Adjuvant chemotherapy in T3 carcinoma of the bladder. A prospective trial: preliminary report

We report the early results of a multi-centre, randomised prospective trial of neoadjuvant and maintenance chemotherapy with methotrexate (MTX) in 376 patients with advanced (T3) carcinoma of the bladder. In patients under 65 years of age, treatment consisted of radical radiotherapy (64 Gy) or, in some centres, pre-operative radiotherapy (44 Gy) and elective cystectomy. All patients over 65 had radical radiotherapy. MTX was administered to 188 patients. There was no increase in toxicity attributable to the MTX. MTX did not significantly increase the proportion of patients whose tumours responded to radiotherapy; 50% (70/141) responded to radiotherapy and 56% (76/136) to MTX radiotherapy. The development of metastases and survival was also similar in both groups (3-year survival: radiotherapy 37.3%, MTX + radiotherapy 38.6%). We report the logistic difficulties of the administration of prolonged courses of maintenance chemotherapy. Further controlled trials of neo-adjuvant chemotherapy in advanced bladder cancer are required, involving more active regimes.     

Adjuvant Radiotherapy for Patients with Locally Advanced Prostate Cancer-A New Standard?

CONTEXT: After radical prostatectomy (RPE) pathologically advanced disease is detected in 38% to 52% of patients. Retrospective data on the role of postoperative radiotherapy (RT) are controversial. OBJECTIVES: To clarify in how far an adjuvant radiation treatment (ART) in cases of locally advanced disease affects outcome, three randomised trials have been started. The available data are critically reviewed. EVIDENCE ACQUISITION: Relevant publications were detected by searching the Medical Literature Analysis and Retrieval System Online (MEDLINE) and the Public/Publisher MEDLINE (PUBMED; National Library of Medicine journal articles database) databases using the medical subject headings "prostatic neoplasms," "radiotherapy," and "adjuvant." A major emphasis was placed on the results of the randomised trials. EVIDENCE SYNTHESIS: The European Organization for Research and Treatment of Cancer (EORTC) trial number 22911, Southwest Oncology Group (SWOG) trial number 8794, and German Intergroup trial ARO 96-02/AUO AP 09/95 randomised patients to receive ART with 60 Gray (Gy) and 60-64 Gy (SWOG trial), respectively. The majority of patients had undetectable PSA levels postoperatively. The data concordantly show that ART improves biochemical progression-free survival rates (EORTC trial, progression-free survival rate after 5 yr: 74.0% with ART vs 52.6% without ART; SWOG trial, after 5 yr: approximately 73% vs approximately 44%, respectively; and ARO 96-02/AUO AP 09/95 trial, after 5 yr: 72% vs 54%, respectively). The EORTC trial shows improved local control of cancer progression (p<0.0001) for treated patients. The SWOG trial demonstrates an improved freedom from hormonal treatment (5-yr: 21% with ART vs 10% without ART). A statistically significant benefit with regard to metastasis-free survival and overall survival was not seen. Genitourinary and gastrointestinal toxicity was moderate, with late side-effects (> or = grade 3) between 3% (in the ARO 96-02 trial) and <5% (in the EORTC trial). CONCLUSION: Biochemical progression-free survival and local control are significantly improved by postoperative RT with 60 Gy. Patients should be offered adjuvant treatment when they are at high risk for local relapse (especially with positive surgical margins).     

