Adjuvant estrogen following radiation therapy for stage C adenocarcinoma of the prostate: long-term results of a prospective randomized study. Phase III radiation therapy oncology group (RTOG) trial 86-10 of androgen deprivation adjuvant to definitive radiotherapy in locally advanced carcinoma of the prostate. Randomized study of neoadjuvant testicular androgen ablation therapy before radical prostatectomy in men with clinically localized prostate cancer. Neoadjuvant hormonal therapy: the Canadian experience. 4-Year follow-up results of a European prospective randomized study on neoadjuvant hormonal therapy prior to radical prostatectomy in T2-3N0M0 prostate cancer. European Study Group on Neoadjuvant Treatment of Prostate Cancer. Neoadjuvant hormone treatment with leuprolide acetate depot 3.75 mg and cyproterone acetate, before radical prostatectomy: a randomized study. Short-term androgen deprivation and radiotherapy for locally advanced prostate cancer: results from the Trans-Tasman Radiation Oncology Group 96.01 randomised controlled trial. Comparison of radiotherapy alone with radiotherapy plus hyperthermia in locally advanced pelvic tumours: a prospective, randomised, multicentre trial. Dutch Deep Hyperthermia Group. The efficacy and sequencing of a short course of androgen suppression on freedom from biochemical failure when administered with radiation therapy for T2-T3 prostate cancer. Acceptability of short term neo-adjuvant androgen deprivation in patients with locally advanced prostate cancer. Immediate hormonal therapy compared with observation after radical prostatectomy and pelvic lymphadenectomy in men with node-positive prostate cancer. Androgen suppression adjuvant to definitive radiotherapy in prostate carcinoma--long-term results of phase III RTOG 85-31. Sequential adjuvant chemotherapy and radiotherapy in endometrial cancer--results from two randomised studies. Adjuvant radiotherapy for pathologically advanced prostate cancer: a randomized clinical trial. Postoperative radiotherapy after radical prostatectomy: a randomised controlled trial (EORTC trial 22911). Adjuvant VHF therapy in locally recurrent and primary unresectable rectal cancer. Combination treatment versus LHRH alone in advanced prostatic cancer. Phase III postoperative adjuvant radiotherapy after radical prostatectomy compared with radical prostatectomy alone in pT3 prostate cancer with postoperative undetectable prostate-specific antigen: ARO 96-02/AUO AP 09/95. Regional hyperthermia combined with radiotherapy for uterine cervical cancers: a multi-institutional prospective randomized trial of the international atomic energy agency. Evaluation of nurse-led follow up for patients undergoing pelvic radiotherapy. The risk of malignancy in the surgical margin at radical prostatectomy reduced almost three-fold in patients given neo-adjuvant hormone treatment.
Seventy-eight patients with clinical Stage C adenocarcinoma of the prostate were prospectively randomized to receive either radiation alone or radiation and adjuvant estrogen (diethylstilbestrol). No patient had received any prior definitive treatment for cancer. Forty patients were randomized to receive radiotherapy only and 38 patients to receive radiotherapy and estrogen. The median follow-up for all surviving patients was 14.5 years. Whether analyzed according to the original randomization or according to the treatment actually received, disease-free survival in the adjuvant estrogen group was strikingly and significantly higher than in the radiation-only group. At 5, 10, and 15 years patients receiving adjuvant estrogen had respective disease-free survival rates of 71%, 63%, and 63% compared with 49%, 43%, and 35% in patients having radiation only (p = 0.008). However, because of greater intercurrent disease-related mortality in patients receiving estrogen, there was no improvement in survival. This study suggests that a prospective randomized evaluation of early androgen deprivation with orchiectomy or with one of the nonestrogenic agents should be undertaken and that patients receiving early androgen deprivation should not be included in series reporting on the curative potential of radiation as a single modality. 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.
                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.
                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.
                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. We determined whether 12 weeks of neoadjuvant testicular androgen ablation therapy using a luteinizing hormone-releasing hormone agonist could improve pathological outcomes in men undergoing radical retropubic prostatectomy for clinically localized (stages T1C, T2A and T2B) prostatic carcinoma.
                A total of 56 participants was randomized to receive either monthly injections of a luteinizing hormone-releasing hormone agonist at 4-week intervals followed by radical retropubic prostatectomy (28) or to undergo immediate radical retropubic prostatectomy alone (28). Operations were performed via similar technique and all prostatic specimens were processed histologically in their entirety.
