Serum Testosterone Level Can Be Predictive Factor for Upstaging in Clinically Localized Prostate Cancer

Article information

Korean J Urol Oncol. 2020;18(2):116-123
Publication date (electronic) : 2020 August 27
doi : https://doi.org/10.22465/kjuo.2020.18.2.116
1Department of Urology, School of Medicine, Kyungpook National University, Daegu, Korea
2Department of Pathology, School of Medicine, Kyungpook National University, Daegu, Korea
3Joint Institute for Regenerative Medicine, Kyungpook National University, Daegu, Korea
Corresponding Author: Jun Nyung Lee Department of Urology, School of Medicine, Kyungpook National University, 807 Hoguk-ro, Buk-gu, Daegu 41404, Korea E-mail: ljnlover@gmail.com Tel: +82-53-200-2675, Fax: +82-53-200-2027
Co-corresponding Author: Tae Gyun Kwon Department of Urology, School of Medicine, Kyungpook National University, 807 Hoguk-ro, Buk-gu, Daegu 41404, Korea E-mail: tgkwon@knu.ac.kr Tel: +82-53-420-5841, Fax: +82-53-200-2027
Received 2020 March 17; Revised 2020 April 3; Accepted 2020 April 13.

Trans Abstract

Purpose

To determine an appropriate surgical technique, it is important to predict pathological results for patients with clinically localized prostate cancer (PCa) eligible for nerve-sparing radical prostatectomy (NSRP). Several studies have highlighted that serum testosterone level was associated with aggressive features of PCa. Therefore, we analyzed factors, including serum testosterone, to predict upstaging and upgrading after surgery for patients with clinically localized PCa eligible for NSRP.

Materials and Methods

We retrospectively evaluated patients who underwent radical prostatectomy (RP) between January 2015 and May 2018 at our institution. Patients with Gleason grade group 1 or 2 on biopsy, prostate-specific antigen<10, and ≤ clinical/radiologic stage T2 were included in this study. Upstaging and upgrading were defined as pathological stage≥ T3a and Gleason grade group≥3, respectively. We evaluated the patients’ demographics and outcomes according to upstaging and upgrading after surgery. Predictive factors for upstaging and upgrading were analyzed using a multivariate logistic regression model.

Results

Of 108 patients included in the study, upstaging and upgrading after surgery were observed in 24 (22.2%) and 36 (33.3%), respectively. Low serum testosterone level, small prostate size, and positive core number≥3 on biopsy were identified as predictive factors for upstaging in multivariate analysis. Although serum testosterone was associated with upgrading in univariate analysis, only clinical/radiologic stage and biopsy Gleason grade group were observed as predictive factors for upgrading in multivariate analysis.

Conclusions

Serum testosterone level was identified as a predictive factor for upstaging after RP for clinically localized PCa eligible for NSRP.

INTRODUCTION

Prostate cancer (PCa) is among the most common male cancers worldwide, and its incidence is gradually increasing.1 Several treatment modalities, including active surveillance (AS), radical prostatectomy (RP), radiation therapy, and an-drogen deprivation therapy, have been established for patients with clinically localized PCa. Generally, RP has been considered as the gold standard definitive treatment for clin-ically localized PCa. However, RP can cause surgical com-plications, including urinary incontinence and erectile dys-function, which can adversely influence quality of life.2,3 To mitigate such complications, nerve-sparing radical prostatec-tomy (NSRP), which preserves the neurovascular bundles, can apply to patients with selected criteria based on pre-operative evaluations, such as prostate-specific antigen (PSA), clinical stage, and biopsy grade.3,4

Although NSRP is currently acceptable for selected patients with PCa, it can sometimes cause incomplete tumor excision, depending on the tumor stage.5 Additionally, re-cent studies have shown that pathological stage and Gleason grade after RP are often inconsistent with clinical stage and biopsy Gleason grade.6 The discrepancy between pre-operative parameters and pathological results is usually ob-served as upstaging or upgrading.611 Therefore, it is neces-sary to determine predictive factors for worse pathological outcomes, such as upgrading and upstaging, relative to pre-operative findings among patients with PCa amenable to NSRP.

