Preoperative Combined Modality Therapy Research Articles

Retrospective analysis of 856 cases with stage 0 to III rectal cancer underwent curative surgery combined modality therapy

To investigate the survival and prognostic factors of stage 0 to III rectal cancer in 10 years. Clinical data and follow-up of 856 rectal cancer patients with stage 0-III underwent curative surgery from January 2000 to December 2010 were retrospective analyzed. There were 470 male and 386 female patients, with a mean age of (58 ± 12) years. Kaplan-Meier method was used to analyze the overall survival and disease free survival. Log-rank test was used to compare the survival between groups. Cox regression was used to analyze the independent prognostic factors of rectal cancer. The patients in each stage were stage 0 with 18 cases, stage I with 209 cases, stage II with 235 cases, and stage III with 394 cases. All patients received curative surgery. There were 296 patients evaluated as cT3, cT4 and any T with N+ received preoperative radiotherapy. 5.4% patients got pathological complete response (16/296), and the recurrence rate was 4.7% (14/296). After a median time of 41.7 months (range 4.1 to 144.0 months) follow-up, the 5-year overall survival rate in stage 0 to I of was 91.0%, stage II 86.2%, and stage III 60.0%, with a significant difference (P=0.000). The cumulative local recurrence rate was 4.8% (41/856), of which 70.7% (29/41) occurred within 3 years postoperatively, 97.6% (40/41) in 5 years. The cumulative distant metastasis rate was 16.4% (140/856), of which 82.9% (129/140) occurred within 3 years postoperatively, 96.4% (135/140) in 5 years. The incidence of abnormal imaging findings was significantly higher in pulmonary than liver and other sites metastases (75.0% vs. 21.7%, χ² =25.691, P=0.000). The incidence of CEA elevation was significantly higher in liver than lung and other sites metastases (56.8% vs. 37.8%, χ² =25.691, P=0.000). Multivariable analysis showed that age (P=0.015, HR=1.385, 95% CI: 1.066 to 1.801), surgical approach (P=0.029, HR=1.337, 95% CI: 1.030 to 1.733), differentiation (P=0.000, HR=1.535, 95% CI: 1.222 to 1.928), TNM stage (P=0.000, HR=1.349, 95% CI: 1.260 to 1.444) and lymphovascular invasion (P=0.001, HR=1.715, 95% CI: 1.258 to 2.342) are the independent prognostic factors for rectal cancer. Age, surgical approach, differentiation, TNM stage and lymphovascular invasion are independent prognostic factors for rectal cancer. Preoperative evaluation and combined modality therapy can significant reduce the local recurrence and improve overall survival for rectal cancer patients.

P-0273 - Still Awaiting That Waiting Be a Validated Affordable Option in Rectal Cancer? Our Watch and Wait Approach Experience in Co-Recto

Introduction: Controversies exist about the proper management of the patients with clinical complete tumor regression after preoperative combined modality therapy. A non-operative management of selected patients has achieved promising long-term outcomes in some Watch and Wait (W&W) single series. Regardless of encouraging results, and in spite of being a readily accepted strategy by patients, reluctance to recommend this strategy as an affordable option still exists in rectal cancer guidelines. Our aim is to evaluate the outcome of the omission of surgery with a close follow up for patients with clinical complete response discussed in Co-Recto (interdisciplinary and cooperative team for the Management of rectal cancer), Argentina.

New directions in perioperative management of locally advanced esophagogastric cancer.

