- Email: [email protected]
MP4-05 USE OF INITIAL ACTIVE SURVEILLANCE AMONG MEN WITH LOW-RISK PROSTATE CANCER – FOLLOW UP AND FALL OUT
THE JOURNAL OF UROLOGYâ
e28
Vol. 193, No. 4S, Supplement, Friday, May 15, 2015
minimum of 6 months of documented follow-up from initial diagnosis was mandated for inclusion. AS was defined as either the specific documentation of AS in the chart, or, in the absence of documented treatment, as the occurrence of at least one PSA and one office visit within 6 months of diagnosis. We performed univariate analysis with the chi-square test and multinomial regression to evaluate the correlation of NCCN risk group, race, age, and urology practice on treatment choice. RESULTS: Of 2464 incident cases, 1401 met inclusion criteria and 252 (17.3%) had very low-, 526 (36.1%) low- and 623 (42.7%) intermediate risk disease. The mean age was 63.6; 72.3% were white, 12.37% black, 4.2% other and 10.3% unknown. Initial primary therapeutic decisions are shown in the table. In multivariate analysis, risk group (p<0.001), age (p<0.001) and urology practice (p<0.001) predicted choice of active surveillance, while race (p¼0.43) did not. Surgery and radiation use was equivalent within risk groups, with a trend toward higher use of surgery among men with intermediate risk disease, of whom 44.6% received surgery and 32.2% received radiation (p<0.06). CONCLUSIONS: This contemporary analysis of 1401 patients from 8 geographically diverse, community-based large urology group practices within the US demonstrates a high adoption of active surveillance as an initial choice for men with newly diagnosed PCa. Variation in the rate of AS between practices may be an opportunity for educational benchmarking. Primary therapy choice by NCCN* risk group among men with incident prostate cancer in 2013 and 2014 treated in community urology practices Primary Therapy
Very Low, n (%)
Low, n (%)
Intermediate, n (%)
Total, n (%)
Active surveillance
177 (70.2)
206 (39.2)
48 (7.7)
431 (30.1)
Surgery
28 (11.1)
147 (28.0)
278 (44.6)
453 (32.3)
Radiotherapy
30 (11.9)
125 (23.8)
207 (32.2)
362 (25.8)
No follow-up
12 (4.8)
34 (6.5)
53 (8.5)
99 (7.1)
Other
5 (2.0)
14 (2.7)
37 (5.9)
56 (4.0)
Total
252
526
623
1,401
* National Comprehensive Cancer Network
Source of Funding: Unrestricted educational grant, Genomic Health Inc.
MP4-04 CLINICAL OUTCOMES OF CONSERVATIVELY MANAGED PROSTATE CANCER AMONG AFRICAN AMERICAN MEN Amar Patel*, Martin Sanda, Dattatraya Patil, Muta Issa, John Petros, Atlanta, GA INTRODUCTION AND OBJECTIVES: Despite increasing utilization of non-intervention conservative care for prostate cancer (PCa), information about outcomes of conservative management among African American (AA) men is sparse. We sought to evaluate the outcomes of conservatively managed prostate cancer among African American men and their counterparts from other racial origin in the communitybased, integrated care setting of the Atlanta VAMC. METHODS: A prospective database of all patients undergoing prostate biopsy at the Atlanta VAMC from 2000 to 2013 was interrogated retrospectively to identify men diagnosed with PCa who were managed conservatively. Demographic, clinical, and histopathological factors were evaluated for association with endpoints including biochemical progression (index PSA <10 with subsequent rise to >10), histopathological progression (conversion from Gleason 6 or less to Gleason > 6), clinical progression (metastatic disease) and death. Statistical analysis was performed by univariate and multivariate measure of associations and/or time-to-event analyses as indicated. RESULTS: There were 163 (6.6%) patients that had conservatively managed PCa. Median follow-up time was 10.9 months. There
