Do clinical criteria reflect pathologic complete response in rectal cancer following neoadjuvant therapy?

Background

Clinical complete response (cCR) in rectal cancer is being evaluated as a tool to identify patients who would not require surgery in the curative management of rectal cancer. Our study reviews mucosal changes after neoadjuvant therapy for rectal cancer in patients treated at our center.

Methods

Pathology reports were retrieved for patients treated with neoadjuvant chemoradiation therapy (CRT) or high-dose rate brachytherapy (HDRBT). The macroscopic appearance of the specimen was compared with pathologic staging.

Results

This study included 282 patients: 88 patients underwent neoadjuvant CRT and 194 patients underwent HDRBT; all patients underwent total mesorectal excision (TME). There were 160 male and 122 female patients with a median age of 65 years (range 29–87). The median time between neoadjuvant therapy and surgery was 50 and 58 days. Sixty patients (21.2%) were staged as ypT0N0, 21.2% had a pathologic complete response (pCR), and only 3.2% had a cCR. Of the 67 patients with initial involvement of the circumferential radial margin (CRM), 44 converted to pathologic CRM?. Two hundred seventy-three patients (96.8%) had mucosal abnormalities. Of the 222 patients with residual tumor, 70 patients had no macroscopic tumor visualized but an ulcer in its place.

Conclusion

Most patients undergoing neoadjuvant therapy for rectal cancer have residual mucosal abnormalities which preclude to a cCR as per published criteria from Brazil. Further studies are required to optimize clinical evaluation and MRI imaging in selected patients.

     

Is there a benefit in using magnetic resonance imaging in the prediction of preoperative neoadjuvant therapy response in locally advanced rectal cancer?

Objective

This meta-analysis aimed to evaluate the accuracy of magnetic resonance imaging (MRI) in predicting responses in patients with locally advanced rectal cancer after preoperative neoadjuvant therapy.

Methods

Articles in English language relating to the accuracy of MRI for this utility were retrieved. Methodological quality was assessed by Quality Assessment of Diagnostic Accuracy Studies tool. Pooled estimation and subgroup analysis data were obtained by statistical analysis.

Results

Fourteen studies involved 751 pathologically confirmed patients met the inclusion criteria. Methodological quality was relatively high. To predict histopathological response in locally advanced rectal cancer by MRI, the pooled sensitivity and specificity were 0.78 [95 % confidence intervals (CI), 0.65, 0.87] and 0.81 (95 % CI, 0.72, 0.87), respectively. Positive likelihood ratio and negative likelihood ratio were 4.1 (95 %CI, 2.9, 5.8) and 0.27 (95 % CI, 0.17, 0.43), respectively. Subgroup analysis showing that imaging was performed at 3.0 T MRI devices had higher pooled sensitivity (0.92, 95 % CI, 0.84, 1.00) than the subgroup of MRI with ≤1.5 T (0.68, 95 % CI, 0.53, 0.82) (p?<?0.05).The sensitivity and specificity of T2-weighted imaging (T2WI) with diffusion-weighted imaging (DWI) were 0.92 (95 % CI, 0.81, 1.00) and 0.75 (95 % CI, 0.54, 0.95); those of T2WI alone were 0.64 (95 % CI, 0.47, 0.82) and 0.88 (95 % CI, 0.81, 0.94) (p?>?0.05).

Conclusion

This meta-analysis indicates that MRI is an accurate tool in predicting pathologic response after preoperative therapy in patients with locally advanced rectal cancer. It is suggested to perform MRI by 3.0 T devices, which might be sensitive to identify responder. The addition of DWI to T2WI showed a non-significant improvement in sensitivity, which deserves further investigation.     

Is there an optimal neoadjuvant therapy for locally advanced pancreatic cancer?