Surgery for non-small cell lung cancer: systematic review and meta-analysis of randomised controlled trials

BACKGROUND: Surgery is considered the treatment of choice for patients with resectable stage I and II (and some patients with stage IIIA) non-small cell lung cancer (NSCLC), but there have been no previously published systematic reviews. METHODS: A systematic review and meta-analysis of randomised controlled trials was conducted to determine whether surgical resection improves disease specific mortality in patients with stages I-IIIA NSCLC compared with non-surgical treatment, and to compare the efficacy of different surgical approaches. RESULTS: Eleven trials were included. No studies had untreated control groups. In a pooled analysis of three trials, 4 year survival was superior in patients undergoing resection with stage I-IIIA NSCLC who had complete mediastinal lymph node dissection compared with lymph node sampling (hazard ratio estimated at 0.78 (95% CI 0.65 to 0.93)). Another trial reported an increased rate of local recurrence in patients with stage I NSCLC treated with limited resection compared with lobectomy. One small study reported a survival advantage among patients with stage IIIA NSCLC treated with chemotherapy followed by surgery compared with chemotherapy followed by radiotherapy. No other trials reported significant improvements in survival after surgery compared with non-surgical treatment. CONCLUSION: It is difficult to draw conclusions about the efficacy of surgery for locoregional NSCLC because of the small number of participants studied and methodological weaknesses of the trials. However, current evidence suggests that complete mediastinal lymph node dissection is associated with improved survival compared with node sampling in patients with stage I-IIIA NSCLC undergoing resection.     

Intra-arterial chemotherapy in the treatment of liver metastases of colorectal cancer]

AIM: The authors evaluate the value of hepatic intrarterial chemotherapy (HAC) as an alternative treatment for hepatic metastases from colo-rectum cancer unsuited to radical surgery. METHODS: This study evaluates the physiopathological and pharmacodynamic bases for this type of treatment, the correct procedure for patient staging and selection, the surgical technique used to insert the infusional system, surgical complications and those linked to endoarterial treatment, the evaluation of response and the results. Complications correlated to the infusional system were evaluated in a total of 1223 patients in 10 non-randomised studies and 7 randomised studies taken from the literature. Complications correlated to chemotherapy were analysed in a total of 777 patients from 8 randomised studies and 7 randomised using FUDR. Special emphasis was placed on the possible association of locoregional and systemic treatment in order to prevent extrahepatic progression, the main cause of death in patients undergoing a single cycle of HAC. RESULTS: By comparing locoregional and systemic treatment taken from a number of randomised and non-randomised studies, the results were evaluated in terms of objective response and survival. CONCLUSIONS: There was no proportional increase in survival rates compared to systemic treatment only, in spite of the large proportion of objective responses achieved using locoregional treatment alone.     

Time course from first symptom to treatment in patients with non-small cell lung cancer referred for radiotherapy: a report by the CHART Steering Committee.

BACKGROUND: Only a small proportion of patients with non-small cell lung cancer (NSCLC) attending radiotherapy centres were suitable for inclusion in a randomised trial which compared continuous hyperfractionated accelerated radiotherapy (CHART) with conventional radical radiotherapy. As this was thought to be partly due to delays in the referral of patients to clinical oncologists, a prospective study was performed to determine the interval between first report of symptoms and first radiotherapy treatment in patients with NSCLC. METHODS: The time course from first symptom to treatment was determined in all patients with NSCLC attending 10 cancer centres for radiotherapy to a primary tumour in a three month period. RESULTS: Only 5% of 484 patients were suitable for the trial of radical radiotherapy. The principal causes for exclusion were poor general condition (37%), too large a tumour (27%), and extrathoracic metastases (19%). The median time from first symptom to diagnosis was 13 weeks, from first symptom to first treatment 19 weeks, and from diagnosis to first treatment five weeks. In a quarter of the patients these intervals were greater than 25,33 weeks, and nine weeks, respectively. CONCLUSION: The reason for these long intervals needs investigation since earlier diagnosis and more immediate referral for consideration of treatment might increase the number of patients with NSCLC suitable for radical radiotherapy.     

