- Email: [email protected]
MP4-06 METASTATIC PROSTATE CANCER IN MEN ON ACTIVE SURVEILLANCE
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
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