                There was no improvement in pathological outcome using luteinizing hormone-releasing hormone agonist preoperatively compared to surgery alone. Of 28 men undergoing immediate radical retropubic prostatectomy 23 had organ-confined (17) or specimen-confined (6) disease versus 22 of 28 who received luteinizing hormone-releasing hormone neoadjuvant therapy for 12 weeks preoperatively (16 with organ-confined and 6 with specimen-confined disease, p = 1.00). In addition, when the study population was analyzed by pretreatment prostate specific antigen (PSA) levels (10 ng./ml. or less, or greater than 10 ng./ml/) there was also no difference in pathological outcome (p = 0.65 for PSA greater than 10 and p = 0.32 for PSA less than 10).
                Neoadjuvant androgen ablation therapy for 12 weeks before radical prostatectomy in patients with clinically localized adenocarcinoma of the prostate does not result in improved pathological outcomes. To assess the effect of neoadjuvant combination therapy with the antiandrogen flutamide and a luteinizing-hormone-releasing hormone (LHRH) agonist administered for 3 months before radical prostatectomy, compared with surgery alone in early stage prostate cancer on histopathologic findings at surgery and serum prostate-specific antigen (PSA).
                A sample of 161 randomly screened patients diagnosed as having stage B (134 patients) or C (27 patients) prostate cancer were randomly assigned to radical prostatectomy alone or to 3 months of neoadjuvant combination therapy with the antiandrogen flutamide and an LHRH agonist before radical prostatectomy.
                Neoadjuvant combination therapy before radical prostatectomy decreased cancer-positive surgical margins from 33.8% in the control group to only 7.8%, thus leaving 92.2% of patients with negative margins at surgery. A net 54% improvement of staging was observed in favor of combination therapy. Organ-confined disease, on the other hand, increased from 49.3% to 77.8% of patients after 3 months of combination therapy, for a 57.8% increase in the incidence of organ-confined disease. No cancer was found in 6 (6.7%) prostatectomy specimens from the treated group. A close correlation was found between serum PSA at diagnosis and the stage of the disease at surgery. Upstaging increased from 30% at serum PSA values of 0 to 3.0 ng/mL up to 100% at serum PSA values above 15 ng/mL.
                Although long-term follow-up of these patients is required to determine the impact on survival, the marked influence of neoadjuvant combination therapy on the stage of the disease suggests the possibility of a major improvement in the morbidity and mortality from prostate cancer. To evaluate the long-term effects of 3-month neoadjuvant hormonal treatment in patients treated by radical prostatectomy for locally confined prostate cancer.
                We report the results of 402 patients (220 with a clinical T2 tumor and 182 with a clinical T3 tumor) of whom 192 randomly received neoadjuvant total androgen deprivation using a LHRH analogue (goserelin) plus flutamide for a period of 3 months and 210 underwent radical prostatectomy only.
                'Clinical downstaging' was seen in 30% of cases in the neoadjuvantly treated group (NEO). 'Pathological downstaging' occurred in 7 and 15% of cases in the direct radical prostatectomy (DP) group and the NEO group, respectively (p<0.01). In patients with clinical T2 as well as in patients with clinical T3 tumors, a significant difference in the number of positive margins was shown in favor of the NEO group (cT2, p<0.01; cT3, p = 0.01). This advantage, although there was a trend in favor of the NEO group, specifically in cT2 tumors, did not translate in a significantly better PSA progression rate (p = 0.18). However, when evaluating the local control rate in cT2 tumors, we observed local recurrence in 3 of 102 (3%) patients in the NEO group versus 12 of 114 (11%) patients in the DP group. The difference is statistically significant (p = 0.03). In the cT3 group, this difference was not statistically significant (NEO group: 15 of 87 (17%), and DP group: 21 of 95 (22%) patients; p = 0.41).
                In this study, the clinical revelance of pathological downstaging and the lower percentage of patients with positive margins in the neoadjuvantly treated group with a clinical T2 tumor is not confirmed by a lower PSA progression rate. However, this study indicates that there may be a trend that this advantage in favor of the NEO group directly translates into a better local control rate in clinical T2 tumors. Better local control in cT2 tumors is only going to be of relevance if subsequently you can show that there is a better survival for these patients. Unfortunately, this article reports a study which is not yet mature enough to show relevant information. Presently, neoadjuvant therapy should not be given outside clinical research settings. To assess the effect of neoadjuvant hormone treatment before radical prostatectomy on: tumor/prostate volume, prostate-specific antigen (PSA) and testosterone levels, surgical margin status and tumor stage, and the ease of surgery following treatment.
                Patients with clinically localized prostatic carcinoma were randomized to receive leuprolide acetate depot 3.75 mg once a month for 3 months and cyproterone acetate 300 mg once a week for 3 weeks prior to surgery (group A). A control group of patients had surgery without any pretreatment (group B).
