829 STANDARD REPEAT BIOPSIES DURING ACTIVE SURVEILLANCE FOR EARLY PROSTATE CANCER: PREDICTORS FOR UPGRADING OR UPSTAGING

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Standard repeat biopsies during active surveillance for early prostate cancer: Predictors for upgrading or upstaging

Candidate selection for focal targeted therapy with unilateral lobe by three-dimensional 26-core prostate biopsy

Van Den Bergh R.C.N.1, Roemeling S.1, Vasarainen H.2, Roobol M.J.1, Rannikko A.2, Schröder F.H.1, Bangma C.H.1

Numao N.1, Kawakami S.1, Fujii Y.1, Masuda H.1, Koga F.1, Sakai Y.1, Yonese J.2, Ishikawa Y.3, Fukui I.2, Kihara K.1

Erasmus University Medical Center, Dept. of Urology, Rotterdam, The Netherlands, 2Helsinki University Medical Center, Dept. of Urology, Helsinki, Finland

1

Introduction & Objectives: Active surveillance (AS) follow-up protocols for monitoring untreated men with early prostate cancer (PC) commonly include repeat prostate biopsies as a standard or dependent of changes in time of the PSA. The aim of rebiopsies is to detect possible disease progression, but also to decrease potential undersampling of the first series of biopsy-cores. We studied which parameters are associated with finding more adverse pathological characteristics at rebiopsy. Material & Methods: All men included had early PC and participated in the international prospective observational PRIAS study on AS (inclusion criteria: PSA=<10, PSA density <0.2, clinical stage =3+3=6; upstaging was defined as >2 positive biopsy-cores. Predictors at diagnosis included: All inclusion parameters; At rebiopsy: PSA, total number of cores, and positive cores; And during follow-up: PSA doubling time (DT) and time to rebiopsy. As the volume-dependent number of cores (8-10-12) as advised in the protocol was not always complied to, we added two predictors: Biopsy-scheme (divided in 4 schemes: ‘2x 12 cores (diagnosis and rebiopsy)’, ‘2x 8-10-12’, ‘2x less than 8-10-12’, and ‘# cores at rebiopsy > # cores at diagnosis’) and difference in number of cores. Significant predictors of upgrading and/or upstaging in a univariate analysis were entered into a multivariable model. Results: Biopsy compliance rate was 86.0%. A total of 160 pairs of biopsies with a median of 1.00 years in between (25-75p 0.95-1.07) were analysed: 3.8% showed upgrading, 10.0% upstaging, and 8.1% both (total 21.9%). In 35.0% no cancer was found. Least adverse findings were found in the rebiopsy in men with the scheme ‘2x less than 8-10-12’ (15.6%), most in the scheme ‘rebiopsy>diagnosis’ (25.0%), with the schemes ‘2x 12’ (22.9%) and ‘2x 8-10-12’ (20.8%) in between. In multivariable analysis, 2 positive cores at diagnosis (compared to 1) was significantly associated with a higher, and biopsy scheme ‘2x less than 8-10-12’ with a lower frequency of adverse findings in the rebiopsies. Other parameters such as PSA-DT showed no association. Almost half of the cases with adverse findings were men with 2 positive cores at diagnosis, while these constituted only a quarter of the total study population. Conclusions: Performing standard 1-year repeat biopsies in an AS cohort results in more adverse findings in more than 1 out of 5 patients, although men with only 1 positive core have a lower chance. From the literature we know that undersampling is the most important mechanism. If detecting most adverse findings at rebiopsy is desirable, our data indicate that a biopsy-scheme less than the volume-dependent 8-10-12 is inadequate.



