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Surgery in asymptomatic patients with colorectal cancer and unresectable liver metastases: the authors’ experience

Surgery in asymptomatic patients with colorectal cancer and unresectable liver metastases: the... OncoTargets and Therapy Dovepress open access to scientific and medical research Open Access Full Text Article O RIG INAL R ESEARCH Surgery in asymptomatic patients with colorectal cancer and unresectable liver metastases: the authors’ experience Carlo Boselli Purpose: In asymptomatic patients with Stage IV colorectal cancer, the debate continues over the efficacy of primary resection compared to chemotherapy alone. The aim of this study Claudio Renzi was to define the optimal management for asymptomatic patients with colorectal cancer and Alessandro Gemini 1 unresectable liver metastases. Elisa Castellani Patients and methods: Patients receiving elective surgery (n = 17) were compared to patients Stefano Trastulli receiving chemotherapy only (n = 31). Data concerning patients’ demographics, location of pri- Jacopo Desiderio mary tumor, comorbidities, performance status, Child–Pugh score, extension of liver metastases, Alessia Corsi size of primary, and other secondary locations were collected. Francesco Barberini Results: Thirty-day mortality after chemotherapy was lower than that after surgical resection Roberto Cirocchi (19.3% versus 29.4%; not significant). In patients with .75% hepatic involvement, mortality Alberto Santoro at 1 month was higher after receiving surgical treatment than after chemotherapy alone (50% Amilcare Parisi versus 25%). In patients with ,75% hepatic involvement, 30-day mortality was similar in Adriano Redler both groups (not significant). Thirty-day mortality in patients with Stage T3 was lower in those Giuseppe Noya receiving chemotherapy (16.7% versus 30%; not significant). Overall survival was similar in 1 both groups. The risk of all-cause death after elective surgery (2.1) was significantly higher Department of General and Oncologic Surger y, University of than in patients receiving chemotherapy only (P = 0.035). Perugia, Perugia, Department of Conclusion: This study demonstrated that in palliative treatment of asymptomatic unresect- General Surger y, University of able Stage IV colorectal cancer, the overall risk of death was significantly higher after elective Perugia, St Maria Hospital, Terni, Department of Surgical Sciences, surgery compared to patients receiving chemotherapy alone. However, in the literature, there Sapienza University of Rome, Rome, is no substantial difference between these treatments. New studies are required to better evalu- Department of Digestive Surgery, ate outcomes. St Maria Hospital, Terni, Italy Keywords: large bowel, tumor, inoperable liver replacement, palliative surgery, 30-day mortality Introduction Colorectal cancer (CRC) represents more than 9% of all new cancer cases worldwide, and in 2002, more than 1 million new cases were diagnosed. In the US, the incidence of this malignancy has decreased by 3.0% in men and 2.2% in women in 1998–2006, with a reduction in male mortality of 3.9% in 2002–2006. However, an increased incidence of CRC has occurred in Europe, particularly in the southeastern countries. Among 4,5 patients with newly diagnosed CRC, 20%–30% have liver metastases, 10%–15% Correspondence: Claudio Renzi 6,7 8–10 have peritoneal carcinomatosis, and 10%–25% have lung metastases. St Maria Hospital, Via Tristano di Joannuccio 4, Terni 05100, Italy According to the European Society for Medical Oncology guidelines, hepatectomy Tel +39 744 205 442 for patients with metastatic CRC is to be performed only with curative intent following Fax +39 744 205 111 Email [email protected] the criteria of oncological radicality and if it is indicated that there is enough remnant submit your manuscript | www.dovepress.com OncoTargets and Therapy 2013:6 267–272 Dovepress © 2013 Boselli et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article