Induction chemotherapy followed by chemoradiotherapy versus chemoradiotherapy alone as neoadjuvant treatment for locally recurrent rectal cancer: study protocol of a multicentre, open-label, parallel-arms, randomized controlled study (PelvEx II)

Background A resection with clear margins (R0 resection) is the most important prognostic factor in patients with locally recurrent rectal cancer (LRRC). However, this is achieved in only 60 per cent of patients. The aim of this study is to investigate whether the addition of induction chemotherapy to neoadjuvant chemo(re)irradiation improves the R0 resection rate in LRRC. Methods This multicentre, international, open-label, phase III, parallel-arms study will enrol 364 patients with resectable LRRC after previous partial or total mesorectal resection without synchronous distant metastases or recent chemo- and/or radiotherapy treatment. Patients will be randomized to receive either induction chemotherapy (three 3-week cycles of CAPOX (capecitabine, oxaliplatin), four 2-week cycles of FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) or FOLFORI (5-fluorouracil, leucovorin, irinotecan)) followed by neoadjuvant chemoradiotherapy and surgery (experimental arm) or neoadjuvant chemoradiotherapy and surgery alone (control arm). Tumours will be restaged using MRI and, in the experimental arm, a further cycle of CAPOX or two cycles of FOLFOX/FOLFIRI will be administered before chemoradiotherapy in case of stable or responsive disease. The radiotherapy dose will be 25 × 2.0 Gy or 28 × 1.8 Gy in radiotherapy-naive patients, and 15 × 2.0 Gy in previously irradiated patients. The concomitant chemotherapy agent will be capecitabine administered twice daily at a dose of 825 mg/m2 on radiotherapy days. The primary endpoint of the study is the R0 resection rate. Secondary endpoints are long-term oncological outcomes, radiological and pathological response, toxicity, postoperative complications, costs, and quality of life. Discussion This trial protocol describes the PelvEx II study. PelvEx II, designed as a multicentre, open-label, phase III, parallel-arms study, is the first randomized study to compare induction chemotherapy followed by neoadjuvant chemo(re)irradiation and surgery with neoadjuvant chemo(re)irradiation and surgery alone in patients with locally recurrent rectal cancer, with the aim of improving the number of R0 resections

Technique for laparoscopic autonomic nerve preserving total mesorectal excision

With the introduction of total mesorectal excision (TME) for treatment of rectal cancer, the prognosis of patients with rectal cancer is improved. With this better prognosis, there is a growing awareness about the quality of life of patients after rectal carcinoma. Laparoscopic total mesorectal excision (LTME) for rectal cancer offers several advantages in comparison with open total mesorectal excision (OTME), including greater patient comfort and an earlier return to daily activities while preserving the oncologic radicality of the procedure. Moreover, laparoscopy allows good exposure of the pelvic cavity because of magnification and good illumination. The laparoscope seems to facilitate pelvic dissection including identification and preservation of critical structures such as the autonomic nervous system. The technique for laparoscopic autonomic nerve preserving total mesorectal excision is reported. A three- or four-port technique is used. Vascular ligation, sharp mesorectal dissection and identification and preservation of the autonomic pelvic nerves are described

Laparoscopic versus open total mesorectal excision:a case-control study

Background and aims: Because definitive long-term results are not yet available, the oncological safety of laparoscopic surgery for treatment of rectal cancer remains unproven. The aim of this prospective non-randomised study was to assess the feasibility and short-term outcome of laparoscopic total mesorectal excision (LTME) after 25-30 Gy preoperative radiotherapy and to compare the results with a matched-control group of open TME (OTME). Materials and methods: A series of 41 patients with primary rectal cancer underwent LTME for rectal cancer and were matched with a historical control group of 41 patients who underwent OTME. Both groups received preoperative short-term radiotherapy. Results: There was no mortality in the LTME group and 2% mortality in the OTME group. The overall postoperative morbidity was 37% in the LTME group and 51% in the OTME group, including an anastomotic leakage of 9 and 14% in the LTME and OTME groups respectively. A positive circumferential margin was found in 7% of patients in the LTME group and in 12% of the patients in the OTME group. Conclusion: This study shows that LTME is technically feasible and can be performed safely. We show at least a similar surgical completeness using a laparoscopic technique compared with open surgery