were a total of 71 (43.6%) patients with intermediate-risk disease and 9 (5.5%) with high-risk disease. The cohort consisted of 104 (63.8%) AA’s of which, 45 (43.3%) had intermediate-risk disease and 8 (7.7%) with high-risk disease. 36/163 (22.1%) patients underwent repeat biopsy and 9/36 (25%) had histopathological progression. There was no significant difference in biochemical progression between AA and nonAA’s (18.9% vs. 10.6%, p¼0.22). Unexpectedly, non-AA’s had a higher rate of clinical progression (8.5% vs. 1.0%, p¼ 0.02), which may be attributed to verification bias secondary to low number of repeat biopsies. There was no difference in deaths from PCa (2.9% vs. 1.7%, p¼1.0) or time to biochemical progression (Log rank p ¼ 0.39) among AA vs Non-AA’s, respectively. Compared to indolent PCa, in patients with aggressive PCa (Gleason’s score >¼7) time to biochemical progression was significantly different between two racial groups (Log rank p¼0.005) with Non-AA’s progressing much rapidly than AA’s. CONCLUSIONS: To our knowledge, this is the first report focusing a PCa conservative care cohort comprised predominantly of AA men. Our findings suggest that clinical outcomes among AA are not substantially worse than those of men with other racial background. Validation of these findings in a prospective active surveillance study of AA patients with PCa is warranted. Source of Funding: None
MP4-05 USE OF INITIAL ACTIVE SURVEILLANCE AMONG MEN WITH LOW-RISK PROSTATE CANCER e FOLLOW UP AND FALL OUT Maria Komisarenko*, Narhari Timilshina, Shabbir Alibhai, Alexandre Zlotta, Robert Hamilton, Girish Kulkarni, Neil Fleshner, Antonio Finelli, Toronto, Canada INTRODUCTION AND OBJECTIVES: As more men are being diagnosed with low risk, localized prostate cancer (PCa), active surveillance (AS) is becoming an increasingly accepted treatment option for men with low risk disease. Thus it is critical to understand the long term oncological outcomes and prognosis for men on AS, as well as for those who chose to go on to treatment after AS. Our goal was to establish the 5 year outcomes of AS in a large academic institution setting, and elucidate predictors of AS discontinuation. METHODS: Men with 5-year AS follow-up were identified using Princess Margaret Cancer Centre (PM) AS cohort, with the following inclusion criteria: PSA 10, clinical stage cT2, Gleason sum 6, number of positive cores 3, no single core >50% involved, and age 75 years. The oncological outcomes and characteristics of men who continued and those who elected to leave AS after at least 2 biopsies were studied. The latter either self-elected to leave or were treated for disease reclassification. Time to discontinuation for any reason and time to treatment were graphed. Univariate analyses and multinomial regression models were done, all statistical analyses were done using SASâ. RESULTS: Of 655 men included with a median follow up of 66 months (IQR 61e98), a total of 32% discontinued AS at any given time. The cumulative % of discontinuation in the first 5 years were: 2, 9, 15, 22, and 32, respectively. Cumulative % going on to treatment were: 1, 5, 11, 17 and 26. When type of progression was considered, 64.7% of men who with volume progression discontinued AS and sought treatment versus 78.2% of those who experienced grade progression (p<0.001). Thus while progression is a predictor of AS discontinuation, the type of progression can significantly affect patient decision to remain on AS. Based on interval year of diagnosis, the proportion of patients choosing to stay on AS increased 34.3%, 46.1%, 59% (1991e99, 2000e04, 2005e09, respectively); and those electing to leave AS without pathologic progression decreased 17.6%, 7.8%, and 6.5%. Oncological outcomes between those leaving AS early without progression and those who left after progression were not significantly different. CONCLUSIONS: AS is an increasingly popular option for men with low risk PCa. Decisions to stay on or discontinue AS were driven by several factors, including patient defined AS criteria, which may differ from clinical recommendations, and type of progression. To improve AS participation it is important to understand predictors of discontinuation in
THE JOURNAL OF UROLOGYâ
Vol. 193, No. 4S, Supplement, Friday, May 15, 2015
an era when AS can improve rate of overtreatment while still enabling detection of high risk PCa. Source of Funding: none.
