Robotic lateral pelvic lymph node dissection after chemoradiation for rectal cancer: a Western perspective.

AIM: There are limited outcome data for lateral pelvic lymph node dissection (LPLND) following neoadjuvant chemoradiotherapy (nCRT), particularly in the West. Our aim was to evaluate the short-term perioperative and oncological outcomes of robotic LPLND at a single cancer centre. METHOD: A retrospective analysis of a prospective database of consecutive patients undergoing robotic LPLND for rectal cancer between November 2012 and February 2020 was performed. The main outcomes were short-term perioperative and oncological outcomes. Major morbidity was defined as Clavien-Dindo grade 3 or above. RESULTS: Forty patients underwent robotic LPLND during the study period. The mean age was 54 years (SD ± 15 years) and 13 (31.0%) were female. The median body mass index was 28.6 kg/m2 (IQR 25.5-32.6 kg/m2 ). Neoadjuvant CRT was performed in all patients. Resection of the primary rectal cancer and concurrent LPLND occurred in 36 (90.0%) patients, whilst the remaining 4 (10.0%) patients had subsequent LPLND after prior rectal resection. The median operating time was 420 min (IQR 313-540 min), estimated blood loss was 150 ml (IQR 55-200 ml) and length of hospital stay was 4 days (IQR 3-6 days). The major morbidity rate was 10.0% (n = 4). The median lymph node harvest from the LPLND was 6 (IQR 3-9) and 13 (32.5%) patients had one or more positive LPLNs. The median follow-up was 16 months (IQR 5-33 months), with 1 (2.5%) local central recurrence and 7 (17.5%) patients developing distant disease, resulting in 3 (7.5%) deaths. CONCLUSION: Robotic LPLND for rectal cancer can be performed in Western patients to completely resect extra-mesorectal LPLNs and is associated with acceptable perioperative morbidity.

Chemoradiation, surgery and adjuvant chemotherapy versus induction chemotherapy followed by chemoradiation and surgery: long-term results of the Spanish GCR-3 phase II randomized trial†.

BACKGROUND: The primary results of our phase II randomized trial suggested that compared with conventional preoperative chemoradiation (CRT), the addition of chemotherapy (CT) before CRT and surgery allows most patients receive their planned treatment with a better toxicity profile without compromising the pathological complete response and complete resection rates. We now report the 5-year outcomes. PATIENTS AND METHODS: Patients with distal or middle third, T3-T4 and/or N+ rectal adenocarcinoma selected by magnetic resonance imaging, were randomly assigned to arm A-preoperative CRT followed by surgery and four cycles of postoperative adjuvant capecitabine and oxaliplatin (CAPOX)-or arm B-four cycles of CAPOX followed by CRT and surgery. The following 5-year actuarial outcomes were assessed: the cumulative incidence of local relapse (LR) and distant metastases (DM), disease-free (DFS) and overall survival (OS). RESULTS: A total of 108 eligible patients were randomly assigned to arm A (n = 52) or arm B (n = 56). With a median follow-up of 69.5 months, 5-year DFS was 64% in arm A and 62% in arm B (P = 0.85) and 5-year OS was 78% in arm A and 75% in arm B (P = 0.64). The 5-year cumulative incidence of LR was 2% and 5% (P = 0.61) and 5-year cumulative incidence of DM was 21% and 23%; (P = 0.79) in arms A and B, respectively. CONCLUSION: Both treatment approaches yield similar outcomes. Given the lower acute toxicity and improved compliance with induction CT compared with adjuvant CT, integrating effective systemic therapy before CRT and surgery is a promising strategy and should be examined in phase III trials.

The diagnosis and management of gastric cancer: expert discussion and recommendations from the 12th ESMO/World Congress on Gastrointestinal Cancer, Barcelona, 2010.

Well-recognized experts in the field of gastric cancer discussed during the 12th European Society Medical Oncology (ESMO)/World Congress Gastrointestinal Cancer (WCGIC) in Barcelona many important and controversial topics on the diagnosis and management of patients with gastric cancer. This article summarizes the recommendations and expert opinion on gastric cancer. It discusses and reflects on the regional differences in the incidence and care of gastric cancer, the definition of gastro-esophageal junction and its implication for treatment strategies and presents the latest recommendations in the staging and treatment of primary and metastatic gastric cancer. Recognition is given to the need for larger and well-designed clinical trials to answer many open questions.