Percutaneous radiotherapy for low-risk prostate cancer: options for 2007

Technical developments of radiotherapy (RT) over the recent years yielded in better conformation to the target volume thus increasing the therapeutic ratio and decreasing side effects. This paper discusses these options for low-risk prostate cancer. There has been evidence from randomized trials, that for low-risk PCA doses >70 Gy are significant better in case of biochemical disease-free survival (bNED). Image-guided radiotherapy (IGRT) has been proven in several studies for reduced safety margins around the prostate target volume. Intensity-modulated radiotherapy (IMRT) allow treatment with higher doses and 5-year results are reported from several studies. Data from several randomized trials about adjuvant RT after radical prostatectomy (RP) have been reported. In two phase-III trials a significant advantage of 20% bNED was demonstrated for doses between 76 and 79 Gy compared with 70 Gy. Using IGRT, the safety margin around the prostate can be reduced for about 30–50%. Doses of >80 Gy can be given safely to the prostate with IMRT and <5% grade-III/IV late side effects. Adjuvant RT for positive margins after RP has been of proven advantage. Three phase-III trials achieved a significant better bNED of 20% for 5 years. The effect of doses >70 Gy have been proven for low-risk PCA. IGRT resulted in reduced safety margins and a decrease of acute and late side effects. The addition of IMRT allowed higher doses to the prostate. Adjuvant RT after RP for positive margins achieved a significant better bNED.     

Phase 1/2 study of synchronous methotrexate, cisplatin, vincristine (MOPq10) chemotherapy and radiation for patients with locally advanced bladder cancer.

PURPOSE: This phase 1/2 study was designed to test toxicity and effectiveness of combination chemotherapy and concurrent radiotherapy in the treatment of invasive bladder cancer. METHODS AND MATERIALS: 17 patients with localised muscle-invasive bladder cancer, clinical stages T2-3 N0, M0, were treated with a radiotherapy schedule of 55 Gy in 20 fractions over 4 weeks restricted to the bladder and 3 cycles of concurrent dose-intensive combination chemotherapy consisting of cisplatin 60 mg/m(2), vincristine 2 mg and methotrexate 60 mg/m(2) at 10-day intervals (MOPq10). RESULTS: The complete remission rate following MOPq10 chemotherapy and radiotherapy was 88% as assessed at first cystoscopy with 82% remaining disease-free at 1 year. Risk factor analysis shows those older than 63 years (median) and those with creatinine clearance equal or less than the mean did worse. Actuarial disease-free survival at 2 years was 68% and of the patients treated 4/17 experienced acute G3/4 toxicity. CONCLUSION: This combination regimen was feasible. Its high initial response rate justifies further exploration in a randomised phase 2/3 trial setting with bladder volume and quality of life assessment.     

Chemotherapy for patients with non-small cell lung cancer: the surgical setting of the Big Lung Trial.

OBJECTIVES: The non-small cell lung cancer (NSCLC) meta-analysis suggested a survival benefit for cisplatin-based chemotherapy when given in addition to surgery, radical radiotherapy or 'best supportive care'. However, it included many small trials and trials with differing eligibility criteria and chemotherapy regimens. The aim of the Big Lung Trial was therefore to run a large pragmatic trial to confirm the survival benefits seen in the meta-analysis. METHODS: In the surgery setting, a total of 381 patients were randomised to chemotherapy (C, 192 patients) or no chemotherapy (NoC, 189 patients). C was three 3-weekly cycles of cisplatin/vindesine, mitomycin/ifosfamide/cisplatin, mitomycin/vinblastine/cisplatin or vinorelbine/cisplatin. RESULTS: Chemotherapy was given before surgery in 3% of patients whilst 97% received adjuvant chemotherapy. Baseline characteristics were: median age 61 years, 69% male, 48% squamous cell, 93% WHO PS 0-1, 27% stage I, 38% stage II, and 34% stage III. Complete resection was achieved in approximately 95% of patients. In the C group, 13% received no chemotherapy, 21% one or two cycles, and 64% all three cycles of their prescribed chemotherapy (60% of the latter with no delays or modification). 30% had grade 3/4 toxicity, mainly haematological, nausea/vomiting and neutropenic fever, and six patients were reported as having a treatment-related death. 198 (52%) of patients have died, but there is currently no evidence of a benefit in overall survival to the C group: HR 1.02 (95% CI 0.77-1.35), P = 0.90). CONCLUSIONS: This trial has failed to observe a survival benefit with adjuvant chemotherapy following complete resection of stage I-III NSCLC. However, the hazard ratio and 95% confidence intervals are consistent with the previously reported meta-analysis and two large recently reported trials, which suggest a small survival benefit with cisplatin-based chemotherapy.     

