Value of radiotherapy and chemotherapy in treatment of operable cancers of the esophagus

Radiotherapy and chemotherapy have been used for more than twenty years as adjuvant treatment of operable cancer of the esophagus. The palliative effect of adjuvant (or neoadjuvant) radio- and/or chemotherapy has been demonstrated in numerous randomized trials. The purpose of this review is to present the principal randomized trials conducted in the treatment of operable cancer of the esophagus. Alone, radiotherapy does not significantly improve survival in patients with operable cancer of the esophagus, irrespective of the pre- or postoperative timing (three trials and one meta-analysis for preoperative, three trials for postoperative, and one trial for pre- and postoperative radiotherapy). Likewise, alone chemotherapy does not significantly improve survival whether given preoperatively (four trials), postoperatively (two trials) or pre- and postoperatively (one trial). Radiochemotherapy combinations appear to provide more hope, but preliminary results are insufficient to draw a clear conclusion. Nevertheless, trial comparing radiotherapy results with chemotherapy, conducted pre- or postoperatively (four trials) appear to demonstrate a significant effect of chemotherapy. The two trials using neoadjuvant therapy have been conducted on patients with adenocarcinomas of the cardia and/or the lower esophagus and have demonstrated very encouraging results for a small number of patients. Finally, the Herslovic trial, while conducted in patients who were initially inoperable, is the only one which has demonstrated superiority of radiochemotherapy over radiotherapy alone. In conclusion, there is still much room for improvement in survival using combined radio- and chemotherapy with different forms (new agents, new associations) and treatment modes (pre- and postoperative or postoperative alone). Despite the wide use of radiotherapy and chemotherapy for cancer of the esophagus, it must be recalled that surgical resection remains the method providing the best chances of survival.     

胸段食管鳞癌的多学科综合治疗

食管癌患者就诊时大多已为中晚期,第七版UICC食管癌新分期Ⅲ期以上肿瘤单纯手术切除往往疗效不满意,系统性的多学科治疗至关重要.越来越多的证据表明术前同期放化疗是最为有效的诱导治疗方式,可使肿瘤降期并提高根治性切除率;针对食管鳞癌中常见的多组、多野淋巴结转移患者,术前诱导化疗不失为可行的选择.对于已根治性手术切除的局部进展期肿瘤,术后辅助放疗或有助于弥补手术清扫范围的不足以加强局控;术后辅助化疗的作用亦有待进一步深入研究.胸段食管鳞癌与西方国家常见的食管下段腺癌有本质的不同,需要积累更多的前瞻性临床研究,以形成适合我国食管癌患者的综合治疗模式.     

Quelle stratégie thérapeutique devant un cancer du rectum avec métastases hépatiques synchrones ?

Rectal cancer with synchronous liver metastases includes a wide variety of clinical presentations. In patients with rectal cancer and synchronous liver metastases, treatment strategy depends on the site and the extent of rectal cancer, the extent of liver metastases and the presence of extra-hepatic disease. In the majority of patients, liver metastases are unresectable and in this setting, the primary goal of treatment strategy is to prolong survival and to preserve quality of life. Most of these patients are treated with systemic chemotherapy and local treatment including radiotherapy or surgical resection is indicated in patients presenting with symptoms or complications related to the primary tumor. In patients with resectable liver metastases, a curative approach to the disease including resection of rectal cancer and liver metastases should be proposed. In this setting, a large number of treatment options can be discussed especially regarding the use of preoperative treatments (radiotherapy, radiochemotherapy or chemotherapy) and the design of surgical strategy (simultaneous resection of rectal cancer and liver metastases or staged resection). Treatment strategy should aim at conciliating optimal treatment for all tumor sites. Accurate pretreatment workup contributes to identify the most advanced tumor site that should be treated first without compromising optimal treatment of the other site. None standard treatment approach can be define for all patients presenting with rectal cancer and synchronous liver metastases because this entity includes a wide variety of clinical presentation and a large number of treatment options are available. Treatment strategy should be discussed during multidisciplinary meeting at diagnosis.     