Cancers of the esophagus arise as adenocarcinomas and squamous cell carcinomas; these represent distinct diseases, with differing prognosis, yet they are often studied in common trials. With surgery alone, 5 year survival for T2-T3N0 disease is less than 30% to 40%, and declines to less than 25% with nodal involvement. The CROSS randomly assigned patients to surgery alone or to weekly carboplatin/paclitaxel X 5 and 41.4 Gy concurrent radiotherapy, followed by surgery. Seventy-five percent of enrolled patients had adenocarcinoma. Preoperative combined-modality therapy improved R0 resection from 69% to 92% (p < 0.001 and improved median survival from 24 months to 49.4 months (p < 0.003). This regimen reduced both locoregional recurrence (34% to 14%; p < 0.001) and the development of peritoneal carcinomatosis (14% to 4%; p < 0.001). Systemic perioperative therapy may have a greater effect on distant disease, the predominant mode of failure for these patients, and current trials compare preoperative chemoradiation with periooperative systemic therapy. PET scan response during preoperative chemotherapy without radiotherapy correlates with improvements in pathologic response and with improved survival. Nonresponse on early PET scan allows identifıcation of patients for earlier surgery and discontinuation of ineffective preoperative chemotherapy, without survival detriment. There is no predictive benefıt for early PET scan during the course of chemotherapy followed by chemoradiotherapy. The use of early PET scan during induction chemotherapy is being evaluated in CALGB/Alliance trial (NCT01333033). Molecular profıling has identifıed somatic gene mutations and pathways that may be oncogenic in upper gastrointestinal cancers. Potential targets include the epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor (VEGFR), HER2, mammalian target of rapamycin (mTOR), fıbroblast growth factor receptor (FGFR), MEK, and others. Targeted therapies with known survival benefit in esophagogastric cancer are currently limited to trastuzumab for HER2 overexpressing cancers, or ramicirumab.

Polo-Like Kinase 1 as Predictive Marker and Therapeutic Target for Radiotherapy in Rectal Cancer

The ability to predict tumor sensitivity toward radiotherapy may significantly impact the selection of patients for preoperative combined-modality therapy. The aim of the present study was to test the predictive value of Polo-like kinase 1 (PLK1) in rectal cancer patients and to investigate whether PLK1 plays a direct role in mediating radiation sensitivity. PLK1 expression was evaluated by immunohistochemistry (n = 76) or Affymetrix HG133 microarray (n = 20) on pretreatment biopsies of patients with advanced rectal cancer. Expression was correlated with both tumor regression in the resected specimen and long-term clinical outcome. Furthermore, we used small interfering RNAs (siRNAs) to down-regulate PLK1 expression in colorectal cancer cells and analyzed the effects of PLK1-specific siRNAs by Western blot and quantitative real-time PCR analysis, FACScan analysis, caspase 3/7 assays, and colony-forming assays. We observed that increased PLK1 protein expression was significantly related to a poorer tumor regression and a higher risk of local recurrence in uni- and multivariate analysis. A significant decrease of PLK1 expression by siRNAs in combination with ionizing radiation induced an increased percentage of apoptotic cells and increased caspase 3/7 activity. Furthermore, enhanced G(2)-M levels, decreased cellular viability, and reduced clonogenic survival were demonstrated, indicating a radiosensitizing effect of PLK1 depletion. Therefore, PLK1 may be a novel predictive marker for radiation response as well as a promising therapeutic target in rectal cancer patients.

Locally advanced rectal cancer: from molecular profiling to clinical practice. A literature review: Part 2

Colorectal cancer is the third most common cause of cancer deaths worldwide. The management of rectal cancer has undergone, and continues to undergo, significant evolutions. In the last two decades, new multimodality strategies have been developed. The ability to predict tumor response before treatment could significantly impact the selection of patients for preoperative combined-modality therapy, as well as potentially modify postoperative treatment plans. The present review analyzes the new molecular targets that could be involved in predicting response and prognosis.

CT3N0 Rectal Cancer: Potential Overtreatment With Preoperative Chemoradiotherapy Is Warranted