                167 patients were evaluated for the efficacy parameters. In group A, 31% of patients had a reduction in tumor/prostate volume following hormone therapy. PSA and testosterone levels were significantly reduced (p = 0.0001) in patients in group A compared to basal values. Centralized histopathological data evaluated in 145 patients (group A and 75 group B) showed that more patients in group B had tumors at stages T3A and T3B than in group A; this difference was close to significance (p = 0.057). Positive surgical margins were more common in group B (60% of patients) compared to group A (39% of patients). Similarly lymph node involvement was more common in group B compared to group A (11 versus 3%). There was little difference between the 2 study groups for the other surgical parameters assessed (ease of dissection, duration of surgery, blood loss).
                Neoadjuvant hormone therapy before radical prostatectomy has some effects in the treatment of prostate cancer. However, long-term follow-up of patients is needed to assess the impact of this therapy on morbidity and mortality.
                Copyright 2004 S. Karger AG, Basel Androgen deprivation is an established treatment regimen for disseminated prostate cancer; however, its role in patients with localised cancer is less clear. We did a large randomised controlled trial to determine whether 3 months or 6 months of androgen deprivation given before and during radiotherapy improves outcomes for patients with locally advanced prostate cancer.
                818 men with locally advanced prostate cancer were randomly assigned to: no androgen deprivation (ie, radiotherapy alone: 66 Gy in 33 fractions of 2 Gy per day over 6.5-7.0 weeks to the prostate and seminal vesicles); 3 months' androgen deprivation with 3.6 mg goserelin given subcutaneously every month and 250 mg flutamide given orally three times a day starting 2 months before radiotherapy (same regimen as control group); or 6 months' androgen deprivation, with the same regimen, starting 5 months before radiotherapy (same regimen as control group). Primary endpoints were time to local failure and prostate-cancer-specific survival; secondary endpoints were distant failure, disease-free survival, and freedom from salvage treatment. Analyses were done by intention to treat.
                802 (98%) patients were eligible for analysis. Median follow-up was 5.9 years (range 0.1-8.5). Compared with patients assigned no androgen deprivation, those assigned 3 months' treatment had significantly improved local failure (hazard ratio [HR] 0.56 [95% CI 0.39-0.79], p=0.001), biochemical failure-free survival (0.70 [0.56-0.88], p=0.002), disease-free survival (0.65 [0.52-0.80], p=0.0001), and freedom from salvage treatment (0.73 [0.56-0.96], p=0.025). 6 months' androgen deprivation significantly improved local failure (0.42 [0.28-0.62], p<0.0001), biochemical failure-free survival (0.58 [0.46-0.74], p<0.0001), disease-free survival (0.56 [0.45-0.69], p<0.0001), freedom from salvage treatment (0.53 [0.40-0.71], p<0.0001), distant failure (0.67 [0.45-0.99], p=0.046) and prostate-cancer-specific survival (0.56 [0.32-0.98], p=0.04) compared with no androgen deprivation.
                6 months' androgen deprivation given before and during radiotherapy improves the outlook of patients with locally advanced prostate cancer. Further follow-up is needed to estimate precisely the size of survival benefits. Increased radiation doses and additional periods of androgen deprivation might lead to further benefit. Local-control rates after radiotherapy for locally advanced tumours of the bladder, cervix, and rectum are disappointing. We investigated the effect of adding hyperthermia to standard radiotherapy.
                The study was a prospective, randomised, multicentre trial. 358 patients were enrolled from 1990 to 1996, in cancer centres in the Netherlands, who had bladder cancer stages T2, T3, or T4, NO, MO, cervical cancer stages IIB, IIIB, or IV, or rectal cancer stage M0-1 were assessed. Patients were randomly assigned radiotherapy (median total dose 65 Gy) alone (n=176) or radiotherapy plus hyperthermia (n=182). Our primary endpoints were complete response and duration of local control. We did the analysis by intention to treat.
                Complete-response rates were 39% after radiotherapy and 55% after radiotherapy plus hyperthermia (p<0.001). The duration of local control was significantly longer with radiotherapy plus hyperthermia than with radiotherapy alone (p=0.04). Treatment effect did not differ significantly by tumour site, but the addition of hyperthermia seemed to be most important for cervical cancer, for which the complete-response rate with radiotherapy plus hyperthermia was 83% compared with 57% after radiotherapy alone (p=0.003). 3-year overall survival was 27% in the radiotherapy group and 51% in the radiotherapy plus hyperthermia group. For bladder cancer, an initial difference in local control disappeared during follow-up.
                Hyperthermia in addition to standard radiotherapy may be especially useful in locally advanced cervical tumours. Studies of larger numbers of patients are needed for other pelvic tumour sites before practical recommendations can be made. We evaluated the benefits and sequencing of androgen suppression (AS) administered with external beam radiation therapy (EBRT) in T2-T3 prostate cancers.