MP4-06 METASTATIC PROSTATE CANCER IN MEN ON ACTIVE SURVEILLANCE Toshihiro Yamamoto*, Danny Vespirini, Andrew Loblaw, Alezandre Mamedov, Liying Zhang, Laurence Klotz, Toronto, Canada INTRODUCTION AND OBJECTIVES: Active surveillance (AS) is an approach to low and intermediate risk prostate cancer designed to reduce overtreatment. However, despite close monitoring, a small subset of patients progress to metastatic disease. The clinical background and long-term natural history of these patients are uncertain. We analyzed their clinical and pathological correlates with progression and metastasis. METHODS: This was a single-centre, prospective cohort study. Eligible patients had favorable risk prostate cancer (prostate specific antigen (PSA) 10ng/ml or less, Gleason score 6 or less, T1c/T2a). Patients over 70 with intermediate risk disease managed with surveillance were included. Patients were assessed by serum PSA level, and digital rectal examination at 3 months intervals for 2 years, and 6 months intervals thereafter. Transrectal ultrasound-guided prostate biopsy was performed within 12 months and then every 3e4 years until the patient reached 80. RESULTS: 27/993 patients developed metastasis. The median patient age and PSA was 70 years (range 59e85 years) and 7.1ng/ml (range 2.49-14.2 ng/ml). The median time to metastasis was 7.3 years (range 0.6-13.2 years). Metastases occurred in the bone in 19 patients (70%) and in lymph node in 9 (33%). Patients with PSA DT less than three years progressed much earlier than the group with longer PSADT (Median 5.12 vs 9.23 years, p¼0.002). Patients upgraded to Gleason score 8e10 on confirmatory biopsies were at high risk for the early development of metastasis (GS6 vs 8, p¼0.034, GS7 vs 8, p¼0.023). Only 2 patients never upgraded from Gleason 6 developed metastasis; neither had surgical grading. CONCLUSIONS: 27 (2.7%) of surveillance patients developed metastasis at a median of 7.3 years. PSA DT less than 3 years and Gleason score 8e10 on confirmatory biopsy were associated with early development of metastasis. Earlier identification of the high risk patients may enhance survival in the surveillance population.
e29
59 months, 15% of GG3þ4 patients had biochemical failure, including 9 cases (2%) of metastasis. Metastasis occurred in 0% (0/304) of patients with prostatectomy tumor volume <20%, but 3% (9/281) of patients with tumor volume 20% (p¼0.0013, Figure 1). Similarly, metastasis occurred in 0% (0/394) of patients with pT2 stage, but 5% (9/191) of patients with pT3/T4 stage (p<0.0001, Figure 1). Hence, all metastatic cases were associated with bulky prostatectomy pathology, and either pT2 stage or tumor volume <20% was 100% accurate for predicting freedom from metastasis. Metastasis was not associated with margin status (p¼0.70) or PSA (p¼0.086). CONCLUSIONS: Low volume (<20% of the prostate), organconfined disease appears to identify a subset of GG3þ4 patients lacking metastatic potential. A threshold bulk of disease may be necessary for Gleason grade 3þ4 prostate cancer to metastasize, supporting the related idea that a limited pattern 4 grade may be insufficient for metastasis. These findings have implications for less stringent follow up in GG3þ4 patients after prostatectomy, and for continued investigation of active surveillance as a first-line option in patients with low volume GG3þ4 on biopsy. Validation in additional GG3þ4 cohorts will be valuable.