Although combined-modality therapy (CMT) is the preferred treatment for T3 and/or lymph node (LN)-positive rectal cancer, the German rectal cancer study published in 2004 demonstrated that 18% of patients deemed suitable for preoperative CMT by endorectal ultrasound (ERUS) may be overstaged. Because data also suggest that LN-negative rectal cancer after total mesorectal excision may not require radiotherapy, it is reasonable to consider omitting radiotherapy for the cT3N0 subset. We therefore determined the accuracy of pre-CMT ERUS or magnetic resonance imaging (MRI) staging, to explore the validity of a nonpreoperative CMT approach for cT3N0 disease. One hundred eighty-eight ERUS-/MRI-staged T3N0 rectal cancer patients received preoperative CMT (fluorouracil based and 45-50.4 Gy) followed by radical resection. Rates of pathologic complete response (pCR) and mesorectal LN involvement were determined. Tumors were located a median of 5 cm from the anal verge. Sphincter-preserving surgery was performed in 143 patients (76%). Overall pCR was 20%, and 41 patients (22%) had pathologically positive mesorectal LNs. The incidence of positive LNs significantly increased with T stage: ypT0, 3%; ypT1, 7%; ypT2, 20%; ypT3-4, 36% (P = .001). The accuracy of preoperative ERUS/MRI for staging mid to distal cT3N0 rectal cancer is limited because 22% of patients have undetected mesorectal LN involvement despite CMT. Therefore, ERUS-/MRI-staged T3N0 rectal cancer patients should continue to receive preoperative CMT. Although 18% may be overstaged and therefore overtreated, our data suggest that an even larger number would be understaged and require postoperative CMT, which is associated with significantly inferior local control, higher toxicity, and worse functional outcome.

Adjuvant Management of Rectal Cancer: The More We Learn, the Less We Know

Two decades ago, the adjuvant management of rectal cancer was less complex and far less controversial. Patients in the United States underwent surgery, commonly by blunt dissection, and if there was pT3 and/or pN1-2 disease, they received 6 months of postoperative fluouracil (FU)-based chemotherapy with pelvic radiation during months 3 and 4 (combined-modality therapy). Subsequent randomized and nonrandomized trials have taught us manynewlessons.Amongthesearetotalmesorectalexcisionasthe preferred surgical technique 1 ; at least 12 examined nodes to accurately determine the nodal stage 2 ; the relationship of local failure notonlytostagebutalsotothelocationofthetumorintherectum and the presence of a positive circumferential margin 3 ; and the subsets of patients with pT3N0 of pT1-2N1 disease who may not require postoperative radiation. 4 Furthermore, for patients with cT3 and or N disease, the German trial confirmed that preoperative combined-modality therapy has significantly improved local control, caused less acute short and long-term toxicity, and increased sphincter preservation compared with postoperative combined-modality therapy. 5

Factors affecting anastomotic complications following anterior resection in rectal cancer

Anastomotic complications following sphincter saving rectal surgery remains a significant clinical problem in rectal cancer surgery. Preoperative combined modality therapy followed by anterior resection with total mesorectal excision (TME) has become the preferred treatment paradigm for locally advanced rectal cancer. However, its impact on anastomotic complications has not been adequately evaluated. This study aimed to assess the relationship between the response of the primary tumour to neo-adjuvant therapy with anastomotic complications and to evaluate the effect of other clinico-pathological factors previously implicated, in this patient cohort. A total of 119 consecutive patients with primary rectal cancer were assessed of which there were 87 anterior resections. A prospectively collected database was queried to determine the incidence of anastomotic complications, association with response to neo-adjuvant therapy and other clinico-pathological factors. Data were analysed with SPSS 14.0. Anterior resection was performed in 87/111 (78.4%) patients of which 46/84 (56%) were low resections, with an abdominoperineal excision of rectum rate of 11/111 (9.9%). Anastomotic complications were seen as clinical leaks in 10/87 (11.5%) and late colo-visceral fistulae in 2/87 (2.2%) patients. Subclinical/ radiological 'leaks' were quantified as 4/87 (4.5%). A good pathological response to neo-adjuvant therapy was found to be strongly associated with anastomotic complications (P = 0.006). Presence of a perioperative cardiac event was the only other clinical factor associated with anastomotic complications (P = 0.004) in our study. Rectal cancer treated with neo-adjuvant therapy and radical resection with TME for better local control may be associated with greater anastomotic complications particularly when a good pathological response is seen.