                Between 1990 and 1999, 481 patients were entered in 2 successive, prospective, randomized studies, including 161 in the study 1 and 325 in study 2. Eligible patients had clinical stages T2-T3 prostate cancer. In the first study (L-101) subjects were randomly allocated among EBRT alone (group 1), EBRT preceded by 3 months of AS (group 2), and neoadjuvant, concomitant and adjuvant AS for a total of 10 months (group 3). In the second study (L-200) we analyzed neoadjuvant and concomitant AS (total 5 months) vs neoadjuvant, concomitant and short course adjuvant (total 10 months) AS with EBRT. In each study we used a total AS (a luteinizing hormone-releasing hormone agonist plus an antiandrogen) and a standard dose of radiation therapy at that time. Patient characteristics were well balanced in regard to age, stage, prostate specific antigen and Gleason score. No biochemical evidence of disease (BNED) was defined as an end point according to the Vancouver rule.
                In the study 1 at a median followup of 5 years 7-year biochemical-free survival rates were 42%, 66% and 69% in groups 1 to 3, respectively. BNED was significantly different between groups 1 and 2 (p = 0.009) and between groups 1 and 3 (p = 0.003) but not between groups 2 and 3 (p = 0.6). Multivariate analysis using a Cox proportional hazards model showed an HR of 6.1 for Gleason score (p = 0.001), 1.4 for PSA (p = 0.002), 0.5 for group 1 vs group 2 (p = 0.01) and 0.35 for group 1 vs group 3 (p = 0.008). In study 2 BNED at 4 years was 65%. There was no significant difference between arms 1 and 2 (p = 0.55).
                The analysis of study 1 shows a benefit of using a short course of neoadjuvant AS with EBRT vs EBRT alone for localized T2-T3 prostate cancers. Moreover, in each study adding a short course of adjuvant AS after neoadjuvant 1 provided no more advantage in these patients. To determine the acceptability of short term neo-adjuvant maximal androgen deprivation (MAD) to patients treated with external beam radiation for locally advanced prostate cancer.
                Between 1996 and 2000, 818 patients with locally advanced, but non-metastatic, prostate cancer were entered into a randomised clinical trial (TROG 96.01), which compared radiation treatment alone with the same radiation treatment and 3 or 6 months neo-adjuvant MAD with goserelin and flutamide. Relevant symptoms, and how troublesome they were to the patient, were scored using a self-assessment questionnaire. This was completed by the patient at registration, and at specified times during and after treatment. Patients taking flutamide had liver function tests checked at regular intervals.
                All patients have completed at least 12 months follow-up after treatment. Nearly all patients completed planned treatment with goserelin, but 27% of patients in the 6-month MAD treatment arm, and 20% in the 3-month arm, had to stop flutamide early. This was mainly due to altered liver function (up to 17% patients) and bowel side effects (up to 8% patients). However, although flutamide resulted in more bowel symptoms for patients on MAD, there was significant reduction in some urinary symptoms on this treatment. Acute bowel and urinary side effects at the end of radiation treatment were similar in all treatment arms. Side effect severity was unrelated to radiation target volume size, which was reduced by MAD, but symptomatology prior to any treatment was a powerful predictor. Of the 36% of patients who were sexually active before any treatment, the majority became inactive whilst on MAD. However, sexual activity at 12 months after radiation treatment was similar in all treatment arms, indicating that the effects of short term MAD on sexual function are reversible.
                Despite temporary effects on sexual activity, and compliance difficulties with flutamide, short-term neo-adjuvant MAD was not perceived by patients to be a major inconvenience. If neo-adjuvant MAD in the way tested can be demonstrated to lead to improved biochemical control and/or survival, then patients would view these therapeutic gains as worthwhile. Compliance with short-term goserelin was excellent, confirming that LH-RH analogues have a potential role in more long-term adjuvant treatment. However, for more protracted androgen deprivation, survival advantages and deleterious effects need to be assessed in parallel, in order to determine the optimal duration of treatment. Because the optimal timing of the institution of antiandrogen therapy for prostate cancer is controversial, we compared immediate and delayed treatment in patients who had minimal residual disease after radical prostatectomy.
                Ninety-eight men who underwent radical prostatectomy and pelvic lymphadenectomy and who were found to have nodal metastases were randomly assigned to receive immediate antiandrogen therapy, with either goserelin, a synthetic agonist of gonadotropin-releasing hormone, or bilateral orchiectomy, or to be followed until disease progression. The patients were assessed quarterly during the first year and then semiannually.
