Adjuvant and salvage radiotherapy following radical prostatectomy

Adjuvant and salvage radiotherapy following radical prostatectomy

S450 I. J. Radiation Oncology 2189 ● Biology ● Physics Volume 60, Number 1, Supplement, 2004 The Impact of the Percent of Positive Prostate Biops...

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S450

I. J. Radiation Oncology

2189

● Biology ● Physics

Volume 60, Number 1, Supplement, 2004

The Impact of the Percent of Positive Prostate Biopsies on Prostate Cancer-Specific Mortality for Patients with Low or Favorable Intermediate Risk Disease

A. V. D’Amico,1 A. A. Renshaw,2 K. Cote,1 M. Hurwitz,1 C. Beard,1 M. Loffredo,1 M. Chen3 Radiation Oncology, Brigham and Women’s Hospital, Boston, MA, 2Pathology, Brigham and Women’s Hospital, Boston, MA, 3Statistics, University of Connecticut, Storrs, CT

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Purpose/Objective: We investigated whether pre-treatment factors predicted time to prostate cancer-specific mortality (PCSM) following conventional dose and 3-dimensional conformal radiation therapy (3DCRT). Materials/Methods: Between 1988 and 2002, 421 patients with low (PSA 10 ng/ml or less and biopsy Gleason score 6 or less) or favorable intermediate-risk (PSA ⬎ 10 to 15 ng/ml or biopsy Gleason 7 but not both factors) disease underwent 3DCRT (planning target volume dose: 70.4 Gy). Cox regression multivariable analysis was performed to determine whether the PSA level, Gleason score, T-category, or the percent of positive prostate biopsies (% ppb) predicted time to PCSM following 3DCRT. The minimum and median number of biopsy cores obtained was 6 with a range from 6 to 16. Results: At a median follow up of 4.5 years, 117 patients had died and 15 had experienced PCSM. The % ppb was the only significant predictor (P ⫽ 0.03 or less using Cox regression). The relative risk of PCSM following 3DCRT for patients with 50% or more as compared to ⬍ 50% ppb was 10.4 [95% confidence interval (CI): 1.2 to 87; P ⫽ 0.03 using Cox regression], 6.1 [95% CI: 1.3 to 28.6; P ⫽ 0.02 using Cox regression], and 12.5 [95% CI: 1.5 to 107; P ⫽ 0.02 using Cox regression] for patients with a PSA 10 ng/ml or less and Gleason score 6 or less, a PSA 10 ng/ml or less and Gleason score 7 or less, and a PSA 15 ng/ml or less and Gleason score 6 or less respectively. By 5 years following 3DCRT, up to 9% as compared to ⬍ 1% (P ⫽ 0.01 or less using the log rank test) of these patients experienced PCSM as shown in the table if they had 50% or more as compared to ⬍ 50% ppb respectively. Conclusions: 3DCRT dose escalation or the addition of hormonal therapy to conventional dose (i.e. 70 Gy) 3DCRT should be considered in the management of patients with low or favorable intermediate-risk disease and at least 50% positive biopsies.

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Adjuvant and Salvage Radiotherapy Following Radical Prostatectomy