Source of Funding: None
Source of Funding: Prostate Cancer Canada
MP4-08 MP4-07 IS A THRESHOLD VOLUME OF DISEASE NECESSARY FOR GG3D4[7 PROSTATE CANCER TO METASTASIZE? Christine Murekeyisoni*, Kristopher Attwood, Shervin Badkhshan, Kurshid Guru, James Mohler, Eric Kauffman, Buffalo, NY INTRODUCTION AND OBJECTIVES: Treatment is typically recommended for Gleason grade (GG) 7 prostate cancer due to concern for metastasis, however only a small subset of GG3þ4¼7 cancers harbor metastatic potential and overtreatment is common. Clinicopathologic features of GG3þ4 cancers which reliably predict metastasis would be helpful but are presently unknown. Here we test the hypothesis that a threshold volume of GG3þ4 disease is necessary for metastasis. METHODS: Medical records of 585 consecutive prostate cancer patients undergoing radical prostatectomy at Roswell Park Cancer Institute with GG3þ4 final pathology and >1 year of follow up were reviewed. Clinicopathologic variables were tested for association with metastasis using Fisher’s Exact and T-test analyses, including tumor volume expressed as percentage of the prostate gland. RESULTS: Median PSA of GG3þ4 prostatectomy patients was 5.5ng/dL. Most GG3þ4 cancers (394, 67%) had pT2 stage, while 173 (30%) and 18 (3%) had pT3 and pT4 stage, respectively. Median GG3þ4 tumor volume was 15% of the prostate. At a median follow up of
ASSOCIATION OF GENETIC POLYMORPHISMS ACROSS THE TERT GENE Jian Kang*, Shanghai, China, People’s Republic of INTRODUCTION AND OBJECTIVES: Telomerase reverse transcriptase, expressed by TERT, is essential for the maintenance of telomere DNA length, chromosomal stability and cellular immortality. The aim of our study was to evaluate the association between common geneticvariations across the TERT gene region and prostate cancer (PCa) aggressiveness in aChinese population. METHODS: We genotyped 12 TERT tagging SNPs on the SEQUENOMâMass-ARRAY iPLEXâ platform in a case-case study with 1,210 Chinese PCapatients. Unconditional logistic regression was used to investigate the association ofgenotypes with PCa aggressiveness, Gleason grade and risk of developing an earlyonset PCa. RESULTS: We observed that allele “C” of the TERT intron2 SNP (rs2736100) was significantly associated with reduced risk of PCa aggressiveness (odds ratio(OR)¼0.81, 95% confidence interval (CI) ¼0.66-0.99, P¼0.037). This allele was alsosignificantly associated with reduced risk of developing a high Gleason grade (>7)tumor (OR¼0.83, 95% CI¼0.70-0.99, P¼0.039). Allele “T” of intron4 SNP(rs10069690) was found to be significantly associated with a decreased risk foraggressive PCa (OR¼0.76, 95%CI¼0.59-0.97, P¼0.030). In addition, allele “A” ofrs10078761 located in the 30 of the TERT gene showed statistically significantassociation with reduced risk of developing higher
e28
Vol. 193, No. 4S, Supplement, Friday, May 15, 2015
minimum of 6 months of documented follow-up from initial diagnosis was mandated for inclusion. AS was defined as either the specific documentation of AS in the chart, or, in the absence of documented treatment, as the occurrence of at least one PSA and one office visit within 6 months of diagnosis. We performed univariate analysis with the chi-square test and multinomial regression to evaluate the correlation of NCCN risk group, race, age, and urology practice on treatment choice. RESULTS: Of 2464 incident cases, 1401 met inclusion criteria and 252 (17.3%) had very low-, 526 (36.1%) low- and 623 (42.7%) intermediate risk disease. The mean age was 63.6; 72.3% were white, 12.37% black, 4.2% other and 10.3% unknown. Initial primary therapeutic decisions are shown in the table. In multivariate analysis, risk group (p<0.001), age (p<0.001) and urology practice (p<0.001) predicted choice of active surveillance, while race (p¼0.43) did not. Surgery and radiation use was equivalent within risk groups, with a trend toward higher use of surgery among men with intermediate risk disease, of whom 44.6% received surgery and 32.2% received radiation (p<0.06). CONCLUSIONS: This contemporary analysis of 1401 patients from 8 geographically diverse, community-based large urology group practices within the US demonstrates a high adoption of active surveillance as an initial choice for men with newly diagnosed PCa. Variation in the rate of AS between practices may be an opportunity for educational benchmarking. Primary therapy choice by NCCN* risk group among men with incident prostate cancer in 2013 and 2014 treated in community urology practices Primary Therapy
Very Low, n (%)
Low, n (%)
Intermediate, n (%)
Total, n (%)
Active surveillance
177 (70.2)
206 (39.2)
48 (7.7)
431 (30.1)
Surgery
28 (11.1)
147 (28.0)
278 (44.6)
453 (32.3)
Radiotherapy
30 (11.9)
125 (23.8)
207 (32.2)
362 (25.8)
No follow-up
12 (4.8)
34 (6.5)
53 (8.5)
99 (7.1)
Other
5 (2.0)
14 (2.7)
37 (5.9)
56 (4.0)
Total
252
526
623
1,401
* National Comprehensive Cancer Network
Source of Funding: Unrestricted educational grant, Genomic Health Inc.