                After a median of 7.1 years of follow-up, 7 of 47 men who received immediate antiandrogen treatment had died, as compared with 18 of 51 men in the observation group (P=0.02). The cause of death was prostate cancer in 3 men in the immediate-treatment group and in 16 men in the observation group (P<0.01). At the time of the last follow-up, 36 men in the immediate-treatment group (77 percent) and 9 men in the observation group (18 percent) were alive and had no evidence of recurrent disease, including undetectable serum prostate-specific antigen levels (P<0.001). In the observation group, the disease recurred in 42 men; 13 of the 36 who were treated had a complete response to local treatment or hormonal therapy (or both), 16 died of prostate cancer, and 1 died of another disease. The remaining men in this group were alive with progressive disease at the time of the last follow-up or had had a recent relapse. Except for the treatment group (immediate therapy or observation), no clinical or histologic characteristic significantly influenced the outcome.
                Immediate antiandrogen therapy after radical prostatectomy and pelvic lymphadenectomy improves survival and reduces the risk of recurrence in patients with node-positive prostate cancer. Radiation Therapy Oncology Group protocol 85-31 was designed to evaluate the effectiveness of adjuvant androgen suppression, using goserelin, in unfavorable prognosis carcinoma of the prostate treated with definitive radiotherapy (RT).
                Eligible patients were those with palpable primary tumor extending beyond the prostate (clinical Stage T3) or those with regional lymphatic involvement. Patients who had undergone prostatectomy were eligible if penetration through the prostatic capsule to the margin of resection and/or seminal vesicle involvement was documented histologically. Stratification was based on histologic differentiation, nodal status, acid phosphatase status, and prior prostatectomy. The patients were randomized to either RT and adjuvant goserelin (Arm I) or RT alone followed by observation and application of goserelin at relapse (Arm II). In Arm I, the drug was to be started during the last week of RT and was to be continued indefinitely or until signs of progression.
                Between 1987 and 1992, when the study was closed, 977 patients were entered: 488 to Arm I and 489 to Arm II. As of July 2003, the median follow-up for all patients was 7.6 years and for living patients was 11 years. At 10 years, the absolute survival rate was significantly greater for the adjuvant arm than for the control arm: 49% vs. 39%, respectively (p = 0.002). The 10-year local failure rate for the adjuvant arm was 23% vs. 38% for the control arm (p <0.0001). The corresponding 10-year rates for the incidence of distant metastases and disease-specific mortality was 24% vs. 39% (p <0.001) and 16% vs. 22% (p = 0.0052), respectively, both in favor of the adjuvant arm.
                In a population of patients with unfavorable prognosis carcinoma of the prostate, androgen suppression applied as an adjuvant after definitive RT was associated not only with a reduction in disease progression but in a statistically significant improvement in absolute survival. The improvement in survival appeared preferentially in patients with a Gleason score of 7-10. Endometrial cancer patients with high grade tumours, deep myometrial invasion or advanced stage disease have a poor prognosis. Randomised studies have demonstrated the prevention of loco-regional relapses with radiotherapy (RT) with no effect on overall survival (OS). The possible additive effect of chemotherapy (CT) remains unclear. Two randomised clinical trials (NSGO-EC-9501/EORTC-55991 and MaNGO ILIADE-III) were undertaken to clarify if sequential combination of chemotherapy and radiotherapy improves progression-free survival (PFS) in high-risk endometrial cancer. The two studies were pooled.
                Patients (n=540; 534 evaluable) with operated endometrial cancer International Federation of Obstetrics and Gynaecology (FIGO) stage I-III with no residual tumour and prognostic factors implying high-risk were randomly allocated to adjuvant radiotherapy with or without sequential chemotherapy.
                In the NSGO/EORTC study, the combined modality treatment was associated with 36% reduction in the risk for relapse or death (hazard ratio (HR) 0.64, 95%confidence interval (CI) 0.41-0.99; P=0.04); two-sided tests were used. The result from the Gynaecologic Oncology group at the Mario Negri Institute (MaNGO)-study pointed in the same direction (HR 0.61), but was not significant. In the combined analysis, the estimate of risk for relapse or death was similar but with narrower confidence limits (HR 0.63, CI 0.44-0.89; P=0.009). Neither study showed significant differences in the overall survival. In the combined analysis, overall survival approached statistical significance (HR 0.69, CI 0.46-1.03; P=0.07) and cancer-specific survival (CSS) was significant (HR 0.55, CI 0.35-0.88; P=0.01).
                Addition of adjuvant chemotherapy to radiation improves progression-free survival in operated endometrial cancer patients with no residual tumour and a high-risk profile. A remaining question for future studies is if addition of radiotherapy to chemotherapy improves the results.
                Copyright 2010 Elsevier Ltd. All rights reserved. Despite a stage-shift to earlier cancer stages and lower tumor volumes for prostate cancer, pathologically advanced disease is detected at radical prostatectomy in 38% to 52% of patients. However, the optimal management of these patients after radical prostatectomy is unknown.
                To determine whether adjuvant radiotherapy improves metastasis-free survival in patients with stage pT3 N0 M0 prostate cancer.