Adjuvant therapy of colorectal cancer: an overview

The substantial recurrence rate of colorectal cancer following potentially curative resection has fuelled the search for effective adjuvant therapy. Previous trials using 5-fluorouracil (5-FU) as a single agent or in combination chemotherapy regimens have not demonstrated meaningful benefits, an impression reflected in the results of a meta-analysis encompassing large patient numbers. Newer developments utilizing intraportal chemotherapy and the combination of 5-FU and levamisole have resulted in lower recurrence rates and improved survival in patients with colon cancer. In advanced disease, the biochemical modulation of 5-FU by Leucovorin has been shown to prolong survival in some studies. Combined chemotherapy and radiotherapy or chemotherapy alone have showed promising results in rectal cancer. These developments have now been incorporated into ongoing trials.     

Adjuvant radiochemotherapy – what is the patients benefit?

Background: Local relapse is a major problem after potentially curative rectal cancer surgery. Although the incidence of local recurrences may be reduced by specialized surgical techniques such as total mesorectal excision (TME), local relapse rates of 20% or higher are the surgical reality today. Studies using adjuvant postoperative radiotherapy, chemotherapy, radiochemotherapy or immunotherapy have tried to reduce local relapse rates and distant progression. Postoperative radiochemotherapy has been the recommended standard, after complete resection of Union Internationale Contra la Cancrum (UICC) stages II and III rectal cancers. In view of recent positive results with preoperative radiotherapy of TME without adjuvant therapy, we found it important to review the literature to update the recommendable adjuvant procedure in rectal cancer. Method/Patients: The literature from 1985 to May 1998 was reviewed for studies trying to either confirm or improve adjuvant therapy in rectal cancer. Only randomized controlled trials were analyzed with regard to their effectiveness in reducing the absolute rates of local recurrence and improving survival. Results: Two trials applying adjuvant radiotherapy were able to demonstrate the reduction of local relapse rates, one trial with marginal significance, both without impact on survival. Four trials involving 1104 patients with rectal cancer stages UICC II–III compared postoperative radiochemotherapy with either surgical controls, adjuvant radiotherapy or conventional radiochemotherapy. In these trials, local relapse rates were significantly reduced by 11–18%, and survival rates significantly improved by 10–14%. Severe acute toxicities occurred in 50–61% of the patients, compromising compatibility, and caused death in 0–1%. Small-bowel obstruction leading to surgery was noted in 2–6% and to death in up to 2% of the patients. Intraoperative radiotherapy (IORT) improved local control and survival after surgery of locally advanced disease/local relapse. Conclusion: In view of four trials demonstrating a significant benefit of postoperative radiochemotherapy and with regard to recent still-debatable results of preoperative short-term radiotherapy optimal surgery with lowest local relapse rates plus postoperative radiochemotherapy remains the actual recommendable standard for rectal cancer surgery in R0 resected tumors stages UICC II+III. Received: 1 September 1998 / Accepted: 15 September 1998     

腹腔镜联合辅助化疗及内镜治疗进展期结直肠癌合并腺瘤的应用研究

目的：探讨腹腔镜结直肠癌切除术加辅助化疗加二期内镜下治疗结直肠癌合并根治术切除范围外结直肠腺瘤的临床应用价值。方法：2005年1月-2010年6月对54例进展期结直肠癌合并根治术切除范围外结直肠腺瘤（〉1．0cm）的患者（研究组）行腹腔镜结直肠癌切除术加辅助化疗（FOLFOX4方案）加二期内镜下腺瘤切除的综合治疗,对同期396例单发进展期结直肠癌患者（对照组）行腹腔镜结直肠癌切除术加辅助化疗（FOLFOX4方案）。通过并发症发生率、长期随访等评价治疗效果。结果：2组患者在年龄、性别、手术方式、手术时间、术中出血量、并发症发生率、平均住院时间、肿瘤大小、淋巴结转移、TNM分期及1、3和5年存活率差异无统计学意义（P〉O．05）。研究组辅助化疗后对合并腺瘤进行内镜下切除治疗,4例出血经保守治疗后成功止血,未发生穿孔、狭窄等严重并发症;3例患者术后病理组织学检查为腺瘤癌变,其中2例癌变局限于腺瘤中,1例癌细胞侵犯达黏膜下层,该例患者再次行腹腔镜下切除,术后随访无复发。结论：腹腔镜联合辅助化疗及内镜为合并结直肠癌根治术切除范围外腺瘤的患者提供了一种安全有效的微创治疗方法,值得临床推厂和应用。     