Laparoscopic vs open total mesorectal excision for rectal cancer

Background: Next to surgical margins, yield of lymph nodes, and length of bowel resected, macroscopic completeness of mesorectal excision may serve as another quality control of total mesorectal excision (TME). In this study, the macroscopic completeness of laparoscopic TME was evaluated. Methods: A series of 25 patients with rectal cancer were managed laparoscopically (LTME) and included in this study. The pathologic specimens of the LTME group were prospectively examined and matched with a historical group of resection specimens from patients who had undergone open TME (OTME). The two groups were matched for gender and type of resection (low anterior or abdominoperineal resection). Special care was given to the macroscopic judgment concerning the completeness of the mesorectum. Results: A three-grade scoring system showed no differences between the LTME and OTME groups. Conclusion: The Current study supports the hypothesis that oncologic resection using laparoscopic TME is feasible and adequate

Adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with colon cancer at high risk of peritoneal carcinomatosis; the COLOPEC randomized multicentre trial

Background: The peritoneum is the second most common site of recurrence in colorectal cancer. Early detection of peritoneal carcinomatosis (PC) by imaging is difficult. Patients eventually presenting with clinically apparent PC have a poor prognosis. Median survival is only about five months if untreated and the benefit of palliative systemic chemotherapy is limited. Only a quarter of patients are eligible for curative treatment, consisting of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CR/HIPEC). However, the effectiveness depends highly on the extent of disease and the treatment is associated with a considerable complication rate. These clinical problems underline the need for effective adjuvant therapy in high-risk patients to minimize the risk of outgrowth of peritoneal micro metastases. Adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) seems to be suitable for this purpose. Without the need for cytoreductive surgery, adjuvant HIPEC can be performed with a low complication rate and short hospital stay. Methods/Design: The aim of this study is to determine the effectiveness of adjuvant HIPEC in preventing the development of PC in patients with colon cancer at high risk of peritoneal recurrence. This study will be performed in the nine Dutch HIPEC centres, starting in April 2015. Eligible for inclusion are patients who underwent curative resection for T4 or intra-abdominally perforated cM0 stage colon cancer. After resection of the primary tumour, 176 patients will be randomized to adjuvant HIPEC followed by routine adjuvant systemic chemotherapy in the experimental arm, or to systemic chemotherapy only in the control arm. Adjuvant HIPEC will be performed simultaneously or shortly after the primary resection. Oxaliplatin will be used as chemotherapeutic agent, for 30 min at 42-43 degrees C. Just before HIPEC, 5-fluorouracil and leucovorin will be administered intravenously. Primary endpoint is peritoneal disease-free survival at 18 months. Diagnostic laparoscopy will be performed routinely after 18 months postoperatively in both arms of the study in patients without evidence of disease based on routine follow-up using CT imaging and CEA. Discussion: Adjuvant HIPEC is assumed to reduce the expected 25 % absolute risk of PC in patients with T4 or perforated colon cancer to a risk of 10 %. This reduction is likely to translate into a prolonged overall survival

Changing outcomes following pelvic exenteration for locally advanced and recurrent rectal cancer

Background Pelvic exenteration for locally advanced rectal cancer (LARC) and locally recurrent rectal cancer (LRRC) is technically challenging but increasingly performed in specialist centres. The aim of this study was to compare outcomes of exenteration over time. Methods This was a multicentre retrospective study of patients who underwent exenteration for LARC and LRRC between 2004 and 2015. Surgical outcomes, including rate of bone resection, flap reconstruction, margin status and transfusion rates, were examined. Outcomes between higher- and lower-volume centres were also evaluated. Results Some 2472 patients underwent pelvic exenteration for LARC and LRRC across 26 institutions. For LARC, rates of bone resection or flap reconstruction increased from 2004 to 2015, from 3.5 to 12.8 per cent, and from 12.0 to 29.4 per cent respectively. Fewer units of intraoperative blood were transfused over this interval (median 4 to 2 units; P = 0.040). Subgroup analysis showed that bone resection and flap reconstruction rates increased in lower- and higher-volume centres. R0 resection rates significantly increased in low-volume centres but not in high-volume centres over time (low-volume: from 62.5 to 80.0 per cent, P = 0.001; high-volume: from 83.5 to 88.4 per cent, P = 0.660). For LRRC, no significant trends over time were observed for bone resection or flap reconstruction rates. The median number of units of intraoperative blood transfused decreased from 5 to 2.5 units (P < 0.001). R0 resection rates did not increase in either low-volume (from 51.7 to 60.4 per cent; P = 0.610) or higher-volume (from 48.6 to 65.5 per cent; P = 0.100) centres. No significant differences in length of hospital stay, 30-day complication, reintervention or mortality rates were observed over time. Conclusion Radical resection, bone resection and flap reconstruction rates were performed more frequently over time, while transfusion requirements decreased