                Randomized, prospective, multi-institutional, US clinical trial with enrollment between August 15, 1988, and January 1, 1997 (with database frozen for statistical analysis on September 21, 2005). Patients were 425 men with pathologically advanced prostate cancer who had undergone radical prostatectomy.
                Men were randomly assigned to receive 60 to 64 Gy of external beam radiotherapy delivered to the prostatic fossa (n = 214) or usual care plus observation (n = 211).
                Primary outcome was metastasis-free survival, defined as time to first occurrence of metastatic disease or death due to any cause. Secondary outcomes included prostate-specific antigen (PSA) relapse, recurrence-free survival, overall survival, freedom from hormonal therapy, and postoperative complications.
                Among the 425 men, median follow-up was 10.6 years (interquartile range, 9.2-12.7 years). For metastasis-free survival, 76 (35.5%) of 214 men in the adjuvant radiotherapy group were diagnosed with metastatic disease or died (median metastasis-free estimate, 14.7 years), compared with 91 (43.1%) of 211 (median metastasis-free estimate, 13.2 years) of those in the observation group (hazard ratio [HR], 0.75; 95% CI, 0.55-1.02; P = .06). There were no significant between-group differences for overall survival (71 deaths, median survival of 14.7 years for radiotherapy vs 83 deaths, median survival of 13.8 years for observation; HR, 0.80; 95% CI, 0.58-1.09; P = .16). PSA relapse (median PSA relapse-free survival, 10.3 years for radiotherapy vs 3.1 years for observation; HR, 0.43; 95% CI, 0.31-0.58; P<.001) and disease recurrence (median recurrence-free survival, 13.8 years for radiotherapy vs 9.9 years for observation; HR, 0.62; 95% CI, 0.46-0.82; P = .001) were both significantly reduced with radiotherapy. Adverse effects were more common with radiotherapy vs observation (23.8% vs 11.9%), including rectal complications (3.3% vs 0%), urethral strictures (17.8% vs 9.5%), and total urinary incontinence (6.5% vs 2.8%).
                In men who had undergone radical prostatectomy for pathologically advanced prostate cancer, adjuvant radiotherapy resulted in significantly reduced risk of PSA relapse and disease recurrence, although the improvements in metastasis-free survival and overall survival were not statistically significant. Trial Registration clinicaltrials.gov Identifier: NCT00394511. Local failure after prostatectomy can arise in patients with cancer extending beyond the capsule. We did a randomised controlled trial to compare radical prostatectomy followed by immediate external irradiation with prostatectomy alone for patients with positive surgical margin or pT3 prostate cancer.
                After undergoing radical retropubic prostatectomy, 503 patients were randomly assigned to a wait-and-see policy, and 502 to immediate postoperative radiotherapy (60 Gy conventional irradiation delivered over 6 weeks). Eligible patients had pN0M0 tumours and one or more pathological risk factors: capsule perforation, positive surgical margins, invasion of seminal vesicles. Our revised primary endpoint was biochemical progression-free survival. Analysis was by intention to treat.
                The median age was 65 years (IQR 61-69). After a median follow-up of 5 years, biochemical progression-free survival was significantly improved in the irradiated group (74.0%, 98% CI 68.7-79.3 vs 52.6%, 46.6-58.5; p<0.0001). Clinical progression-free survival was also significantly improved (p=0.0009). The cumulative rate of locoregional failure was significantly lower in the irradiated group (p<0.0001). Grade 2 or 3 late effects were significantly more frequent in the postoperative irradiation group (p=0.0005), but severe toxic toxicity (grade 3 or higher) were rare, with a 5-year rate of 2.6% in the wait-and-see group and 4.2% in the postoperative irradiation group (p=0.0726).
