669 ACTIVE SURVEILLANCE FOR FAVORABLE-RISK PROSTATE CANCER: AN UPDATE OF THE UNIVERSITY OF MIAMI PROGRAM

Vol. 189, No. 4S, Supplement, Sunday, May 5, 2013

667 PER-LESION BASED ACTIVE SURVEILLANCE FOR PROSTATE CANCER: IMAGE-BASED MONITORING OF TARGETED BIOPSY-PROVEN CANCER Andre Luis de Castro Abreu*, Duke Bahn, Sunao Shoji, Scott Leslie, Mehrdad Alemozaffar, Jie Cai, Los Angeles, CA; Paul Silverman, Ventura, CA; Inderbir Gill, Osamu Ukimura, Los Angeles, CA INTRODUCTION AND OBJECTIVES: To report the outcomes of our Active Surveillance (AS) program focusing on monitoring of targeted-biopsy proven cancer using modern imaging. METHODS: 240 patients with low (n⫽197, 82%) to intermediate (n⫽43, 18%) risk prostate cancer (PCa) were enrolled on AS protocol including PSA (every 6mos), surveillance biopsy (every 2yrs or when indicated) and multi-parametric transrectal ultrasound (TRUS) annually. Every hypo-echoic lesion (HEL) of targeted biopsy-proven cancer was monitored with its dimensions digitally recorded for monitoring. The primary endpoint was to determine progression disease: defined as upgrade on Gleason score, increase of cancer core length (⬎4mm) or percent core involvement (⬎25%), or clinical progression. PSA indices, biopsy, and characteristics of visible cancer were compared between patients with progression (PG) versus no progression (NPG). RESULTS: The median (range) follow up, age and PSA were 4yrs (1-15.5 yrs), 63yrs (43-85 yrs) and 4.8ng/dl (0.1-16.8), respectively. Gleason score was 6 (n⫽210, 88%) or 7 (n⫽30, 12%) and clinical stage was T1c (n⫽213, 89%) or T2a (n⫽27, 11%). Surveillance biopsy was performed in 137 (57%) patients. 70 (29%) patients experienced PG and the upgrade Gleason occurred in 80% (n⫽56) of the PG. The estimated probability of progression free-survival was 97% and 73% at 2 and 5 years, respectively. No patient died or developed metastases. PG and NPG had comparable baseline with no significant difference (p⬎0.05) in median PSA (4.8 vs 4.8 ng/nl), Gleason (6 vs 6), number of positive biopsy core (1 vs 1), cancer core length (1.8 mm vs 1.3 mm) and percent core (6% vs 10%), respectively. 33 (47%) patients on PG and 68 (40%) on NPG had an experience using 5 alphareductase inhibitors (5ARI) during AS. On follow up of the patients without 5ARI, PSA velocity greater than 0.75ng/ml/year occurred in 43% (n ⫽ 16) vs 16% (n ⫽ 16) in PG vs NPG (p⫽0.003), respectively. At latest surveillance biopsy, median number of positive core, cancer core length and percent core for PG vs NPG were 3 vs 1 (p ⬍ 0,001), 6 mm vs 2.2 mm (p⬍0.001) and 40% vs 20% (p⬍0.001) respectively. All patients had at least once, and 189 (79%) patients had 3 or more multi-parametric TRUS monitoring. Median dimension of the dominant HEL for PG vs NPG were: 10mm vs 11mm at 1st-year (p⫽0.74), 10mm vs 12mm at 2nd-year (p⫽0.03) and 11mm vs 13mm at 4-year (p⫽0.003), respectively. CONCLUSIONS: The median 4-year follow up of AS for low to intermediate risk PCa is encouraging. Targeted biopsy and monitoring using modern imaging could enhance AS protocol by per-lesion based strategy. Source of Funding: None

668 CAN BIOPSY GLEASON SCORE 3ⴙ4 BE INDICATED FOR ACTIVE SURVEILLANCE CRITERIA? Koji Mitsuzuka*, Sendai, Japan; Shintaro Narita, Akita, Japan; Takuya Koie, Hirosaki, Japan; Narihiko Kakoi, Natori, Japan; Yasuhiro Kaiho, Sendai, Japan; Norihiko Tsuchiya, Akita, Japan; Takahiro Yoneyama, Hirosaki, Japan; Sadafumi Kawamura, Tatsuo Tochigi, Natori, Japan; Tomonori Habuchi, Akita, Japan; Chikara Ohyama, Hirosaki, Japan; Yoichi Arai, Sendai, Japan INTRODUCTION AND OBJECTIVES: Whether to include a biopsy Gleason score of 3⫹4 as an active surveillance criterion is debatable, and we examined the validity of including a Gleason score of 3⫹4 for active surveillance by using the pathological outcomes of patients who underwent radical prostatectomy.