http://dx.doi.org/10.2147/OTT.S39448 which permits unrestricted noncommercial use, provided the original work is properly cited. Boselli et al Dovepress liver parenchyma following the resection (.30%) and/or in Thirty-one patients (nonoperative group) received the absence of unresectable multivisceral spreading of the chemotherapy alone, leaving the primary tumor in place, 11,12 disease or carcinomatosis. ie, nonoperative management (NOM). In this group, Treatment of advanced stages of CRC, especially in 24 patients received FOLFOX plus bevacizumab as first- patients not eligible for curative surgery, consists of medical line therapy. FOLFOX only was administered to the therapies. The availability of new polychemotherapeutic regi- remaining seven patients who were not able to tolerate the mens (5-u fl orouracil, folinic acid, and oxaliplatin; FOLFOX) combination. Switching to second-line therapy was not in combination with biologic agents (monoclonal antibod- needed. Administration of bevacizumab was suspended at ies such as bevacizumab, cetuximab, and panitumumab) 3 months in six patients because of drug-related toxicity or has markedly improved the median survival of patients worsening of their condition and in two patients because in advanced stages, with no increase in the incidence of disease control was reached. 13–16 complications. Age, comorbidities, and performance status, and the risk of In a retrospective study, 93% of patients with Stage IV complications (obstruction and perforation) were the criteria CRC on chemotherapy did not develop complications related used to choose between the resection of the primary tumor and to the primary tumor. In patients with obstructive tumor, the NOM (Table 1). Thirty-day overall mortality and overall sur- use of stents allowed them to be quickly started on systemic vival were the primary and secondary endpoints assessed. 18,19 chemotherapy. Nevertheless, in asymptomatic patients Statistics on the clinical characteristics of patients were with Stage IV CRC, the debate continues over the efficacy calculated by Fisher’s exact test for 2 × 2 comparisons and by of primary neoplasia resection compared to chemotherapy Pearson’s Chi-squared test for comparisons greater than 2 × 2 alone. (95% confidence interval, α = 0.05). A multivariate analysis The aim of this study was to determine if there was any for 30-day mortality and overall survival was performed by improvement in overall survival and a reduction of posttreat- Cox logistic regression. ment mortality after resection of the primary tumor, with The mean age of the patients was lower in the opera- respect to nonoperative treatment in patients with Stage IV tive group (Table 1). Local extension of the disease was CRC and unresectable liver metastases. Table 1 Clinical characteristics of the patients according to Patients and methods treatment Data on patients with synchronous unresectable liver metas- Clinical characteristic Elective NOM P tases from CRC who consecutively underwent palliative surgery therapy between January 2010 and December 2011 were Average age (range), years 70 (54–84) 73 (60–87) retrospectively reviewed. Among patients with rectal cancer, Primary tumor localization Right colon 4 (23.5%) 7 (22.6%) 0.22 only those with intraperitoneal localization were selected Left colon 7 (41.4%) 6 (19.4%) because extraperitoneal rectal cancer with unresectable liver Rectosigmoid colon 6 (35.3%) 18 (58%) metastases is best treated with chemotherapy and radiation Number of comorbidities therapy as an effective palliative treatment. None of the 0 4 (23.5%) 7 (22.6%) 0.60 1 9 (52.9%) 11 (35.5%) 48 patients included in this multicentric study had bowel 2 3 (17.6%) 10 (32.2%) obstruction, bleeding, or perforation. 