Preoperative Long-course Radiotherapy Research Articles

Healthcare Cost Analysis of Short-Course vs. Long-Course Pre-Operative Radiotherapy Schedules for Rectal Cancer

Purpose/Objective(s)One aspect of alternate radiotherapy (RT) techniques for rectal cancer not well studied in the United States is cost. Herein, we report a financial analysis to assess cost savings associated with short course (SC) versus long course (LC) RT and determine which parties (payor, patient, or both) benefit from the aforementioned savings.Materials/MethodsA focused analysis on neoadjuvant RT for operable rectal cancer was designed to study four regimens: (1) SC utilizing three-dimensional conformal RT (3DCRT) [SC-3D], (2) SC utilizing intensity-modulated RT (IMRT) [SC-IMRT], (3) LC utilizing 3DCRT [LC-3D], and (4) LCRT utilizing IMRT [LC-IMRT]. Variable and fixed patient costs were reported. Patient and payor costs based on regimen were summated to determine societal costs. A sensitivity analysis based on 40 rectal cancer patients per year using SC and LC RT was performed.ResultsTechnical costs account for most of the disparity between payor costs when selecting between IMRT and 3D ($2,472.25-7,623.13), while professional costs remain somewhat stable ($651.25-1,645.58). LCRT-related patient costs ($1,382.94) were found to be higher than SCRT patient costs ($353.22) as patients undergoing LCRT had a greater number of treatment days. This disparity persists when evaluating total societal cost, as the costliest regimen, LC-IMRT ($20,810.77), is almost twice the next expensive regimen, LC-3D ($11,503.00).ConclusionSocietal burden varies significantly with technique and length of treatment for pre-operative rectal cancer RT. Anticipated changes in health policy and reimbursement patterns are likely to disincentivize routine LC and IMRT use in rectal cancer. Further study into patient-centric and resource-conscious medical decision making is warranted. One aspect of alternate radiotherapy (RT) techniques for rectal cancer not well studied in the United States is cost. Herein, we report a financial analysis to assess cost savings associated with short course (SC) versus long course (LC) RT and determine which parties (payor, patient, or both) benefit from the aforementioned savings. A focused analysis on neoadjuvant RT for operable rectal cancer was designed to study four regimens: (1) SC utilizing three-dimensional conformal RT (3DCRT) [SC-3D], (2) SC utilizing intensity-modulated RT (IMRT) [SC-IMRT], (3) LC utilizing 3DCRT [LC-3D], and (4) LCRT utilizing IMRT [LC-IMRT]. Variable and fixed patient costs were reported. Patient and payor costs based on regimen were summated to determine societal costs. A sensitivity analysis based on 40 rectal cancer patients per year using SC and LC RT was performed. Technical costs account for most of the disparity between payor costs when selecting between IMRT and 3D ($2,472.25-7,623.13), while professional costs remain somewhat stable ($651.25-1,645.58). LCRT-related patient costs ($1,382.94) were found to be higher than SCRT patient costs ($353.22) as patients undergoing LCRT had a greater number of treatment days. This disparity persists when evaluating total societal cost, as the costliest regimen, LC-IMRT ($20,810.77), is almost twice the next expensive regimen, LC-3D ($11,503.00). Societal burden varies significantly with technique and length of treatment for pre-operative rectal cancer RT. Anticipated changes in health policy and reimbursement patterns are likely to disincentivize routine LC and IMRT use in rectal cancer. Further study into patient-centric and resource-conscious medical decision making is warranted.

Preoperative short-course radiotherapy (5 × 5Gy) with delayed surgery versus preoperative long-course radiotherapy for locally resectable rectal cancer: a meta-analysis.

