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M V Pilepich

Publications and source records attributed to M V Pilepich.

At least 19 recordsLinked to original sources
PubMed2001

Phase III radiation therapy oncology group (RTOG) trial 86-10 of androgen deprivation adjuvant to definitive radiotherapy in locally advanced carcinoma of the prostate.

PURPOSE: To test the hypothesis that androgen ablation before and during radiotherapy for locally advanced carcinoma of the prostate may, by reducing tumor bulk and enhancing tumor cell kill, improve locoregional control and ultimately survival. METHODS AND MATERIALS: The study was conducted from 1987 to 1991. Eligible patients were those with bulky tumors (T2--T4) with or without pelvic lymph node involvement and without evidence of distant metastases. They were randomized to receive goserelin, 3.6 mg every 4 weeks; and flutamide, 250 mg t.i.d. for 2 months before radiation therapy and during radiation therapy (Arm I), or radiation therapy alone (Arm II). Of 471 randomized patients, 456 were evaluable: 226 on Arm I and 230 on Arm II. RESULTS: As of November 1999, the median follow-up has reached 6.7 years for all patients and 8.6 years for alive patients. At 8 years, androgen ablation has been associated with an improvement in local control (42% vs. 30%, p = 0.016), reduction in the incidence of distant metastases (34% vs. 45%, p = 0.04), disease-free survival (33% vs. 21%, p = 0.004), biochemical disease-free survival = PSA <1.5 (24% vs. 10%, p < 0.0001), and cause-specific mortality (23% vs. 31%, p = 0.05). However, subset analysis indicates that the beneficial effect of short-term androgen ablation appears preferentially in patients with Gleason score 2--6. In that population, there is a highly significant improvement in all endpoints, including survival (70% vs. 52%, p = 0.015). In patients with Gleason 7--10 tumors, the regimen has not resulted in a significant enhancement in either locoregional control or survival. CONCLUSION: In patients with Gleason score 2--6 carcinoma of the prostate, a short course of androgen ablation administered before and during radiotherapy has been associated with a highly significant improvement in local control, reduction in disease progression, and overall survival.

Adenocarcinoma↗
PubMed2001

Updated results of the phase III Radiation Therapy Oncology Group (RTOG) trial 85-31 evaluating the potential benefit of androgen suppression following standard radiation therapy for unfavorable prognosis carcinoma of the prostate.

PURPOSE: To determine the potential advantage of androgen ablation following standard external-beam radiation therapy in patients with locally advanced (clinical or pathologic T3; clinical or pathologic node positive) carcinoma of the prostate. METHODS AND MATERIALS: In 1987 the RTOG initiated a Phase III trial of long-term adjuvant goserelin in definitively irradiated patients with carcinoma of the prostate. A total of 977 patients were accrued to the study of which 945 remain analyzable: 477 on the adjuvant hormone arm (Arm I); and 468 on the radiation only arm (Arm II) with hormones initiated at relapse. The initial results were reported in the Journal of Clinical Oncology in 1997. RESULTS: With a median follow up of 5.6 years for all patients and 6.0 years for living patients local failure at 8 years was 23% for Arm I and 37% for Arm II (p < 0.0001). Distant metastasis was likewise favorably impacted with the immediate use of hormonal manipulation with a distant metastasis rate in Arm I of 27% and 37% in Arm II (p < 0.0001). Disease-free survival (NED survival) and NED survival with PSA of 1.5 ng/mL (bNED) or less were both statistically significant in favor of the immediate hormone arm (both p < 0.0001). Cause-specific failure was not statistically different with a cause-specific failure of 16% for Arm I and 21% in Arm II (p = 0.23). Overall survival was likewise not statistically different between two arms, with a 49% overall survival at 8 years in Arm I and 47% in Arm II (p = 0.36). Subset analysis of centrally reviewed Gleason 8-10 patients who did not undergo prostatectomy showed that for patients receiving radiation therapy plus adjuvant hormones there was a statistically significant improvement in both absolute (p = 0.036) and cause-specific survival (p = 0.019). CONCLUSIONS: Use of long-term adjuvant androgen deprivation in addition to definitive radiation therapy results in a highly significant improvement in regards to local control, freedom from distant metastasis, and biochemical free survival in unfavorable prognosis patients with carcinoma of the prostate.

