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RADIATION THERAPY AFTER RADICAL PROSTATECTOMY: IMPACT ON METASTASES AND SURVIVAL
THE JOURNAL OF UROLOGY®
Vol. 181, No. 4, Supplement, Monday, April 27, 2009
cases showed LVI - 108 of 125 (86%) cases showed EPE and 45 (37%) demonstrated SVI (17 R, 12 L, and 17 bilateral) - Among cases with SVI, 27/46 (59%) had > 1 LN+, compared with 22/78 (28%) without SVI - Volumetric studies revealed mean and median total TV of 6.38 and 3.92 cc, respectively (range: 0.03 to 45.7) - Predominantly high grade Gleason patterns (4-5) accounted for > 50% of total TV in 105 (84%) cases and > 90% of total TV in 73 (58%) cases Correlation of Dominant Lesion Location and LN+ - Dominant lesions on RP: 50 R lobe, 44 L lobe, 31 bilateral lobes - R lobe dominant tumors: 14/50 (28%) showed LN+ on the L side (9 exclusively left LN+, 5 bilateral LN+). L lobe dominant tumors: 17/44 (39%) showed LN+ on the R side (8 exclusively right LN+, 9 bilateral LN+) - 102/125 were posterior/posterolateral, 18 were both anterior/posterior, and 5 were anterior only - 79 primary tumors involved the base, while 46 were located primarily in the apex-mid gland - 13 of 16 CA with LN+, but without EPE or SVI, were predominantly in the apex-mid gland. CONCLUSIONS: LN+ cases are overwhelmingly associated with large volume, high grade, high stage (> pT3a) disease and LVI. Interestingly, one-third of LN+ occur contralateral to the dominant RP cancer. In this series, LN+ were infrequently associated with anteriordominant tumors. Organ-confined LN+ cases were predominantly situated in the apex-mid gland. Source of Funding: None
763 WHAT ARE THE OUTCOMES OF RADICAL PROSTATECTOMY FOR HIGH-RISK PROSTATE CANCER? Edward M. Schaeffer*, Stacy Loeb, Patrick C. Walsh, Elizabeth B. Humphreys, Bruce J. Trock, Baltimore, MD INTRODUCTION AND OBJECTIVE: Despite considerable stage migration associated with widespread PSA screening, as many as 1/3 of incident prostate cancers have high-risk features. These patients are often treated with combined radiation and androgen deprivation therapy, and less is known about the long-term survival in this population after radical prostatectomy. METHODS: From 1992 to 2008, 175 men underwent radical prostatectomy by a single surgeon with D’Amico high-risk prostate cancer (clinical stage qT2c, biopsy Gleason score 8 to 10, or PSA >20 ng/ml). In this population, we examined the rates and predictors of biochemical progression, metastatic disease and cancer-specific mortality. RESULTS: The median age was 59 years (range, 38-71), and median follow-up was 8 years (range, 1-16). The D’Amico high-risk criteria included 63 (36%) of men with a biopsy Gleason score of 8 to 10, 66 (38%) with clinical stage qT2c, and 58 (33%) with preoperative PSA >20 ng/ml (6% of men had more than 1 high risk factor). At radical prostatectomy, 63 (36%) had organ-confined disease, whereas extracapsular extension and seminal vesicle invasion were present in 79 (45%) and 8 (5%), respectively. Positive surgical margins were reported in 32 (18%) and lymph node metastases in 25 (14%). At 10 years, biochemical recurrence-free survival was 68%, metastasis-free survival was 84%, and prostate cancer-specific survival was 92% (Figure). In addition, the 10-year rate of freedom from any hormonal therapy was 71%. Of the high-risk criteria, a biopsy Gleason score of 8-10 (vs. a7) was the strongest independent predictor of all outcomes, with hazard ratio and p-value of 3.17 (p=0.027), 4.19 (p=0.015), and 6.57 (p=0.011) for biochemical recurrence, metastases, and prostate cancer death, respectively. CONCLUSIONS: National data suggest that radical prostatectomy may be underutilized for the management of high-risk clinically localized prostate cancer. Our data suggest that surgical treatment can result in long-term progression-free survival in a subset of carefully selected highrisk men. Further prospective studies are warranted to directly compare the outcomes of radical prostatectomy versus combined radiation and hormonal therapy in high-risk patients.