Preoperative short-course radiotherapy (PSRT) and preoperative long-course radiotherapy (PLRT) are standard treatment regimens for locally advanced rectal cancer. However, whether the efficacy and safety of PSRT with delayed surgery (more than 4weeks) are superior to those of PLRT remains unresolved and was explored in this meta-analysis. Studies published in PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov databases were systematically searched. RevMan 5.3 was used to calculate pooled hazard ratios (HR) and relative risk (RR). Seven studies including 4973 patients were identified in the meta-analysis. Pooled statistics showed that there was no statistically significant difference in overall survival (HR = 1.30, 95% CI 0.58-2.89, P = 0.52) or disease-free survival (HR = 1.10, 95% CI 0.73-1.66, P = 0.64) between the preoperative short-course and long-course radiotherapy groups. Moreover, pathological complete remission, early postoperative complications, treatment-related grade 3/4 toxicity, local recurrence, and distant metastasis were similar between the two groups. Interestingly, a subgroup analysis revealed that preoperative short-course radiotherapy without adjuvant chemotherapy not only resulted in lower treatment-related grade 3/4 toxicity than the long-course radiotherapy group (RR = 0.19, 95% CI 0.08-0.48, P < 0.01) but also resulted in significantly lower overall survival and pathological complete remission (P = 0.02, P < 0.01, respectively). Disappointingly, pooled statistics observed few advantages over long-course radiotherapy in short-course radiotherapy with the adjuvant chemotherapy subgroup. PSRT with delayed surgery was as effective as PLRT for the management of locally resectable rectal cancer. However, not adding additional chemotherapy to PSRT not only significantly decreased grade 3/4 toxicity but also decreased pathological complete remission and overall survival. The protocol for this meta-analysis was prospectively registered with PROSPERO (CRD42019133641).

Neoadjuvant chemotherapy in the combination treatment for locally advanced rectal cancer: currently available options

Objective:to analyze treatment outcomes in patients with locally advanced rectal cancer that received various combinations of neoadjuvant chemotherapy and chemoradiotherapy.Materials and methods. In this retrospective study, we analyzed a cohort of prospectively recruited patients with stage mrT3(CRM+)/ T4N0–2M0 locally advanced rectal cancer. Participants were divided into three groups. Patients in Group 1 received preoperative longcourse radiotherapy given concurrently with capecitabine, followed by 2–6 cycles of consolidation chemotherapy with capecitabine and oxaliplatin (CapOx). In Group 2, patients initially received 1–2 cycles of induction chemotherapy with CapOx, followed by radiotherapy + capecitabine, and then consolidation chemotherapy with CapOx (“sandwich” method). Participants in Group 3 were treated with 1–3 cycles of induction CapOx chemotherapy with subsequent long-course chemoradiotherapy. After the combination treatment, all patients underwent surgery. The primary endpoint of this study was therapeutic pathomorphosis. Secondary endpoints included complete clinical response, toxicity, local recurrence, distant metastasis, and relapse-free survival.Results.This study included 155 patients (98 in Group 1, 44 in Group 2, and 13 in Group 3). Grade III toxicity was documented in 6.12 %, 4.55 %, and 23.08 % of cases in Groups 1, 2, and 3 respectively. None of the patients had grade IV toxicity. Grade III therapeutic pathomorphosis was achieved in 33.7 %, 22.7 %, and 23.1 % of patients in Groups 1, 2, and 3 respectively. Grade IV therapeutic pathomorphosis was observed in 14.3 %, 15.9 %, and 7.69 % of patients in Groups 1, 2, and 3 respectively. Complete clinical response was registered in 16.3 %, 11.4 %, and 0 % of cases in Groups 1, 2, and 3 respectively. Median follow-up was 47.2 months with no signs of progression. Relapses were observed in 1.02 % and 2.27 % of patients from Group 1 and Group 2 respectively, whereas Group 3 demonstrated no relapses. A total of 11.22 %, 13.64 %, and 23.1 % of participants from Groups 1, 2, and 3 respectively developed distant metastasis.Conclusion.Polychemotherapy used within the consolidation and «sandwich» treatment regimens is a promising option for the treatment of locally advanced rectal cancer. The efficacy of induction chemotherapy should be further studied with a larger sample.