Perioperative therapy for esophageal cancer

Traditionally, surgery is considered the best treatment for esophageal cancer in terms of locoregional control and long-term survival, but survival after surgery alone for locally advanced esophageal cancer is not satisfactory. A multidisciplinary approach that includes surgery, radiotherapy, and chemotherapy, alone or in combination, has been developed to improve the prognosis. Multiple clinical trials have addressed the preferred treatment strategy, such as neoadjuvant or adjuvant and chemotherapy, radiotherapy, or chemoradiotherapy, in managing locally advanced esophageal cancer. In this review, we provide an update on treatment strategies for locally advanced esophageal cancers. Recent studies indicate that neoadjuvant chemoradiotherapy or chemotherapy has a survival benefit over surgery alone in this patient group. Neoadjuvant chemoradiotherapy is an accepted standard of care in the United States while neoadjuvant chemotherapy is regarded as standard treatment in Japan and the United Kingdom. The standard treatment differs among countries because two large randomized controlled trials that evaluated the effectiveness of neoadjuvant chemotherapy reported conflicting results and no trial has made a comparison between neoadjuvant chemoradiotherapy and neoadjuvant chemotherapy directly. Future trials in locally advanced esophageal cancer should focus on identifying the optimum strategy and its regimen and aim to minimize treatment toxicities and effects on quality of life.     

Neoadjuvant therapy of esophageal cancer

Neoadjuvant (preoperative) chemotherapy, with or without radiotherapy, is under intense study. There are theoretical and practical reasons for the preoperative use of systemic therapy: (a) laboratory studies support the use of preoperative treatment in animal models, (b) the relapse pattern of esophageal cancer is primarily systemic and (c) the impact on palliation if response is associated with an improved resection rate. Three techniques involving systemic therapy are currently under investigation: (a) chemotherapy alone followed by a planned surgical procedure; (b) chemotherapy and concurrent radiotherapy followed by a planned surgical procedure; (c) chemotherapy and radiotherapy without surgery. Phase II trials of the first technique have demonstrated its feasibility without an increase in operative morbidity or mortality. Two small-scale phase III trials have confirmed chemotherapy's efficacy but have not clearly demonstrated an impact on survival. Large-scale phase III trials are under way, or about to begin, to test definitively the hypothesis that neoadjuvant chemotherapy improves disease-free and overall survival in operable patients. The second technique has also been tested in small-scale phase II trials. Most recently, a large-scale phase II trial has been reported which suggests that this technique has not had a major effect on resection rates or on long-term survival for most patients. These treatment plans are tolerable if careful attention to detail is given. Definitive phase III trials testing the superiority of multimodality treatments over radiotherapy alone or surgery alone are under way.     

Adjuvant therapy for locally advanced gastric cancer

D2 gastrectomy is now the globally accepted surgical standard for locally advanced gastric cancer. However, since 2000, different evidence has emerged regarding the efficacy of adjuvant chemoradiation, perioperative adjuvant chemotherapy, and postoperative chemotherapy for locally advanced gastric cancer. This review summarizes the background, current status, and future perspectives of adjuvant therapy for locally advanced gastric cancer. The Intergroup 0116 study was the first to show the significant overall survival benefits of adjuvant (chemoradiation) therapy for gastric cancer. The second study was the MAGIC trial, which showed the efficacy of perioperative adjuvant chemotherapy. Although the findings from the Intergroup 0116 study and the MAGIC trial were positive, recent studies, such as the ARTIST and EORTC 40954 studies, found no survival benefit for patients who had undergone D2 gastrectomy for gastric cancer. Regarding the adjuvant chemotherapy strategy, two pivotal phase III trials: the ACTS-GC and the CLASSIC, demonstrated the efficacy of postoperative adjuvant chemotherapy following D2 gastrectomy. However, more intensive chemotherapy is necessary to improve the survival rate. Several studies have analyzed the effectiveness of molecular-targeted therapy against metastatic gastric or gastroesophageal junction carcinoma. Further studies should focus on the survival benefit of more-intensive adjuvant therapy with D2 resection, or with concurrent molecular-targeted therapy.     