A Prospective Pathologic Analysis Using Whole-Mount Sections of Rectal Cancer Following Preoperative Combined Modality Therapy

The aims of this study were to use a comprehensive whole-mount pathologic analysis to characterize microscopic patterns of residual disease, as well as circumferential and distal resection margins, in rectal cancer treated with preoperative CMT; and to identify clinicopathologic factors associated with residual disease. Recent studies have shown that preoperative combined modality therapy (CMT) for rectal cancer enhances rates of sphincter preservation. However, the efficacy of preoperative CMT in conjunction with a total mesorectal excision (TME)-based resection, in terms of resection margins using whole-mount sections, has not been reported. Furthermore, since patterns of residual disease and extent of distal spread following preoperative CMT are largely unknown, intraoperative determination of distal rectal transection remains a surgical challenge. We prospectively accrued 109 patients with endorectal ultrasound (ERUS)-staged, locally advanced rectal cancer (T2-T4 and/or N1), located a median distance of 7 cm from the anal verge, requiring preoperative CMT, and undergoing a TME-based resection. Comprehensive whole-mount pathologic analysis was performed, with particular emphasis on extent of residual disease, margin status, and intramural tumor extension. Clinicopathologic factors associated with residual disease were identified. A sphincter-preserving resection was feasible in 87 patients (80%), and in all 109 patients, distal margins were negative (median, 2.1 cm; range, 0.4-10 cm). Intramural extension beyond the gross mucosal edge of residual tumor was observed in only 2 patients (1.8%), both < or =0.95 cm. There were no positive circumferential margins (median, 10 mm; range, 1-28 mm), although 6 were less than or equal to 1 mm. On multivariate analysis, residual disease was observed more frequently in distally located tumors (distance from anal verge <5 cm) (P = 0.03). Our comprehensive pathologic analysis suggests that, following preoperative CMT and a TME-based resection, distal margins of 1 cm may provide for complete removal of locally advanced rectal cancer. Although residual cancer following preoperative CMT was more likely in the setting of distally located tumors, occult tumor beneath the mucosal edge was rare and, when present, limited to less than 1 cm. Our results extend the indications for sphincter preservation, as distal resection margins of only 1 cm may be acceptable for rectal cancer treated with preoperative CMT.

Prognostic Markers of Local Relapse in Rectal Cancer: Are We Any Further Forward?

Rectal cancer is a major health problem affecting more than 100,000 patients in the United States and Europe each year. 1 Although it is a highly treatable and often curable disease when localized to the bowel, the prognosis for locally advanced disease varies, with local recurrence rates ranging from 4% to 40%; local recurrenceoftenisthecauseofseveremorbidityandpoormortalityin this disease. 2 Therefore, clinical approaches to prevent early recurrence are one of the major goals in the treatment of rectal cancer. The treatment for patients with clinically resectable, locally invasive rectal cancer has begun to evolve away from more radical surgical approaches such as abdominoperitoneal resection toward attempts at preservation of the anal sphincter and maintenance of anorectal function. 3 In the postoperative setting, there is clear evidence that adjuvant fluorouracil (FU) -based chemotherapy combined with radiotherapy significantly improves disease-free survival and overall survival in patients with rectal cancer. 4 More recently, several groups clearly have shown the benefit in reducing local recurrence rates and toxicity using neoadjuvant preoperative chemotherapy/radiotherapy combinations as opposed to adjuvant treatment. 5,6 Onesuchstudy,theGermanCAO/ARO/AIO-94rectalcancer group trial, randomly assigned 823 patients with T3/4 and/or node-positive rectal cancer to receive preoperative versus postoperative combined-modality therapy consisting of FU on weeks 1 and 5 and 50.4 Gy of concurrent radiation therapy. 4 There was a significant improvement in local recurrence rates (6% in the preoperative group v 13% in the postoperative group) as well as improvements in acute and long-term toxicity. Moreover, in the preoperative group, 39% of the patients initially requiring an abdominoperitoneal resection were able to undergo a sphinctersparing operation, whereas in the postoperatively treated group only 19% were eligible for a sphincter-sparing procedure. Although there was no difference in overall survival between the two groups, the preoperative combined-modality approach significantlyimprovedthechancesofsphincterpreservationandalsoled