Treatment of locally advanced pancreatic cancer is challenging. Despite continuing research, effective treatments continue to be elusive with median survival of only 8-12 months. Treatment options for locally advanced pancreatic cancer include radiation therapy, concurrent chemoradiation or chemotherapy. It is felt that radiation therapy is a suboptimal treatment as most of patients will die of systemic disease. In the past, radiation with 5-FU was the standard treatment for locally advanced pancreatic cancer. But now radiation has been used with combination other chemo agents such as paclitaxel or gemcitabine in order to increase the efficacy. Chemotherapy such as gemcitabine alone or gemcitabine doublet also has been studied in patients with locally advanced pancreatic cancer as well with overall survival being approximately the same magnitude as chemoradiation. The exact role of chemoradiation or chemotherapy in treatment of locally advanced pancreatic cancer is yet to be defined. Hence, this review summarizes and compares of role of radiation, chemoradiation and chemotherapy in treating this disease.     

Is adjuvant chemotherapy necessary for patients with pathological complete response after neoadjuvant chemoradiotherapy and radical surgery in locally advanced rectal cancer? Long-term analysis of 40 ypCR patients at a single center

Objectives

According to practice guidelines, adjuvant chemotherapy (ACT) is required for all patients with locally advanced rectal cancer who have received neoadjuvant chemoradiotherapy (NCRT) and total mesorectal excision (TME). The objective of this study was to determine whether ACT is necessary for patients achieving pathological complete response (pCR) after NCRT followed by surgery.

Methods

By retrospectively reviewing a prospectively collected database in our single tertiary care center, 210 patients with locally advanced rectal cancer who underwent NCRT followed by TME were identified between February 2005 and August 2013. All patients achieving ypCR were enrolled in this study, in which who underwent ACT (chemo group) and who did not (non-chemo group) were compared in terms of local recurrence (LR) rate, 5-year disease-free survival (DFS) rate and overall survival (OS) rate.

Results

Forty consecutive patients with ypCR were enrolled, 19 (47.5 %) in chemo group and 21 (52.5 %) in non-chemo group. After a median follow-up of 57 months, five patients developed systemic recurrences, with the 5y-DFS rate of 83.5 %. No LR occurred in the two groups. The 5y-DFS rates for patients in chemo group and non-chemo group was 90.9 and 76.0 %, respectively, showing no statistically significant difference (p?=?0.142). Multivariate analysis showed that tumor grade was the only independent prognostic factor for 5y-DFS and 5y-OS.

Conclusions

Results of this study suggested that it may not be necessary for all rectal cancer patients with ypCR after NCRT and radical surgery to receive ACT. Prospective randomized trials are warranted to further determine the value of ACT for ypCR patients.

     

Tumor response to neoadjuvant chemoradiation in rectal cancer: predictor for surgical morbidity?

Background Increasing the rate of pathological complete remissions after neoadjuvant chemoradiation of rectal cancer has become a strategy to further improve the long-term oncological outcome of patients. This report evaluates the influence of preoperative intensified radiochemotherapy on the rate and outcome of surgical complications. Materials and Methods Patients with primary rectal cancer at stages cT3/4cNx or N+ without metastasis were preoperatively treated either with capecitabine and irinotecan or with capecitabine, irinotecan and ceutximab with a concurrent radiation (50.4 Gy). Surgery was scheduled 4–7 weeks after completion of the chemoradiation. Perioperative complications were prospectively documented during the patient’s hospital stay. Results Fifty-nine patients (median age 60; male/female: 46/13) undergoing surgery at a single center were analysed. The median distance of the tumour from the dentate line was 5 cm. The operations performed were low anterior resection (n=45), Hartmann’s procedure (n=4) and abdominoperineal resection (n=10). Total mesorectal excision with R0-resection was accomplished in all but one patients. Histopathological regression was described in four grades (0–3) as defined by the Japanese Society for Cancer of the Colon and Rectum. Tumors were called major responsive when assigned to the regression grades 3 or 2, and minor or nonresponsive at regression grades 1 or 0. In total, 33 patients (55.9%) had a regression grade 2 or 3. Among them, 12 patients showed a pathological complete response without any residual cancer cell (20.3%). Seven out of 45 patients (15.5%) with sphincter-preserving surgery suffered from suture breakdown; they all had previously shown a major response of the resected tumor. Two of them died during the hospital stay. Conclusions While in general, patients undergoing neoadjuvant intensified treatment suffer from a slight increase in surgical complications, this is markedly enhanced in patients with good treatment responses. Our results underline the oncological benefit of intensified neoadjuvant chemoradiation, but the severity of complications in low rectal anastomosis of patients with good response after neoadjuvant therapy should alert surgeons and oncologists. R.D. Hofheinz contributed equally with K. Horisberger to the study.     