Effect of Adjuvant Radiotherapy on Local Recurrence in Stage II Rectal Cancer

Background Prospective trials have demonstrated that chemotherapy combined with radiotherapy decreases local recurrence rates in stage II and stage III rectal cancer. Some patients with stage II lesions, however, have relatively low risks of local recurrence. We evaluated the effect of radiotherapy on local recurrence in patients with stage IIA rectal cancer. Methods From the colorectal cancer database, we identified 390 stage IIA rectal cancer patients who underwent curative resection followed by adjuvant therapy from 1995 to 2002; a total of 72 patients who received preoperative chemoradiotherapy and who did not receive adjuvant therapy were excluded. Mean follow-up period was 65 months (range, 2–133 months). Results Of the 390 patients, 110 had primary tumors in the upper rectum, 136 in the midrectum, and 144 in the lower rectum. Lymphovascular invasion was observed in 35 patients (9.0%). Mean (± SD) number of examined lymph nodes was 18 (± 12). Adjuvant chemotherapy was provided to 180 patients (46.2%), and chemotherapy plus radiotherapy was provided to 210 patients (53.8%). Radiotherapy was significantly more common in younger patients (P = .01) and those with lower rectal cancer (P < .001). Local recurrence rate did not differ between patients who did and did not receive radiotherapy. In patients with mid and lower rectal cancer, the local recurrence rate was not affected by radiotherapy. Conclusions Radiotherapy did not seem to provide additional benefit in decreasing local recurrence rate of stage IIA rectal cancers. In selected patients, however, the role of radiotherapy needs to be carefully evaluated.     

Therapeutic approach in locally advanced and complicated rectosigmoid and genital cancers

Locally advanced and complicated rectosigmoidian and genital cancers raise many therapeutic problems for surgeons. The most frequently used therapeutic methods nowadays are: radiotherapy, chemotherapy, surgical procedures, immunotherapy and other modern methods that aren't in the current clinical use yet. In a trial of 456 patients with locally advanced and complicated rectosigmoidian cancers and 632 patients with genital cancers we performed 573 (52.6%) radical surgical procedures and 515 (47.4%) palliative procedures, 301 (27.6%) of these being permanent colostomy (257 terminal and 44 in continuity). All of the patients received radiotherapy or chemotherapy pre and/or after surgery. The survival was between 5-7 months in the trial of patients with permanent colostomy, between 12-36 months in the trial of patients with palliative surgical procedures and adjuvant treatment and between 5-17 years in the trial of patients with radical surgical procedures and neo- and adjuvant therapy.     

Colorectal cancer patterns of care in the Western Sydney and Wentworth Area Health Services

INTRODUCTION: Colorectal cancer is a leading cause of morbidity and mortality in Australia. Recent clinical trials show that the recurrence of colorectal cancer decreases with chemotherapy and/or radiotherapy in advanced disease. The present study aimed to document the patterns of care by the type of treatment, document the preoperative investigations and provide results to the Area Health Services. METHODS: A prospective data collection was initiated in May 1994 and ended in May 1996 in the Western Sydney and Wentworth Area Health Services of New South Wales. Deaths and recurrences were followed up until July 2002. RESULTS: There were 253 colon cancers, 107 rectal cancers and 10 patients with tumours in both the colon and rectum. Forty-one surgeons performed 299 curative procedures with 78% of them performing one to four procedures annually. One hundred and twenty-two patients had non-fatal complications and six (2%) died postoperatively. Twenty-eight per cent of rectal cancer patients underwent abdomino-perineal resection and 56% underwent low anterior resection. Forty-five per cent of rectal cancer patients and 51% of colon cancer patients who were potentially eligible received appropriate adjuvant therapy. Ninety-one per cent of patients who received chemotherapy had no or mild toxicity. By the end of follow-up period, 30% of rectal cancer patients and 24% of colon cancer patients had developed recurrence. At last follow up, 197 patients had died. Median overall survival from time of diagnosis was 73 months. Overall 5-year survival for colonic and rectal cancers was 50% and 57%, respectively. For the 299 patients who had curative procedures, the 5-year survival was 63% and 62% for colonic and rectal cancers, respectively. CONCLUSION: Colorectal cancer patients who were eligible for and received adjuvant therapy had significantly better survival. Rectal cancer patients whose tumours only required low anterior resection had a better survival than those who needed an abdomino-perineal resection. High-volume surgeons have less postoperative complications than low-volume surgeons. The high proportion of late presentations seen in colon cancer patients supports the need for screening to improve early detection.     