                Immediate external irradiation after radical prostatectomy improves biochemical progression-free survival and local control in patients with positive surgical margins or pT3 prostate cancer who are at high risk of progression. Further follow-up is needed to assess the effect on overall survival. In a prospective randomized study, 434 mHz microwave therapy combined with external beam radiotherapy (VHF + RT) was compared with standard external beam radiotherapy (RT) in controlling locally recurrent or unresectable primary adenocarcinoma of the rectum. Independent assessors documented quality of life scores, performance status, toxicities, local response to treatment, and systemic disease progression before treatment and after treatment and every 8 weeks thereafter. Of 75 patients randomized, 73 were eligible for inclusion in the study. Forty-three of these patients had local pelvic tumour recurrence only and 21 also had distant metastases. In addition, nine patients had primary inoperable carcinomas, two of whom also had metastases. Thirty-seven patients were randomized to RT and 36 to VHF + RT. The median dose of radiation in the VHF+RT arm was 4275 cGy with a median fraction size of 150 cGy and median duration of therapy of 48.5 days versus 4500 cGy in the RT-only arm with a median fraction size of 180 cGy and median duration of therapy of 38 days. These doses are unlikely to be significantly different in biological effect. No significant difference between the two groups was observed in extent and duration of local control, measures of toxicity or quality of life scores. Additionally, survival and cumulative incidence of pelvic site of first progression did not differ significantly between the groups. We conclude that VHF microwave therapy in conjunction with radiotherapy produces no therapeutic advantage over conventional radiation therapy alone in the treatment of locally recurrent rectal carcinoma. Androgen deprivation based on hormone manipulation is the treatment of choice in advanced prostatic cancer. The unequivocal role of adrenal androgens in the growth of prostatic cancer after medical or surgical castration requires a new logical approach (complete androgen blockade) in the treatment of advanced prostate cancer. One hundred and fifty patients with biopsy-proven advanced prostatic cancer were randomized into two groups. One group (74 patients) received leuprolide + flutamide (complete androgen blockade); the second group (76 patients) received only leuprolide and, during the first 3 weeks of treatment, cyproterone acetate (150 mg/day) to prevent flare-up phenomena. The aim of the study was to evaluate the differences between the two groups on overall survival and time to progression (log-rank test). One hundred and twenty-five patients were evaluable, 62 in the leuprolide-only group and 63 in the leuprolide + flutamide group. Median duration of follow-up was 102 weeks. No statistical difference between the two groups was observed in overall survival, in time to disease progression, and in time to treatment failure. In the combination (leuprolide + flutamide) treatment group, a positive trend for overall survival and in time to progression was observed in a subgroup of patients with good performance status and no bone metastases. We observed mild gastrointestinal toxicity (diarrhea, nausea) in the group treated with leuprolide + flutamide. The aim of this study was to compare the effectiveness of total androgen withdrawal with medical testicular suppression in advanced prostatic cancer. No significant statistical difference was observed between the two groups in overall survival and in time to progression, but probably too few patients were enrolled in each treatment arm to give a statistical interpretation of our results. We conclude that there is a positive trend in the combination treatment arm in patients with good prognostic factors. Local failure after radical prostatectomy (RP) is common in patients with cancer extending beyond the capsule. Two randomized trials demonstrated an advantage for adjuvant radiotherapy (RT) compared with a wait-and-see policy. We conducted a randomized, controlled clinical trial to compare RP followed by immediate RT with RP alone for patients with pT3 prostate cancer and an undetectable prostate-specific antigen (PSA) level after RP.
                After RP, 192 men were randomly assigned to a wait-and-see policy, and 193 men were assigned to immediate postoperative RT. Eligible patients had pT3 pN0 tumors. Patients who did not achieve an undetectable PSA after RP were excluded from treatment according to random assignment (n = 78; 20%). Of the remaining 307 patients, 34 patients on the RT arm did not receive RT and five patients on the wait-and-see arm received RT. Therefore, 114 patients underwent RT and 154 patients were treated with a wait-and-see policy. The primary end point was biochemical progression-free survival.
                Biochemical progression-free survival after 5 years in patients with undetectable PSA after RP was significantly improved in the RT group (72%; 95% CI, 65% to 81%; v 54%, 95% CI, 45% to 63%; hazard ratio = 0.53; 95% CI, 0.37 to 0.79; P = .0015). On univariate analysis, Gleason score more than 6 and less than 7, PSA before RP, tumor stage, and positive surgical margins were predictors of outcome. The rate of grade 3 to 4 late adverse effects was 0.3%.
                Adjuvant RT for pT3 prostate cancer with postoperatively undetectable PSA significantly reduces the risk of biochemical progression. Further follow-up is needed to assess the effect on metastases-free and overall survival. Hyperthermia can be used to enhance the effects of radiation, and a combined treatment may, in some circumstances, be an advantage. Uterine cervical cancer is very common in developing countries. The control of locally advanced pelvic tumors is difficult with conventional treatment modalities. Based upon the biologic rationale and in view of the recent advances in heating and thermometry techniques, radiotherapy in combination with hyperthermia was investigated in a multi-institutional prospective randomized trial sponsored by the International Atomic Energy Agency. The primary purpose was to clarify whether the combination of hyperthermia and radiotherapy improves the rate of local control, compared with radiotherapy alone.
                A total of 110 patients with biopsy-proven, locally advanced carcinoma of the uterine cervix were randomized to treatment by radiotherapy with or without hyperthermia. The patients were stratified by institution, stage, and histologic type. Each patient received external beam radiation therapy and brachytherapy. For the patients randomized to receive hyperthermia, a minimum of five sessions (60 min each, once per week) were administered, employing a radiofrequency (RF) capacitive heating device. Intratumoral temperature was measured at the first hyperthermic treatment, and at least once more during the course of treatment. The equipment and the policies and procedures at each participating institution except one (Pusan) were personally inspected at least once by the corresponding author, to ensure that quality assurance procedures were in place and were followed for treatment according to the protocol guidelines. The median follow-up period was 466 days for all the patients and 512 days for the surviving patients.