Several studies have revealed that preoperative serum tes-tosterone level is associated with aggressive features of PCa, such as high stage and high grade.1216 Additionally, a recent study showed that low serum testosterone (<300 ng/dL) was associated with a high rate of upgrading and upstaging after RP.8 Another study also reported that low serum testosterone was associated with a positive surgical margin in RP specimens.17

In this study, we evaluated factors, including preoperative serum testosterone, to predict upstaging and upgrading after NSRP for PCa.

MATERIALS AND METHODS

We retrospectively reviewed PCa patients who underwent NSRP, performed by a single experienced surgeon between January 2015 and May 2018 at Kyungpook National University Chilgok Hospital. Patients with biopsy Gleason grade group 1 or 2, PSA<10 ng/mL, and clinical/radiologic stage≤ T2 (using the 2009 TNM staging system) on pre-operative evaluations were included in this study. We ex-cluded patients who underwent neoadjuvant therapy, such as radiotherapy or hormonal therapy, and those with known medical problems that might affect testosterone status, such as thyroid disease, liver disease, and hypoalbuminemia. Patients with a history of 5 RI medication administration or testosterone replacement therapy were also excluded.

All patients were diagnosed with PCa by 12-core trans-rectal needle prostatic biopsies at our institution and under-went multiparametric magnetic resonance imaging for pre-operative radiologic staging.

All patients underwent open RP or robot-assisted RP ac-cording to preoperative counseling. Open RP or robot-as-sisted RP were conducted in an ante-grade fashion using a nerve-sparing technique and a continuous urethrovesical anastomosis suture in the manner previously reported.18 Gleason grade was assessed according to the 2014 International Society of Urological Pathology Modified Gleason System.19 Prostate volume was measured by standard meth-ods using transrectal ultrasonography, and PSA density (PSAD) was calculated by dividing PSA with prostate volume. Using an immunoassay at our institution's labo-ratory, the preoperative serum testosterone level (ng/dL) was measured. Considering diurnal fluctuations of the tes-tosterone level, serum samples were collected in the morning between 8 AM and 10 AM when testosterone levels are high and stable.

The upstaging and upgrading were defined as nonorgan confined disease (pathological stage≥ T3a) and pathological Gleason grade group≥3 after RP, respectively. We eval-uated the incidence of upstaging and upgrading after RP in patients with biopsy Gleason grade group 1 or 2, PSA<10 ng/mL, and clinical/radiologic stage≤ T2 on preoperative evaluation.

We also compared the patients’ characteristics according to upstaging and upgrading using Student t-test and the chi-square test. Predictive factors for upstaging and upgrading after RP were analyzed using a multivariate logistic re-gression model. Statistical analyses were performed using IBM SPSS Statistics ver. 23.0 (IBM Co., Armonk, NY, USA), and statistical significance was established with p-value of <0.05.

The present study protocol was reviewed and approved by the Institutional Review Board of Kyungpook National University Chilgok Hospital (Reg. No. KNUMC 2019-12-0 21). Informed consent was submitted by all subjects when they were enrolled.

RESULTS

A total of 108 patients were included in the study. The mean age was 65.5±6.2 years, mean preoperative PSA was 6.3±1.8 ng/mL, and mean preoperative serum testosterone was 347.2±154.1 ng/dL. Clinical/radiologic T stage was cT1c for 18 patients (16.7%) and cT2 for 90 patients (83.3%). Sixty-nine patients (63.9%) were classified as Gleason grade group 1, and 39 patients (36.1%) were classi-fied as grade group 2. Table 1 shows the clinical and patho-logical characteristics of patients included in this study. Upstaging and upgrading after surgery were observed in 22.2% (24 of 108) and 33.3% (36 of 108) patients, respectively. Among the 24 patients in the upstaging group, 20 (83.3%) were upstaged to pT3a, and 4 (16.7%) were up-staged to pT3b. Among the 36 patients who were upgraded, 30 (83.3%) were upgraded to Gleason grade group 3, and 6 (16.7%) were upgraded to Gleason grade group 4 (Fig. 1).

Clinical and pathological characteristics of patients included in the study (n=108)

Fig. 1.

The rates of upstaging (A) and upgrading (B) after surgery.