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Characterization of prostate cancers missed by transrectal 12-core biopsy Numao N.1, Kawakami S.1, Fujii Y.1, Masuda H.1, Koga F.1, Sakai Y.1, Yonese J.2, Ishikawa Y.3, Fukui I.2, Kihara K.1 Tokyo Medical and Dental University, Graduate School, Dept. of Urology, Tokyo, Japan, 2Cancer Institute Hospital, Japanese Foundation For Cancer Research, Dept. of Urology, Tokyo, Japan, 3Cancer Institute Hospital, Japanese Foundation For Cancer Research, Dept. of Pathology, Tokyo, Japan 1

Introduction & Objectives: Transrectal 12-core prostate biopsy (TR12PBx) is now one of the most preferred biopsy methods worldwide, however, cancers missed by this biopsy method are poorly characterized. With a three-dimensional 26-core prostate biopsy (3D26PBx), a combination of TR12PBx and transperineal 14-core biopsy (TP14PBx), we have demonstrated that a substantial number of cancers would be missed by either TR12PBx or TP14PBx (Kawakami S, et al. Int J Urol, 14:719, 2007). The aim of this study is to characterize cancers missed by TR12PBx and to clarify to whom additional samplings would be required. Material & Methods: Of 751 consecutive Japanese men who underwent 3D26PBx as an initial biopsy, prostate cancer was detected in 280 (37.2%) men. These cancers were grouped into TR12-ve cancers (n = 53, 19%) which were missed by TR12PBx but detected by TP14PBx and TR12+ve cancers (n = 227, 81%) which were detected by TR12PBx. Clinicopathological variables including age, PSA, prostate volume, DRE, biopsy Gleason grade and number of positive cores were compared between the groups. Results: Of the 53 TR12-ve cancers, 25 (47%) would not be missed if only two far anterior transperineal samplings were added to the TR12PBx. When compared with TR12+ve cancer, TR12-ve cancers associated with lower incidence of high grade cancer and smaller number of positive cores. Multivariate analysis of clinical variables demonstrated that lower PSA, larger prostate volume and negative DRE were significant and independent predictors of the TR12-ve cancers. As of October 2008, 16 patients of the TR12-ve cancer group and 109 patients of the TR12+ve cancer group underwent radical prostatectomy without neoadjuvant treatment. In the prostatectomy specimen, incidence of significant cancer and incidence of pT3a or higher cancer were not different between the two groups. Variable PSA [ng/mL]

Prostate volume [mL]

DRE

Category <6 6-10 ≧10 <25 25-40 ≧40 Positive Negative

%TR12-ve cancer 23 20 12 11 21 26 8 23

Conclusions: The majority of the cancers missed by TR12PBx were significant cancers. Sampling of anterior apical region should be considered in patients with lower PSA, larger prostate or negative DRE at initial biopsy setting.

Eur Urol Suppl 2009;8(4):328

Tokyo Medical and Dental University Graduate School, Dept. of Urology, Tokyo, Japan, Cancer Institute Hospital, Japanese Foundation For Cancer Research, Dept. of Urology, Tokyo, Japan, 3Cancer Institute Hospital, Japanese Foundation for Cancer Research, Dept. of Pathology, Tokyo, Japan

