Igor Proscurshim

Patterns of failure and survival for nonoperative treatment of stage c0 distal rectal cancer following neoadjuvant chemoradiation therapy.

Neoadjuvant chemoradiation therapy (CRT) is the preferred treatment option for distal rectal cancer. Complete pathological response after CRT has led to the proposal of nonoperative approach as an alternative treatment for highly selected patients with complete clinical response. However, patterns of failure following this strategy remains undetermined. Three hundred sixty-one patients with distal rectal cancer were managed by neoadjuvant CRT including 5-FU, leucovorin, and 5040 cGy. Tumor response assessment was performed at 8 weeks following CRT. Patients with complete clinical response were not immediately operated on and were closely followed. One hundred twenty-two patients were considered to have complete clinical response after the first tumor response assessment. Of these, only 99 patients sustained complete clinical response for at least 12 months and were considered stage c0 (27.4%) and managed nonoperatively. Mean follow-up was 59.9 months. There were 13 (13.1%) recurrences: 5 (5%) endorectal, 7 (7.1%) systemic, and 1 (1%) combined recurrence. All 5 isolated endorectal recurrences were salvaged. Mean recurrence interval was 52 months for local failure and 29.5 months for systemic failure. There were five cancer-related deaths after systemic recurrences. Overall and disease-free 5-year survivals were 93% and 85%. Even though surgery remains the standard treatment for rectal cancer, nonoperative treatment after complete clinical response following neoadjuvant CRT may be safe and associated with good survival rates in a highly selected group of patients. Survival in these patients is significantly affected by systemic failure. Exclusive local failure occurs late after CRT completion and is frequently amenable to salvage therapy.

Local Recurrence After Complete Clinical Response and Watch and Wait in Rectal Cancer After Neoadjuvant Chemoradiation: Impact of Salvage Therapy on Local Disease Control

PURPOSE To review the risk of local recurrence and impact of salvage therapy after Watch and Wait for rectal cancer with complete clinical response (cCR) after chemoradiation therapy (CRT). METHODS AND MATERIALS Patients with cT2-4N0-2M0 distal rectal cancer treated with CRT (50.4-54 Gy + 5-fluorouracil-based chemotherapy) and cCR at 8 weeks were included. Patients with cCR were enrolled in a strict follow-up program with no immediate surgery (Watch and Wait). Local recurrence-free survival was compared while taking into account Watch and Wait strategy alone and Watch and Wait plus salvage. RESULTS 90 of 183 patients experienced cCR at initial assessment after CRT (49%). When early tumor regrowths (up to and including the initial 12 months of follow-up) and late recurrences were considered together, 28 patients (31%) experienced local recurrence (median follow-up time, 60 months). Of those, 26 patients underwent salvage therapy, and 2 patients were not amenable to salvage. In 4 patients, local re-recurrence developed after Watch and Wait plus salvage. The overall salvage rate for local recurrence was 93%. Local recurrence-free survival at 5 years was 69% (all local recurrences) and 94% (after salvage procedures). Thirteen patients (14%) experienced systemic recurrence. The 5-year cancer-specific overall survival and disease-free survival for all patients (including all recurrences) were 91% and 68%, respectively. CONCLUSIONS Local recurrence may develop in 31% of patients with initial cCR when early regrowths (≤ 12 months) and late recurrences are grouped together. More than half of these recurrences develop within 12 months of follow-up. Salvage therapy is possible in ≥ 90% of recurrences, leading to 94% local disease control, with 78% organ preservation.

Watch and wait approach following extended neoadjuvant chemoradiation for distal rectal cancer: are we getting closer to anal cancer management?