Table 2 shows patients’ characteristics according to up-staging and upgrading status. Mean prostate size was small-er and PSA density was higher among patients who were upstaged compared with those who were not (25.5±5.5 vs. 34.5±10.8, p<0.001 and 0.28±0.13 vs. 0.20±0.09, p=0.012, respectively). Mean preoperative serum testosterone was significantly lower in the upstaged patients compared with those who were not upstaged (284.6±108.8 vs. 367.6±156.8, p=0.017). The proportion of patients with a positive core number ≥3 at biopsy was higher in the upstaged group compared with the nonupstaged group (75.0% vs. 35.7%, p=0.001). There were no significant differences in age, body mass index, PSA, biopsy Gleason grade group, or op-erative method (robot-assisted RP vs. open RP) according upstaging status after RP.

Comparison of variables according to upstaging and upgrading after surgery

In terms of upgrading status, mean preoperative serum testosterone level was significantly lower among upgraded patients compared with those who were not upgraded (308.4±106.9 vs. 369.5±165.7, p=0.047). In addition, biopsy Gleason grade group and clinical/radiologic stage were sig-nificantly different between patients who were upgraded and those who were not (p=0.034 and p=0.006, respectively). Other variables did not show any significance.

The multivariate logistic regression model revealed that preoperative serum testosterone level (odds ratio [OR], 0.993; 95% confidence interval [CI], 0.987–0.999; p= 0.034), prostate size (OR, 0.765; 95% CI, 0.669–0.875; p<0.001), and a positive core number ≥3 at biopsy (OR, 9.856; 95% CI, 2.230–43.557; p=0.003) were associated with upstaging after RP (Table 3). The cutoff value for pre-operative serum testosterone level for upstaging was 273.7 ng/dL (sensitivity, 71.3%; specificity, 66.7%, as determined by receiver operating curve analysis) (Fig. 2). In addition, clinical/radiologic stage (T2 vs. T1c) and Gleason grade group at biopsy (2 vs. 1) were significantly associated with upgrading in the multivariate analysis (OR, 11.260; 95% CI, 1.410–89.914; p=0.022 and OR, 2.526; 95% CI, 1.063–5.998; p=0.036, respectively).

Factors associated with upstaging and upgrading by multivariable logistic regression

Fig. 2.

Receiver-operating characteristic (ROC) curve of pre-operative serum testosterone level for upstaging after surgery. Cutoff point for testosterone level was 273.7 ng/dL (sensitivity,71.3%; specificity, 66.7%; area under the curve, 0.649) on the ROC curve analysis.

DISCUSSION

Currently, NSRP is a widely accepted surgical method for select patients with clinically localized PCa, to minimize postoperative complications, including erectile dysfunction and postprostatectomy incontinence. However, postoperative upstaging and upgrading— which might have altered the op-erative technique selection if they had been predicted— are not uncommon after NSRP. Recently, several studies re-vealed that preoperative serum testosterone reflects tumor aggressiveness among PCa patients.1216 Therefore, we as-sessed the incidence and predictive factors for upstaging and upgrading among PCa patients after NSRP at our institution. We observed significant incidences of upstaging (22.2%) and upgrading (33.3%). Furthermore, preoperative serum testosterone was negatively associated with upstaging and upgrading after RP. Multivariate analysis revealed pre-operative serum testosterone as a significant predictor up-staging, despite its lack of a significant association with postoperative upgrading.

The key objectives of RP for PCa include ensuring good postoperative erectile function and urinary continence with-out compromising oncological outcomes. Techniques that emphasize the preservation of neurovascular bundles during RP have been developed to minimize postoperative compli-cations for appropriately selected patients.3 Several studies have confirmed the benefits of NSRP for the recovery of erectile function and urinary continence.2023 While nerve- sparing techniques have several advantages in terms of quality of life, dissection closer to the prostate capsule during NSRP may increase the risk of incising the tumor or incomplete tumor excision, resulting in a positive surgical margin, and may increase risk of biochemical progression and cancer recurrence.5

When choosing the treatment method, particularly when considering NSRP, the surgeon most strongly considered the index PSA, clinical stage, and the biopsy Gleason grade group. However, recent research has shown that patho-logical stage and grade after surgery are often inconsistent with clinical stage and biopsy grade, and this is usually ex-pressed as upgrading or upstaging.611 For patients whose re-al pathological stage and grade exceed the clinical stage and biopsy grade, the selected surgical method— nerve-sparing surgery, for example— could underestimate the aggressive-ness of the PCa and compromise cancer control. Therefore, it is necessary to identify predictive factors for upstaging and upgrading for selecting a proper treatment strategy or surgical method for PCa patients for whom there are several options.