Androgen Antagonists↗
PubMed2000

Randomized phase III study comparing Best Supportive Care to Biafine as a prophylactic agent for radiation-induced skin toxicity for women undergoing breast irradiation: Radiation Therapy Oncology Group (RTOG) 97-13.

PURPOSE: To determine if Biafine compared to Best Supportive Care (BSC) is effective in minimizing or preventing radiation-induced dermatitis in women undergoing breast irradiation. METHODS AND MATERIALS: Patients were randomized between Biafine (n = 83) vs. BSC (n = 89). The institutions identified preference for BSC at the time of randomization. A no-treatment arm was allowed (16% received no treatment). Patients were instructed to apply randomized product three times a day, but not within 4 h of their daily RT session. Application began following their first radiation treatment and continued 2 weeks postradiation. Skin dermatitis was scored weekly utilizing the RTOG and ONS (Oncology Nursing Society) skin toxicity scales, a weekly patient satisfaction and quality-of-life questionnaire. RESULTS: Using the RTOG toxicity scale there was no overall difference for maximum dermatitis during RT between Biafine and BSC (p = 0.77). There was no difference in maximum toxicity by arm or breast size. There was an interaction between breast size and toxicity, with large-breasted women exhibiting more toxicity. Large-breasted women receiving Biafine were more likely to have no toxicity 6 weeks post RT. CONCLUSION: There was no overall difference between BSC and Biafine in the prevention, time to, or duration of radiation-induced dermatitis.

Adult↗
PubMed2000

Predicting long-term survival, and the need for hormonal therapy: a meta-analysis of RTOG prostate cancer trials.

PURPOSE: To assess the impact of short-term and long-term androgen suppression on the disease-specific and overall survival of 2200 men treated with radiotherapy on one of 5 prospective randomized trials when stratified by prognostic risk groups. METHODS AND MATERIALS: Between 1975 and 1992, 2742 men were treated for clinically localized prostate cancer on one of 5 consecutive prospective Phase III randomized trials. Patients were selected for this analysis if they were deemed evaluable and eligible for the trial, and if follow-up information was available. For this analysis patients were stratified into four previously described prognostic risk groups: Group 1 patients had a Gleason score (GS) = 2-6, and T1-2Nx; Group 2: GS = 2-6, T3Nx; or GS = 2-6, N+, or GS = 7, T1-2Nx; Group 3: T3Nx, GS = 7; or N+, GS = 7, or T1-2Nx, GS = 8-10; and Group 4 patients were T3Nx, GS = 8-10, or N+, GS = 8-10. The median pretreatment prostate-specific antigen (PSA) was 25 ng/ml for the 434 evaluable patients for whom this information was available. The median follow-up times for patients treated on early studies exceeded 11 years, and for more recent studies 6 years. RESULTS: Risk group 2 patients with "bulky" or T3 disease appeared to have a disease-specific survival benefit at 8 years with the addition of 4 months of goserelin and flutamide. Group 3 and 4 patients were noted to have an approximately 20% higher survival at 8 years with the addition of long-term hormonal therapy (p < or =0.0004). CONCLUSIONS: Based on this meta-analysis of RTOG trials, subsets of patients can be identified who either do not appear to benefit from the use of hormonal therapy, benefit from short-term hormonal therapy, or who benefit only from long-term hormonal therapy. These observations should be confirmed by prospective randomized trials before they can be considered conclusive. In the meantime, however, these observations provide rational guidelines for deciding who should receive hormonal therapy and for how long.

Androgen Antagonists↗
PubMed2000

Four prognostic groups predict long-term survival from prostate cancer following radiotherapy alone on Radiation Therapy Oncology Group clinical trials.