The diagnosis and management of rectal cancer: expert discussion and recommendations derived from the 9th World Congress on Gastrointestinal Cancer, Barcelona, 2007.

Knowledge of the biology and management of rectal cancer continues to improve. A multidisciplinary approach to a patient with rectal cancer by an experienced expert team is mandatory, to assure optimal diagnosis and staging, surgery, selection of the appropriate neo-adjuvant and adjuvant strategy and chemotherapeutic management. Moreover, optimal symptom management also requires a dedicated team of health care professionals. The introduction of total mesorectal excision has been associated with a decrease in the rate of local failure after surgery. High quality surgery and the achievement of pathological measures of quality are a prerequisite to adequate locoregional control. There are now randomized data in favour of chemoradiotherapy or short course radiotherapy in the preoperative setting. Preoperative chemoradiotherapy is more beneficial and has less toxicity for patients with resectable rectal cancer than postoperative chemoradiotherapy. Furthermore chemoradiotherapy leads also to downsizing of locally advanced rectal cancer. New strategies that decrease the likelihood of distant metastases after initial treatment need be developed with high priority. Those involved in the care for patients with rectal cancer should be encouraged to participate in well-designed clinical trials, to increase the evidence-based knowledge and to make further progress. Health care workers involved in the care of rectal cancer patients should be encouraged to adopt quality control processes leading to increased expertise.

Small-cell carcinoma of the esophagus and gastroesophageal junction: review of the Memorial Sloan-Kettering experience.

BACKGROUND: Esophageal small-cell carcinoma (SCC) is rare, highly malignant and the optimal treatment approach has not been defined. PATIENTS AND METHODS: We report the largest single-institution retrospective review of patients with esophageal and gastroesophageal (GE) junction SCC. RESULTS: Twenty-five patients were identified, with complete records available for 22. Eighty-two percent were male, 82% had pure SCC histology and 86% of tumors were in the lower esophagus or GE junction. On the basis of the Veterans' Administration Lung Study Group criteria, 14 patients (64%) presented with limited disease (LD). Median survival was 19.8 months (range, 1.5 months to 11.2+ years); for LD patients, 22.3 months (range, 6 months to 11.2+ years); for extensive disease (ED) patients, 8.5 months (range, 1.5 months to 2.2 years, P = 0.02). With a median follow-up of 38 months, six patients (27%) are alive, one with ED and five with LD. Two LD patients are alive and free of disease for >5 years. Four of the five LD patients who are long-term survivors received induction chemotherapy followed by chemoradiotherapy without surgery. CONCLUSIONS: Our data indicate that patients with LD esophageal SCC treated with induction chemotherapy followed by consolidative chemoradiation can achieve long-term survival. The contribution of surgery remains unclear.

Combined modality chemoradiation in elderly oesophageal cancer patients.

We present a single institution experience with 5-FU, mitomycin-C based chemoradiation for the primary treatment of elderly patients with oesophageal cancer. Twenty-five patients with a median age of 77 years (range 66-88) with a diagnosis of stage II-III squamous cell or adenocarcinoma of the oesophagus were treated at Memorial Sloan Kettering from 1996 to 2001 with two cycles of concurrent 5-FU, mitomycin-C and 50.4 Gy. Owing to age and comorbidity, these patients were not considered surgical candidates. The Charlson comorbidity score was used to evaluate patient comorbidity. Nine patients (36%) experienced grade 3-4 haematologic toxicity. Of the 23 patients evaluable for response, 17 patients (68%) had a negative post-treatment endoscopy and CT scan without evidence of progressive disease. Eleven patients (44%) are alive and 10 (40%) remain without evidence of recurrent or progressive oesophageal cancer at a median follow-up of 35 months. The median overall survival was 35 months and 2-year survival 64%. There was no significant difference in overall survival between Charlson score /=2 (P=0.10). Similar survival was observed for patients with adenocarcinoma or squamous carcinoma. Primary chemoradiation with two cycles of 5-FU, mitomycin-C, and 50.4 Gy in elderly patients is an active regimen with moderate toxicity, despite the advanced age and heavy comorbidity burden of this cohort. Patients with local/regional oesophageal cancer with adequate functional status should not be excluded from potentially curative treatment based on age alone.