50例晚期胰腺癌三维适形放疗的近期疗效分析

目的 分析三维适形放疗治疗晚期胰腺癌的疗效及相关预后因素.方法 50例不能手术的晚期胰腺癌病人,采用常规分割的三维适形放疗;其中14例采用姑息性放疗(A组),给予10.8～56 Gy;27例采用单一三维适形放疗(B组),剂量范围为8～60.5 Gy;9例采用同步放化疗的方法(C组),剂量范围为10～64 Gy.同步放化疗中化疗采用吉西他滨(200～600 mg/m~2,1次/周).结果 随访时间为3～35个月,死亡43例,死亡原因主要为肝脏和(或)腹腔内的广泛转移、恶液质、继发感染和出血.存活7例中3例为同步放化疗,3例为单一放疗,1例为姑息治疗.A组存活1人,放疗后局部症状缓解率46%(6/13),平均生存时间5.07个月;其中放疗剂量小于45 Gy的病人有10例,平均存活时间为4.33个月;放疗剂量≥45 Gy者3例,平均存活时间为7.33个月.B组存活3例,治疗后疼痛缓解率为81%(22/27),平均存活6.65个月,其中放疗剂量小于45 Gy的有11例,平均存活时间为4.36个月;放疗剂量≥45 Gy者16例,平均存活时间为8.33个月.C组存活3例,治疗后疼痛缓解率为89%(8/9),放疔后平均存活9.89个月,其中放疗剂量小于45 Gy的有1例,存活时间为3个月;放疗剂量≥45 Gy者8例,平均存活时间为10.73个月.结论 三维适形放疗对晚期胰腺癌有姑息治疗的作用,疗效与治疗方式的选择、放疗剂量、病变累及范围和病人一般状态密切相关.对于部分晚期胰腺癌病人,采用积极同步放化三维适形放疗可获得较长的生存时间.     

The role of radio-oncology in the treatment of bronchial cancer

The treatment results obtained in patients with both small and non small cell lung cancer have remained stagnant for years. Therefore, in order to select patients who will have a profit from radiotherapy the indication has to take into account prognostic factors such as tumor stage, extent of resection, patient's age, lymph node status, weight loss and the patient's performance status. Non small cell lung cancer: Postoperative radiotherapy seems to benefit only in patients with hilar or mediastinal lymph node involvement, where a five-year survival rate of up to 30% of cases can be achieved. Postoperative irradiation should not be applied following curative resection and negative lymph node status (R0 N0). In inoperable cases conventional fractionated radiotherapy may definitively have a favourable effect on the patient's survival time, even when the treatment was originally intended to be merely palliative. Only those patients will live five years, who received more than 50 Gy to the hilar and mediastinal nodes and at least 60 Gy to the primary lesion. The volume to be irradiated must include the primary tumor, the ipsilateral and contralateral hilum, the mediastinum, and both supraclavicular regions. If a Pancoast tumor is present, radiotherapy alone obtains a similar result as preoperative irradiation followed by resection. Small cell lung cancer: Radiation treatment of the primary tumor region and the lymph drainage area increases the remission rate by roughly 20% compared with chemotherapy alone, considerably reduces the incidence of local recurrences and exerts a beneficial effect on the survival of the patients. Recently, this has been confirmed by prospectively randomised protocols. Prophylactic brain irradiation has been found to decrease the risk of cerebral metastases to 4-6% in patients affected by limited disease and complete tumor remission under chemotherapy, and to improve the quality of life without, however, showing the benefit on survival time. Future efforts in radiotherapy should be aimed not only at increasing dose intensities but also at developing less toxic treatment modalities to the benefit of the quality of life.     

