 2001, were applied to Turkish patients and the prediction of organ confinement, seminal vesicle and lymph node invasion was calculated. Receiver Operating Characteristics (ROC) analysis was done to assess the discriminative ability of the Partin tables in our patient group. Power value of ROC curves was calculated by using NCSSPASS program.
Median age of the patients was 60 (45–74). The clinical and pathological characteristics such as clinical stage, serum PSA, Gleason score and final pathological result of the prostate of the patients were compared to Partin tables updated in 2001 (Table 1).
Fig. 1. ROC curve analysis comparing predicted probabilities of organ confinement from Partin tables and actual incidence of organ confined prostate cancers in Turkish patients.
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value of 14 ng/ml. For the whole group organ confined disease, seminal vesicle involvement and lymph node metastases ratios were 64.7%, 10.3% and 1.8% respectively (Table 1). The predictive value of Partin tables was evaluated with ROC curve analyses. Area Under Curve (AUC) values for organ confined disease, seminal vesicle involvement and lymph node involvement were 0.665 ( p < 0.0001), 0.733 ( p < 0.0001) and 0.759 ( p < 0.0001), respectively (Figs. 1–3). One-sided ROC curve power analysis for organ confined disease revealed 1.00 power value.
4. Discussion
Fig. 2. ROC curve analysis comparing predicted probabilities of seminal vesicle involvement from Partin tables and actual incidence of seminal vesicle involvement in Turkish patients.
In our study group, percentage of patients with clinical stage T1c was 43%. Patients with Gleason score of 2–4 in biopsy constituted 23,4% of the study group (Table 1). In the present study, the ratio of the patients with serum PSA higher than 10 ng/ml was 39.6% (Table 1). Patients who had PSA over 10 ng/ml had a median PSA
Fig. 3. ROC curve analysis comparing predicted probabilities of lymph node involvement from Partin tables and actual incidence of lymph node involvement in Turkish patients.
The validation studies of the former Partin tables (1997) confirmed its accuracy not only for the United States, but also for Europe [11–14]. Only one validation study of the 2001 Partin tables revealed acceptable accuracy in a patient population of a single tertiary referral center [15]. Our aim was to carry out a multicenter validation study of current Partin tables in Turkish patients. Our study population was heterogeneous including patients from 13 clinics, which varied from tertiary referral academic centers to community hospitals. Thus there was no bias in recruitment of the patients. Area under curve (AUC) values had been previously assessed for the validation studies evaluating the predictive capacity of the former 1997 Partin tables [12– 14]. AUC values for the organ-confined disease were 0.727, 0.757, 0.684 and 0.817 for the 1997 Partin cohort, Mayo cohort, CaPSURE cohort and Hamburg study group, respectively [5,12–14]. The area under curve (AUC) values for the lymph node involvement were 0.818, 0.837, 0.766 and 0.807 for Partin cohort (1997), Mayo cohort, CaPSURE cohort and Hamburg study group, respectively [5,12–14]. Although the values were lower for the CaPSURE study, all studies concluded that Partin tables (1997) could be used effectively to predict the final pathological outcome. The validation study of 2001 Partin tables also found AUC values as 0.787, 0.775 and 0.790 for organconfined disease, seminal vesicle and lymph node involvement respectively [15]. Likewise we performed ROC analysis to determine the predictive capacity of the 2001 Partin tables. Our area under curve values for organ-confined disease, seminal vesicle and lymph node involvement were 0.665, 0.733 and 0.759 respectively and all ROC analyses were statistically significant. AUC values were not as high as the previous studies validating the 1997 and 2001 Partin tables. In
188
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ROC curve analysis AUC values less than 0.700 may be considered as a poor result. In this respect, we performed power analysis for the AUC value (0.665) of organ-confined disease and found 1.00 value, which was highly acceptable. So we can clearly say that we can use Partin tables for the prediction of organ confined disease in Turkish patients. Our findings demonstrate that the current Partin tables have a reasonable predictive value for organ-confined disease, seminal vesicle and lymph node involvement in patients who undergo radical prostatectomy in Turkish patients. Since Partin tables do not provide information beyond pathological outcome, they cannot predict clinical outcome and also they are not ideal tools for further treatment planning. However, prediction of organ-confined disease may be useful to select the patients for nerve sparing surgery. Different nomograms to predict the recurrence probability for individual patients were also developed and were thought to be more useful