3 1 (6%) 3 (9.7%) Seventeen patients (operative group) underwent elec- Performance status tive palliative surgery consisting of colonic resection, 14 of ASA I/ECOG 0 6 (35.3%) 7 (22.6%) 0.60 ASA II/ECOG 1 8 (47.1%) 16 (51.6%) whom had open surgery by median laparotomy, two with ASA III/ECOG 2 3 (17.6%) 8 (25.8%) primary tumor in rectosigmoid colon underwent laparoscopic Child before treatment colorectal dissection followed by suprapubic laparotomy in A 11 (64.7%) 14 (45.2%) 0.24 which total mesorectal excision and colorectal anastomosis B 6 (35.3%) 17 (54.8%) Hepatic parenchyma replaced by metastases were performed, and one with right CRC had laparoscopic 9 (53%) 13 (42%) 0.51 ,50% exploration followed by total laparotomic right colectomy due 50%–75% 6 (35%) 10 (32%) to local extension of the disease. Seven of the patients who .75% 2 (12%) 8 (26%) underwent elective surgery had neoplastic stenosis; however, Abbreviations: ASA, American Society of Anesthesiologists; ECOG, Eastern despite this, obstinate constipation was reported. Cooperative Oncology Group; NOM, nonoperative management. submit your manuscript | www.dovepress.com OncoTargets and Therapy 2013:6 Dovepress Dovepress Palliative surgery in metastatic colorectal cancer determined by computed tomography scan and pathological mortality since the difference between the two groups was examination in the operative group, and by computed tomog- minimal (2/7 versus 4/19 for elective surgery and NOM, raphy scan only in the NOM group (Table 1). respectively) (Tables 2 and 3). Secondary localizations in addition to hepatic replace- Results ment did not affect 30-day mortality. The two groups were Overall mortality within 30 days of commencing palliative not comparable because not all patients presented extrahe- chemotherapy was lower than that of surgical resection (five patic metastases (Tables 2 and 3). versus six), even though this outcome was not statistically Of the patients who underwent elective surgery, eleven signic fi ant. In the operative group, three patients died of liver started palliative chemotherapy (six received FOLFOX plus failure presenting hepatorenal syndrome, two patients died of bevacizumab and v fi e received FOLFOX only) and six died of heart failure, and six patients had postoperative complications disease or complications before starting it. The mean interval (three wound infections, one urinary tract infection, and two between surgery and starting postoperative chemotherapy with bronchopneumonia). Of the six patients who received was 5 weeks. chemotherapy only, four died of hepatorenal syndrome and The mean and median follow-up was 8 months and two died of heart failure. 7 months, respectively. The mean and median overall sur- In patients with .75% of the parenchyma replaced vival of the patients receiving elective surgery was 6 months by metastases, mortality after treatment was found to be and 4 months, respectively. For the patients who under- 50% if on elective surgery and 25% if on chemotherapy went palliative chemotherapy only, the mean and median alone. The reported difference between the two groups overall survival was 7 months and 5 months, respectively. of patients for ,75% hepatic involvement of the volume The 1-year overall survival rate was 17.6% versus 19.4% was minimal (50%–75%: 2/6 versus 2/10 and ,50%: 2/9 for elective surgery and chemotherapy alone, respectively versus 2/13 for elective surgery and NOM, respectively) (Figure 1). (Tables 2 and 3). Multivariate analysis of the data demonstrated that there Thirty-day mortality in patients with Stage T3 was lower were no statistically significant differences in 30-day mortal - in the group receiving chemotherapy, although this outcome ity. On the other hand, data analysis using the Cox regression was not statistically significant (3/10 versus 2/12 for elective model demonstrated that the risk of all-cause death was sig- surgery and NOM, respectively). In patients with Stage T4, nificantly higher after elective surgery (2.1; 95% confidence local extension of the tumor did not appear to affect 30-day interval 1.06–4.5; P = 0.035; adjusted to liver replacement Table 2 Factors affecting 30-day overall mortality and overall survival after elective surgery Patient Overall survival from the