MP4-04 CLINICAL OUTCOMES OF CONSERVATIVELY MANAGED PROSTATE CANCER AMONG AFRICAN AMERICAN MEN Amar Patel*, Martin Sanda, Dattatraya Patil, Muta Issa, John Petros, Atlanta, GA INTRODUCTION AND OBJECTIVES: Despite increasing utilization of non-intervention conservative care for prostate cancer (PCa), information about outcomes of conservative management among African American (AA) men is sparse. We sought to evaluate the outcomes of conservatively managed prostate cancer among African American men and their counterparts from other racial origin in the communitybased, integrated care setting of the Atlanta VAMC. METHODS: A prospective database of all patients undergoing prostate biopsy at the Atlanta VAMC from 2000 to 2013 was interrogated retrospectively to identify men diagnosed with PCa who were managed conservatively. Demographic, clinical, and histopathological factors were evaluated for association with endpoints including biochemical progression (index PSA <10 with subsequent rise to >10), histopathological progression (conversion from Gleason 6 or less to Gleason > 6), clinical progression (metastatic disease) and death. Statistical analysis was performed by univariate and multivariate measure of associations and/or time-to-event analyses as indicated. RESULTS: There were 163 (6.6%) patients that had conservatively managed PCa. Median follow-up time was 10.9 months. There
were a total of 71 (43.6%) patients with intermediate-risk disease and 9 (5.5%) with high-risk disease. The cohort consisted of 104 (63.8%) AA’s of which, 45 (43.3%) had intermediate-risk disease and 8 (7.7%) with high-risk disease. 36/163 (22.1%) patients underwent repeat biopsy and 9/36 (25%) had histopathological progression. There was no significant difference in biochemical progression between AA and nonAA’s (18.9% vs. 10.6%, p¼0.22). Unexpectedly, non-AA’s had a higher rate of clinical progression (8.5% vs. 1.0%, p¼ 0.02), which may be attributed to verification bias secondary to low number of repeat biopsies. There was no difference in deaths from PCa (2.9% vs. 1.7%, p¼1.0) or time to biochemical progression (Log rank p ¼ 0.39) among AA vs Non-AA’s, respectively. Compared to indolent PCa, in patients with aggressive PCa (Gleason’s score >¼7) time to biochemical progression was significantly different between two racial groups (Log rank p¼0.005) with Non-AA’s progressing much rapidly than AA’s. CONCLUSIONS: To our knowledge, this is the first report focusing a PCa conservative care cohort comprised predominantly of AA men. Our findings suggest that clinical outcomes among AA are not substantially worse than those of men with other racial background. Validation of these findings in a prospective active surveillance study of AA patients with PCa is warranted. Source of Funding: None
MP4-05 USE OF INITIAL ACTIVE SURVEILLANCE AMONG MEN WITH LOW-RISK PROSTATE CANCER e FOLLOW UP AND FALL OUT Maria Komisarenko*, Narhari Timilshina, Shabbir Alibhai, Alexandre Zlotta, Robert Hamilton, Girish Kulkarni, Neil Fleshner, Antonio Finelli, Toronto, Canada INTRODUCTION AND OBJECTIVES: As more men are being diagnosed with low risk, localized prostate cancer (PCa), active surveillance (AS) is becoming an increasingly accepted treatment option for men with low risk disease. Thus it is critical to understand the long term oncological outcomes and prognosis for men on AS, as well as for those who chose to go on to treatment after AS. Our goal was to establish the 5 year outcomes of AS in a large academic institution setting, and elucidate predictors of AS discontinuation. METHODS: Men with 5-year AS follow-up were identified using Princess Margaret Cancer Centre (PM) AS cohort, with the following inclusion criteria: PSA 10, clinical stage cT2, Gleason sum 6, number of positive cores 3, no single core >50% involved, and age 75 years. The oncological outcomes and characteristics of men who continued and those who elected to leave AS after at least 2 biopsies were studied. The latter