Radiotherapy and Prostate Cancer: Quo Vadis?

ContextRadiotherapy (RT) is one of the curative treatment options for clinically localised prostate cancer. Technical developments over recent years have yielded better conformation to the target volume, thus increasing the therapeutic ratio and decreasing side-effects.ObjectiveOur aim was to summarise current controversies in prostate cancer RT.Evidence acquisitionThis paper is based on a presentation given at the 7th Meeting of the European Association of Urology Section of Oncological Urology in Vienna, Austria. Data from reviews and original papers were compiled and interpreted.Evidence synthesisEvidence from randomised trials has indicated that total doses >72 Gy are significantly better in cases of biochemical disease-free survival. Image-guided radiotherapy resulted in reduced safety margins around the prostate target volume and decreased acute and late side-effects. To date, data from two randomised controlled trials have indicated comparable results between hypofractionation and normofractionation without an increase of side-effects. Until now, no prospective data have been published to support the hypothesis that proton therapy decreases late side-effects with comparable results to three-dimensional conformal intensity-modulated RT. Adjuvant RT for positive margins after radical prostatectomy (RP) has proved to be an advantage. Three phase 3 trials achieved a significant better biochemical nonevidence of disease of 20% for 5 yr. In one of these trials, survival also improved significantly with adjuvant radiation. However, salvage radiotherapy (SRT) is a possible option for a persisting or increasing prostate-specific antigen after RP. To date, there are no published randomised trials to compare adjuvant RT with SRT.ConclusionsDuring the few last years, there have been tremendous technological improvements with a focus on boosting the cure rate by increasing dose delivery while maintaining a similar or improved side-effect profile. Currently, efforts are also focused on shortening treatment times and improving efficacy through new technology.     

Vermeidung des Lokalrezidivs durch eine adjuvante Strahlentherapie nach radikaler Prostatektomie

Depending on the tumor stage, 15-60% of patients develop a rise in PSA from levels around zero following radical prostatectomy. It is unclear whether this involves a local, systemic, or a mixed form of local/systemic progression. In addition to a multitude of retrospective studies, the results of three randomized trials are available that have already been published in full or in abstract form.For pT3 prostate cancer with extraprostatic extension, data are available from three randomized trials that consistently evidence an absolute decrease in biochemical progression rate of 20% after 4-5 years. These findings confirm the results of numerous retrospective studies. The large majority of authors employ total radiation doses of 60 Gy with single doses of 2 Gy. One randomized trial has shown that an increased local control rate is the basis for prolonged biochemical progression-free survival. The rate of acute and late radiation sequelae after three-dimensionally planned prostatic fossa radiotherapy (RT) with 60 Gy is very low; the rate of more severe late sequelae is <2%. Data on the status of pT2 prostate cancer with positive surgical margins are worse. The current findings are controversial and require further investigations. Basically, however, adjuvant RT is also possible for pT2 cancers with positive surgical margins. The efficacy of adjuvant RT for patients with positive surgical margins of pT3 carcinomas, whether or not they achieve PSA levels around zero, has been substantiated. A prolongation of survival time has, however, not yet been established because the follow-up period is too short. Randomized trials are still needed for cases of organ-confined prostate cancer (pT2 R1). It is unclear whether adjuvant RT is superior to RT when PSA levels increase beyond zero after radical prostatectomy. Randomized trials addressing this issue are still lacking.     