Laparoscopic resection with intraoperative radiotherapy: a new step in the multimodal treatment of advanced colorectal cancer

BACKGROUND: Local recurrence is one of the most important problems related to resection of rectal cancer in locally advanced cases (T3-T4). Total mesorectal excision (TME) is the mainstay of surgical therapy, although many articles have been published about the availability of intraoperative radiotherapy (IORT) for the control of locally advanced rectal cancers. METHODS: The authors describe six patients affected by advanced rectal cancer (T3N1) whom they treated with neoadjuvant radiochemotherapy and laparoscopic rectal resection combined with TME and IORT. RESULTS: The operative time did not exceed 6 h in any case with IORT treatment. The procedure itself and the transfer of patients to the radiotherapy room accounted for about 2 h. The postoperative course was uneventful in every case, and all the patients were discharged within the first 8 postoperative days. CONCLUSIONS: This report describes the technical aspect and the feasibility of IORT associated with laparoscopic surgical resection for rectal cancer.     

新辅助化疗方案在可切除结肠癌中的应用进展

新辅助化疗（NACT）是指针对潜在可根治切除的肿瘤患者,以消除微转移、降低肿瘤分期和手术难度、改善术后局部复发和远处转移等为目的,在肿瘤手术切除或放疗之前,先予以全身化疗,待手术或放疗之后继续完成全程化疗的综合方案。结肠癌是最常见的癌症之一,肿瘤根治性切除联合术后辅助化疗是临床潜在可根治切除结肠癌的主要治疗方式。虽然这种治疗模式较前显著改善了患者的预后,但术后局部复发和远处转移仍是患者最主要的致死因素。近年来NACT方案开始被引入局部进展期结肠癌和原发灶可切除的肝转移患者等潜在可根治切除结肠癌患者的治疗。然而,结肠癌患者是否适合NACT及其方案的选择还存在较大的争议。笔者就局部进展期结肠癌、可切除结肠癌肝转移等在NACT中的进展与争议,以及影像学检查对NACT的作用作一综述。     

Defining risk levels in locally advanced head and neck cancers: a comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501)

BACKGROUND: In 2004, level I evidence was established for the postoperative adjuvant treatment of patients with selected high-risk locally advanced head and neck cancers, with the publication of the results of two trials conducted in Europe (European Organization Research and Treatment of Cancer; EORTC) and the United States (Radiation Therapy Oncology Group; RTOG). Adjuvant chemotherapy-enhanced radiation therapy (CERT) was shown to be more efficacious than postoperative radiotherapy for these tumors in terms of locoregional control and disease-free survival. However, additional studies were needed to identify precisely which patients were most suitable for such intense treatment. METHODS: Both studies compared the addition of concomitant relatively high doses of cisplatin (on days 1, 22, and 43) to radiotherapy vs radiotherapy alone given after surgery in patients with high-risk cancers of the oral cavity, oropharynx, larynx, or hypopharynx. A comparative analysis of the selection criteria, clinical and pathologic risk factors, and treatment outcomes was carried out using data pooled from these two trials. RESULTS: Extracapsular extension (ECE) and/or microscopically involved surgical margins were the only risk factors for which the impact of CERT was significant in both trials. There was also a trend in favor of CERT in the group of patients who had stage III-IV disease, perineural infiltration, vascular embolisms, and/or clinically enlarged level IV-V lymph nodes secondary to tumors arising in the oral cavity or oropharynx. Patients who had two or more histopathologically involved lymph nodes without ECE as their only risk factor did not seem to benefit from the addition of chemotherapy in this analysis. CONCLUSIONS: Subject to the usual caveats of retrospective subgroup analysis, our data suggest that in locally advanced head and neck cancer, microscopically involved resection margins and extracapsular spread of tumor from neck nodes are the most significant prognostic factors for poor outcome. The addition of concomitant cisplatin to postoperative radiotherapy improves outcome in patients with one or both of these risk factors who are medically fit to receive chemotherapy.     