PURPOSE: Gleason score (GS), T stage, and pathologic lymph node status have been described as major independent predictors of death due to prostate cancer in men treated with external beam radiotherapy (XRT). In this analysis we combine these three factors to define prognostic subgroups that correlate with disease-specific survival (DSS) death from prostate cancer. METHODS AND MATERIALS: Men entered on one of four Radiation Therapy Oncology Group (RTOG) Phase III randomized trials between 1975 and 1992, for clinically localized prostate cancer (CAP) (n = 1557), were selected for this analysis. Patients were included if: 1) they were evaluable, and eligible for the trial; 2) they received no hormonal therapy with their initial treatment; and 3) follow-up was available. For this study a DSS event was declared if: 1) death was certified as due to CAP; 2) death was due to complications of treatment; or 3) death was from unknown causes with active malignancy. The median follow-up for patients treated on early and late RTOG studies exceeded 11 and 6 years respectively. Subgroups were identified based on their pretreatment GS, T-stage, and lymph node such that patients with similar risk of dying from prostate cancer were combined. RESULTS: By combining patients with similar DSS, four subgroups were identified. Risk Group 1 patients had a GS = 2-6, and T1-2Nx; Group 2: GS = 2-6, T3Nx; or GS = 2-6, N+, or GS = 7, T1-2Nx; Group 3: T3Nx, GS = 7; or N+, GS = 7, or T1-2Nx, GS = 8-10; and Group 4 patients were T3Nx, GS = 8-10, or N+, GS = 8-10. The 5-, 10-, and 15-year DSS was 96%, 86%, and 72%; 94%, 75%, and 61%; 83%, 62%, and 39%; and 64%, 34%, and 27% for Groups 1 through 4, respectively. CONCLUSIONS: Recognition of these four risk groups provides a basis for estimating the long-term DSS for men treated with XRT alone and should facilitate the design of future prospective randomized trials.

Aged↗
PubMed1999

Long-term survival after radiotherapy alone: radiation therapy oncology group prostate cancer trials.

PURPOSE: We assess the relative importance of the several pretreatment characteristics in predicting death from prostate cancer in patients treated with curative intent with external beam radiotherapy alone. MATERIALS AND METHODS: Patients entered on 4 prospective phase III randomized trials conducted by the Radiation Therapy Oncology Group between 1975 and 1992 were selected for this analysis if they were deemed evaluable and eligible for the trial, they had received no hormonal therapy with initial treatment and followup information was available. A disease specific survival event was declared if death was certified as due to prostate cancer, complications of treatment or unknown causes with clinically active malignancy. Median followup for patients treated on early and late studies exceeded 11 and 6 years, respectively. RESULTS: Most of the patients (1,557) had tumors clinically staged as T3 (59%), and 87 (36%) with clinically staged T1-2 tumors had pathologically positive lymph nodes. On multivariate analysis Gleason score, clinical stage and nodal status were associated with a less favorable overall and disease specific survival, whereas others factors, such as age and race, were not. A Gleason score of 8 to 10 was associated with a high risk of dying of prostate cancer in the first 5 years (risk ratio 20.0, p = 0.0001). The 10-year disease specific survival for patients with a Gleason score of 2 to 5, 6 to 7 and 8 to 10 was 87, 75 and 44%, respectively, following radiotherapy. Based on published reports these rates were higher than expected with observation alone. CONCLUSIONS: In the first 10 years Gleason score was the single most important predictor of death. Gleason score should be incorporated into the current clinical staging system.

Aged↗
PubMed1999

Does androgen suppression enhance the efficacy of postoperative irradiation? A secondary analysis of RTOG 85-31. Radiation Therapy Oncology Group.