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METHODS: The records of 1,268 patients undergoing radical prostatectomy from January 2000 to December 2009 and who had not undergone neoadjuvant therapy were retrospectively reviewed. Of these, patients who preoperatively had a prostate-specific antigen (PSA) level ⱕ 10 ng/ml, PSA density ⱕ 0.2, biopsy cores taken ⱖ 8, positive biopsy cores ⱕ 2, clinical stage ⱕ T2, and biopsy Gleason score ⱕ 3⫹4 were divided into the biopsy Gleason score ⱕ 3⫹3 group (Group A, n⫽81) and the biopsy Gleason score 3⫹4 group (Group B, n⫽66). Upstaging to pathological T3 or T4, upgrading to pathological Gleason score ⱖ 4⫹3, tumor volume, and biochemical recurrence (PSA ⱖ 0.2 ng/ml) between the two groups were compared. RESULTS: Age, PSA, PSA density, positive biopsy cores, and clinical T stage did not differ between the two groups. Pathological upstaging was seen in 8.6% of Group A and 10.6% of Group B (p⫽0.69). Pathological upgrading to Gleason score ⱖ 4⫹3 was not significantly different between the two groups (22.0% vs. 30.3%, p⫽0.28); however, upgrading to Gleason score ⱖ 8 was significantly different between the two groups (5.0% vs. 15.2%, p⫽0.04). The median tumor volume was 0.84 cc (range, 0.03-2.62 cc) of Group A and 0.52 cc (range, 0.06-6.86 cc) of Group B (p⫽0.76). The 5- and 7-year rates of PSA recurrence-free survival were 95.7% and 85.6% for Group A and 87.9% and 67.1% for Group B (p⫽0.10, log rank test). When the cut-off of PSA density was reduced to 0.15 or 0.12, upgrading decreased proportionally. In Group B, upgrading to pathological Gleason scores ⱖ 4⫹3 and ⱖ 8 were 25.6% and 12.8% at a 0.15 cut-off of PSA density and 15.0% and 0% at a 0.12 cut-off of PSA density. CONCLUSIONS: If we included a biopsy Gleason score of 3⫹4 as an active surveillance criterion, pathological upgrading to a Gleason score ⱖ 8 significantly increased. However, if we used a lower PSA density cut-off, upgrading decreased significantly. A biopsy Gleason score of 3⫹4 might be safely included as an active surveillance criterion while considering the PSA density cut-off.

Source of Funding: None

669 ACTIVE SURVEILLANCE FOR FAVORABLE-RISK PROSTATE CANCER: AN UPDATE OF THE UNIVERSITY OF MIAMI PROGRAM Mark S. Soloway, Ahmed Eldefrawy*, Murugesan Manoharan, Viacheslav Iremashvili, Miami, FL INTRODUCTION AND OBJECTIVES: Although active surveillance has been accepted as a management option for patient with low-risk prostate cancer, our knowledge of the middle- and long-term outcomes of this strategy remains limited. The goal of this study is to provide an update on the outcomes of our active surveillance protocol. METHODS: We offer active surveillance for patients with clinical stage T1c-T2a, Gleason score ⱕ6, ⱕ2 biopsy cores with ⱕ20% tumor present in each core and prostate-specific antigen (PSA) ⬍15 ng/ml. From October 1998 to October 2012, 334 patients met these criteria. 299 patients with at least one repeat biopsy were included in this analysis. Patients were followed every 3-6 months with PSA and rectal exam. Repeat prostate biopsies were performed every 1-2 years. RESULTS: Patient characteristics are presented in Table 1. Over a median follow-up of 3.1 (interquartile range 2.1-4.8) years 81 (27%) patients had biopsy progression. The median time to progression was 2.2 years. The rates of progression and of positive biopsies were relatively stable over the first 3 surveillance biopsies and decreased on later biopsies (Figure 2). The majority of patients who

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progressed had radical prostatectomy (37, 46%) or radiation therapy (34, 30%); 12 (17%) patients elected to continue active surveillance. Type of treatment is not known for 8 patients. None of the patients have developed metastatic prostate cancer. CONCLUSIONS: The great majority of patients with low-risk prostate cancer do not progress when closely followed with regular biopsies over a course of several years. Thus, active surveillance is an effective alternative to treatment in patients with low grade and low volume prostate cancer.