Short-course versus Long-Course Preoperative Radiotherapy in Rectal Cancer: an Evidence Based Case report

Background Surgery is the mainstay therapy for colorectal carcinoma with curative intent, while radiotherapy and chemotherapy act as adjuvant or neoadjuvant therapy. The desicion for surgery depends on tumor resectability. Neoadjuvant radiotherapy, both short-course radiotherapy (SRT) or long-course radiotherapy (LRT) with or without concurent chemtherapy, is aimed to increase tumor resectability. This article compares advantages of SRT and LRT. Method We designed a search filter using relevant synonyms for the domain: “rectal carcinoma”, “resectable”, “preoperative radiotherapy”, and “short-course”. Publications are retrieved from PubMed, Cochrane Library, and EBSCO using MESH terms and search terms in title and abstract fields. Articles’ titles and abstracts from search result are screened for relevance. Eligible articles are selected based on inclusion and exclusion criterias. Selected articles are critically appraised for methods validity. Result Six articles are included in our study, consists of four randomized clinical trials and four metaanalyses. Conclusion SRT is as effective as LRT with or without chemotherapy in terms of overall survival, disease free survival, local recurrence rate, disease metastasis rate, free resection rate, and grade 3-4 toxicity. LRT with or without chemotherapy showed superiority in increasing pathological complete response rate and sphincter preservation rate. SRT is a better choice in centers with a long waiting list.

Evolving Treatment Paradigm in the Treatment of Locally Advanced Rectal Cancer.

Locally advanced rectal cancer (LARC) carries higher risks of local and distant recurrence when treated with surgical resection alone. Multiple treatment strategies have been investigated to reduce recurrence risk and improve survival. Currently, there are 3 primary strategies for managing LARC: (1) preoperative long-course radiotherapy (RT) combined with radiosensitizing chemotherapy, which is better tolerated than postoperative chemoradiotherapy and provides tumor downstaging and improved pathologic complete response (pCR), followed by postoperative chemotherapy; (2) preoperative short-course RT alone as an alternative strategy for reducing the risk of local recurrence, followed by adjuvant postoperative chemotherapy; and (3) total neoadjuvant therapy with induction chemotherapy followed by chemoradiotherapy to improve pCR and reduce the difficulty of delivering chemotherapy in the postoperative setting. In addition to these currently recommended treatment paradigms, promising new strategies are available for treatment reduction. Neoadjuvant chemotherapy alone may allow for omission of RT in select patients with favorable LARC. For patients who have complete clinical responses to neoadjuvant chemotherapy and RT, nonoperative management is being considered for sphincter preservation, with surgery used as salvage. These are active areas of investigation in both institutional and cooperative group trials. The results are anticipated to provide better tailoring of neoadjuvant therapy based on patient tumor and disease response characteristics.

Preoperative radiotherapy or chemoradiotherapy in rectal cancer – Is survival improved? An update of the “Nordic” LARC study in non-resectable cancers

The randomized “Nordic” LARC study compared preoperative long-course radiotherapy alone (RT) or with chemotherapy (CRT) in the most locally advanced/ugly rectal cancers. Despite significantly better local control in the CRT group, no overall survival benefit was seen after 10 years follow-up. The relations between local control and survival are discussed.

Bowel Dysfunction After Low Anterior Resection With Neoadjuvant Chemoradiotherapy or Chemotherapy Alone for Rectal Cancer: A Cross-Sectional Study from China.