273
Source of Funding: None
764 RADIATION THERAPY AFTER RADICAL PROSTATECTOMY: IMPACT ON METASTASES AND SURVIVAL Stephen A Boorjian*, Rockledge, PA; R. Jeffrey Karnes, Paul L Crispen, Laureano J Rangel, Eric J Bergstralh, Michael L Blute, Rochester, MN INTRODUCTION AND OBJECTIVE: Although secondary local treatment with radiation therapy (RT) has been shown to reduce the risk of biochemical progression (BCR) following radical prostatectomy (RRP), the impact of RT after RRP on the endpoints of metastases and death from prostate cancer has been less well established. Here, then, we evaluated the impact of adjuvant (ART) and salvage (SRT) radiotherapy on clinical disease progression and mortality. METHODS: We evaluated 13,308 consecutive patients who underwent RRP at the Mayo Clinic between 1987-2003. Patients who received ART were matched based on clinicopathological features to patients who did not receive ART (controls) in a 2:1 case-control ratio. Postoperative survival was estimated using the Kaplan-Meier method and compared using the log-rank test. A second cohort of men who experienced BCR following RRP was separately evaluated. Cox proportional hazard regression models were used to analyze the impact of SRT on disease progression and survival in this group. RESULTS: We identified 361 patients who received ART following RRP. Median postoperative follow-up in this cohort was 11.0 years (range 1.8-19.7). A total of 131 and 386 patients from the ART and control groups, respectively, experienced BCR, 9 and 125 patients had LR, 34 and 68 patients relapsed systemically, and 76 and 174 patients died, with 17 and 42 patients dying of prostate cancer. ART was associated with significantly improved 10-year BCR-free survival (63% vs. 45%, p<0.001), local recurrence (LR)-free survival (97% vs. 82%, p<0.001), and a decreased need for salvage androgen deprivation therapy (ADT) (17% vs. 28%, p=0.002), but did not impact systemic progression (SP) (p=0.94) or prostate cancer death (p=0.43). Meanwhile, of 2,657 patients who experienced BCR after RRP, 856 (32.3%) received SRT. Median PSA at SRT was 0.8 ng/ml, and median follow-up after SRT was 5.9 years (range 0-19). On multivariate analysis, SRT significantly reduced the risks of LR (HR 0.12; 95% CI 0.06-0.26; p<0.0001), delayed ADT (HR 0.63; 95% CI 0.55-0.74; p<0.001), and SP (HR 0.30; 95% CI 0.160.56; p=0.0002), but did not impact mortality (HR 1.06; 95% CI 0.791.42; p=0.70). CONCLUSIONS: Both ART and SRT provide durable local control, improve long-term BCR-free survival, and decrease the need for delayed ADT. SRT was further associated with a decreased rate of SP, but neither ART nor SRT improved survival. These results must be weighed against the potential morbidity of postoperative RT in counseling patients. Source of Funding: None
Vol. 181, No. 4, Supplement, Monday, April 27, 2009
cases showed LVI - 108 of 125 (86%) cases showed EPE and 45 (37%) demonstrated SVI (17 R, 12 L, and 17 bilateral) - Among cases with SVI, 27/46 (59%) had > 1 LN+, compared with 22/78 (28%) without SVI - Volumetric studies revealed mean and median total TV of 6.38 and 3.92 cc, respectively (range: 0.03 to 45.7) - Predominantly high grade Gleason patterns (4-5) accounted for > 50% of total TV in 105 (84%) cases and > 90% of total TV in 73 (58%) cases Correlation of Dominant Lesion Location and LN+ - Dominant lesions on RP: 50 R lobe, 44 L lobe, 31 bilateral lobes - R lobe dominant tumors: 14/50 (28%) showed LN+ on the L side (9 exclusively left LN+, 5 bilateral LN+). L lobe dominant tumors: 17/44 (39%) showed LN+ on the R side (8 exclusively right LN+, 9 bilateral LN+) - 102/125 were posterior/posterolateral, 18 were both anterior/posterior, and 5 were anterior only - 79 primary tumors involved the base, while 46 were located primarily in the apex-mid gland - 13 of 16 CA with LN+, but without EPE or SVI, were predominantly in the apex-mid gland. CONCLUSIONS: LN+ cases are overwhelmingly associated with large volume, high grade, high stage (> pT3a) disease and LVI. Interestingly, one-third of LN+ occur contralateral to the dominant RP cancer. In this series, LN+ were infrequently associated with anteriordominant tumors. Organ-confined LN+ cases were predominantly situated in the apex-mid gland. Source of Funding: None