OBJECTIVES: To evaluate the effect of immediate androgen suppression in conjunction with standard external beam irradiation (RT) versus RT alone on a group of men after prostatectomy who had indications for adjuvant treatment. METHODS: A national prospective randomized trial (Radiation Therapy Oncology Group [RTOG] 85-31) comparing standard external beam RT plus immediate androgen suppression versus external beam RT alone with delayed hormonal treatment at relapse was initiated for patients with locally advanced adenocarcinoma of the prostate. One hundred thirty-nine of the patients in this trial had indications for adjuvant treatment after prostatectomy (eg, capsular penetration, seminal vesicle involvement). Seventy-one of the patients received RT with immediate androgen suppression (luteinizing hormone-releasing hormone [LHRH] agonist); 68 patients received RT alone with hormonal manipulation instituted only at the time of relapse. RESULTS: With a median follow-up of 5 years, the estimated progression-free survival rate (failure defined as prostate-specific antigen [PSA] greater than 0.5 ng/mL) was 65% for the men who received combination therapy and 42% for those treated by RT alone with hormones reserved for relapse (P = 0.002). Differences in the rates of freedom from biochemical relapse were observed when failure was defined as PSA of 1.0 to 3.9 ng/mL (71% versus 46%; P = 0.008) and PSA greater than 4.0 ng/mL (76% versus 55%; P = 0.05), respectively. No differences were observed between the groups with respect to the end points of local control, distant failure, and overall survival. The use of immediate androgen suppression (ie, LHRH agonists) and the absence of pathologic nodal involvement were independently associated with prolongation of freedom from biochemical relapse by multivariate analysis. CONCLUSIONS: Patients with prostate cancer and indications for postoperative RT should be considered for combined RT and hormonal manipulation. Because statistically significant advantages for this experimental approach could not be defined for all end points studied (in particular, overall survival), efforts should be made to enroll these patients in the recently activated RTOG trial (96-01) comparing RT plus placebo to the combination of RT plus Casodex in the postoperative setting.

Adenocarcinoma↗
PubMed1998

Ten-year outcomes for pathologic node-positive patients treated in RTOG 75-06.

PURPOSE: This study was conducted to see what fraction of prostate cancer patients with biopsy-proven nodes are free of cancer 10 years after radiation treatment. METHODS AND MATERIALS: RTOG protocol #75-06 included 90 patients with biopsy-proven pelvic nodal involvement treated with radiation. They have been continuously follow-up since treatment. When feasible, current prostate-specific antigen (PSA) levels have been solicited from patients clinically cancer-free (no evidence of disease, NED) at 10 years, to confirm cure. RESULTS: The 10-year survival was 29%, the 10-year clinical NED survival 7%. PSA levels were obtained in 2 of 5 10-year clinical NED patients, they were both less than 0.8 ng/ml. The 2 proven cures were both clinical stage T-3, Gleason Score 6 and 8, and had 2 and 1 positive nodes, respectively. Multivariate analysis showed Gleason sum was significantly associated with clinical survival without disease. CONCLUSION: A small fraction of node-positive patients are cured at 10-year follow-up by radiation therapy (2 of 90 with PSA +3 of 90 by clinical endpoints). Innovative treatment programs should be directed at node-positive patients in an effort to improve the fraction cured.

Disease-Free Survival↗
PubMed1998

Impact of surgical staging in evaluating the radiotherapeutic outcome in RTOG #77-06, a phase III study for T1BN0M0 (A2) and T2N0M0 (B) prostate carcinoma.

PURPOSE: To evaluate survival and time to metastatic disease in patients treated for localized prostatic carcinoma in a Phase III radiotherapy (RT) protocol, Radiation Therapy Oncology Group (RTOG) 77-06. Patients with T18N0M0 (A2) or T2N0M0 (B) disease after lymphangiogram (LAG) or staging laparotomy (SL) were randomized between prophylactic radiation to the pelvic lymph nodes and prostatic bed vs. prostatic bed alone. The outcome of both treatment arms, as well as a comparison of the LAG group, to that of the SL group, are updated. METHODS AND MATERIALS: A total of 449 eligible males were entered into RTOG protocol 7706 between 1978 and 1983. Lymph node staging was mandatory but at the physician's discretion; 117 (26%) patients had SL, while 332 (74%) had LAG. Follow-up was a median of 12 years and a maximum of 16 years. For those randomized to receive prophylactic pelvic lymph nodal irradiation, 45 Gy of megavoltage RT was delivered via multiple portals in 4.5-5 weeks, while all patients received 65 Gy in 6.5-8 weeks to the prostatic bed. RESULTS: There was no significant difference in survival whether treatment was administered to the prostate or prostate and pelvic lymph nodes. The SL group had greater 12-year survival than the LAG group (48% vs. 38%, p = 0.02). Disease-free survival was statistically significant, with 38% for the SL group vs. 26% for the LAG group (p = 0.003). Bone metastasis was less common in the SL group (14%) than the LAG group (27%) (p = 0.003). CONCLUSION: At 12-year median follow-up, there still was no survival difference in those patients treated prophylactically to the pelvic nodes and prostatic bed vs. the prostatic bed alone. Those patients not surgically staged with only LAG for lymph node evaluation were less accurately staged, as reflected by a statistically significant reduced survival and earlier metastases.