Complete pathological response following down-staging chemoradiation in locally advanced pancreatic cancer： Challenging the boundaries

Pancreatic cancer is an aggressive malignancy,relatively resistant to chemotherapy and radiotherapy,which usually presents late. Disease specific mortality approaches unity despite advances in adjuvant therapy. We present the first reported case of complete pathological response following neoadjuvant therapy in a locally advanced pancreatic adenocarcinoma.     

Local excision of low rectal cancer treated by chemoradiotherapy: is it safe for all patients with suspicion of complete tumor response?

Purpose

The purpose of this study is to assess if local excision (LE) could be proposed if suspicion of complete tumor response (CR) after neoadjuvant chemoradiotherapy (CRT) for low rectal cancer (LRC) and this despite a potential risk of nodes (N+) or other tumor deposits (OTD) left in place. The aim was to assess in patients with LRC treated by CRT: (a) pathologic results of LE and total mesorectal excision (TME) in case of preoperative suspicion of CR and (b) the risk of N+ or OTD on TME if ypT0-Tis-T1 tumor.

Patients

Among 202 patients with LRC after CRT, 33 (16 %) with suspicion of CR underwent LE (n?=?20) because of comorbidities and/or indication of definitive stoma or TME (n?=?13). Pathologic examination of LE and TME specimens and oncological outcomes were assessed. Furthermore, 40/202 patients with pathologic CR on TME specimen (ypT0-Tis-T1) were assessed for possible N+ or OTD.

Results

In the 33 patients with suspicion of CR: (a) after LE, tumor was ypT0-Tis-T1 in only 15/20 cases (75 %); (b) after TME, tumor was ypT0-Tis-T1 in only 7/13 cases (54 %). Among 40 patients with ypT0-Tis-T1 tumor on TME specimen, 4 (10 %) presented N+ and/or OTD.

Conclusion

In LRC with suspicion of CR after CRT, LE deserves a word of caution: 25 % of patients have in fact ypT2-T3 tumors. Furthermore, in patients with ypT0-Tis or T1 on TME specimen, a 10 % risk of N+ and/or ODT is observed. Thus, patient with suspicion of CR after CRT and treated by LE is exposed to a possible incomplete oncologic treatment.

     

Laparoscopic rectal cancer surgery: Where do we stand?

Large comparative studies and multiple prospective randomized control trials (RCTs) have reported equivalence in short and long-term outcomes between the open and laparoscopic approaches for the surgical treatment of colon cancer which has heralded widespread acceptance for laparoscopic resection of colon cancer. In contrast, laparoscopic total mesorectal excision (TME) for the treatment of rectal cancer has been welcomed with significantly less enthusiasm. While it is likely that patients with rectal cancer will experience the same benefits of early recovery and decreased postoperative pain from the laparoscopic approach, whether the same oncologic clearance, specifically an adequate TME can be obtained is of concern. The aim of the current study is to review the current level of evidence in the literature on laparoscopic rectal cancer surgery with regard to short-term and long-term oncologic outcomes. The data from 8 RCTs, 3 meta-analyses, and 2 Cochrane Database of Systematic Reviews was reviewed. Current data suggests that laparoscopic rectal cancer resection may benefit patients with reduced blood loss, earlier return of bowel function, and shorter hospital length of stay. Concerns that laparoscopic rectal cancer surgery compromises short-term oncologic outcomes including number of lymph nodes retrieved and circumferential resection margin and jeopardizes long-term oncologic outcomes has not conclusively been refuted by the available literature. Laparoscopic rectal cancer resection is feasible but whether or not it compromises short-term or long-term results still needs to be further studied.     

Are we doing too much?: local excision before radical surgery in early rectal cancer

Purpose

In early rectal cancer cases, the use of local excision is increasing. The general indication for local excision is based on the preoperative stage, but there is often a discrepancy between pre and postoperative stages. We sought to determine the indications for local excision in T1 rectal adenocarcinoma patients by comparing the preoperative clinical and postoperative pathological stages. A second aim was to compare the oncologic outcomes between local excision and radical resection.