J. P. Kirkpatrick,1,2 B. Calingaert,3 R. W. Clough,1 J. R. Oleson,1,2 B. P. Quaranta,1 C. A. Hahn,1 G. S. Montana,1,2 S. S. Ingram,1,2 M. S. Anscher1 1 Radiation Oncology, Duke University Medical Center, Durham, NC, 2Radiation Oncology, Durham VA Medical Center, Durham, NC, 3Biostatistics and Bioinformation, Duke University Medical Center, Durham, NC Purpose/Objective: To identify the disease and treatment characteristics associated with outcome in patients undergoing adjuvant or salvage radiotherapy (RT) after radical prostatectomy (RP). Materials/Methods: This is a retrospective review of 237 men who were treated with definitive adjuvant or salvage radiotherapy at Duke University Medical Center and the Durham VA Medical Center between 1990 and 2002, following RP. Adjuvant RT was defined by a PSA ⱕ 0.1 immediately prior to the initiation of RT. Progression-free survival (PFS) was calculated from the date of completion of RT to either the date midway between the PSA nadir and the first of three successive rises in PSA or the date of the detection of locally advanced or metastatic disease (whichever occurred first.) Patients who never exhibited a PSA decrease following RT were considered to have failed at time zero. PFS and overall survival (OS) curves were generated by the Kaplan-Meier method. The association of patient/tumor characteristics (age, pathologic T stage, surgical margin, seminal vesicle invasion, extracapsular extension, Gleason score and pre-operative and pre-RT PSA) and treatment factors (interval between RP and RT, radiation dose, adjuvant vs. salvage RT, and 2D vs. 3D planning) with outcome was determined by univariate and multivariate Cox proportional-hazards analyses. Results: The median age for the entire group was 64 years with a median pre-operative PSA 10.7 ng/ml (range 1.5–200 ng/ml), median Gleason Score 7 (3– 6 33%, 7 44%, 8 –10 21%, unknown 2%) and median pathologic T stage of T3 (T1/T2 16%, T3 79%, T4 1%, TX 3%). At surgery, surgical margins were positive in 78%, seminal vesicle invasion present in 31% and extracapsular extension positive in 58% of patients. The median interval from surgery to RT was 11.5 months. 57% of the patients were treated using 2D technique and the remaining 43% received 3D conformal RT. All patients were treated with a 4-field box technique with a median dose of 6600 cGy (range 5490 –7000 cGy.) Thirty-six patients (15%) underwent adjuvant RT and 182 patients (77%) received salvage RT; in 19 patients (8%) no post-operative/pre-RT PSA was available. Forty-nine patients received hormonal therapy prior to failure (10 in the adjuvant and 39 in the salvage RT group) and these patients were excluded from the outcome analyses. Median follow-up was 3.6 years. At the time of analysis, 62% of men were alive without evidence of disease, 27% were alive with disease, 3% were dead without evidence of disease and 7% were dead with disease. Of the 76 post-RT failures, the first sign of failure was rising PSA in 62, distant metastases in 12 and local recurrence in 2 patients. For all patients considered together, 5-year PFS and OS were 57 and 88 % respectively. For the adjuvant vs. salvage groups, 5-year PFS were 58 vs. 52%, respectively (p ⫽ 0.036). 5-yr OS did not differ significantly between the adjuvant and salvage RT groups (92 vs.86%, p ⫽ 0.47). On univariate analysis, pathologic T stage (Hazard ratio [HR] ⫽ 3.36, p ⫽ 0.002), salvage vs. adjuvant RT (HR ⫽ 2.95, p ⫽ 0.036), 3D vs. 2D planning (HR ⫽ 0.55, p ⫽ 0.035), extracapsular extension (HR ⫽ 1.86, p ⫽ 0.018), Gleason score (HR ⫽ 1.24, p ⫽ 0.017) and seminal vesicle invasion (HR ⫽ 1.61, p ⫽ 0.044) were significant

Proceedings of the 46th Annual ASTRO Meeting

factors associated with PFS. When the pathologic T stage was included in the multivariate analysis of PFS, no other factor attained statistical significance. Conclusions: This is the largest single-institution analysis to date of post-prostatectomy radiotherapy. The majority of patients treated with either adjuvant or salvage RT following RP were free from progression at 5 years after RT. No factor in addition to pathologic T stage was significantly associated with improved PFS on multivariate analysis. However, there is a suggestion of an advantage in PFS for early adjuvant treatment vs. delayed salvage therapy and for 3D vs. 2D planning.

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Hormonal Therapy Reduces the Risk of Post-Implant Urinary Retention in Symptomatic Prostate Cancer Patients with Glands Larger Than 50 cc

D. T. Marshall,1 N. N. Stone,2,1 J. J. Stone,1 J. Cesaretti,1 R. G. Stock1 Radiation Oncology, Mount Sinai School of Medicine, New York, NY, 2Urology, Mount Sinai School of Medicine, New York, NY 1