BACKGROUND: No immediate surgery (Watch and Wait) has been considered in select patients with complete clinical response after neoadjuvant chemoradiation to avoid postoperative morbidity and functional disorders after radical surgery. OBJECTIVE: The purpose of this study was to demonstrate the long-term results of patients who had a complete clinical response following an alternative chemoradiation regimen and were managed nonoperatively. DESIGN: This is a prospective study. SETTINGS: This study was conducted at a single center. PATIENTS: Seventy consecutive patients with T2-4N0-2M0 distal rectal cancer were studied. Neoadjuvant chemoradiotherapy included 54 Gy and 5-fluorouracil/leucovorin delivered in 6 cycles every 21 days. Patients were assessed for tumor response at 10 weeks from radiation completion. Patients with incomplete clinical response were referred to immediate surgery. Patients with complete clinical response were not immediately operated on and were monitored. MAIN OUTCOME MEASURES: The primary outcomes measured were the initial complete clinical response rates after 10 weeks and the sustained complete clinical response rates after 12 months from chemoradiotherapy. RESULTS: One patient died during chemoradiotherapy because of cardiac complications. Forty-seven (68%) patients had initial complete clinical response. Of these, 8 developed local regrowth within the first 12 months of follow-up (17%). Thirty-nine sustained complete clinical response at a median follow-up of 56 months (57%). An additional 4 patients (10%) developed late local recurrences (>12 months of follow-up). Overall, 35 patients never underwent surgery (50%). LIMITATIONS: This study is limited by the short follow-up and small sample size. CONCLUSION: Extended chemoradiation therapy with additional chemotherapy cycles and 54 Gy of radiation may result in over 50% of sustained (>12 months) complete clinical response rates that may ultimately avoid radical rectal resection. Local failures occur more frequently during the initial 12 months of follow-up in up to 17% of cases, whereas late recurrences are less common but still possible, leading to 50% of patients who never required surgery. Strict follow-up may allow salvage therapy in the majority of these patients (see Video, Supplemental Digital Content 1, http://links.lww.com/DCR/A113.)

Interval Between Surgery and Neoadjuvant Chemoradiation Therapy for Distal Rectal Cancer: Does Delayed Surgery Have an Impact on Outcome?

BACKGROUND The optimal interval between neoadjuvant chemoradiation therapy (CRT) and surgery in the treatment of patients with distal rectal cancer is controversial. The purpose of this study is to evaluate whether this interval has an impact on survival. METHODS AND MATERIALS Patients who underwent surgery after CRT were retrospectively reviewed. Patients with a sustained complete clinical response (cCR) 1 year after CRT were excluded from this study. Clinical and pathologic characteristics and overall and disease-free survival were compared between patients undergoing surgery 12 weeks or less from CRT and patients undergoing surgery longer than 12 weeks from CRT completion and between patients with a surgery delay caused by a suspected cCR and those with a delay for other reasons. RESULTS Two hundred fifty patients underwent surgery, and 48.4% had CRT-to-surgery intervals of 12 weeks or less. There were no statistical differences in overall survival (86% vs. 81.6%) or disease-free survival rates (56.5% and 58.9%) between patients according to interval (< or =12 vs. >12 weeks). Patients with intervals of 12 weeks or less had significantly higher rates of Stage III disease (34% vs. 20%; p = 0.009). The delay in surgery was caused by a suspected cCR in 23 patients (interval, 48 +/- 10.3 weeks). Five-year overall and disease-free survival rates for this subset were 84.9% and 51.6%, not significantly different compared with the remaining group (84%; p = 0.96 and 57.8%; p = 0.76, respectively). CONCLUSIONS Delay in surgery for the evaluation of tumor response after neoadjuvant CRT is safe and does not negatively affect survival. These results support the hypothesis that shorter intervals may interrupt ongoing tumor necrosis.

Nonoperative Approaches to Rectal Cancer: A Critical Evaluation

A neoadjuvant multimodality approach with chemoradiation therapy (CRT) is the preferred treatment strategy for most distal rectal cancers. Significant downstaging and complete pathologic response may develop after this strategy, and there is still controversy regarding the management of these patients. In this setting, a nonoperative approach has been suggested in select patients with complete clinical response after thorough clinical, endoscopic, and radiologic assessment. However, the assessment of these patients is not straightforward and remains complex. Available data regarding this approach are limited to a single institutions experience from retrospective analyses. Standardization of the assessment of tumor response and the development of radiological/molecular tools may clarify the role of no immediate surgery in patients with complete clinical response after neoadjuvant CRT. Advances in radiation and medical oncology could potentially lead to significant improvements in complete tumor regression rates, leading to an increase in importance of a minimally invasive approach in patients with rectal cancer.