Symposium on rectal cancer: 3. The case for adjuvant radiotherapy for rectal cancer

Adjuvant radiotherapy for rectal cancer is intended to eradicate subclinical deposits of cancer cells not removed at surgery. These residual cells are found most commonly at the resection margin of the primary tumour and in transected cancer-bearing lymphatics or vessels. Refinements in surgical technique have been associated with a reduction in the risk of pelvic recurrence in some nonrandomized series. However, clinical trials have shown that the combinations of radiotherapy and chemotherapy, and in some instances radiotherapy alone, reduce the risk of recurrence and may improve survival rates compared with those of surgery alone. It is premature to consider that adjuvant pelvic radiotherapy is unnecessary.     

Multimodality management of locally advanced rectal cancer

Despite the routine use of adjuvant chemoradiation for curatively resected stage II and III rectal cancer a significant percentage of patients ultimately fail locally and/or distally; this underscores the need for continued improvement in the efficacy of combined-modality therapy and quality of rectal cancer resection. The recognition of the significance of lateral or circumferential margins of resection has paralleled the widespread use of total mesorectal excision. In addition to facilitating negative margins of resection and local control, sharp mesorectal techniques also facilitate identification and preservation of pelvic autonomic nerves thereby greatly reducing the incidence of urinary and sexual dysfunction following radical resection. Lastly, restorative options can result in excellent bowel function in carefully selected patients undergoing a "very low" anterior resection. Efforts are currently directed at identifying the subset of locally advanced rectal cancer patients who may be adequately treated with a resection alone thereby avoiding the added morbidity of adjuvant radiation and chemotherapy.     

Resection and radiochemotherapy of pancreatic cancer – the future?

Background: To improve the surgical outcome after resection of pancreatic adenocarcinomas, multimodal treatment concepts need to be applied and improved. The controversies among those being pro and contra adjuvant treatment need an up-to-date review of the indications and results achievable with various treatment modalities. Patients/Methods: The literature regarding the indications and results of adjuvant/neoadjuvant therapies in pancreatic cancer was reviewed to provide a solid base for current recommendations and future developments. The biology of the disease in the spontaneous course, after surgery and during/after various palliative and adjuvant/neoadjuvant treatment modalities was focussed on, to characterise the disease for an optimally targeted treatment in conjunction with surgical removal of the tumour. The results of systemic and regional chemotherapy and radiotherapy, either alone or in combination, before, during and after surgery were critically analysed with respect to the oncological possibilities and pitfalls of each treatment method. Results: In two randomised trials, one testing postoperative radiochemotherapy (GITSG), and one postoperative chemotherapy, the adjuvant treatment achieved a significant prolongation of the median survival time. The 5-year and 10-year survival rates were improved in the GITSG study. The EORTC-GITCCG trial could not confirm the benefit of adjuvant radiochemotherapy. This study had a different design than the GITSG trial. Several historical control studies supported the beneficial effect of postoperative radiochemotherapy. In three historical control trials using regional chemotherapy, one with intraoperative radiotherapy , the survival times were improved compared with surgery alone. Intraoperative or postoperative radiotherapy as single modalities might reduce local relapses, but a survival advantage is still debated. Preoperative neoadjuvant radiochemotherapy has several advantages (downstaging, devitalising margins and lymph node metastases, compatibility of treatment vs. postoperative radiochemotherapy), and does not seem to increase the postoperative morbidity. Several trials have confirmed the feasibility of this concept, but no survival advantage has yet been proven. Systemic and regional chemotherapy is able to downstage primarily nonresectable pancreatic cancers. Conclusions: Postoperative adjuvant radiochemotherapy with up-to-date protocols can be recommended for routine treatment, if the surgeon or the patient desires to improve the usually remote prognosis after surgery alone. For those being indecisive or against adjuvant therapy, the participation in trials, e.g. the ESPAC 1 and 2 studies, is strongly recommended. Regarding our own positive experience with adjuvant regional chemotherapy and in view of the postresectional progression pattern, we currently favour adjuvant radiochemotherapy, with the chemotherapy delivered regionally via the celiac axis. This concept will be tested against surgery alone in the ESPAC 2 trial. Neoadjuvant therapies have a great potential, but should be conducted within studies, such as pre-, intra-, or postoperative radiotherapy. Received: 13 February 1998     