Purpose/Objective: Controversy exists regarding the optimal management of men with prostate glands ⬎ 50 cc who undergo permanent seed implantation. Previous studies have suggested that pre-treatment with hormonal therapy (HT) may actually increase the risk of urinary retention or urinary symptoms when compared to patients not receiving HT. Unfortunately, no prior studies have analyzed the influence of urinary symptoms prior to the initiation of HT. In this study we compare a cohort of men with prostate glands ⬎ 50 cc treated by implant alone to a similar cohort also treated with pre-implant HT in whom the pre-HT data was available for analysis. Materials/Methods: 404 patients with Gleason score ⬍7, PSA ⬍10, T1c-T2b prostate cancer were treated with implant alone (n ⫽ 176) or with 3 months of HT (n ⫽ 228) prior to implant. 338 (84%) received I-125 and 66 Pd-103. Prostate volumes (PV) and international prostate symptom scores (IPSS) were determined prior to initiation of HT and just before implantation. IPSS were collected at 3, 6 and every 6 months post implant. Urinary retention (UR) was designated if a patient required reinsertion of a urinary catheter post-implant. PSA failure was determined by ASTRO definition. The effects of hormonal therapy on prostate size, urinary retention and IPSS scores were tested by Chi-Square method. Survival (PSA) was calculated by Kaplan Meier method. Results: Mean follow-up was 36 months (range 1–139). Mean pre-treatment gland size was 74 cc (range 50 –151) in the group that received HT and 60.3 cc (range 50 –117) in the group that did not (p ⫽ 0.037). In the HT group, PV decreased to a mean of 48.6 cc (mean reduction 35%, p ⬍ 0.001) prior to implantation. UR occurred in 11.4% in those treated with HT vs. 11.9% without HT (p ⫽ 0.84). UR risk did not increase with increasing PV. The mean maximum post implant IPSS score was 16.7 without HT vs. 15.6 with HT (p ⫽ 0.261). In patients with initial IPSS ⬎ 15, UR occurred in 4/12 (33.3%) of those not receiving HT vs. 0/27 in the HT group (p ⫽ 0.002, RR 4.4, 95% CI 2.1– 8.1). 24 month mean IPSS remained elevated (10.4 vs. 5.9 pre-implant, p ⬍ 0.001) for those without HT, while it returned to baseline in the HT patients (8.2 vs. 9.7, p ⫽ 0.06). Urinary QOL also remained elevated in the non HT patients (1.3 vs. 2.3, p ⬍ 0.001) compared to the HT group (1.2 vs. 1.7, p ⫽ 0.195). 6-year PSA failure free rates were similar for each group (93%). Conclusions: The data from this study confirms the benefit of using pre-implant HT in patients with PV ⬎ 50 cc. HT mostly benefits the subgroup of patients who present with symptomatic prostatism and an IPSS ⬎ 15. Minor benefit was also noted in 24 month IPSS and QOL scores in the HT group. PSA freedom from failure was no different in the two groups, confirming the lack of benefit for HT in improving disease control in low risk patients.

2192

The Dose Response Characteristics of Low and Intermediate Risk Prostate Cancer Treated with External Beam Radiotherapy

R. Cheung,1 S. Tucker,2 A. Lee,1 R. de Crevoisier,1 L. Dong,3 A. Kamat,4 L. Pisters,4 D. Kuban1 Radiation Oncology, UT MD Anderson Cancer Center, Houston, TX, 2Biostatistics and Applied Mathematics, UT MD Anderson Cancer Center, Houston, TX, 3Radiation Physics, UT MD Anderson Cancer Center, Houston, TX, 4Urology, UT MD Anderson Cancer Center, Houston, TX

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Purpose/Objective: In this era of dose escalation, the benefit of higher doses for low-risk prostate cancer remains controversial. For the intermediate risk patients, the literature suggests a benefit from the higher doses. However, the quantitative characterization of the benefit for these patients is scarce. Here we investigated the radiation dose response of PSA control probability in low-risk and intermediate-risk prostate cancer patients treated with radiotherapy alone. Further, we investigated the differences in dose response using the ASTRO definition versus an alternative biochemical failure definition. Materials/Methods: This study included 235 low-risk and 387 intermediate-risk prostate cancer patients treated with external beam radiotherapy without hormonal treatment from 1987 to 1998. The low-risk patients had 1992 AJCC DRE stage ⱕ T2a and PSA ⱕ10 ng/mL and biopsy Gleason score ⱕ6. The intermediate-risk patients had one or more of the following: Stage T2b-c, 20ng/mL ⱖ PSA ⬎10 ng/mL or Gleason score 7; and without any of the following high-risk features: Stage ⱖ T3, PSA ⬎20 ng/mL or Gleason score ⱖ8. The logistic models were fitted to the data at various time points after treatment, and the dose response parameters were estimated. We used two biochemical failure definitions. The ASTRO PSA failure was defined as three consecutive PSA rises with the time to failure backdated to the mid-point between the nadir and the first rise. We also used an alternative biochemical failure definition: PSA rise ⱖ2ng/mL above the current nadir PSA (CN⫹2). The failure date was defined as the time at which the event occurred. Local, nodal, distant relapses and use of salvage hormone were also failures. Results: Based on the ASTRO definition, at 5 years post radiotherapy, the dose required for 50% tumor control, TCD50 (95% C.I.), for low-risk patients is 57.3 (47.6 to 67.0) Gy. The ␥50 (95% C.I.) is 1.4 (⫺0.1 to 2.9) around 57Gy. There is a statistically significant dose response using the ASTRO definition. However, there is no dose response using CN⫹2 definition for these low-risk patients. For the intermediate-risk patients, using ASTRO definition, the TCD50 is 67.5 (65.5 to 69.5) Gy and the ␥50 (95% C.I.) is 2.2 (1.1 to 3.2) around TCD50. Using CN⫹2 definition, the TCD50 is 57.8(49.8 to 65.9) Gy and the ␥50 (95% C.I.) is 1.4(0.2 to 2.5). Recursive partitioning analysis identified two subgroups within the low-risk group as well as the

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