Aged↗
PubMed1997

Androgen suppression plus radiation versus radiation alone for patients with D1 (pN+) adenocarcinoma of the prostate (results based on a national prospective randomized trial, RTOG 85-31). Radiation Therapy Oncology Group.

PURPOSE: To evaluate the effect of immediate androgen suppression in conjunction with standard external beam irradiation vs. radiation alone on a group of pathologically staged lymph node-positive patients with adenocarcinoma of the prostate. METHODS AND MATERIALS: A national prospective randomized trial (RTOG 85-31) of standard external beam irradiation plus immediate androgen suppression vs. external beam irradiation alone was initiated in 1985 for patients with locally advanced adenocarcinoma of the prostate. One hundred seventy-three of the patients in this trial had biopsy-proven pathologically involved lymph nodes. Ninety-eight of these patients received radiation plus the immediate androgen suppression (LHRH agonist), while 75 received radiation alone with hormonal manipulation instituted at the time of relapse. RESULTS: With a median followup of 4.9 years, estimated progression-free survival with PSA < 1.5 ng/ml at 5 years was 55% for the patients who received radiation plus immediate LHRH agonist vs. 11% of the patients who received radiation alone with hormonal manipulation at relapse (p = 0.0001). Because all of these patients had locally advanced disease (i.e., pathologically positive lymph nodes), stage does not explain this difference in outcome, and Gleason grade was not statistically different between the two groups. Estimated absolute survival at 5 years for the radiation and LHRH group was 73 vs. 65% for the radiation alone group who received androgen suppression at relapse. Estimated disease-specific survival at 5 years was 82% for the radiation and immediate LHRH agonist group and 77% for the radiation-alone group. CONCLUSION: Patients with adenocarcinoma of the prostate and pathologically involved pelvic lymph nodes (pN+ or clinical stage D1) should be seriously considered for external beam irradiation plus immediate hormonal manipulation over radiation alone with hormonal manipulation at the time of relapse.

Adenocarcinoma↗
PubMed1997

p53 status and prognosis of locally advanced prostatic adenocarcinoma: a study based on RTOG 8610.

BACKGROUND: The p53 tumor suppressor gene (also known as TP53) is one of the most frequently mutated genes in human cancer. Several studies have shown that p53 mutations are infrequent in prostate cancer and are associated with advanced disease. PURPOSE: We assessed the prognostic value of identifying abnormal p53 protein expression in the tumors of patients with locally advanced prostate cancer who were treated with either external-beam radiation therapy alone or total androgen blockade before and during the radiation therapy. METHODS: The study population consisted of a subset of patients entered in Radiation Therapy Oncology Group protocol 8610 ("a phase III trial of Zoladex and flutamide used as cytoreductive agents in locally advanced carcinoma of the prostate treated with definitive radiotherapy"). Immunohistochemical detection of abnormal p53 protein in pretreatment specimens (i.e., needle biopsies or transurethral resections) was achieved by use of the monoclonal anti-p53 antibody DO7; specimens in which 20% or more of the tumor cell nuclei showed positive immunoreactivity were considered to have abnormal p53 protein expression. Associations between p53 protein expression status and the time to local progression, the incidence of distant metastases, progression-free survival, and overall survival were evaluated in univariate (logrank test) and multivariate (Cox proportional hazards model) analyses. Reported P values are two-sided. RESULTS: One hundred twenty-nine (27%) of the 471 patients entered in the trial had sufficient tumor material for analysis. Abnormal p53 protein expression was detected in the tumors of 23 (18%) of these 129 patients. Statistically significant associations were found between the presence of abnormal p53 protein expression and increased incidence of distant metastases (P = .04), decreased progression-free survival (P = .03), and decreased overall survival (P = .02); no association was found between abnormal p53 protein expression and the time to local progression (P = .58). These results were independent of the Gleason score and clinical stage. A significant treatment interaction was detected with respect to the development of distant metastases: Among patients receiving both radiation therapy and hormone therapy, those with tumors exhibiting abnormal p53 protein expression experienced a reduced time to the development of distant metastases (P = .001); for patients treated with radiation therapy alone, the time to distant metastases was unrelated to p53 protein expression status (P = .91). CONCLUSIONS: Determination of p53 protein expression status yield significant, independent prognostic information concerning the development of distant metastases, progression-free survival, and overall survival for patients with locally advanced prostate cancer who are treated primarily with radiation therapy. IMPLICATIONS: The interaction of radiation therapy plus hormone therapy and abnormal p53 protein expression may provide a clinical link to experimental evidence that radiation therapy and/or hormone therapy act, at least in part, by the induction of apoptosis (a cell death program) and suggests that this mechanism may be blocked in patients whose tumors have p53 mutations.