Several recent studies have focused on determining predictors of upstaging and upgrading among PCa patients.611 In a large cohort study including 7,643 patients who under-went RP, 36.3% of patients had their needle biopsy Gleason score upgraded from 5 or 6 to a higher grade after RP.6 Sooriakumaran et al.10 reported that 40.4% patients were ei-ther upstaged (3.9%) or upgraded (39.6%) after RP among 750 patients with low-risk PCa, clinically eligible for AS. In a Korean multicenter study with 324 RP specimens from low-risk PCa patients, upstaging and upgrading were ob-served in 9.6% and 43.8% samples, respectively.9 In another study of Korean PCa patients who were eligible for AS (clinical stage T1c/T2a, PSA level 10 ng/mL or less, and Gleason score 6 or less), upstaging and upgrading were ob-served in 11.0% and 57.8% of 593 patients, respectively.11 A recent study with similar inclusion criteria (biopsy Gleason score≤6, clinical stage≤ T2c, and PSA<10 ng/mL) to our study revealed that upstaging occurred in 43.7%, and upgrading occurred in 37.1% of 167 patients.8 Unlike pre-vious studies, however, our study showed relatively high upstaging (33.3%) and low upgrading (22.2%). We assumed that this discrepancy from previous research was caused by differences in the participant characteristics and radiologic staging using multiparametric magnetic resonance imaging in the present study. This study was conducted on patients eligible for NSRP (biopsy Gleason grade group 1 or 2, PSA<10, and clinical/radiologic stage≤ T2) at our in-stitution, while previous studies investigated patients who were eligible for AS.

In the present study, preoperative serum testosterone was negatively correlated with upstaging and upgrading after RP, and it was identified as a predictive factor for upstaging in multivariate analysis. Although it is still controversial, testosterone has been widely evaluated as a predictive factor for worse pathological outcomes, such as upstaging and up-grading, and oncologic outcomes.1317,24,25 Previous studies have suggested that serum testosterone level is inversely correlated with tumor aggressiveness, which is a descriptor that encompasses both high stage13,14 and high grade.15,16 Teloken et al.17 reported that low serum testosterone levels were associated with positive surgical margins after RP, while not with PSA levels, Gleason score (biopsy or speci-men), pathological stage, or capsular perforation. Moreover, Asian studies have identified preoperative serum testoster-one level as an independent predictor of biochemical recurrence after RP among patients with clinically localized PCa.24,25

Recently, several reports have highlighted the association of low serum testosterone levels with upstaging and upgrading after RP among patients with localized PCa.8,12 Gao et al.8 investigated the association between serum testosterone and upgrading or upstaging among PCa patients with biopsy Gleason scores≤6, clinical stage≤ T2c, and PSA<10 ng/mL. They confirmed preoperative serum testosterone level as a unique independent predictor of pathological upstaging and upgrading after RP. Moreover, Ferro et al.12 assessed the impact of serum testosterone for predicting unfavorable out-comes among PCa patients eligible for AS, which is cur-rently considered acceptable for clinically localized PCa. They suggested that patients with hypogonadism were not eligible for AS because low serum testosterone is associated with unfavorable pathological outcomes, including upstaging, upgrading, and positive surgical margins. Our findings also supported the clinical impact of low serum testosterone as a predictive factor of upstaging and upgrading among patients with localized PCa eligible for NSRP on preoperative evaluation. Therefore, surgeons should be cautious when se-lection of a treatment course and proceeding with NSRP for eligible patients with low serum testosterone.

Recent studies, including the present study, have demon-strated that serum testosterone level is predictive of tumor aggressiveness, including the potential for upstaging and upgrading. Although the exact mechanism is not yet fully understood, it may be assumed that involves the inhibition of testosterone by highly aggressive prostate tumors and negative feedback control of pituitary gonadotropin secretion.8 Moreover, metabolic disorders that are associated with hypogonadism might contribute to unfavorable PCa outcomes.12,26,27

In this study, small prostate size and positive core number ≥3 on biopsy were also identified as predictive factors for upstaging in multivariate analysis. Previous studies have shown small prostate size and high positive core number on prostate biopsy to be associated with aggressive features of PCa.9,11,2830. Similar with our results, 2 Korean studies found that prostate volume and positive core number were significantly associated with upstaging11 or worsening prog-nosis9 in multivariate analyses. Additionally, a Japanese study29 and a Swedish study30 also reported that smaller prostate volume was associated with adverse pathology. Regarding the mechanism by which prostate volume and positive core number are predictors of PCa aggressiveness, they might reflect a relatively larger tumor burden with a high probability of disease that has progressed beyond the prostate capsule.