Combined modality therapy of resectable rectal cancer: current approaches.

There are two conventional treatments for clinically resectable rectal cancer. First is surgery and, if the tumor is in stage T3 or N1-2, this is followed by postoperative combined modality therapy. The second is preoperative combined modality therapy followed by surgery and postoperative combined modality therapy if the tumor is classified at ultrasound as uT3-4 or N+. A number of new chemotherapeutic agents have been developed for the treatment of patients with colorectal cancer. Ongoing phase I and II trials are examining the use of these new chemotherapeutic agents in combination with pelvic radiation therapy, most commonly in the preoperative setting; early results suggest that the complete response rates are higher. Based on results from phase I and II trials, the standard regimen for patients who receive combined modality therapy is continuous infusion 5-fluorouracil (5-FU) and pelvic radiation. Regimens using CPT-11 or oxaliplatin-based combined modality therapy plus either continuous infusion 5-FU or capecitibine are under active development.

Adjuvant therapy for rectal cancer--the transatlantic view.

In North America there are two conventional treatments for clinically resectable rectal cancer. First is surgery and, if the tumour is T3 and/or N1-2, this is followed by postoperative combined modality therapy. The second, for patients with ultrasound T3 or clinical T4 disease, is pre-operative combined modality therapy followed by surgery and postoperative chemotherapy. Pre-operative therapy (most commonly combined modality therapy) has gained acceptance as a standard adjuvant therapy. The potential advantages of this approach compared with postoperative therapy include less acute toxicity and enhanced sphincter preservation. Recently completed randomized trials in the US and Germany will provide a definitive answer to this theory. In contrast to the combined modality approach to pre-operative therapy a number of European centres advocate an intensive short course of radiation (5 Gy x 5 followed one week later by surgery). The only randomized trial which has revealed a significant advantage in survival is the Swedish Rectal Cancer Trial. The Dutch CKVO 95-04 TME trial did not confirm a survival advantage and two metanalyses report conflicting results. Due to selection bias, it is not possible accurately to compare the local recurrence and survival results of intensive short course radiation with conventional pre-operative combined modality therapy. The intensive short course radiation approach is not used in North America due to its higher toxicity and lack of sphincter preservation. In the Dutch trial the 5-year local recurrence was 12% with TME and was significantly decreased to 6% with pre-operative radiation. The 5-year local recurrence rate in the 324 patients with stage III disease who underwent a TME alone with negative margins was 20%. Therefore, despite TME surgery, radiation therapy is still a necessary component in the adjuvant management of rectal cancer.

Results after rectal cancer resection with in-continuity partial vaginectomy and total mesorectal excision.

BACKGROUND: Although sharp mesorectal excision reduces circumferential margin involvement and local recurrence, a concomitant partial vaginectomy may be required in women with locally advanced rectal cancer. METHODS: Sixty-four patients requiring a partial vaginectomy during resection of primary rectal cancer were identified. Survival was determined by the Kaplan-Meier method, and distributions were compared by the log-rank test. RESULTS: Locally advanced disease was reflected by presentation with malignant rectovaginal fistulae (n = 6) or cancers described as bulky or adherent/tethered to the rectovaginal septum (n = 32). Thirty-five patients received adjuvant radiation with or without chemotherapy. At a median follow-up of 22 months, 27 (42%) patients developed recurrent disease, with most of these occurring at distant sites. The 5-year overall survival was 46%, with a median survival of 44 months. The 2-year local recurrence-free survival was 84%. The crude local failure rate was 16% (10 of 64), and local recurrence was more common in patients with a positive as opposed to a negative microscopic margin (2 [50%] of 4 vs. 8 [13%] of 60, respectively). Positive nodal status had a significant effect on overall survival (P <.001). CONCLUSIONS: Partial vaginectomy is indicated for locally advanced rectal cancers involving the vagina. The results are most favorable in patients with negative surgical margins and node-negative disease.

Preoperative radiation with or without chemotherapy and full-thickness transanal excision for selected T2 and T3 distal rectal cancers.