A Pathologic Complete Response of Rectal Cancer to Preoperative Combined-Modality Therapy Results in Improved Oncological Outcome Compared With Those Who Achieve No Downstaging on the Basis of Preoperative Endorectal Ultrasonography

Preoperative combined-modality therapy (CMT) is the preferred treatment for locally advanced rectal cancer (endorectal ultrasonography [ERUS] T3-4, N1, or clinically bulky) and achieves a pathologic complete response (pCR) in 4% to 33% of patients. However, the prognostic significance of pCR remains unclear. A prospectively collected database was queried to identify 200 patients with locally advanced disease treated from 1992 to 2002. The pCR group was defined as having no evidence of viable tumor on pathologic analysis. The no-downstaging group was defined as no difference between the pre-CMT ERUS stage and the pathologic stage. Those achieving some downstaging but not pCR were excluded. Patients were treated with CMT (5040 cGy of radiation and 5-fluorouracil-based chemotherapy) followed by surgery, and 51 (85%) in the pCR group and 129 (92%) in the no-downstaging group (P = .1) received postoperative chemotherapy. Recurrence-free survival (RFS) and overall survival (OS) were determined by using the Kaplan-Meier method. The median follow-up was 38.6 months (range, 18.2-124.9 months). The pCR (n = 60) and control (n = 140) groups were similar in age (P = .6), sex (P = .4), distance of the tumor from the anal verge (P = .3), pre-CMT ERUS stage (P = .2), and comorbidities (P = .2). The 5-year RFS was 96% and 54% in the pCR and control groups, respectively (P < .00001); the 5-year OS was 90% and 68% (P = .009). Sphincter-preservation rates were higher in the pCR group (P = .01). Rectal cancer patients with pCR after preoperative CMT have improved RFS, OS, and sphincter preservation compared with patients without downstaging. Because pCR seems to be associated with better outcome, an understanding of the factors governing the response to CMT should be pursued.

Phase II, parallel-design study of preoperative combined modality therapy and the matrix metalloprotease (mmp) inhibitor prinomastat in patients with esophageal adenocarcinoma

This randomized phase II, parallel-design study evaluated preoperative combined modality therapy and the matrix metalloprotease (MMP) inhibitor prinomastat in patients with resectable adenocarcinoma of the esophagus that were stage II or greater. The objectives of the trial were to determine pathologic complete response rate (pCR), overall response rate, progression-free survival, pattern of disease relapse, and two-year and overall survival. Preoperative staging included computed tomography, endoscopic ultrasound, and, when feasible, laparoscopy. Eligible patients were randomized to preoperative prinomastat or placebo, plus continuous infusion 5-FU, cisplatin, paclitaxel, and concurrent radiotherapy. Esophagectomy was performed on day 71. Adjuvant paclitaxel and prinomastat were available to all study patients. Between August 2000 and June 2001, 15 of a planned 78 patients were randomized into the trial. One patient after randomization withdrew consent. Fourteen patients, 7 in each arm, completed preoperative treatment and surgery. pCR was achieved in 5 patients; 1/ 7 prinomastat and 4/ 7 placebo. Disease improvement was achieved in 7 patients; 5 /7 prinomastat and 2 /7 placebo. At a median follow-up of 28 months, 7 patients (2 prinomastat, 5 placebo) are alive with no evidence of disease. The primary prinomastat related toxicity was moderate to severe musculoskeletal toxicity interfering with daily function. This toxicity was managed with treatment rest, dose reduction, or discontinuation. Five patients (3 prinomastat and 2 placebo) had life-threatening thrombo-embolic events, which led to early evaluation of safety and efficacy, and subsequent termination of the study. All patients, regardless of treatment arm, were able to successfully undergo neoadjuvant combined modality therapy and esophagectomy. However, early closure of the study due to unexpected thrombo-embolic events precluded any conclusions regarding clinical activity of prinomastat in locally advanced esophageal cancer patients.