Several limitations of our study should be considered. First, this was a retrospective analysis of the records of a relatively small sample of patients treated at a single insti-tution. Although the criteria for NSRP eligibility were fol-lowed in this study, selection bias regarding the surgical in-dication was unavoidable. Additionally, we did not access to data reflecting long-term oncologic outcomes, such as bi-ochemical recurrence and metastasis-free survival. These limitations highlight the need for more standardized study designs and outcome reporting methods in the future. Furthermore, additional studies are necessary to elucidate the underlying mechanisms involving serum testosterone in relation to PCa. Although this retrospective study had sev-eral limitations, it demonstrated that low preoperative serum testosterone level, small prostate size, and positive core number≥3 on biopsy should be considered valuable pre-dictors of upstaging after RP in clinically localized PCa amenable to NSRP. We hope that the results of this study can help clinicians develop appropriate management strat-egies and choose appropriate surgical methods to treat clin-ically localized PCa.

CONCLUSIONS

Low preoperative serum testosterone level, small prostate size, and positive biopsy core number≥3 were identified as predictive factors for upstaging after RP in clinically lo-calized PCa eligible for nerve-sparing surgery. Therefore, preoperative serum testosterone should be measured and considered as a predictor of non-organ confined disease in patients with clinically localized PCa eligible for nerve-sparing surgery.

Notes

CONFLICT OF INTEREST

The authors claim no conflicts of interest.