Neoadjuvant therapy plays a vital role in the treatment of locally advanced rectal cancer but impairs bowel function after restorative surgery. Optimal decision making requires adequate information of functional outcomes. This study aimed to assess postoperative bowel function and to identify predictors for severe dysfunction. The study included a cross-sectional cohort and retrospective assessments of pelvic anatomic features. The study was conducted at a tertiary GI hospital in China. Included patients underwent neoadjuvant chemoradiotherapy or chemotherapy without radiation and curative low anterior resection for rectal cancer between 2012 and 2014. Bowel function was assessed using the validated low anterior resection syndrome score. The thicknesses of the rectal wall, obturator internus, and levator ani were measured by preoperative MRI. A total of 151 eligible patients were identified, and 142 patients (94.0%) participated after a median of 19 months from surgery. Bowel dysfunction was observed in 71.1% (101/142) of patients, with 44.4% (63/142) reporting severe dysfunction. Symptoms of urgency and clustering were found to be major disturbances. Regression analysis identified preoperative long-course radiotherapy (p < 0.001) and a lower-third tumor (p = 0.002) independently associated with severe bowel dysfunction. Irradiated patients with a lower-third tumor (OR = 14.06; p < 0.001) or thickening of the rectal wall (OR = 11.09; p < 0.001) had a markedly increased risk of developing severe dysfunction. The study was based on a limited cohort of patients and moderate follow-up after the primary surgery. Bowel function deteriorates frequently after low anterior resection for rectal cancer. Severe bowel dysfunction is significantly associated with preoperative long-course radiotherapy and a lower-third tumor, and the thickening of rectal wall after radiation is a strong predictor. Treatment decisions and patient consent should be implemented with raising awareness of bowel symptom burdens. See Video Abstract at http://links.lww.com/DCR/A317.

Risk-Adapted Adjuvant Chemotherapy After Concomitant Fluoropyrimidine–Radiotherapy Neoadjuvant Treatment for Patients With Resectable CT3-4 or N+ Rectal Cancer: Five-Year Disease-Free Survival Results of a Single-Center Series

BackgroundProviding adjuvant chemotherapy in locally advanced rectal cancer after neoadjuvant chemoradiation is currently a matter of debate. Recommendations from clinical guidelines range from offering no treatment to oxaliplatin-based combinations. We present a risk-adapted approach based on the response to initial chemoradiation as the strongest prognostic factor for disease-free survival (DFS). Patients and MethodsOne hundred one patients were treated at a single institution with preoperative long-course radiotherapy plus concurrent fluoropyrimidines. Patients with disease downstaged to pT0-2N0 received adjuvant fluoropyrimidines alone, while the remaining received an oxaliplatin-based combination. The primary study end point was 5-year DFS. ResultsOverall, the disease of 54 patients was downstaged to pT0-2N0 (53.5%), while that of 47 patients was staged as pT3-4 or N+ (46.5%) after surgery. In the intention-to-treat analysis, 5-year DFS for patients in the good-prognosis group (downstaging to pT0-2 N0) and for those with poor prognosis (pT3-4 or N+) were 79.4% and 66.3%, respectively (hazard ratio, 0.489; P = .043). Downstaging and pN+ were independent prognostic factors for DFS. ConclusionA risk-adapted adjuvant therapy strategy based on pathologic stage after neoadjuvant chemoradiation is feasible and achieves high rates of 5-year DFS. Patients with good prognostic factors can be treated with adjuvant fluoropyrimidines alone, thus permitting the avoidance of oxaliplatin-derived toxicities.

Prognostic significance of lymph node yield after long‐course preoperative radiotherapy in patients with rectal cancer: a systematic review

A literature review was performed to elucidate whether long-course preoperative radiotherapy for patients with rectal cancer affects lymph node yield, and whether this influences prognosis. Cochrane Database, PubMed/MEDLINE, Scopus, Web of Knowledge, Embase and CINAHL databases and reference lists from published journal articles published between 1 January 1990 and 30 June 2011 were searched. Studies examining lymph node yield and prognosis were selected for review. One thousand and twenty-nine articles were found, of which 11 met the inclusion criteria. None was a randomized controlled trial and all were cohort studies. Four studies showed that long-course preoperative radiotherapy reduced lymph node yield; however only one demonstrated a statistically significant survival benefit in patients with higher lymph node yields. Five-year survival was 48% in patients with fewer than and 69% in those with more than 11 lymph nodes identified in the operative specimen (P = 0.04). Whilst long-course preoperative radiotherapy appears to reduce lymph node yield in patients with rectal cancer, no causal relationship between lymph node yield and survival can be established in this group of patients.