Complications After Preoperative Combined Modality Therapy and Radical Resection of Locally Advanced Rectal Cancer: A 14-Year Experience From a Specialty Service

Complications After Preoperative Combined Modality Therapy and Radical Resection of Locally Advanced Rectal Cancer: A 14-Year Experience From a Specialty Service

Presence of distal intramural spread after preoperative combined-modality therapy for adenocarcinoma of the rectum: What is now the appropriate distal resection margin?

Preoperative combined-modality therapy (CMT) is considered the treatment approach of choice for rectal cancer. To examine the effect of CMT on distal intramural spread (DIS), we determined the extent of DIS in rectal cancer specimens after CMT. Specimens from 20 patients after preoperative CMT and total mesorectal excision for rectal cancer were analyzed for extent of DIS. Specimens were washed, fixed in formalin, and sectioned in 5-mm cuts from the distal border of the residual tumor to the distal resection margin. Eleven patients (55%) had DIS. Two patients had a complete pathologic response (10%). The mean extent of DIS was 0.50 cm (standard deviation, 0.64 cm; range, 0.0 to 2.5 cm). Only 1 patient in the study had DIS beyond 1 cm from the residual tumor. Six of the patients have died at a median of 30.4 months after operation (range, 19.0 to 51.1 months). No correlation was found between the extent of residual DIS and survival. Our study shows that the vast majority of patients with rectal cancer after neoadjuvant CMT have no tumor cells beyond 1 cm from the residual tumor. Our data suggest that a 2-cm margin of resection when feasible from the macroscopic tumor margin after neoadjuvant CMT is adequate.

Treatment of Unresectable/Recurrent Rectal Cancer with External Beam and/or Intraoperative Radiation Techniques

The standard treatment for patients with primary unresectable or recurrent rectal cancer is preoperative combined modality therapy. Given the high local recurrence rate, novel approaches using IORT, new chemotherapeutic agents, and altered radiation fractionation schemes had been developed and are being actively investigated.

Invited Commentary

BACKGROUND: Preoperative combined modality therapy followed by total mesorectal excision has emerged as the optimal treatment paradigm for locally advanced rectal cancer (T3 to 4, N1, or both). But its impact on postoperative complications has not been adequately evaluated. Our aims were to evaluate our comprehensive experience and identify factors predictive of complications in this patient population. STUDY DESIGN: The study group consisted of 297 consecutive patients with locally advanced rectal adenocarcinoma treated with preoperative combined modality therapy (radiation: 5,040 cGy; chemotherapy: 5-FU-based) and then operation. Major complications were defined as those requiring medical or surgical treatment. A prospectively collected database was queried to determine the incidence of postoperative complications and associated clinicopathologic factors. RESULTS: Median followup was 43.9 months (range 0.8 to 128.6 months). There were no postoperative mortalities (within 30 days of operation). But there were 145 major complications in 98 patients (33% of study population). The most common complications were small bowel obstruction (n = 32 [11%]) and wound infection (n = 31 [10%]). There were eight anastomotic leaks (4%) and nine pelvic abscesses (4%) in patients treated with low anterior resection (n = 210). Preoperative comorbidity was the only clinicopathologic factor associated with postoperative complications (p = 0.02). Postoperative complications had no significant impact on oncologic outcomes. CONCLUSIONS: Although postoperative mortalities are rare, complications requiring treatment can be anticipated in one-third of patients undergoing preoperative combined modality therapy and total mesorectal excision. A policy of selective fecal diversion after preoperative combined modality therapy and total mesorectal excision for locally advanced rectal cancer can achieve low rates of pelvic sepsis, but may lead to an increased incidence of small bowel obstruction.

Positron emission tomography during preoperative combined modality therapy for rectal cancer may predict ultimate pathologic response: A prospective analysis

3612 Introduction: Early knowledge of rectal cancer response to preoperative combined modality therapy (CMT) may provide an opportunity to identify patients with minimal response and who may benefit from alternative treatment regimens. We prospectively evaluated the novel concept of assessing rectal cancer response with fluorodeoxyglucose positron emission tomography (PET) early after the commencement of preoperative CMT. Methods: 21 prospectively accrued patients with locally advanced rectal cancer (ERUS T3–4/N1) received preoperative CMT (5040 cGy with 5-FU-based chemotherapy). Patients were imaged with a PET scan prior to and 10–12 days after (early PET) commencement of CMT. PET scans were interpreted by two Nuclear Medicine physicians using four specific parameters [(SUVmax, SUVaverage, total lesion glycolysis (TLG), and visual response score (VRS)]. Percent pathologic response was quantified using whole mount sections. Pathologic complete response (pCR) was defined as no viable tumor cells on patholo...