for both patients and physicians [8]. The dataset of our study population appeared to be similar to Partin cohort in many aspects. In Turkish study, two major differences from Partin series were observed. The clinical stage T1c ratio was 43% in our study and 63% in Partin series. This ratio was 33% for the former Partin cohort in 1997 [5]. In recent years the number of localized prostate cancer increased with increasing usage of serum PSA throughout the world and in our country. Our ratio of 43% is in somewhere between the two Partin cohorts of 1997 and 2001. Organ confinement ratios of the present study and that of current Partin tables were similar albeit the relatively high percentage of patients with serum PSA levels >10 ng/ml in the present study. Although this seems to be a conflicting result, same trend was also observed in Hamburg validation study [14]. In the Hamburg study although overall 41% had high serum PSA levels (>10 ng/ml) compared to 29% in 1997 Partin tables they have reported a surprisingly high organ confined ratio of 56% compared to 48% in the former Partin study. Interestingly, similar to our results they had higher seminal vesicle involvement compared to Partin cohort. It is not clear whether this is a European phenomenon or that PSA to a certain level is not the main predictor of organ confinement. It must be emphasized that although almost 40% of our patients had serum PSA levels >10 ng/ml with the median value of 14 ng/ml. The second difference in our series was a 23.4% ratio of biopsy Gleason score 2–4 in our study while it was 0.6% in Partin series. The number of Gleason scores lower than 5 is extremely low such as 0–1% in the modern series [10,14]. But in former series the ratios of
biopsy Gleason of 2–4 were 5%, 17%, and 19% for Partin cohort 1997, Mayo cohort and CaPSURE cohorts, respectively. Epstein offered to improve the Gleason score by not assigning Gleason scores 2 to 4 for adenocarcinoma of prostate on needle biopsy [18]. There were three reasons for such approach: First, the vast majority of the tumors with Gleason score 2 to 4 were graded as Gleason score 5 to 6 by experts in urologic pathology. Second the reproducibility of Gleason score 2 to 4 is low and third assigning Gleason score 2 to 4 can adversely affect the patient care because clinicians may assume low-grade cancers do not need definitive therapy. Epstein stated that 55% of the patients with Gleason score 2 to 4 diagnosed outside clinics other than Johns Hopkins Hospital had extraprostatic extension. In order to overcome this low reproducibility education of the pathologists is of paramount importance. The help of these educational efforts will achieve standardization of grading in the coming years. Our study is limited by the lack of central pathological review. There may be considerable variations in the interpretation of the radical prostatectomy specimens [19]. Although some studies reported acceptable interobserver reliability among pathologists when reporting biopsy results [20], there could be some variability for the interpretation of the pathological results. Thus one can prefer a single pathologist to review each pathological specimen. However this will not reflect the real world practice [21]. Despite those differences with two study groups in pretreatment variables, Partin tables were adequate in predicting the final pathological features in Turkish patients as well. The differences in some of the preoperative parameters reflect the differences of the patient’s attitude to screening and the availability of serum PSA testing in two countries.
5. Conclusions It appears that Partin tables have a reasonable predict value for the final pathological features like organ confined disease, seminal vesicle and lymph node involvement in Turkish patients. This multicenter study showed that current Partin tables could also be used in Turkish patients with comparable accuracy.
Appendix A The list of the centers and the investigators included in the study: From the departments of Urology:
S.Y. Eskicorapci et al. / European Urology 47 (2005) 185–189
1. Hacettepe University Hospital: Saadettin Eskicorapci, MD and Haluk Ozen, MD. 2. Marmara University Hospital: Levent Tu¨ rkeri MD. 3. Ankara University Hospital: Sumer Baltacı MD. 4. Ege University Hospital: Cag Cal MD. 5. SSK Istanbul Egitim Hospital: Gokhan Toktas MD. 6. Florans Nightingale Hospital: Haluk Akpınar MD. 7. Yuksek Ihtisas Hospital: Gokhan Ozer MD. 8. Gazi University Hospital: Sinan Sozen MD. 9. Goztepe SSK Egitim Hospital: Resit Tokuc MD.
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10. Manisa Celal Bayar University Hospital: Murat Lekili MD. 11. Inonu University Hospital: Ahmet Soylu MD. 12. Dr. L. Kirdar Kartal Egitim ve Arastirma Hospital: Selami Albayrak MD. 13. Dicle University Hospital: Hayrettin Sahin MD. From the department of Biostatistics of Hacettepe University Hospital: Erdem Karabulut MD, Reha Alpar MD.
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