Diagnostic Accuracy of MRI for Assessment of T Category, Lymph Node Metastases, and Circumferential Resection Margin Involvement in Patients with Rectal Cancer: A Systematic Review and Meta-analysis

Magnetic resonance imaging (MRI) is increasingly being used for rectal cancer staging. The purpose of this study was to determine the accuracy of phased array MRI for T category (T1-2 vs. T3-4), lymph node metastases, and circumferential resection margin (CRM) involvement in primary rectal cancer. Medline, Embase, and Cochrane databases were searched using combinations of keywords relating to rectal cancer and MRI. Reference lists of included articles were also searched by hand. Inclusion criteria were: (1) original article published January 2000-March 2011, (2) use of phased array coil MRI, (3) histopathology used as reference standard, and (4) raw data available to create 2×2 contingency tables. Patients who underwent preoperative long-course radiotherapy or chemoradiotherapy were excluded. Two reviewers independently extracted data. Sensitivity, specificity, and diagnostic odds ratio were estimated for each outcome using hierarchical summary receiver-operating characteristics and bivariate random effects modeling. Twenty-one studies were included in the analysis. There was notable heterogeneity among studies. MRI specificity was significantly higher for CRM involvement [94%, 95% confidence interval (CI) 88-97] than for T category (75%, 95% CI 68-80) and lymph nodes (71%, 95% CI 59-81). There was no significant difference in sensitivity between the three elements as a result of wide overlapping CIs. Diagnostic odds ratio was significantly higher for CRM (56.1, 95% CI 15.3-205.8) than for lymph nodes (8.3, 95% CI 4.6-14.7) but did not differ significantly from T category (20.4, 95% CI 11.1-37.3). MRI has good accuracy for both CRM and T category and should be considered for preoperative rectal cancer staging. In contrast, lymph node assessment is poor on MRI.

Does long-course radiotherapy influence postoperative perineal morbidity after abdominoperineal resection of the rectum for cancer?

The aim of the study was to define risk factors for perineal wound complications after abdominoperineal resection (APR), with particular reference to preoperative radiotherapy. Patients undergoing APR at our institution between 1985 and 2009 were reviewed. Wound complications were classified according to the Center for Disease Control and Prevention classification of surgical site infection (SSI). Perineal complications were identified in patients who had preoperative long-course radiotherapy (Group 1) and those who had surgery alone (Group 2). One hundred and fifty-seven patients met the inclusion criteria. Preoperative radiotherapy was performed in 68 (44.7%) patients (Group 1), and 89 (65.3%) patients (Group 2) underwent surgery alone. The overall rate of perineal wound complications was 14.8%. The wound infection rate was similar in each group (Group 1, 10/68, 14.7%; Group 2, 13/89, 14.9%; P = 0.9). An elevated BMI (>30) was the only factor correlated with perineal morbidity on univariate analysis (P = 0.01). Preoperative radiotherapy does not influence perineal healing other than in patients with obesity.

Locally Advanced Rectal Cancer

Traditionally, there has been a high local recurrence rate in rectal cancer and 10-40% of patients require a permanent stoma. Both short-course preoperative radiotherapy (SCPRT) and long-course preoperative chemoradiation (CRT) are used to reduce the risk of local recurrence and enable a curative resection. Total mesorectal excision has reduced the rate of local recurrence (even without radiotherapy) to below 10%, but has highlighted a high risk of metastatic disease in 30-40% of patients. Current trials suggest that in resectable cancers, where the preoperative magnetic resonance imaging (MRI) suggests the circumferential resection margin (CRM) is not potentially involved, then SCPRT and CRT are equivalent in terms of outcomes such as local recurrence, disease-free survival (DFS) and overall survival (OS). For patients with more advanced disease, where the CRM is breached or threatened according to the MRI, the integration of more active chemotherapy and biological agents into chemoradiation is an attractive strategy because of the high risk of metastases. However, in none of the trials published in the last decade has chemoradiation impacted on DFS or OS. We examine the strategies of neoadjuvant, concurrent, consolidation (after chemoradiation and before surgery) and postoperative adjuvant chemotherapy with cytotoxic agents, and the integration of biological agents for future potential strategies of treatment. We also compare the trials and compare the different strategies of long-course preoperative radiotherapy and SCPRT; the intensification of preoperative radiation and chemoradiation with dose escalation of external beam radiotherapy, using brachytherapy, intra-operative radiotherapy, hyperfractionation, and various available techniques such as intensity-modulated radiotherapy. We recommend examining dose escalation of radiotherapy to the primary tumour where MRI predicts a threatened CRM. Of the potential treatment strategies involving cytotoxic agents, such as neoadjuvant, concurrent, consolidation and postoperative adjuvant chemotherapy, the most promising would appear to be consolidation chemotherapy following chemoradiation in locally advanced disease, and neoadjuvant chemotherapy in MRI-selected patients who do not require radiation. Improvement in the quality of surgery is also an important future goal.