763 WHAT ARE THE OUTCOMES OF RADICAL PROSTATECTOMY FOR HIGH-RISK PROSTATE CANCER? Edward M. Schaeffer*, Stacy Loeb, Patrick C. Walsh, Elizabeth B. Humphreys, Bruce J. Trock, Baltimore, MD INTRODUCTION AND OBJECTIVE: Despite considerable stage migration associated with widespread PSA screening, as many as 1/3 of incident prostate cancers have high-risk features. These patients are often treated with combined radiation and androgen deprivation therapy, and less is known about the long-term survival in this population after radical prostatectomy. METHODS: From 1992 to 2008, 175 men underwent radical prostatectomy by a single surgeon with D’Amico high-risk prostate cancer (clinical stage qT2c, biopsy Gleason score 8 to 10, or PSA >20 ng/ml). In this population, we examined the rates and predictors of biochemical progression, metastatic disease and cancer-specific mortality. RESULTS: The median age was 59 years (range, 38-71), and median follow-up was 8 years (range, 1-16). The D’Amico high-risk criteria included 63 (36%) of men with a biopsy Gleason score of 8 to 10, 66 (38%) with clinical stage qT2c, and 58 (33%) with preoperative PSA >20 ng/ml (6% of men had more than 1 high risk factor). At radical prostatectomy, 63 (36%) had organ-confined disease, whereas extracapsular extension and seminal vesicle invasion were present in 79 (45%) and 8 (5%), respectively. Positive surgical margins were reported in 32 (18%) and lymph node metastases in 25 (14%). At 10 years, biochemical recurrence-free survival was 68%, metastasis-free survival was 84%, and prostate cancer-specific survival was 92% (Figure). In addition, the 10-year rate of freedom from any hormonal therapy was 71%. Of the high-risk criteria, a biopsy Gleason score of 8-10 (vs. a7) was the strongest independent predictor of all outcomes, with hazard ratio and p-value of 3.17 (p=0.027), 4.19 (p=0.015), and 6.57 (p=0.011) for biochemical recurrence, metastases, and prostate cancer death, respectively. CONCLUSIONS: National data suggest that radical prostatectomy may be underutilized for the management of high-risk clinically localized prostate cancer. Our data suggest that surgical treatment can result in long-term progression-free survival in a subset of carefully selected highrisk men. Further prospective studies are warranted to directly compare the outcomes of radical prostatectomy versus combined radiation and hormonal therapy in high-risk patients.
273
Source of Funding: None
764 RADIATION THERAPY AFTER RADICAL PROSTATECTOMY: IMPACT ON METASTASES AND SURVIVAL Stephen A Boorjian*, Rockledge, PA; R. Jeffrey Karnes, Paul L Crispen, Laureano J Rangel, Eric J Bergstralh, Michael L Blute, Rochester, MN INTRODUCTION AND OBJECTIVE: Although secondary local treatment with radiation therapy (RT) has been shown to reduce the risk of biochemical progression (BCR) following radical prostatectomy (RRP), the impact of RT after RRP on the endpoints of metastases and death from prostate cancer has been less well established. Here, then, we evaluated the impact of adjuvant (ART) and salvage (SRT) radiotherapy on clinical disease progression and mortality. METHODS: We evaluated 13,308 consecutive patients who underwent RRP at the Mayo Clinic between 1987-2003. Patients who received ART were matched based on clinicopathological features to patients who did not receive ART (controls) in a 2:1 case-control ratio. Postoperative survival was estimated using the Kaplan-Meier method and compared using the log-rank test. A second cohort of men who experienced BCR following RRP was separately evaluated. Cox proportional hazard regression models were used to analyze the impact of SRT on disease progression and survival in this group. RESULTS: We identified 361 patients who received ART following RRP. Median postoperative follow-up in this cohort was 11.0 years (range 1.8-19.7). A total of 131 and 386 patients from the ART and control groups, respectively, experienced BCR, 9 and 125 patients had LR, 34 and 68 patients relapsed systemically, and 76 and 174 patients died, with 17 and 42 patients dying of prostate cancer. ART was associated with significantly improved 10-year BCR-free survival (63% vs. 45%, p<0.001), local recurrence (LR)-free survival (97% vs. 82%, p<0.001), and a decreased need for salvage androgen deprivation therapy (ADT) (17% vs. 28%, p=0.002), but did not impact systemic progression (SP) (p=0.94) or prostate cancer death (p=0.43). Meanwhile, of 2,657 patients who experienced BCR after RRP, 856 (32.3%) received SRT. Median PSA at SRT was 0.8 ng/ml, and median follow-up after SRT was 5.9 years (range 0-19). On multivariate analysis, SRT significantly reduced the risks of LR (HR 0.12; 95% CI 0.06-0.26; p<0.0001), delayed ADT (HR 0.63; 95% CI 0.55-0.74; p<0.001), and SP (HR 0.30; 95% CI 0.160.56; p=0.0002), but did not impact mortality (HR 1.06; 95% CI 0.791.42; p=0.70). CONCLUSIONS: Both ART and SRT provide durable local control, improve long-term BCR-free survival, and decrease the need for delayed ADT. SRT was further associated with a decreased rate of SP, but neither ART nor SRT improved survival. These results must be weighed against the potential morbidity of postoperative RT in counseling patients. Source of Funding: None