strate disease upgrading or upstaging. We aimed to evaluate the clinical importance of a single microfocal prostate cancer at biopsy in patients subsequently treated with radical prostatectomy. METHODS: 337 cases that underwent radical prostatectomy after 12 core-extended prostate biopsies were retrospectively reviewed. Microfocal prostate cancer was defined as a single positive core with ⱕ5% cancer involvement after 12 cores biopsy. RESULTS: Of the 337 prostatectomy specimens, 22 cases were microfocal prostate cancer on prostate biopsy.On final pathology, microfocal patients were found to have 45% (N⫽10) Gleason upgrading, 50% (N⫽11) staging upgrading and 27% (N⫽6) positive surgical margins despite of low PSA (p⫽0.02). Gleason upgrading was significantly higher in the microfocal prostate cancer group where as Gleason downgrading was significantly higher in the non microfocal prostate cancer group. 7 (53.8%) out of 13 Gleason scores or stage upgrading cases, were detected with prostate cancer located at the apex portion of the prostate. However, only one case (11.1%) out of 9 no Gleason scores or stage upgrading cases, was detected at the apex. Biochemical recurrence rate was no different between microfocal and non microfocal prostate cancer at mean 21 months. CONCLUSIONS: Microfocal prostate cancer behaves similarly to higher volume disease and shows higher rate of Gleason upgrading rather than non microfocal prostate cancer. Microfocal prostate cancer at the apex might show more aggressive tumor characteristics compared with prostate cancer at other location.

Number Table 1. Characteristics of the study cohort at diagnosis Characteristic Mean age (range), years 61.8 (42.4-78.9) Race, n (%) Caucasian

268 (90)

African American

31 (10)

Ethnicity, n (%) Non-Hispanic

188 (63)

Hispanic

111 (37)

Family history of prostate cancer, n (%)

55 (18)

Median PSA at diagnosis (IQR), ng/ml

4.8 (3.4-6.2)

Median PSA density at diagnosis (IQR), ng/ml

0.12 (0.09-0.17)

T stage, n (%) T1c

285 (95)

T2a

14 (5)

Median total No. of biopsy cores (IQR)

P value

Age (years)

63.6 (49-71)

63.5 (48-74)

PSA (ng/mL)

5.6 (2.5-11.3)

13.2 (3.2-21.7)

0.49 0.02

PSA density

0.18 (0.07-0.37)

0.36 (0.10-0.78)

0.01

Prostate volume (cc)

30.2 (16.4-64.5)

36.7 (14.8-121.3)

0.48

surgical margin ⫹

6 (27.2%)

45 (14.3%)

0.04

Gleason scores upgrading

Pathology (N)

10 (45.4%)

69 (21.9%)

0.02

Gleason scores downgrading

1 (4.5%)

101 (32.1%)

⬍0.01

Stage upgrading

11 (50%)

152 (48.3%)

0.55

Biochemical recurrence

3 (13.6%)

56 (17.6%)

0.18

Source of Funding: None

12 (10-12)

Positive biopsy cores, n (%) 1

236 (80)

2

63 (20)

Median average core involvement (IQR), % PSA - prostate-specific antigen, IQR - interquartile range

Comparison of microfocal and non microfocal PCA Non microfocal Microfocal PCA PCA 22 315

5 (5-10)

Source of Funding: None

670 CAN A MICROFOCAL PROSTATE CANCER BE REGARDED AS LOW RISK PROSTATE CANCER? Seung Hwan Lee, Kwang Hyun Kim*, Kyung Kgi Park, Dong Hoon Lee, Byung Ha Chung, Seoul, Korea, Republic of INTRODUCTION AND OBJECTIVES: Recently, Prostate specific antigen (PSA) screening for prostate cancer has become common, the prostate biopsy technique has evolved, and the occurrence of low risk prostate cancer is increasing. Even low risk patients may demon-

671 DEVELOPMENT AND MULTI-INSTITUTIONAL VALIDATION OF A BIOPSY-INTEGRATED ALGORITHM FOR DETERMINING GLEASON 6 UPGRADING RISK Matthew Truong*, Madison, WI; Viacheslav Iremashvili, Miami, FL; Chee Paul Lin, Jon Slezak, Martins Sado, Madison, WI; Aria Razmaria, Chicago, IL; Mark Soloway, Miami, FL; Scott Eggener, Chicago, IL; E Jason Abel, Tracy Downs, David Jarrard, Madison, WI INTRODUCTION AND OBJECTIVES: Men with low risk prostate cancer (PCa) frequently undergo Gleason score upgrading (GSU) after radical prostatectomy (RP). There are currently no validated nomograms employing variables available before surgery for predicting GSU in lower risk PCa patients. Thus, we developed a nomogram for predicting upgrading in Gleason 6 patients that is validated in modern, external populations. METHODS: Nomogram development was performed using 431 consecutive Gleason 6 biopsy patients who underwent RP using clinical and pathological data. Clinical variables included age, BMI, PSA, AUA symptom score, race, family history of PCa, smoking history, ASA