Adenocarcinoma↗
PubMed1997

Phase III trial of androgen suppression using goserelin in unfavorable-prognosis carcinoma of the prostate treated with definitive radiotherapy: report of Radiation Therapy Oncology Group Protocol 85-31.

PURPOSE: Although androgen suppression results in a tumor response/remission in the majority of patients with carcinoma of the prostate, its potential value as an adjuvant has not been substantiated. MATERIALS AND METHODS: In 1987, the Radiation Therapy Oncology Group (RTOG) initiated a randomized phase III trial of adjuvant goserelin in definitively irradiated patients with carcinoma of the prostate. A total of 977 patients had been accessioned to the study. Of these, 945 remained analyzable: 477 on the adjuvant arm and 468 on the observation arm. RESULTS: Actuarial projections show that at 5 years, 84% of patients on the adjuvant goserelin arm and 71% on the observation arm remain without evidence of local recurrence (P < .0001). The corresponding figures for freedom from distant metastases and disease-free survival are 83% versus 70% (P < .001) and 60% and 44% (P < .0001). If prostate-specific antigen (PSA) level greater than 1.5 ng is included as a failure (after > or = 1 year), the 5-year disease-free survival rate on the adjuvant goserelin arm is 53% versus 20% on the observation arm (P < .0001). The 5-year survival rate (for the entire population) is 75% on the adjuvant arm versus 71% on the observation arm (P = .52). However, in patients with centrally reviewed tumors with a Gleason score of 8 to 10, the difference in actuarial 5-year survival (66% on the adjuvant goserelin arm v 55% on the observation arm) reaches statistical significance (P = .03). CONCLUSION: Application of androgen suppression as an adjuvant to definitive radiotherapy has been associated with a highly significant improvement in local control and freedom from disease progression. At this point, with a median follow-up time of 4.5 years, a significant improvement in survival has been observed only in patients with centrally reviewed tumors with a Gleason score of 8 to 10.

Adenocarcinoma↗
PubMed1995

Correlation of survival with quantitative tissue staining of prostate specific acid phosphatase in patients with prostate carcinoma by using microscopic image analysis: a preliminary report of correlative studies on RTOG protocols 75-06, 77-06, and 83-07.