Palliative pelvic exenteration: A systematic review of patient-centered outcomes

Objective: Palliative pelvic exenteration (PPE) is a technically complex operation with high morbidity and mortality rates, considered in patients with limited life expectancy. There is little evidence to guide practice. We performed a systematic review to evaluate the impact of PPE on symptom relief and quality of life (QoL). Methods: A systematic review was conducted according to the PRISMA guidelines using Ovid MEDLINE, EMBASe, and PubMed databases for studies reporting on outcomes of PPE for symptom relief or QoL. Descriptive statistics were used on pooled patient cohorts. Results: Twenty-three historical cohorts and case series were included, comprising 509 patients. No comparative studies were found. Most malignancies were of colorectal, gynaecological and urological origin. Common indications for PPE were pain, symptomatic fistula, bleeding, malodour, obstruction and pelvic sepsis. The pooled median postoperative morbidity rate was 53.6% (13–100%), the median in-hospital mortality was 6.3% (0–66.7%), and median OS was 14 months (4–40 months). Some symptom relief was reported in a median of 79% (50–100%) of the patients, although the magnitude of effect was poorly measured. Data for QoL measures were inconclusive. Five studies discouraged performing PPE in any patient, while 18 studies concluded that the procedure can be considered in highly selected patients. Conclusion: Available evidence on PPE is of low-quality. Morbidity and mortality rates are high with a short median OS interval. While some symptom relief may be afforded by this procedure, evidence for improvement in QoL is limited. A highly selective individualised approach is required to optimise the risk:benefit equation

Simultaneous pelvic exenteration and liver resection for primary rectal cancer with synchronous liver metastases: results from the PelvEx Collaborative

Aim At presentation, 15-20% of patients with rectal cancer already have synchronous liver metastases. The aim of this study was to determine the surgical and survival outcomes in patients with advanced rectal cancer who underwent combined pelvic exenteration and liver (oligometastatic) resection.Method Data from 20 international institutions that performed simultaneous pelvic exenteration and liver resection between 2007 and 2017 were accumulated. Primarily, we examined perioperative outcomes, morbidity and mortality. We also assessed the impact that margin status had on survival.Results Of 128 patients, 72 (56.2%) were men with a median age of 60 years [interquartile range (IQR) 15 years]. The median size of the liver oligometastatic deposits was 2 cm (IQR 1.8 cm). The median duration of surgery was 406 min (IQR 240 min), with a median blood loss of 1090 ml (IQR 2010 ml). A negative resection margin (R0 resection) was achieved in 73.5% of pelvic exenterations and 66.4% of liver resections. The 30-day mortality rate was 1.6%, and 32% of patients had a major postoperative complication. The 5-year overall survival for patients in whom an R0 resection of both primary and metastatic disease was achieved was 54.6% compared with 20% for those with an R1/R2 resection (P = 0.006).Conclusion Simultaneous pelvic exenteration and liver resection is feasible, with acceptable morbidity and mortality. Simultaneous resection should only be performed where an R0 resection of both pelvic and hepatic disease is anticipated

Pelvic Exenteration for Advanced Nonrectal Pelvic Malignancy

Objective: To determine factors associated with outcomes following pelvic exenteration for advanced nonrectal pelvic malignancy. Background: The PelvEx Collaborative provides large volume data from specialist centers to ascertain factors associated with improved outcomes. Methods: Consecutive patients who underwent pelvic exenteration for nonrectal pelvic malignancy between 2006 and 2017 were identified from 22 tertiary centers. Patient demographics, neoadjuvant therapy, histopathological assessment, length of stay, 30-day major complication/mortality rate were recorded. The primary endpoints were factors associated with survival. The secondary endpoints included the difference in margin rates across the cohorts, impact of neoadjuvant treatment on survival, associated morbidity, and mortality. Results: One thousand two hundred ninety-three patients were identified. 40.4% (n ¼ 523) had gynecological malignancies (endometrial, ovarian, cervical, and vaginal), 35.7% (n ¼ 462) urological (bladder), 18.1% (n ¼ 234) anal, and 5.7% had sarcoma (n ¼ 74). The median age across the cohort was 63 years (range, 23–85). The median 30-day mortality rate was 1.7%, with the highest rates occurring following exenteration for recurrent sarcoma or locally advanced cervical cancer (3.3% each). The median length of hospital stay was 17.5 days. 34.5% of patients experienced a major complication, with highest rate occurring in those having salvage surgery for anal cancer. Multivariable analysis showed R0 resection was the main factor associated with long-term survival. The 3-year overall-survival rate for R0 resection was 48% for endometrial malignancy, 40.6% for ovarian, 49.4% for cervical, 43.8% for vaginal, 59% for bladder, 48.3% for anal, and 48.1% for sarcoma. Conclusion: Pelvic exenteration remains an important treatment in selected patients with advanced or recurrent nonrectal pelvic malignancy. The range in 3-year overall survival following R0 resection (40%–59%) reflects the diversity of tumor types