BACKGROUND AND AIMS: To evaluate the clinical outcome of selected patients with distal rectal cancer treated by preoperative radiation with or without chemotherapy and full-thickness local excision (FTLE). PATIENTS AND METHODS: Ten patients with invasive distal rectal cancer (six T2, four T3) were treated with preoperative radiotherapy (3600-5040 cGy) with or without 5-fluorouracil based chemotherapy. FTLE was performed 4-6 weeks after completion of radiotherapy, primarily because of comorbid diseases or patient refusal of a permanent colostomy. Median follow-up was 28.5 months. RESULTS: There were no prolonged wound complications, and only one positive microscopic margin was detected. Among three cases of complete pathological response, two remain without evidence of disease. All patients retained sphincter function and avoided creation of a stoma. Two patients developed recurrence, one with widespread disease including pelvic recurrence 26 months after surgery and the other with distant disease only at 23 months. There were four deaths: two unrelated to cancer, one of undetermined cause after 7 years, and one after widespread recurrence at 26 months, with death 4 months later. Two-year actuarial survival was 78%. CONCLUSIONS: This pilot study demonstrates that preoperative radiotherapy and FTLE avoids major abdominal surgery yet facilitates sphincter preservation, excision with negative margins, and short-term local control in selected patients with distal rectal cancer.

Who gets adjuvant treatment for stage II and III rectal cancer? Insight from surveillance, epidemiology, and end results--Medicare.

PURPOSE: To examine the relationship between patient characteristics and the use of adjuvant pelvic radiation with and without chemotherapy among patients aged 65 years and older with stage II and III rectal cancer. PATIENTS AND METHODS: A retrospective cohort study using the Surveillance, Epidemiology, and End Results-Medicare linked database identified 1,411 patients aged 65 and older with resected stage II and III rectal cancers diagnosed between 1992 and 1996. From claims submitted to Medicare, we measured the use of pelvic radiation therapy with or without chemotherapy and pre- or postoperatively. RESULTS: Fifty-seven percent of patients received radiation, 42% received chemotherapy and radiation, and 7% had treatment delivered preoperatively. Age was the strongest determinant of treatment: 73% of patients aged 65 to 69, 66% aged 70 to 75, 52% aged 75 to 79, 39% aged 80 to 84, and 21% aged 85 to 89 received radiation. The age trend remained strong after adjusting for other factors that predict receipt of treatment and after exclusion of patients with any evident comorbidity (P <.001). Patients were more likely to receive radiation treatment if they had an abdominal perineal resection, stage III disease, or a T4 tumor. CONCLUSION: Because pelvic recurrences are a substantial cause of morbidity, further efforts are needed to ensure that elderly patients have the opportunity to make informed decisions regarding adjuvant treatment.

Conservative management of rectal cancer with local excision and adjuvant therapy.

The standard surgical treatment of distal, resectable, invasive rectal cancers is an abdominoperineal resection or a low anterior resection. Given the morbidity associated with these standard treatments and the frequent need for postoperative adjuvant therapy, the use of a more conservative approach, such as local excision with adjuvant therapy as primary therapy for selected cases of rectal cancer is appealing. Data from single-institution series as well as recent data from prospective, multi-institutional studies, suggest that local excision with adjuvant therapy is a reasonable alternative to radical surgery in selected patients. Local excision alone is acceptable treatment only for T1 tumors without adverse pathologic features, while local excision with adjuvant therapy is an alternative treatment for T1 tumors with adverse pathologic features and T2 tumors. Some series suggest that preoperative therapy with local excision may be a possible treatment for selected T3 tumors; however, the high local failure rates seen in T3 tumors treated with local excision and postoperative therapy cautions against this approach. Functional results with local excision are generally good, and postoperative morbidity and mortality is acceptable. In summary, the results of local excision and radiation therapy are encouraging. Randomized trials are needed to determine whether this approach has local control and survival rates comparable to those of radical surgery.

Preoperative combined modality therapy for clinically resectable uT3 rectal adenocarcinoma.