Methods

Between 2004 and 2014, 152 T1 rectal adenocarcinoma patients were enrolled. We divided the subjects into two groups, local excision and radical resection, depending on the modality of treatment the patients initially received. The group of patients who underwent radical resection was subsequently subdivided into “excisable” and “non-excisable” groups based on the postoperative pathology.

Results

Of 152 patients, 28 patients (18.4%) underwent local excision, while 124 patients (81.6%) underwent radical resection. Of 124 patients, in clinically suspected T2 or less and N0 (93) cases, 50 patients (53.8%) needed treatment beyond local excision, and local excision was sufficient for 43 patients (46.2%). The 3-year overall survival (p?=?0.393) and 3-year disease-free survival (p?=?0.076) between the local excision and radical resection groups showed no significant difference.

Conclusions

The clinical T stage was overestimated in more than half of the cases. Therefore, if cT1/2 tumors with cN0 are suspected preoperatively, local excision is initially recommended and will allow for determination of underlying pathology. The clinician can then decide whether to monitor or intervene with radical resection.

     

Robotic versus laparoscopic surgery for mid–low rectal cancer after neoadjuvant chemoradiation therapy: comparison of oncologic outcomes

Purpose

Minimal invasive surgery for mid and low rectal cancer after neoadjuvant long-course chemoradiotherapy (LCRT) can be challenging. The aim of our study was to compare outcomes of laparoscopic and robotic resections in mid and low rectal cancers after LCRT.

Methods

Between Jan 2006 and Dec 2010, all patients who underwent robotic or laparoscopic resections for mid and low rectal cancers after LCRT were identified from a prospective database. These patients received treatment (5FU-based chemotherapy, 50.4 Gy radiotherapy), as they were T3 or T4 and/or node?+?ve. Patients in the two groups were compared with respect to demographics, clinical safety, and oncological outcomes.

Results

One hundred thirty-eight patients underwent rectal cancer resection after LCRT, either robotic (n?=?74) or laparoscopic (n?=?64). The patients in both groups were comparable in terms of demographics, distance of tumor from anal verge, and type of procedures. There were four (6.3 %) conversions in laparoscopic group and one (1.4 %) in the robotic group (p?=?0.183). The morbidity rates in the laparoscopic and robotic group were 26.6 % and 16.2 %, respectively (p?=?0.137). With a median follow up of 3 years, the local recurrence in the laparoscopic and robotic group was four (6.3 %) and two (2.7 %), respectively (p?=?0.420). The 3-year overall survival rate for laparoscopic and robotic group was 92.1 and 90.0 %, respectively (p?=?0.803). The 3-year disease-free survival was also comparable, 78.8 % (laparoscopic) versus 77.7 % (robotic) (p?=?0.390).

Conclusion

With a median follow up of 3 years, robotic surgery for mid and low rectal cancer was associated with oncological outcomes comparable to laparoscopic surgery.     

A single institution’s long-term follow-up of patients with pathological complete response in locally advanced rectal adenocarcinoma following neoadjuvant chemoradiotherapy

Purpose

This paper aimed to study the long term follow-up of patients with primary rectal adenocarcinoma receiving neoadjuvant chemoradiotherapy who obtained a pathological complete response (pCR) and identify factors predicting complete response.

Methods

Retrospective review of notes, histology, pre-operative full blood count and imaging of patients with primary rectal adenocarcinoma diagnosed in our institute from 2000 to 2012 from a prospectively maintained database were used. SPSS version 22.0 was used for statistical analysis.

Results

Three hundred eighty patients diagnosed with primary rectal adenocarcinoma were identified, 277 received neoadjuvant chemoradiotherapy followed by curative resection. Forty-six patients obtained a pCR (ypT0N0) with no local recurrence and two metastatic recurrences on follow-up. Patients with a pCR have a significantly improved overall survival and disease-free survival compared to a non-pCR (150.0 and 136.1 vs 77.5 and 84.7 months, p = 0.001). On univariate analysis, increased tumour height above anal verge, low lymph node yield, high pre-operative haemoglobin and a low neutrophil-lymphocyte ratio are significant factors identifying a pCR. Multivariable analysis of the above factors confirmed tumour height above anal verge as significant in obtaining a pCR.