1

2

Introduction & Objectives: Focal targeted therapy has emerged as a potential treatment for localized prostate cancer to reduce morbidity without deteriorating cancer control. However, it is reported that identifying cancer localization or laterality before treatment is difficult even by extended transrectal 12-core biopsy. Aim of this study is to evaluate ability of three-dimensional 26-core prostate biopsy (3D26PBx), a combination of transrectal 12core and transperineal 14-core biopsy, to predict cancer laterality for focal targeted therapy with unilateral lobe. Material & Methods: A total of 158 men with prostate cancer detected by the 3D26PBx and who subsequently underwent radical prostatectomy (RP) were evaluated. RP specimens were divided into right and left lobe, and a total of 316 lobes were analyzed. All of the pathological specimens were re-evaluated according to the 2005 International Society of Urological Pathology (ISUP) Consensus by a single pathologist. Each lobe was categorized into three groups, including lobe with no cancer (LNC), with indolent cancer (LIC) and with significant cancer (LSC). Indolent cancer was defined as organ-confined disease and a tumour volume < 0.25 cc with no Gleason grade 4 or 5 cancer. We considered that LNC and LIC was possible area in which prostate gland would be preserved without treatment. Whether clinical and pathological variables can predict LNC and/or LIC were investigated. Results: Median PSA was 7.0 ng/mL (IQR; 5.3-9.9). Biopsy Gleason score was /= 8 in 34, 109 and 17 patients, respectively. There were 7.3% LNC (23/316) and 29% LIC (93/316) in the entire cohort. Positive predictive value (PPV) and negative predictive value (NPV) of unilateral negative biopsy for LNC were 24% (20/84) and 99% (231/234), respectively. PPV and NPV of unilateral negative biopsy for LNC or LIC were 73% (61/84) and 87% (203/234), respectively. PPV for LNC or LIC were improved only a few if considering other clinical and pathological variables. Conclusions: The 3D26PBx can predict a lobe with no or indolent cancer in RP specimens with PPV of 73%, and therefore would be useful for selecting candidate for focal targeted therapy with unilateral lobe.



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Nomogram with transrectal ultrasound findings has a better accuracy in predicting the detection of high grade prostate cancer on initial biopsy Kwon T.1, Jeong I.G.1, Park S.2, Ji Y.H.2, Chung H.3, Hong J.H.1, Ahn H.1, Kim C.S.1 1 Asan Medical Center, Dept. of Urology, Seoul, South Korea, 2Ulsan University Hospital, Dept. of Urology, Ulsan, South Korea, 3Gil Medical Center, Dept. of Urology, Incheon, South Korea

Introduction & Objectives: Because patients with high grade prostate cancer have a significantly worse prognosis compared with those with low grade prostate cancer, prediction of the presence of high grade prostate cancer is important on initial biopsy in men with elevated prostate specific antigen (PSA) to treat these patients aggressively. The aim of this study is to develop the nomogram with TRUS-derived information predicting high grade prostate cancer on initial biopsy and to examine whether this model outperform the model without TRUSderived information. Material & Methods: Data were collected on 1,048 Korean men with serum PSA levels 4.0 to 10.0 ng/ml who underwent an initial prostate biopsy at Asan Medical Center. Logistic regression-based nomogram 1 was constructed to assess risk for any and high grade prostate cancer (Gleason score ≥7) incorporating age, digital rectal examination (DRE), PSA level, percent free PSA and nomogram 2 incorporating TRUS findings and prostate volume. 20% of the data were reserved randomly for study validation and predictive accuracy was compared directly. Results: Of the 1,048 men, 216 (20.6%) and 97 (9.3%) were found to have any and high grade prostate cancer, respectively. All risk factors were significantly important predictors for any and high grade prostate cancer by multivariate analysis (p=0.047 to <0.001). The area under curve (AUC) for the nomogram 2 using TRUS-derived information in predicting cancer was 0.76 (95% CI 0.72-0.81) and 0.83 (95% CI 0.79-0.88) for high grade prostate cancer. This was significantly greater than the AUC for the nomogram 1 without TRUS-derived information (0.72; 95% CI 0.68-0.76 for any cancer; 0.78; 95% CI 0.72-0.83 for high grade cancer). The incremental drop in the AUC was 0.025 in predicting high grade prostate cancer compared with a drop of 0.003 for any prostate cancer if the TRUS findings were removed from the model. External validation revealed that AUC for the nomogram 2 was 0.78 in predicting cancer and 0.83 for high grade prostate cancer. Conclusions: We developed new nomograms predicting any and high grade prostate cancer on initial biopsy in men with PSA levels 4.0 to 10.0 ng/ml. Nomogram using TRUS-derived information had a better predictive accuracy for the detection of both any and high grade prostate cancer. Our results suggest that TRUS-derived information should be included at predictive nomogram for high grade prostate cancer which most physicians are desirable to detect on initial biopsy.