Chemotherapy versus supportive care in advanced non-small cell lung cancer: improved survival without detriment to quality of life

BACKGROUND: In 1995 a meta-analysis of randomised trials investigating the value of adding chemotherapy to primary treatment for non-small cell lung cancer (NSCLC) suggested a small survival benefit for cisplatin-based chemotherapy in each of the primary treatment settings. However, the meta-analysis included many small trials and trials with differing eligibility criteria and chemotherapy regimens. METHODS: The aim of the Big Lung Trial was to confirm the survival benefits seen in the meta-analysis and to assess quality of life and cost in the supportive care setting. A total of 725 patients were randomised to receive supportive care alone (n = 361) or supportive care plus cisplatin-based chemotherapy (n = 364). RESULTS: 65% of patients allocated chemotherapy (C) received all three cycles of treatment and a further 27% received one or two cycles. 74% of patients allocated no chemotherapy (NoC) received thoracic radiotherapy compared with 47% of the C group. Patients allocated C had a significantly better survival than those allocated NoC: HR 0.77 (95% CI 0.66 to 0.89, p = 0.0006), median survival 8.0 months for the C group v 5.7 months for the NoC group, a difference of 9 weeks. There were 19 (5%) treatment related deaths in the C group. There was no evidence that any subgroup benefited more or less from chemotherapy. No significant differences were observed between the two groups in terms of the pre-defined primary and secondary quality of life end points, although large negative effects of chemotherapy were ruled out. The regimens used proved to be cost effective, the extra cost of chemotherapy being offset by longer survival. CONCLUSIONS: The survival benefit seen in this trial was entirely consistent with the NSCLC meta-analysis and subsequent similarly designed large trials. The information on quality of life and cost should enable patients and their clinicians to make more informed treatment choices.     

An assessment of quality of life following radical prostatectomy, high dose external beam radiation therapy and brachytherapy iodine implantation as monotherapies for localized prostate cancer

PURPOSE: Monotherapy with radical prostatectomy, high dose external beam radiotherapy or a (125)I implant is reported to produce equivalent outcomes. We assessed the health related quality of life associated with these 3 treatment approaches. MATERIALS AND METHODS: Extended Prostate Index Composite surveys were mailed to all 960 patients treated with a (125)I implant, high dose external beam radiotherapy or radical prostatectomy with or without hormonal therapy at our institution from 1998 to 2000. A total of 625 patients (65%) completed the surveys. Nerve sparing radical prostatectomy was performed when appropriate. The (125)I implant consisted of 145 Gy and high dose external beam radiotherapy consisted of 78 Gy. For urinary, rectal and sexual domains mean scores were calculated, compared by treatment modality and compared to normative values. RESULTS: A total of 234 patients with radical prostatectomy, 135 with external beam radiotherapy and 74 with a (125)I implant were treated with a monotherapy approach. Median age was 61 years in the radical prostatectomy group, 68 years in the high dose external beam radiotherapy group and 64 years in the (125)I implant group (p <0.001). Of the patients 97% [corrected] had cT1-2 disease and Gleason score 7 or less [corrected] Median time from treatment was 4.0 years for radical prostatectomy, 4.7 years for high dose external beam radiotherapy and 3.5 years for (125)I implantation. Radiation caused significantly worse bowel bother and bowel function than radical prostatectomy (p < or =0.018). Patients with high dose external beam radiotherapy had significantly better urinary function than patients with radical prostatectomy (p <0.001). While patients with radical prostatectomy had significantly worse urinary incontinence than those with a (125)I implant or high dose external beam radiotherapy (p <0.0001), patients with a (125)I implant had more urinary irritation than those with high dose external beam radiotherapy and radical prostatectomy (p <0.01 and <0.0001, respectively). Patients with a (125)I implant had significantly better sexual function than those with high dose external beam radiotherapy and radical prostatectomy (p = 0.01 and 0.0003, respectively). CONCLUSIONS: Of patients with prostate cancer treated with a monotherapy approach we noted better urinary continence in those who underwent radiation based therapies, and better bowel function and less urinary irritation in those who underwent surgery. Sexual function was impaired across all monotherapies but higher scores were seen in men who selected brachytherapy.     