PURPOSE: We have previously shown that the intensity (graded semiquantitatively as 1-4+) of tissue prostate-specific acid phosphatase (PSAP) staining determined immunocytochemically in a cohort of prostate carcinoma patients from Radiation Therapy Oncology Group Protocols (RTOG) protocols 75-06 and 77-06 correlated with survival. The extent of this staining was heterogeneous and was estimated. The extent of staining was not found to be significantly associated with survival. We undertook the present quantitative study to see if the improved precision and reliability of measurement of the intensity and extent of prostate specific acid phosphatase staining would confirm and extend our previous observations. METHODS AND MATERIALS: Patient cohorts representative of the entire group were obtained from RTOG 75-06 plus 77-06 and 83-07. The RTOG 77-06 plus 75-06 patients (No-Hormone population) did not receive preradiation hormonal therapy. RTOG 83-07 patients (Prehormone population) received one of two types of preradiation chemical androgen ablation. In this study, histologic slides of tumors were immunocytochemically stained for PSAP by the peroxidase-antiperoxidase (PAP) technique using diaminobenezidene (DAB) as a substrate and hematoxylin as a nuclear counterstain. The intensity and extent of immunocytochemical PSAP staining (IPSAP stain) was quantified using our dual wavelength and batch mode image process technique. RESULTS: Our study of 151 cases confirmed that overall survival of patients in both populations was positively correlated with the intensity and extent of IPSAP stain. Results of the two studies were similar. The statistical significance of the relationship of both extent and intensity was greater in the cohort from protocol 83-07, which was the patient group receiving pretreatment with hormones. In a Cox multiple regression analysis including clinical stage, Gleason and M. D. Anderson grades, and the cohort of patients (Prehormone or No-Hormone group) as covariables, both the intensity and extent of the IPSAP stain significantly correlated with survival along with M. D. Anderson grade of the tumor. CONCLUSION: Quantitative image analysis of the IPSAP stain predicts survival in patients treated with external beam radiotherapy with and without prior hormonal therapy.

Acid Phosphatase↗
PubMed1995

Phase II trial of hormonal cytoreduction with megestrol and diethylstilbestrol in conjunction with radiotherapy for carcinoma of the prostate: outcome results of RTOG 83-07.

PURPOSE: RTOG 83-07 is a Phase II randomized protocol designed to compare the efficacy and toxicity of Megestrol vs. Diethylstilbestrol (DES) used as cytoreductive agents prior to and during radiotherapy. The end points of this study include tumor clearance rate, effect on serum testosterone, loco-regional control, disease-free interval, and survival. METHODS AND MATERIALS: Eligible patients were those with histologically confirmed locally advanced adenocarcinoma, clinical Stage B2 (T2B) and C (T3) without regional lymph node involvement, or with lymph node involvement limited to the pelvis. Patients were stratified by clinical stage, histological grade, and nodal status, and were randomized to receive either Megestrol 40 mg three times per day by mouth, or Diethylstilbestrol 1 mg three times per day by mouth. The drugs were started 2 months prior to initiation of radiotherapy and were continued throughout the radiotherapy course. Radiotherapy consisted of 44-46 Gy, 1.8-2 Gy per day to the regional lymphatics, followed by a boost to the prostate consisting of 20-25 Gy, 1.8-2 Gy per day, to a total of 65-70 Gy. Serum testosterone levels were recorded throughout the treatment course. Tumor response was assessed clinically and radiographically (CT scan). From March 1983 through June 1986 a total of 203 patients were accessioned to the study; 198 were analyzable. RESULTS: Correlation of the incidence of drug-related toxicity and treatment arm assignment revealed a significantly higher incidence of complications in the Diethylstilbestrol (DES) arm. The most prominent were the differences in the incidence of gynecomastia (55% vs. 7%) and fluid retention (21% vs. 6%). The incidence of thromboembolic phenomena was comparable (8% vs. 5% in the Megestrol arm). Patients on the DES arm demonstrated a significantly greater median decrease in testosterone level. Correlation of the treatment arm assignment and the rate of tumor regression and the incidence of complete response revealed no significant difference between the arms. At 7 years, 16% of patients on the Megace arm and 21% of patients on the DES arm manifested evidence of local failure. CONCLUSIONS: The results of the study indicate comparable efficacy (using tumor clearance as an end point) of DES and Megestrol. Although DES appears more effective in suppressing testosterone, it is also associated with a higher incidence of drug-related toxicity.

Adenocarcinoma↗
PubMed1995

Androgen deprivation with radiation therapy compared with radiation therapy alone for locally advanced prostatic carcinoma: a randomized comparative trial of the Radiation Therapy Oncology Group.