Transanal Endoscopic Microsurgery for Residual Rectal Cancer After Neoadjuvant Chemoradiation Therapy Is Associated With Significant Immediate Pain and Hospital Readmission Rates

BACKGROUND: Transanal endoscopic microsurgery may represent appropriate diagnostic and therapeutic procedure in selected patients with distal rectal cancer following neoadjuvant chemoradiation. Even though this procedure has been associated with low rates of postoperative complications, patients undergoing neoadjuvant chemoradiation seem to be at increased risk for suture line dehiscence. In this setting, we compared the clinical outcomes of patients undergoing transanal endoscopic microsurgery with and without neoadjuvant chemoradiation. METHODS: Thirty-six consecutive patients were treated by transanal endoscopic microsurgery at a single institution. Twenty-three patients underwent local excision after neoadjuvant chemoradiation therapy for rectal adenocarcinoma, and 13 patients underwent local excision without any neoadjuvant treatment for benign and malignant rectal tumors. Chemoradiation therapy included 50.4 to 54Gy and 5-fluorouracil-based chemotherapy. All patients underwent transanal endoscopic microsurgery with primary closure of the rectal defect. Complications (immediate and late) and readmission rates were compared between groups. RESULTS: Overall, median hospital stay was 2 days. Immediate (30-d) complication rate was 44% for grade II/III complications. Patients undergoing neoadjuvant chemoradiation therapy were more likely to develop grade II/III immediate complications (56% vs 23%; P = .05). Overall, the 30-day readmission rate was 30%. Wound dehiscence was significantly more frequent among patients undergoing neoadjuvant chemoradiation therapy (70% vs 23%; P = .03). Patients undergoing neoadjuvant chemoradiation therapy were at significantly higher risk of requiring readmission (43% vs 7%; P = .02). CONCLUSION: Transanal local excision with the use of endoscopic microsurgical approach may result in significant postoperative morbidity, wound dehiscence, and readmission rates, in particular, because of rectal pain secondary to wound dehiscence. In this setting, the benefits of this minimally invasive approach either for diagnostic or therapeutic purposes become significantly restricted to highly selected patients that can potentially avoid a major operation but will still face a significantly morbid and painful procedure.

Transanal endoscopic microsurgery for residual rectal cancer (ypT0-2) following neoadjuvant chemoradiation therapy: another word of caution.

BACKGROUND: Significant tumor downstaging among patients with rectal cancer following neoadjuvant chemoradiation has raised the issue of offering patients with small residual cancers restricted to the bowel wall an alternative treatment strategy to total mesorectal excision. Transanal endoscopic microsurgery may allow proper primary tumor resection with promising oncological outcomes, less postoperative morbidity, and minimal long-term sexual, urinary, and fecal continence disorders in comparison with radical resection. OBJECTIVE: The aim of this study was to determine the oncological outcomes of patients with residual rectal cancers restricted to the rectal wall (ypT0-2) following neoadjuvant chemoradiation and transanal endoscopic microsurgery. DESIGN: This study considered a prospective cohort of patients with residual rectal cancers following neoadjuvant chemoradiation treated by transanal endoscopic microsurgery and no additional systemic therapy. SETTINGS: This study was a single-institution experience. PATIENTS: Patients with adenocarcinoma of the rectum located no more than 7 cm from the anal verge and endorectal ultrasound- or magnetic resonance-staged cT2-4N0-2M0 treated by neoadjuvant chemoradiation (50.4–54 Gy and 5-fluorouracil-based chemotherapy) were eligible for the study. Patients with small residual tumors (⩽3 cm) radiologically staged ycT0-2N0 were treated by transanal endoscopic microsurgery. INTERVENTIONS: Transanal endoscopic microsurgery was performed. MAIN OUTCOME MEASURES: The primary outcome measured was local recurrence. RESULTS: Of the 27 patients treated by transanal endoscopic microsurgery, 3 had ypT0, 6 had ypT1, and 18 had ypT2 cancers. All patients underwent R0 transanal endoscopic microsurgery excision. Local recurrence was observed in 4 (15%) patients after a median follow-up of 15 months. Only lymphovascular invasion was an independent predictive factor for local failure (p = 0.04). Tumor size, ypT status, T-status downstaging, lateral/radial margins, and tumor regression grade were not predictors of local failure. LIMITATIONS: This study was limited by the small sample size and limited follow-up. CONCLUSIONS: A local failure rate of 15% after transanal endoscopic microsurgery for patients with residual rectal cancers restricted to the bowel wall (ypT0-2) may limit the indication of this procedure to highly selected patients as an alternative to standard radical total mesorectal excision.