Clinical and molecular comparison between short- and long-course preoperative radiotherapy for rectal cancer.

e14093 Background: Conventional chemoradiotherapy (CRT) or short course radiotherapy are most frequent regimens in the preoperative treatment for rectal cancer. Debate is still going on which is mo...

A national cohort study of long‐course preoperative radiotherapy in primary fixed rectal cancer in Denmark

Preoperative radiotherapy has been shown to enable a fixed rectal cancer to become resectable which in turn may result in long-time survival. In this study, we analysed the outcome of long-course preoperative radiotherapy in fixed rectal cancer in a national cohort including all Danish patients registered with primary inoperable rectal cancer and treated in the period May 2001 to December 2005. The study was based on surgical and demographic data from a continuously updated and validated national database. In addition, retrospective data were retrieved from all departments of radiotherapy concerning technique of radiotherapy, dose and fractionation and use of concomitant chemotherapy. Outcome was determined by actuarial analysis of local control, disease-free survival and overall survival. A total of 258 patients with fixed rectal cancer received long-course radiotherapy (> 45 Gy). The median age at diagnosis was 66 years (range: 32-85) and 185 (72%) patients were male. The resectability rate was 80%, and a R0 resection was obtained in 148 patients (57% of all patients and 61% of those operated). The 5-year local recurrence rate for all patients was 5% (95% CI: 3-7%), and the actuarial distant recurrence rate was 41% (95% CI: 35-47%). The cumulative 5-year disease-free survival was 27% (95% CI: 22-32%) and overall 5-year survival was 34% (95% CI: 29-39%). This study is the first population-based report on outcome of preoperative long-course radiotherapy in a large unselected patient group with clinically fixed rectal cancer. Most patients could be resected with the intention of cure and one in three was alive after 5 years.

A randomized trial comparing local recurrence (LR) rates between short-course (SC) and long-course (LC) preoperative radiotherapy (RT) for clinical T3 rectal cancer: An intergroup trial (TROG, AGITG, CSSANZ, RACS).

3509 Background: Both SC and LC preoperative radiotherapy have been accepted as standard of care for locally advanced rectal cancer. The primary aim of the trial was to compare LR rates (cumulative incidences) at 3 years between SC and LC. Methods: Main eligibility criteria were clinical T3NxM0 rectal adenocarcinoma, with the lower border within 12 cm of the anal verge, and ECOG performance status 0-2. SC consisted of pelvic RT 25 Gy in 5 fractions in 1 week, followed by surgery the following week, and 6 (monthly) courses of postoperative chemotherapy. LC consisted of pelvic RT 50.4 Gy, 1.8 Gy/fraction, in 5.5 weeks, continuous infusion 5-FU 225 mg/m2/day during RT, followed by surgery in 4 to 6 weeks, and 4 (monthly) courses of postoperative chemotherapy. Each course of postoperative chemotherapy was to be 5-FU 425 mg/m2 and folinic acid 20 mg/m2 for 5 days. The trial was powered (80%; 310 patients) to detect a difference of 15% versus 5% in LR rates at 3 years. Results: 326 patients, accrued from 2001-0...