                The two arms were well balanced with regard to the patient factors, tumor factors, and treatment factors. The overall survival rate at 3 years was 73.2%, and the local control rate was 68.5%. There were no significant differences between the patients treated with or without hyperthermia, either with regard to the survival (p = 0.1893) or the rate of local control (p = 0.58). The survival was significantly worse among the patients with Stage IIb disease who received hyperthermia (p = 0.0162) although there was no difference in their rate of local control (p = 0.7988). Further analysis is necessary to determine if the difference in survival is due to a greater incidence of distant metastases or some other cause. Acute Grade 2-3 toxicity was seen in 10/55 patients (18%) treated by hyperthermia and in 2/55 of the patients (4%) treated without hyperthermia (p = 0.01). There was no significant difference in the late toxicity observed in the two arms.
                This prospective randomized study failed to show any benefit from the addition of hyperthermia to radiotherapy in the treatment of locally advanced carcinoma of the uterine cervix. The acute toxicity was significantly greater among the patients receiving hyperthermia, and the survival was significantly worse among the Stage IIb patients receiving hyperthermia even though there was no difference in the local control rate. This study reports results from a randomised controlled trial of nurse-led care and was designed to determine whether nurse-led follow up improved patients morbidity and satisfaction with care in men treated with radical radiotherapy for prostate and bladder cancer. The aim was to compare outcomes in terms of toxicity, symptoms experienced, quality of life, satisfaction with care and health care costs, between those receiving nurse-led care and a group receiving standard care. The study population was of men prescribed radical radiotherapy (greater than 60 Gy). Participants completed self-assessment questionnaires for symptoms and quality of life within the first week of radiotherapy treatment, at week 3, 6 and 12 weeks from start of radiotherapy. Satisfaction with clinical care was also assessed at 12 weeks post-treatment. Observer-rated RTOG toxicity scores were recorded pre-treatment, weeks 1, 3, 6 and 12 weeks from start of radiotherapy. The results presented in this paper are on 115 of 132 (87%) of eligible men who agreed to enter the randomised trial. 6 men (4%) refused and 11 (8%) were missed for inclusion in the study. Data were analysed as a comparison at cross-sectional time points and as a general linear model using multiple regression. There was no significant difference in maximum symptom scores over the time of the trial between nurse-led follow-up care and conventional medical care. Differences were seen in scores in the initial self assessment of symptoms (week 1) that may have been as a result of early nursing intervention. Those men who had received nurse-led care were significantly more satisfied (P < 0.002) at 12 weeks and valued the continuity of the service provided. There were also significant (P < 0.001) cost benefits, with a 31% reduction in costs with nurse-led, compared to medically led care. Evidence from this study suggests that a specialist nurse is able to provide safe follow up for men undergoing radiotherapy. The intervention focused on coping with symptoms, and provided continuity of care and telephone support. Further work is required to improve the management of patients during and after radiotherapy. To investigate the outcome of neo-adjuvant hormone treatment before radical prostatectomy regarding local tumour extension, peri-operative blood loss and operation time.
                Of 111 surgically treated patients with prostate cancer (T1b-T3a, N0, M0, G1-3), 55 were randomised to immediate radical prostatectomy and 56 to 3 months of neo-adjuvant treatment with triptorelin (3.75 mg i.m. every 28 days) and cyproterone acetate (50 mg b.i.d. for 3 weeks to prevent flare).
                No differences were found in blood loss or operation time but patients who had neo-adjuvant treatment had a significantly lower frequency of positive margins (41 vs. 23%, p = 0.013). Conclusion: Neo-adjuvant treatment does not facilitate radical prostatectomy but may improve the chance of local cure. This must, however, be documented with long-term follow-up in randomised patients.
Hormone therapy combined with either prostatectomy or radiotherapy is associated with significant clinical benefits in patients with local or locally advanced prostate cancer. Significant local control may be achieved when given prior to prostatectomy or radiotherapy, which may improve patient's quality of life. When given adjuvant to these primary therapies, hormone therapy, not only provides a method for local control, but there is also evidence for a significant survival advantage. However, hormone therapy is associated with significant side effects, such as hot flushes and gynaecomastia, as well as cost implications. The decision to use hormone therapy should, therefore, be taken at a local level, between the patient, clinician and policy maker, taking into account the clinical benefits, toxicity and cost. More research is needed to guide the choice, the duration, and the schedule of hormonal deprivation therapy, and the impact of long-term hormone therapy with regard to toxicity and the patient's quality of life.