References

1. Jung KW, Won YJ, Kong HJ, Oh CM, Cho H, Lee DH, et al. Cancer statistics in Korea: incidence, mortality, survival, and prevalence in 2012. Cancer Res Treat 2015;47:127–41.
2. Mandel P, Graefen M, Michl U, Huland H, Tilki D. The effect of age on functional outcomes after radical prostatectomy. Urol Oncol 2015;33:203.e11–8.
3. Mottet N, Bellmunt J, Bolla M, Briers E, Cumberbatch MG, De Santis M, et al. EAU-ESTRO-SIOG guidelines on prostate cancer. Part 1: screening, diagnosis, and local treatment with curative intent. Eur Urol 2017;71:618–29.
4. Michl U, Tennstedt P, Feldmeier L, Mandel P, Oh SJ, Ahyai S, et al. Nerve-sparing surgery technique, not the preservation of the neurovascular bundles, leads to improved long-term continence rates after radical prostatectomy. Eur Urol 2016;69:584–9.
5. Catalona WJ, Bigg SW. Nerve-sparing radical prostatectomy: evaluation of results after 250 patients. J Urol 1990;143:538–43.
6. 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.
7. Fine SW, Epstein JI. A contemporary study correlating prostate needle biopsy and radical prostatectomy Gleason score. J Urol 2008;179:1335–8.
8. Gao Y, Jiang CY, Mao SK, Cui D, Hao KY, Zhao W, et al. Low serum testosterone predicts upgrading and upstaging of prostate cancer after radical prostatectomy. Asian J Androl 2016;18:639–43.
9. Hwang I, Lim D, Jeong YB, Park SC, Noh JH, Kwon DD, et al. Upgrading and upstaging of low-risk prostate cancer among Korean patients: a multicenter study. Asian J Androl 2015;17:811–4.
10. Sooriakumaran P, Srivastava A, Christos P, Grover S, Shevchuk M, Tewari A. Predictive models for worsening prognosis in potential candidates for active surveillance of presumed low-risk prostate cancer. Int Urol Nephrol 2012;44:459–70.
11. Jeon HG, Yoo JH, Jeong BC, Seo SI, Jeon SS, Choi HY, et al. Comparative rates of upstaging and upgrading in Caucasian and Korean prostate cancer patients eligible for active surveillance. PLoS One 2017;12:e0186026.
12. Ferro M, Lucarelli G, Bruzzese D, Di Lorenzo G, Perdonà S, Autorino R, et al. Low serum total testosterone level as a predictor of upstaging and upgrading in low-risk prostate cancer patients meeting the inclusion criteria for active surveillance. Oncotarget 2017;8:18424–34.
13. Imamoto T, Suzuki H, Fukasawa S, Shimbo M, Inahara M, Komiya A, et al. Pretreatment serum testosterone level as a predictive factor of pathological stage in localized prostate cancer patients treated with radical prostatectomy. Eur Urol 2005;47:308–12.
14. Isom-Batz G, Bianco FJ Jr, Kattan MW, Mulhall JP, Lilja H, Eastham JA. Testosterone as a predictor of pathological stage in clinically localized prostate cancer. J Urol 2005;173:1935–7.
15. Schatzl G, Madersbacher S, Thurridl T, Waldmüller J, Kramer G, Haitel A, et al. High-grade prostate cancer is associated with low serum testosterone levels. Prostate 2001;47:52–8.
16. Pichon A, Neuzillet Y, Botto H, Raynaud JP, Radulescu C, Molinié V, et al. Preoperative low serum testosterone is associated with high-grade prostate cancer and an increased Gleason score upgrading. Prostate Cancer Prostatic Dis 2015;18:382–7.
17. Teloken C, Da Ros CT, Caraver F, Weber FA, Cavalheiro AP, Graziottin TM. Low serum testosterone levels are associated with positive surgical margins in radical retro-pubic prostatectomy: hypogonadism represents bad prognosis in prostate cancer. J Urol 2005;174:2178–80.
18. Kwon SY, Lee JN, Ha YS, Choi SH, Kim TH, Kwon TG. Open radical prostatectomy reproducing robot-assisted radical prostatectomy: involving antegrade nerve sparing and continuous anastomosis. Int Braz J Urol 2017;43:1043–51.
19. Epstein JI, Egevad L, Amin MB, Delahunt B, Srigley JR, Humphrey PA, et al. 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.
20. Murphy DG, Costello AJ. How can the autonomic nervous system contribute to urinary continence following radical prostatectomy? A “boson-like” conundrum. Eur Urol 2013;63:445–7.
21. Reeves F, Preece P, Kapoor J, Everaerts W, Murphy DG, Corcoran NM, et al. Preservation of the neurovascular bundles is associated with improved time to continence after radical prostatectomy but not long-term continence rates: results of a systematic review and meta-analysis. Eur Urol 2015;68:692–704.
22. Steineck G, Bjartell A, Hugosson J, Axén E, Carlsson S, Stranne J, et al. Degree of preservation of the neuro-vascular bundles during radical prostatectomy and urinary continence 1 year after surgery. Eur Urol 2015;67:559–68.
23. Narayan P, Konety B, Aslam K, Aboseif S, Blumenfeld W, Tanagho E. Neuroanatomy of the external urethral sphincter: implications for urinary continence preservation during radical prostate surgery. J Urol 1995;153:337–41.
24. Yamamoto S, Yonese J, Kawakami S, Ohkubo Y, Tatokoro M, Komai Y, et al. Preoperative serum testosterone level as an independent predictor of treatment failure following radical prostatectomy. Eur Urol 2007;52:696–701.
25. Kim HJ, Kim BH, Park CH, Kim CI. Usefulness of preoperative serum testosterone as a predictor of extraprostatic extension and biochemical recurrence. Korean J Urol 2012;53:9–13.
26. Freedland SJ, Isaacs WB, Mangold LA, Yiu SK, Grubb KA, Partin AW, et al. Stronger association between obesity and biochemical progression after radical prostatectomy among men treated in the last 10 years. Clin Cancer Res 2005;11:2883–8.
27. Iremashvili V, Soloway MS, Rosenberg DL, Manoharan M. Clinical and demographic characteristics associated with prostate cancer progression in patients on active surveillance. J Urol 2012;187:1594–9.
28. Liu JJ, Brooks JD, Ferrari M, Nolley R, Presti JC Jr. Small prostate size and high grade disease–biology or artifact? J Urol 2011;185:2108–11.
29. Yashi M, Mizuno T, Yuki H, Masuda A, Kambara T, Betsunoh H, et al. Prostate volume and biopsy tumor length are significant predictors for classical and redefined insignificant cancer on prostatectomy specimens in Japanese men with favorable pathologic features on biopsy. BMC Urol 2014;14:43.
30. Vellekoop A, Loeb S, Folkvaljon Y, Stattin P. Population based study of predictors of adverse pathology among candidates for active surveillance with Gleason 6 prostate cancer. J Urol 2014;191:350–7.