PURPOSE: To determine the acute toxicity, outcome, and sphincter preservation rates in patients with clinically resectable uT3 adenocarcinoma of the rectum treated with preoperative combined modality therapy. METHODS AND MATERIALS: A total of 72 patients were treated from 12/90-7/98 with preoperative 50.4 Gy plus 2 cycles of concurrent 5-fluorouracil (5-FU) and leucovorin (LV) bolus daily x 5 followed by sharp or total mesorectal excision and 4 cycles of postoperative 5-FU and LV. RESULTS: Individual Grade 3+ toxicities during preoperative therapy included diarrhea, 11%; bowel movements, 9%; leukopenia, 18%; tenesmus, 1%; and thrombocytopenia, 1%. Total Grade 3+ toxicity was 28%. The pathologic complete response (CR) rate was 13%, and an additional 9% had a clinical CR for a total CR rate of 22%. Of the 35 patients who were judged clinically by their operating surgeon to require an abdominoperineal resection (APR) and were therefore treated with the goal of sphincter preservation, 89% were able to undergo sphincter-preserving surgery. Of the 21 patients eligible for analysis, 81% had good to excellent sphincter function. The 3-year actuarial patterns of failure were 2% local, 8% abdominal, and 13% distant. The 3-year actuarial survival was 95%. CONCLUSIONS: Our data confirm our preliminary reports of encouraging rates of acute toxicity, local control, survival, sphincter preservation and function with preoperative combined modality therapy. It is an alternative approach for the treatment of uT3 clinically resectable rectal cancer.

UFT plus oral leucovorin calcium (Orzel) and radiation in combined modality therapy: a comprehensive review.

5-fluorouracil (5-FU) has become the most commonly used drug in combination with radiation therapy. The recent availability of oral formulations of 5-FU in conjunction with the ability to modulate the anabolic and catabolic metabolism of 5-FU with leucovorin and dihydropyrimidine dehydrogenase (DPD) inhibitors, respectively, may provide a substantial improvement in the ease of administration and the efficacy of fluoropyrimidine therapy. Several oral fluoropyrimidines are under investigation. UFT (uracil:tegafur) plus oral leucovorin (Orzel) is the first oral DPD-inhibitory fluoropyrimidine. With daily administration, Orzel achieves similar concentrations of 5-FU obtained with continuous-infusion 5-FU. This paper summarizes the therapeutic rationale for Orzel and reviews the clinical experience with UFT and UFT/LV in combined modality therapy regimens.

Present indications for adjuvant therapy in resectable rectal cancer.

Combined modality therapy is an effective adjuvant therapy for many patients with clinically resectable rectal cancer. The indications for adjuvant therapy for rectal cancer are based on the pattern of failure after surgery. Despite radical surgery, local-regional failure frequently occurs in patients with transmural or node-positive rectal cancers. The incidence of treatment failure in the pelvis is directly correlated with the extent of transmural penetration (microscopic vs gross) and the additional risk of lymph node metastases. In the post-operative setting its use is dictated by pathologic stage and the type of operation (i.e. conventional surgery or a local excision). The choice of which post-operative adjuvant regimen to recommend in the non-protocol setting remains controversial. If 5-FU alone is used, then it is best administered by continuous infusion. In the preoperative setting, the use of adjuvant therapy depends on the clinical stage and the need for sphincter preservation. Phase I/II trials examining the use of newer chemotherapeutic agents such as Tomudex, UFT/leucovorin, CPT-11, oxaliplatin, eniluracil and capecitabine with preoperative radiation therapy are in progress. This review examines both the selection criteria and results of adjuvant combined modality therapy for patients with clinically resectable rectal cancer.

Postoperative radiation therapy for rectal cancer combined with UFT/leucovorin.

Postoperative combined-modality therapy with fluorouracil (5-FU) and radiation therapy is accepted practice for high-risk rectal cancer. Postoperative pelvic radiotherapy alone may improve pelvic control, but is not associated with an improvement in survival. Protracted infusional 5-FU has been associated with decreased tumor recurrence and improved survival when combined with postoperative adjuvant pelvic radiotherapy. The use of new drugs and alternative ways of administering 5-FU is desirable. UFT plus leucovorin is an oral 5-FU prodrug with efficacy equal to 5-FU plus leucovorin in metastatic colorectal cancer. A combination of postoperative adjuvant UFT plus leucovorin concurrent with radiation therapy should be feasible, and the design of an ongoing phase I trial is presented.