Conclusion

Patients with rectal adenocarcinoma who develop a pCR following neoadjuvant chemoradiotherapy have improved overall and disease-free survival. We have identified distance from anal verge, low lymph node yield, high pre-operative haemoglobin and low neutrophil-lymphocyte ratio as significant predictors of developing a pCR.

     

Complete clinical response after preoperative chemoradiation in rectal cancer: is a "wait and see" policy justified?

PURPOSE: A proportion of patients, who receive preoperative chemoradiation for locally advanced (T3, T4, NX) rectal cancer achieve a complete clinical response and a pathologic complete response in the region of 15 to 30 percent. Support is growing in the United Kingdom for the concept of "waiting to see" and not proceeding to radical surgery when a complete clinical response is observed. The purpose of this review was to use a literature search to assess how often complete clinical response is achieved after neoadjuvant chemoradiation, the concordance of this finding with pathologic complete response, and to determine whether it is feasible to observe patients who achieve complete clinical response rather than proceed to surgery. RESULTS: In total, 218 Phase I/II or retrospective studies and 28 Phase III trials of preoperative radiotherapy or chemoradiation were identified: 96 percent of trials documented the pathologic complete response, but only 38 trials presented data on the achievement of a complete clinical response/partial clinical response. Only five studies were found in which patients with clinically staged T2/T3 tumors were treated with radiotherapy/chemoradiation and did not routinely proceed to surgery and also reported on the long-term outcome of a "wait and see" policy. DISCUSSION: It remains uncertain whether the degree of response to chemoradiation in terms of complete clinical response or pathologic complete response is a useful clinical end point. Studies that include T3 rectal cancer are associated with high local recurrence rates after nonsurgical treatment. Few studies report long-term outcome after achievement of a complete clinical response. CONCLUSIONS: The end point of complete clinical response is inconsistently defined and seems insufficiently robust with only partial concordance with pathologic complete response. The rationale of a "wait and see" policy when complete clinical response status is achieved relies on retrospective observations, which are currently insufficient to support this policy except in patients who are recognized to be unfit for or refuse radical surgery.     

Can endoscopic ultrasonography-guided fine-needle aspiration predict response to chemoradiation in non-small cell lung cancer? A pilot study

BACKGROUND: Accurate prediction of pathologic response to chemoradiation (CHEMO-XRT) has a significant impact on the treatment of patients with non-small cell lung cancer (NSCLC) and mediastinal lymph node (LN) metastasis (N2 disease). Objective: This pilot study evaluates the ability of EUS-FNA to predict pathologic response in LN following CHEMO-XRT in NSCLC patients with N2 disease. Patients and METHODS: Retrospective analysis of prospectively collected data on patients with NSCLC and biopsy-proven N2 disease who underwent restaging by EUS following CHEMO-XRT. At restaging, FNA was performed on the same LN, if present, or any other visible LN in the posterior mediastinum. Response to therapy (N0 disease) was defined by either absence of mediastinal LN or residual disease on FNA. Those staged N0 by EUS underwent tumor resection with complete LN dissection. RESULTS: Fourteen patients met the criteria for evaluation. Restaging by EUS suggested disease response in 7 patients and residual disease in 6; tissue yield was unsatisfactory in 1 patient. Eleven of 14 patients in whom mediastinal LN were seen at restaging by EUS underwent FNA: the aspirate was benign in 4, residual disease was found in 6, and an inadequate sample was obtained in 1 patient. In 3 patients no mediastinal LN were evident at EUS. Final diagnosis on the 7 patients in whom EUS suggested N0 disease was established at surgery: EUS was true negative in 6 and false negative in 1. Of the 6 patients with residual disease, 5 underwent palliative CHEMO-XRT and 1 underwent extended tumor resection. The patient in whom tissue sampling was inadequate was found to have residual disease at surgery. The diagnostic accuracy of EUS-FNA for predicting mediastinal response to preoperative CHEMO-XRT was 86%. CONCLUSIONS: EUS-FNA appears to qualify as an accurate, safe and minimally invasive diagnostic technique for restaging of mediastinal LN after CHEMO-XRT in NSCLC patients. Given this promising preliminary data, a prospective evaluation is justified.