either self-elected to leave or were treated for disease reclassification. Time to discontinuation for any reason and time to treatment were graphed. Univariate analyses and multinomial regression models were done, all statistical analyses were done using SASâ. RESULTS: Of 655 men included with a median follow up of 66 months (IQR 61e98), a total of 32% discontinued AS at any given time. The cumulative % of discontinuation in the first 5 years were: 2, 9, 15, 22, and 32, respectively. Cumulative % going on to treatment were: 1, 5, 11, 17 and 26. When type of progression was considered, 64.7% of men who with volume progression discontinued AS and sought treatment versus 78.2% of those who experienced grade progression (p<0.001). Thus while progression is a predictor of AS discontinuation, the type of progression can significantly affect patient decision to remain on AS. Based on interval year of diagnosis, the proportion of patients choosing to stay on AS increased 34.3%, 46.1%, 59% (1991e99, 2000e04, 2005e09, respectively); and those electing to leave AS without pathologic progression decreased 17.6%, 7.8%, and 6.5%. Oncological outcomes between those leaving AS early without progression and those who left after progression were not significantly different. CONCLUSIONS: AS is an increasingly popular option for men with low risk PCa. Decisions to stay on or discontinue AS were driven by several factors, including patient defined AS criteria, which may differ from clinical recommendations, and type of progression. To improve AS participation it is important to understand predictors of discontinuation in
THE JOURNAL OF UROLOGYâ
Vol. 193, No. 4S, Supplement, Friday, May 15, 2015
an era when AS can improve rate of overtreatment while still enabling detection of high risk PCa. Source of Funding: none.
MP4-06 METASTATIC PROSTATE CANCER IN MEN ON ACTIVE SURVEILLANCE Toshihiro Yamamoto*, Danny Vespirini, Andrew Loblaw, Alezandre Mamedov, Liying Zhang, Laurence Klotz, Toronto, Canada INTRODUCTION AND OBJECTIVES: Active surveillance (AS) is an approach to low and intermediate risk prostate cancer designed to reduce overtreatment. However, despite close monitoring, a small subset of patients progress to metastatic disease. The clinical background and long-term natural history of these patients are uncertain. We analyzed their clinical and pathological correlates with progression and metastasis. METHODS: This was a single-centre, prospective cohort study. Eligible patients had favorable risk prostate cancer (prostate specific antigen (PSA) 10ng/ml or less, Gleason score 6 or less, T1c/T2a). Patients over 70 with intermediate risk disease managed with surveillance were included. Patients were assessed by serum PSA level, and digital rectal examination at 3 months intervals for 2 years, and 6 months intervals thereafter. Transrectal ultrasound-guided prostate biopsy was performed within 12 months and then every 3e4 years until the patient reached 80. RESULTS: 27/993 patients developed metastasis. The median patient age and PSA was 70 years (range 59e85 years) and 7.1ng/ml (range 2.49-14.2 ng/ml). The median time to metastasis was 7.3 years (range 0.6-13.2 years). Metastases occurred in the bone in 19 patients (70%) and in lymph node in 9 (33%). Patients with PSA DT less than three years progressed much earlier than the group with longer PSADT (Median 5.12 vs 9.23 years, p¼0.002). Patients upgraded to Gleason score 8e10 on confirmatory biopsies were at high risk for the early development of metastasis (GS6 vs 8, p¼0.034, GS7 vs 8, p¼0.023). Only 2 patients never upgraded from Gleason 6 developed metastasis; neither had surgical grading. CONCLUSIONS: 27 (2.7%) of surveillance patients developed metastasis at a median of 7.3 years. PSA DT less than 3 years and Gleason score 8e10 on confirmatory biopsy were associated with early development of metastasis. Earlier identification of the high risk patients may enhance survival in the surveillance population.