Accuracy of positron emission tomography/computed tomography and clinical assessment in the detection of complete rectal tumor regression after neoadjuvant chemoradiation Long-Term Results of a Prospective Trial (National Clinical Trial 00254683)

Neoadjuvant chemoradiation (CRT) therapy may result in significant tumor regression in patients with rectal cancer. Patients who develop complete tumor regression have been managed by treatment strategies that are alternatives to standard total mesorectal excision. Therefore, assessment of tumor response with positron emission tomography/computed tomography (PET/CT) after neoadjuvant treatment may offer relevant information for the selection of patients to receive alternative treatment strategies.

Absence of Lymph Nodes in the Resected Specimen After Radical Surgery for Distal Rectal Cancer and Neoadjuvant Chemoradiation Therapy: What does it Mean?

PurposeThe number of retrieved lymph nodes during radical surgery has been considered of great importance to ensure adequate staging and radical resection. However, this finding may not be applicable after neoadjuvant therapy in which, not only is there a decrease in lymph nodes recovered, but also a subgroup of patients with absence of lymph nodes in the resected specimen.MethodsPatients with absence of lymph nodes were compared with patients with ypN0 disease and patients with ypN+ disease.ResultsThirty-two patients (11 percent) had absence of lymph nodes, 171 patients (61 percent) had ypN0 disease, and 78 patients (28 percent) had ypN+ disease. Patients with absence of lymph nodes had significantly lower ypT status (ypT0-1, 40 vs. 13 percent; P < 0.001) and decreased risk of perineural invasion (6 vs. 21 percent; P = 0.04) compared with ypN0 patients. Five-year disease-free survival (74 percent) was similar to patients with ypN0 (59 percent; P = 0.2), and both were significantly better than patients with ypN+ disease (30 percent; P < 0.001).ConclusionsAbsence of lymph nodes retrieved from the resected specimen is associated with favorable pathologic features (ypT and perineural invasion status) and good disease-free survival rates. In this setting, absence of retrieved lymph nodes may reflect improved response to neoadjuvant chemoradiation therapy rather than inappropriate or suboptimal oncologic radicality.

The role of carcinoembriogenic antigen in predicting response and survival to neoadjuvant chemoradiotherapy for distal rectal cancer.

PURPOSE: Carcinoembriogenic antigen (CEA) is the most frequently used tumor marker in rectal cancer. A decrease in carcinoembriogenic antigen after radical surgery is associated with survival in these patients. Neoadjuvant chemoradiotherapy may lead to significant primary tumor downstaging, including complete tumor regression in selected patients. Therefore, we hypothesized that a decrease in CEA after neoadjuvant chemoradiotherapy could reflect tumor response to chemoradiotherapy, affecting final disease stage and ultimately survival. METHODS: Patients with distal rectal cancer managed by neoadjuvant chemoradiotherapy and available pretreatment and postchemoradiotherapy levels of CEA were eligible for the study. Outcomes studied included final disease stage, relapse, and survival, and these were compared according to initial CEA level, post-chemoradiotherapy CEA level, and the reduction in CEA. RESULTS: Overall 170 patients were included. Post-chemoradiotherapy CEA levels <5 ng/ml were associated with increased rates of complete clinical response and pathologic response. Additionally, postchemoradiotherapy CEA levels <5 ng/ml were associated with increased overall and disease-free survival (P = 0.01 and P = 0.03). There was no correlation between initial CEA level or reduction in CEA and complete response or survival. CONCLUSION: A postchemoradiotherapy CEA level <5 ng/ml is a favorable prognostic factor for rectal cancer and is associated with increased rates of earlier disease staging and complete tumor regression. Postchemoradiotherapy CEA levels may be useful in decision making for patients who may be candidates for alterative treatment strategies.