Brachytherapy for prostate cancer: a systematic review of clinical and cost effectiveness

OBJECTIVES: Brachytherapy is emerging as a new treatment option for prostate cancer, and is increasingly being used in Europe and North America. METHODS: A systematic review of studies that compared clinical or cost effectiveness of prostate brachytherapy with radical prostatectomy or external beam radiation for patients with localised prostate cancer. RESULTS: No randomised controlled trials were identified, but five observational studies with comparable patient groups were included in the review. There were no valid data on overall or disease-free survival. There was no difference in disease-free survival based on PSA as a surrogate measure, or in rates of complications. No cost effectiveness studies were found. Based on Norwegian data, the one-year cost of the three treatment options seem fairly similar, while long term cost data are lacking due to lack of data on long term clinical outcome. CONCLUSION: The evidence on the clinical effectiveness of therapies for localised prostate cancer is scarce, but the outcome appears to be comparable for radical prostatectomy, external beam radiotherapy and brachytherapy.     

Adjuvant goserelin improves clinical disease-free survival and reduces disease-related mortality in patients with locally advanced or localized prostate cancer

This article reviews the clinical disease-free survival (DFS) and disease-related mortality (DRM) data from published prospective, randomized trials of goserelin, given alone as adjuvant treatment or combined with a nonsteroidal antiandrogen as neoadjuvant treatment in patients with locally advanced or localized prostate cancer. Four trials were of radiotherapy and one of radical prostatectomy. The five trials included > 3500 patients and the median follow-up was 4.8-7.1 years. There were statistically significant improvements in clinical DFS with goserelin support relative to the control treatment in all five trials (each log-rank P 相似文献   

The present status of postoperative adjuvant chemotherapy for completely resected non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) constitutes approximately 85% of all lung cancers, with patients having a poor prognosis. Approximately one third of NSCLC patients present with early-stage disease in which potentially curative resection and multi-modality therapy. Although adjuvant chemotherapy is the standard practice for patients with stages I-III breast and colorectal cancer, the therapeutic efficacy of adjuvant chemotherapy, following complete surgical resection of early stage NSCLC, has not been fully established. Several prospective randomized trials for patients with early stage NSCLC (stages I-IIIA) have confirmed a survival benefit with cisplatin-based adjuvant chemotherapy, as demonstrated in the 1995 meta-analysis performed by the NSCLC Collaborative Group. Studies from Japan have reported that adjuvant therapy with uracil-tegaful (UFT) afforded an improvement of 4% in the 5-year survival rate and a relative risk reduction of 26% in mortality at 5 years among patients with T1-2N0 (stage I) disease. In particular, the Japan Lung Cancer Research Group has demonstrated an improvement in the 5-year survival rate of 11%, favoring chemotherapy with UFT in the subset of patients with T2N0 (stage IB) disease. Two published meta-analyses based on abstracts have estimated a relative risk reduction in mortality of 11-13% at 5 years. The Lung Adjuvant Cisplatin Evaluation (LACE), which was based on a pooled analysis of five randomized trials, has demonstrated that cisplatin-based adjuvant chemotherapy improved survival in patients with completely resected NSCLC. This benefit depended on stage, being greatest in patients with stage II or IIIA disease. This analysis has suggested that platinum-based adjuvant chemotherapy may have no benefit for patients with stage IA and only a marginal benefit for patients with stage IB. Thus, the information available at the current time supports the administration of adjuvant chemotherapy for patients who have undergone complete resection of stages IB-IIIA NSCLC. Further research is needed to define the role of adjuvant platinum-based chemotherapy and its use, in conjunction with chest radiotherapy as the treatment for patients with resected stages IB and IIIA NSCLC.     