e29
59 months, 15% of GG3þ4 patients had biochemical failure, including 9 cases (2%) of metastasis. Metastasis occurred in 0% (0/304) of patients with prostatectomy tumor volume <20%, but 3% (9/281) of patients with tumor volume 20% (p¼0.0013, Figure 1). Similarly, metastasis occurred in 0% (0/394) of patients with pT2 stage, but 5% (9/191) of patients with pT3/T4 stage (p<0.0001, Figure 1). Hence, all metastatic cases were associated with bulky prostatectomy pathology, and either pT2 stage or tumor volume <20% was 100% accurate for predicting freedom from metastasis. Metastasis was not associated with margin status (p¼0.70) or PSA (p¼0.086). CONCLUSIONS: Low volume (<20% of the prostate), organconfined disease appears to identify a subset of GG3þ4 patients lacking metastatic potential. A threshold bulk of disease may be necessary for Gleason grade 3þ4 prostate cancer to metastasize, supporting the related idea that a limited pattern 4 grade may be insufficient for metastasis. These findings have implications for less stringent follow up in GG3þ4 patients after prostatectomy, and for continued investigation of active surveillance as a first-line option in patients with low volume GG3þ4 on biopsy. Validation in additional GG3þ4 cohorts will be valuable.
Source of Funding: None
Source of Funding: Prostate Cancer Canada
MP4-08 MP4-07 IS A THRESHOLD VOLUME OF DISEASE NECESSARY FOR GG3D4[7 PROSTATE CANCER TO METASTASIZE? Christine Murekeyisoni*, Kristopher Attwood, Shervin Badkhshan, Kurshid Guru, James Mohler, Eric Kauffman, Buffalo, NY INTRODUCTION AND OBJECTIVES: Treatment is typically recommended for Gleason grade (GG) 7 prostate cancer due to concern for metastasis, however only a small subset of GG3þ4¼7 cancers harbor metastatic potential and overtreatment is common. Clinicopathologic features of GG3þ4 cancers which reliably predict metastasis would be helpful but are presently unknown. Here we test the hypothesis that a threshold volume of GG3þ4 disease is necessary for metastasis. METHODS: Medical records of 585 consecutive prostate cancer patients undergoing radical prostatectomy at Roswell Park Cancer Institute with GG3þ4 final pathology and >1 year of follow up were reviewed. Clinicopathologic variables were tested for association with metastasis using Fisher’s Exact and T-test analyses, including tumor volume expressed as percentage of the prostate gland. RESULTS: Median PSA of GG3þ4 prostatectomy patients was 5.5ng/dL. Most GG3þ4 cancers (394, 67%) had pT2 stage, while 173 (30%) and 18 (3%) had pT3 and pT4 stage, respectively. Median GG3þ4 tumor volume was 15% of the prostate. At a median follow up of
ASSOCIATION OF GENETIC POLYMORPHISMS ACROSS THE TERT GENE Jian Kang*, Shanghai, China, People’s Republic of INTRODUCTION AND OBJECTIVES: Telomerase reverse transcriptase, expressed by TERT, is essential for the maintenance of telomere DNA length, chromosomal stability and cellular immortality. The aim of our study was to evaluate the association between common geneticvariations across the TERT gene region and prostate cancer (PCa) aggressiveness in aChinese population. METHODS: We genotyped 12 TERT tagging SNPs on the SEQUENOMâMass-ARRAY iPLEXâ platform in a case-case study with 1,210 Chinese PCapatients. Unconditional logistic regression was used to investigate the association ofgenotypes with PCa aggressiveness, Gleason grade and risk of developing an earlyonset PCa. RESULTS: We observed that allele “C” of the TERT intron2 SNP (rs2736100) was significantly associated with reduced risk of PCa aggressiveness (odds ratio(OR)¼0.81, 95% confidence interval (CI) ¼0.66-0.99, P¼0.037). This allele was alsosignificantly associated with reduced risk of developing a high Gleason grade (>7)tumor (OR¼0.83, 95% CI¼0.70-0.99, P¼0.039). Allele “T” of intron4 SNP(rs10069690) was found to be significantly associated with a decreased risk foraggressive PCa (OR¼0.76, 95%CI¼0.59-0.97, P¼0.030). In addition, allele “A” ofrs10078761 located in the 30 of the TERT gene showed statistically significantassociation with reduced risk of developing higher