Phase II trial of preoperative combined modality therapy for esophageal carcinoma: Induction cisplatin-irinotecan followed by concurrent cisplatin-irinotecan and radiotherapy

4017 Background: We reported in a phase I trial that weekly cisplatin (C), irinotecan (I) and concurrent radiotherapy (RT) can be administered with minimal toxicity and acceptable response rates in...

Complications after Preoperative Combined Modality Therapy and Radical Resection of Locally Advanced Rectal Cancer: A 14-Year Experience from a Specialty Service

Preoperative combined modality therapy followed by total mesorectal excision has emerged as the optimal treatment paradigm for locally advanced rectal cancer (T3 to 4, N1, or both). But its impact on postoperative complications has not been adequately evaluated. Our aims were to evaluate our comprehensive experience and identify factors predictive of complications in this patient population. The study group consisted of 297 consecutive patients with locally advanced rectal adenocarcinoma treated with preoperative combined modality therapy (radiation: 5,040 cGy; chemotherapy: 5-FU-based) and then operation. Major complications were defined as those requiring medical or surgical treatment. A prospectively collected database was queried to determine the incidence of postoperative complications and associated clinicopathologic factors. Median followup was 43.9 months (range 0.8 to 128.6 months). There were no postoperative mortalities (within 30 days of operation). But there were 145 major complications in 98 patients (33% of study population). The most common complications were small bowel obstruction (n = 32 [11%]) and wound infection (n = 31 [10%]). There were eight anastomotic leaks (4%) and nine pelvic abscesses (4%) in patients treated with low anterior resection (n = 210). Preoperative comorbidity was the only clinicopathologic factor associated with postoperative complications (p = 0.02). Postoperative complications had no significant impact on oncologic outcomes. Although postoperative mortalities are rare, complications requiring treatment can be anticipated in one-third of patients undergoing preoperative combined modality therapy and total mesorectal excision. A policy of selective fecal diversion after preoperative combined modality therapy and total mesorectal excision for locally advanced rectal cancer can achieve low rates of pelvic sepsis, but may lead to an increased incidence of small bowel obstruction.

Clinical Examination Following Preoperative Chemoradiation for Rectal Cancer Is Not a Reliable Surrogate End Point

Clinical assessment of rectal cancer response to preoperative combined-modality therapy (CMT) using digital rectal examination (DRE) has been proposed as a means of assessing efficacy of therapy. However, because the accuracy of this approach has not been established, we conducted a prospective analysis to determine the operating surgeon's ability to assess response using DRE. Ninety-four prospectively accrued patients with locally advanced rectal cancer (T3/4 or N1) were evaluated with DRE and sigmoidoscopy in order to determine the following tumor characteristics: size, location, mobility, morphology, and circumference. Following preoperative CMT (50.40 Gy with fluorouracil-based chemotherapy) and under general anesthesia, the same surgeon estimated tumor response based on changes in these tumor characteristics, assessed via DRE. Percent pathologic tumor response was determined prospectively by a single pathologist using whole mount sections of the resected cancer. Clinical assessment using DRE underestimated pathologic response in 73 cases (78%). In addition, DRE was able to identify only 3 of 14 cases (21%) with a pathologic complete response. There were no clinical overestimates of response. None of the clinicopathologic tumor characteristics examined had a significant impact on DRE estimation of response. Clinical examination underestimates the extent of rectal cancer response to preoperative CMT. Given the inaccuracy of DRE following preoperative CMT, it should not be used as a sole means of assessing efficacy of therapy nor for selecting patients following CMT for local surgical therapies.