Preoperative radiotherapy downregulates the nuclear expression of hypoxia-inducible factor-1α in rectal cancer

Objective. To assess the value of hypoxia-inducible factor-1α (HIF-1α) expression as a predictor of disease outcome in rectal cancer treated by preoperative radio- or chemoradiotherapy. Material and methods. Operative samples from 168 rectal cancer patients and 79 respective preoperative biopsies were analyzed for nuclear HIF-1α protein expression using immunohistochemistry by three approaches: (a) positive/negative, (b) the percentage of HIF-positive cancer cells and (c) staining intensity. The patients had received either short- (n = 75) or long-course radiotherapy with or without chemotherapy (n = 39) or no treatment preoperatively (n = 54). Results. HIF-1α staining was positive in 70% of the diagnostic biopsies but negative in most of the post-radiotherapy specimens (60%). HIF-1α expression in the biopsies was downregulated in 56% of samples taken after preoperative treatment, while negative HIF-1α expression was upregulated in 25% of samples. Patients who had HIF-negative tumours after long-course radiotherapy had significantly (P = 0.001) better disease-specific survival (DSS) in univariate analysis. In the multivariate (Cox) regression model, HIF-1α lost its significance and only being in the preoperative treatment group was an independent predictor of disease-free survival. In a similar Cox model, disease recurrence and the number of metastatic lymph nodes were independent predictors of DSS. Conclusions. HIF-1α expression was positive in most of the preoperative biopsies but downregulated in most of the operative samples, implicating that preoperative radiotherapy downregulates HIF-1α expression in rectal cancer. Negative HIF expression after preoperative long-course radiotherapy was associated with significantly better DSS.

Staging, prognostic factors, and therapy of localized rectal cancer

Many recent developments have taken place in the management of rectal cancer. Appropriate staging plays an increasingly important role in rectal cancer, because many treatment decisions must be based on preoperative staging. Also critical is the role of prognostic factors such as the pathologic T (tumor) and N (nodal) classification, circumferential resection margin, and response to preoperative therapy. For stage II and III rectal cancer, preoperative chemo-radiation and radiotherapy have been accepted widely as a standard of care. The German Rectal Cancer Trial demonstrated the superiority of preoperative chemoradiation over postoperative chemoradiation, whereas the trials from the European Organisation for Research and Treatment of Cancer and Fédération Francophone de Cancérologie Digestive showed the benefits of preoperative chemoradiation over preoperative long-course radiotherapy. Multiple randomized trials also have established the role of hypofractionated or short-course radiotherapy. For stage I rectal cancer, local excision is being used increasingly, but recent studies show the need for caution with the use of this technique. This article reviews recent studies on staging, prognostic factors, and therapy of localized rectal cancer.

611 POSTER Serious adverse events in the EORTC randomized phase III trial 22921 comparing preoperative pelvic irradiation to preoperative chemo-irradiation with or without post-operative adjuvant chemotherapy for T3-T4 resectable rectal cancer

Providing adjuvant chemotherapy in locally advanced rectal cancer after neoadjuvant chemoradiation is currently a matter of debate. Recommendations from clinical guidelines range from offering no treatment to oxaliplatin-based combinations. We present a risk-adapted approach based on the response to initial chemoradiation as the strongest prognostic factor for disease-free survival (DFS).One hundred one patients were treated at a single institution with preoperative long-course radiotherapy plus concurrent fluoropyrimidines. Patients with disease downstaged to pT0-2N0 received adjuvant fluoropyrimidines alone, while the remaining received an oxaliplatin-based combination. The primary study end point was 5-year DFS.Overall, the disease of 54 patients was downstaged to pT0-2N0 (53.5%), while that of 47 patients was staged as pT3-4 or N+ (46.5%) after surgery. In the intention-to-treat analysis, 5-year DFS for patients in the good-prognosis group (downstaging to pT0-2 N0) and for those with poor prognosis (pT3-4 or N+) were 79.4% and 66.3%, respectively (hazard ratio, 0.489; P = .043). Downstaging and pN+ were independent prognostic factors for DFS.A risk-adapted adjuvant therapy strategy based on pathologic stage after neoadjuvant chemoradiation is feasible and achieves high rates of 5-year DFS. Patients with good prognostic factors can be treated with adjuvant fluoropyrimidines alone, thus permitting the avoidance of oxaliplatin-derived toxicities.