Radical resection of rectal cancer primary tumor provides effective local therapy in patients with stage IV disease

Background The optimal use of radical surgery to palliate primary rectal cancers presenting with synchronous distant metastases is poorly defined. We have reviewed stage IV rectal cancer patients to evaluate the effectiveness of radical surgery without radiation as local therapy. Methods Eighty stage IV patients with resectable primary rectal tumors treated with radical rectal surgery without radiotherapy were identified. Sixty-one (76%) patients received chemotherapy; response information was available for 34 patients. Results Radical resection was accomplished by low anterior resection (n=65), abdominoperineal resection (n=11), and Hartmann’s resection (n=4). Surgical complications were seen in 12 patients (15%), with 1 death and 4 reoperations. The local recurrence rate was 6% (n=5), with a median time to local recurrence of 14 months. Only one patient received pelvic radiotherapy as salvage treatment. One patient required subsequent diverting colostomy. Median survival was 25 months. On multivariate analysis, the extent of metastasis and response to chemotherapy were determinants of prolonged survival. Conclusions For patients who present with distant metastases and resectable primary rectal cancers, radical surgery without radiotherapy can provide durable local control with acceptable morbidity. The extent of metastatic disease and the response to chemotherapy are the major determinants of survival. Effective systemic chemotherapy should be given high priority in the treatment of stage IV rectal cancer.     

SO01NEOADJUVANT: RECTAL CANCER

Neoadjuvant therapy is given before surgery to improve resectability, local control and/or survival. Post‐operative radiation therapy for locally advanced rectal cancer has been long accepted, and since 1990 adding fluorouracil (5FU) chemotherapy became the NIH standard. However, trials then showed that pre‐operative radiotherapy followed by surgery improved local control over surgery alone, but had a less consistent effect on overall survival. The German trial (Sauer, NEJM, 2004, 351:1731) showed a 5 year local relapse rate of 6% for pre‐operative chemo‐radiotherapy and 13% for post‐operative chemo‐radiotherapy for T3 or T4 or node‐positive rectal cancer treated by TME. The EORTC 22921 trial (37% had TME) showed a similar reduction in local recurrence whether 5FU/leucovorin chemotherapy was given with pre‐operative radiotherapy, after pre‐operative radiotherapy plus surgery, or both (Bosset, NEJM, 2006, 355:1114). Trials show increased rates of complete pathological remission, increased acute toxicity, but no consistent effects on sphincter preservation rates or overall survival when chemotherapy is combined with pre‐operative radiation. Many questions remain. The TROG/AGITG trial compares pre‐operative radiotherapy as a short course (5 Gy X 5♯) or long course with chemotherapy (50.4 Gy plus 5 FU infusion), with accrual just completed. Ongoing phase III trials explore capecitabine, adding other drugs to 5 FU, and post‐operative adjuvant chemotherapy. Neo‐adjuvant pre‐operative radiation with concurrent chemotherapy, unless contra‐indicated by comorbidity, has become widely accepted for T3 or T4 or node‐positive rectal cancer based on MRI staging. Individual patient care is best planned by a multidisciplinary team.