Results of surgery following radical radiotherapy for invasive bladder cancer

Five hundred and ninety-one of 889 patients with T1 to T4 transitional cell carcinoma of the bladder had persistent or recurrent cancer after radical radiotherapy. Durable local control was significantly poorer for patients with grade 1 or T4 cancer before radiotherapy. Three hundred and twenty-two patients received additional surgical treatment: 211 were endoscopically managed and 111 had secondary cystectomy. The survival of patients with residual or recurrent cancer after radiotherapy was significantly improved by secondary local treatment (P less than 0.0001). A comparison was made between endoscopic treatment and cystectomy after radiotherapy. Patients having secondary cystectomy were younger (mean age 60.0 years) than those managed endoscopically (66.8 years). The 5-year actuarial survival rate (from the date of radiotherapy) for patients who had endoscopic treatment was 47.1% compared with 62.5% for those who had cystectomy (P = 0.16). After both treatments survival was significantly correlated with the T category of the tumour before radiotherapy. Local tumour control was better after cystectomy; 85.6% of patients were locally tumour-free at the end of follow-up compared with 44.5% of those managed endoscopically. There was no overall difference in the subsequent risk of metastases between the two forms of surgery. However, seven of 12 patients managed endoscopically prior to secondary cystectomy died of their cancer. Five of these patients died from metastases even though they were locally disease-free. There was a significantly increased risk of metastases in patients managed endoscopically who were not locally disease-free after treatment (P = 0.0003). Caution is advised in persisting with endoscopic treatment after radiotherapy if local control is not readily achieved.     

The integrated radiosurgical treatment of rectal cancer

The value of radio-surgical protocols in the treatment of advanced rectal cancer has been studied retrospectively. 21 patients operated between 1986 and 1990 fulfilling some criteria were considered for this study. They were 9 men and 12 women with rectal cancer Duke's stage B2-C; 16 were treated with preoperative radiotherapy (30-35 Gy), 5 were treated with postoperative radiotherapy (40-60 Gy). The operative procedures were 12 anterior resections and 9 Miles operations. The 5 years results were: a) cancer free survival 52%; 2 patients alive with relapse; 2 patients with non cancer related death (DIC, radiation enteritis); d) cancer related deaths 28%; e) local recurrence was observed (3 pts) only in association with metastatic disease; f) no isolated local recurrence was observed. Preoperative radiotherapy with 30-35 Gy is judged the preferred protocol for decreasing the rate of isolated local recurrence and for increasing the survival rate. Omental flap transposition plays an important role in the radio-surgical treatment of advanced rectal cancer.     

Brachytherapy for the treatment of recurrent prostate cancer after radiotherapy or radical prostatectomy

What's known on the subject? and What does the study add? The curative treatment of prostate cancer includes surgery, external beam radiation or interstitial radiation. However, a high percentage of patients may develop recurrent disease, which is often localised. The possibilities of treatment in these cases, including surgery or adjuvant radiotherapy, are not well defined. Brachytherapy is a well established first-line treatment option. We review and update the use of brachytherapy in the treatment of recurrences post-radiotherapy, brachytherapy or radical prostatectomy as an alternative to surgery and radiotherapy, with a focus on functional and oncological outcomes. Salvage therapeutic options following radical prostatectomy or radiotherapy for patients with local relapse of prostate cancer include radical prostatectomy, radiotherapy, brachytherapy or cryotherapy. Salvage radical prostatectomy following radiotherapy failure is associated with a 5-year PSA relapse-free rate of 30-40%. Biochemical relapse-free survival rates after salvage radiotherapy following radical prostatectomy failure range from 10% to 77% after a follow-up of 22-60 months. A number of studies have evaluated salvage brachytherapy for radiotherapy failure and 5-year biochemical disease-free survival (bDFS) rate results reported are of the order of 20-87%; one study reported a 10-year bDFS rate of 54%. Fewer studies in small numbers of patients and with shorter follow-up have been conducted on brachytherapy for radical prostatectomy failure and bDFS rates reported include 25.8% at a median of 29 months to 70% at a median of 20 months. The side-effects were as expected for brachytherapy. A newer initiative conducted in Spain in a larger series of 42 patients with failure following radical prostatectomy involves brachytherapy with RAPID Strand?(125) I seeds and real-time placement. The 5-year bDFS rate was 88.6% and cancer-specific survival was 97%; complication rates were low. Optimization of salvage brachytherapy is under way and involves accurate placement of seeds, dose optimization and optimal patient selection.