OBJECTIVES: Androgen deprivation therapy before and during radiation therapy could, by reducing tumor volume, increase local tumor control, disease-free survival, and overall survival in patients with locally advanced adenocarcinomas of the prostate. METHODS: In a randomized controlled clinical trial, patients with large T2, T3, and T4 prostate tumors, but no evidence of osseous metastasis, were randomized to receive goserelin 3.6 mg subcutaneously every 4 weeks and flutamide 250 mg orally three times daily 2 months before and during the radiation therapy course (Arm I) compared with radiation therapy alone (Arm II). Pelvic irradiation was administered with 1.8 to 2.0 Gy per day to a total dose of 45 +/- 1 Gy followed by a boost to the prostate target volume to a total dose of 65 to 70 Gy. RESULTS: Of 471 randomized patients, 456 were evaluable, 226 on Arm I and 230 on Arm II. With a median potential follow-up of 4.5 years, the cumulative incidence of local progression at 5 years was 46% in Arm I and 71% in Arm II (P < 0.001). The 5-year incidence of distant metastasis on Arms I and II was 34% and 41%, respectively (P = 0.09). Progression-free survival rates including normal prostate-specific antigen (PSA) levels for 396 patients with at least one PSA recorded were 36% in Arm I and 15% in Arm II at 5 years (P < 0.001). At this time, no significant difference in overall survival could be detected (P = 0.7). CONCLUSIONS: Short-term androgen deprivation with radiation therapy results in a marked increase in local control and disease-free survival compared with pelvic irradiation alone in patients with locally advanced carcinoma of the prostate. Long-term surveillance is required to assess effects on overall survival.

Adenocarcinoma↗
PubMed1994

PSA confirmation of cure at 10 years of T1B, T2, N0, M0 prostate cancer patients treated in RTOG protocol 7706 with external beam irradiation.

PURPOSE: This study was done to correlate prostatic specific antigen values with clinical no evidence of disease status for 28 long-term survivors of external beam irradiation from Radiation Therapy Oncology Group Study #77-06, and confirm the clinical observation of cure. METHODS AND MATERIALS: One hundred and four patients in Radiation Therapy Oncology Group 77-06 with T1B T2 N0, M0 with pathologically known negative lymph node status, were previously shown to have a 10 year actuarial outcome equal to radical prostatectomy patients. Of these 104, 28 were 9-13 year survivors with clinically no evidence of disease by physical examination and imaging. RESULTS: Prostatic specific antigen was available or obtained in 17 patients, 15 of the 17 had prostatic specific antigen values of < 3.5 ngm/%, while 11 had values of < 1.5 ngm/%. Depending on which level one selects, 88% or 65% of clinical no evidence of disease 9-13 year survivors have a normal or low prostatic specific antigen. CONCLUSION: Prostatic specific antigen adds to the accuracy of determining clinical long-term cure and shows that 65-88% of patients who are clinical no evidence of disease are "biochemical" cures as well. These correlation percentages are quite similar to the largest contemporary surgical series, and strongly support the concept and fact of cure of prostate cancer with radiation.

Aged↗
PubMed1994

Patterns of Care and RTOG studies in prostate cancer: long-term survival, hazard rate observations, and possibilities of cure.

PURPOSE: This study was undertaken to show the long-term survival and probability of cure of prostate cancer patients treated with external beam radiation in USA national surveys and in the prospective clinical trials of the RTOG. METHODS AND MATERIALS: Two national patterns of care surveys of patients treated in 1973 and 1978 are reported along with two RTOG prospective trials (7506 and 7706). Hazard rates represent the risk of death and are compared to the rate expected for a normal population. RESULTS: For patients with Stage A cancers, the survival is not different from the expected survival for any of the reported surveys. The hazard rate for death does not significantly exceed the expected hazard rate out to 15 years. For patients with Stage B cancer, there is a decrease in survival below expected and hazard rates show a continuing excess mortality as long as 15 years after treatment. For patients with Stage C cancers, there is a more rapid decrease in survival that then becomes parallel to the expected survival. Hazard rates indicate there has been a return to expected mortality at 15 years. CONCLUSION: These data make a strong argument for the long-term cure of prostate cancer by external beam radiation, and support the continued use and study of radiation therapy as a curative modality in prostate cancer. No similar national data is available for any other method of management.

Follow-Up Studies↗