Article information Continued

Table 1.

Clinical and pathological characteristics of patients included in the study (n=108)

Characteristic Value
Age (yr) 65.5±6.2
Body mass index (kg/m2) 24.3±2.9
PSA (ng/mL) 6.3±1.8
Size (mL) 32.2±10.9
PSAD 0.5±3.1
Testosterone level (ng/dL) 347.2±154.1
Total positive core number 3.1±2.3
Positive core number
  ≥ 3 48 (44.4)
  <3 60 (55.6)
Biopsy Gleason grade
  Group 1 69 (63.9)
  Group 2 39 (36.1)
Pathological Gleason grade
  Group 1 13 (12.0)
  Group 2 59 (54.6)
  Group 3 30 (27.8)
  Group 4 6 (5.6)
Clinical/radiologic stage
  T1c 18 (16.7)
  T2 90 (83.3)
Pathological stage
  pT2 84 (77.8)
  pT3a 20 (18.5)
  pT3b 4 (3.7)
Operative method
  RARP 85 (78.7)
  Open RP 23 (21.3)

Values are presented as mean±standard deviation or number (%). PSA: prostate-specific antigen, PSAD: prostate-specific antigen density, RARP: robot-assisted radical prostatectomy, RP: radical prostatectomy.

Fig. 1.

The rates of upstaging (A) and upgrading (B) after surgery.

Table 2.

Comparison of variables according to upstaging and upgrading after surgery

Variable Upstaging
Upgrading
Yes (n=24) No (n=84) p-value Yes (n=36) No (n=72) p-value
Age (yr) 66.7±4.4 65.2±6.7 0.216 65.7±4.8 65.4±6.9 0.828
BMI (kg/m2) 24.4±3.3 24.3±2.7 0.926 24.5±2.6 24.2±3.0 0.628
PSA (ng/mL) 6.49±2.0 6.26±1.7 0.616 6.15±1.6 6.42±1.8 0.432
Size (mL) 25.5±5.5 34.5±10.8 <0.001 33.4±11.7 32.0±10.0 0.529
PSAD 0.28±0.13 0.20±0.09 0.012 0.21±0.10 0.22±0.11 0.378
Testosterone level (ng/dL) 284.6±108.8 367.6±156.8 0.017 308.4±106.9 369.5±165.7 0.047
Total positive core number 3.8±2.1 2.9±2.3 0.733 2.9±2.0 3.2±2.4 0.564
Positive core number     0.001     1.000
  ≥ 3 18 30   16 32  
  <3 6 54   20 40  
Biopsy Gleason grade     0.108     0.034
  Group 1 12 57   18 51  
  Group 2 12 27   18 21  
Clinical/radiologic stage     0.758     0.006
  T1c 3 15   1 17  
  T2 21 69   35 55  
Operative method     0.286     0.406
  RARP 17 68   30 55  
  Open RP 7 16   6 17  

Values are presented as mean±standard deviation or number.

BMI: body mass index, PSA: prostate-specific antigen, PSAD: prostate-specific antigen density, RARP: robot-assisted radical prostatectomy, RP: radical prostatectomy.

Table 3.

Factors associated with upstaging and upgrading by multivariable logistic regression

Variable Upstaging
Upgrading
OR (95% CI) p-value OR (95% CI) p-value
Testosterone level (continuous) 0.993 (0.987–0.999) 0.034 0.997 (0.994–1.000) 0.072
Prostate size (continuous) 0.765 (0.669–0.875) <0.001
Positive core number ≥ 3 vs <3 9.856 (2.230–43.557) 0.003
Clinical/radiologic stage T2 vs. T1c 11.260 (1.410–89.914) 0.022
Biopsy Gleason grade group 2 vs. 1 2.526 (1.063–5.998) 0.036

OR: odds ratio, CI: confidence interval.

Fig. 2.

Receiver-operating characteristic (ROC) curve of pre-operative serum testosterone level for upstaging after surgery. Cutoff point for testosterone level was 273.7 ng/dL (sensitivity,71.3%; specificity, 66.7%; area under the curve, 0.649) on the ROC curve analysis.