Impact of Colloid Response on Survival After Preoperative Radiotherapy in Locally Advanced Rectal Carcinoma

Neoadjuvant therapy for rectal carcinoma modifies morphology and natural history of the tumor. Colloid response defined by predominant colloid changes with or without residual tumor cells is a form of tumor response whose impact on survival is unknown. This study evaluated influence of tumor histologic response, especially of colloid response, on survival in patients treated by long-course preoperative radiotherapy for rectal cancer. In 200 patients with uT3-T4 or N1 rectal carcinomas, influence of type of surgery, dose of radiotherapy, residual tumor size, surface tumor aspect, tumor response (downstaging vs. colloid or no response), tumor grade, vascular and neural invasion, circumferential margin, and postoperative chemotherapy on 5-year overall and disease-free survival were studied by univariate and multivariate analyses. A colloid response was observed in 20% of the cases. Tumor response, circumferential margin, and vascular invasion were independently associated with the disease-free survival. Patients with downstaging had a better disease-free survival than patients without response (80% vs. 54%), whereas those with colloid response had an intermediate survival (64%). After colloid response, the rate of recurrence was similar to patients with downstaging for local recurrence (0%-3%) and to those with no response for distant recurrence (28%). After preoperative radiotherapy for rectal cancer, survival and type of recurrence are influenced by the tumor response. The intermediate natural history of patients with colloid response suggests taking colloid response into account in postoperative tumor staging to optimize adjuvant therapy.

Quantification of histologic regression of rectal cancer after irradiation: a proposal for a modified staging system.

Long-course preoperative radiotherapy has been recommended for rectal carcinoma when there is concern about the ability to perform a curative resection, for example, in larger tethered tumors or those sited anteriorly or near the anal sphincter. "Downstaging" of the tumor may occur, and this is of importance when estimating the prognosis and selecting postoperative therapy for patients. We studied the effects of preoperative chemoradiotherapy on the pathology of rectal cancer, and we propose a simplified measurement of tumor regression, the Rectal Cancer Regression Grade. We have reviewed those patients who received preoperative chemoradiotherapy followed by surgical resection for carcinomas of the mid or distal third of the rectum found to be Stage T3/4 on transrectal ultrasound or CT between January 1995 and December 1998. Patients received 45 to 50 Gy irradiation and an infusion of 5-fluorouracil. The surgical specimens were examined by one pathologist, and the Rectal Cancer Regression Grade was quantified. Forty-two patients, mean age 60 (range, 42-86) years, underwent chemoradiotherapy before surgery for rectal carcinoma. There were 28 anterior resections (67 percent; 9 with a colonic pouch), 12 abdominoperineal resections (27 percent), and 2 Hartmann's procedures (5 percent). Comparison of preoperative and pathologic staging revealed that the depth of invasion was downstaged in 17 patients (38 percent), and the status of involved lymph nodes was downstaged in 13 (50 percent) of 26 patients. Tumor regression was more than 50 percent (Rectal Cancer Regression Grades 1 and 2) in 36 patients (86 percent), with 7 patients (17 percent) having complete regression with absence of residual cancer cells. Significant tumor regression was seen in 86 percent of cases after chemoradiotherapy, with 19 patients showing a "good" responsiveness. We propose a modified pathologic staging system for irradiated rectal cancer, the Rectal Cancer Regression Grade, which includes a measurement of tumor regression. The utility of the proposed Rectal Cancer Regression Grade must be tested against long-term outcomes before its value in predicting prognosis and survival can be determined.