Hepatic Local Lung Peritoneal (by date) start of therapy (months) involvement extension (T) metastases metastases 1 1 ,50% 4 x x 2 2 50%–75% 4 x 3 9 3 x ,50% 4 1 50%–75% 3 x 5 8 4 ,50% 6 15 ,50% 3 7 3 3 x x ,50% 8 4 50%–75% 3 9 1 50%–75% 4 x 10 20* ,50% 3 11 1 3 .75% 12 10 3 ,50% 13 3 .75% 4 14 12 3 ,50% 15 4 50%–75% 4 x 16 1 ,50% 4 x 17 6 50%–75% 3 Note: *Alive October 2012. Abbreviations: X, positive; –, negative. submit your manuscript | www.dovepress.com OncoTargets and Therapy 2013:6 Dovepress Boselli et al Dovepress Table 3 Factors affecting 30-day overall mortality and overall survival after nonoperative management Patient Overall survival from the Hepatic Local Lung Peritoneal (by date) start of therapy (months) involvement extension (T) metastases metastases 1 11 ,50% 3 2 1 50%–75% 4 x x 3 22 ,50% 4 4 7 3 x .75% 5 4 4 x .75% 6 11 4 ,50% 7 3 .75% 4 x x 8 12 4 ,50% 9 4 50%–75% 3 x 10 1 3 x .75% 11 8 4 ,50% 12 6 3 x ,50% 13 2 .75% 4 x 14 1 50%–75% 3 x 15 16 ,50% 3 16 5 4 x .75% 17 19* 3 ,50% 18 1 50%–75% 4 x 19 4 50%–75% 4 x 20 13 3 ,50% 21 5 50%–75% 4 x 22 1 4 .75% 23 3 50%–75% 3 x 24 8 4 ,50% 25 2 .75% 4 x 26 10 4 ,50% 27 3 50%–75% 4 x x 28 12* 3 ,50% 29 1 50%–75% 4 x 30 4 50%–75% 4 x 31 7 3 x ,50% Note: *Alive October 2012. Abbreviations: X, positive; –, negative. and other metastases) compared to patients receiving che- to Galizia et al, this occurrence may be balanced by a better motherapy only (Tables 2 and 3). response rate to chemotherapy in selected patients before Overall the two groups showed similar performance primary tumor debulking. The current analysis doesn’t status. The difference between the two groups was greatest suggest that primary tumor resection is a safe and effective for American Society of Anesthesiologists I/ Eastern Coop- treatment of asymptomatic patients with Stage IV CRC when erative Oncology Group 0 (Table 1). Furthermore, patients not radically resectable. undergoing surgery had a better hepatic function since they Liver tumor burden has been recognized as an indepen- had a smaller metastatic liver replacement than those receiv- dent risk factor for poor outcome, regardless of therapy. ing chemotherapy alone (Table 1). Thus, patients with extensive (.75%) hepatic tumor involve- ment carry an extremely unfavorable prognosis. Hepatic Discussion parenchymal replacement is significantly related to survival. Resection of the primary tumor is necessary for patients with Hepatic tumor burden . 50% is related to poor overall complications, whereas chemoradiotherapy in combination survival. Bilobar liver involvement is related with an even with targeted agents appears safe and seems a suitable alter- greater unfavorable prognosis. native for patients without complications. After resection In palliative treatment of uncomplicated patients of the primary tumor, adjuvant therapy should be promptly affected by CRC with unresectable liver metastases, undertaken as a delay may decrease its efficacy. According chemoradiotherapy combined with biological agents is submit your manuscript | www.dovepress.com OncoTargets and Therapy 2013:6 Dovepress Dovepress Palliative surgery in metastatic colorectal cancer 1.00 0.75 0.50 0.25 0.00 0 5 10 15 20 Months Chemotherapy Surgery Figure 1 Kaplan–Meier survival curves according to treatment. a suitable alternative to surgical resection of the primary no significant difference in 30-day mortality and overall sur - tumor. vival was found between the two groups of patients. Asymptomatic patients with a liver metastasis involving ,50% of the parenchyma, when undergoing resection of the Conclusion primary tumor, display a survival rate similar to patients on This study shows that in palliative treatment of asymptom- chemotherapy alone (Tables 2 and 3). In asymptomatic patients atic unresectable Stage IV CRC, the risk of all-cause death with a replaced liver volume of 50%–75%, surgery showed was significantly higher after elective surgery compared to no benet fi s in terms of survival over NOM (posttreatment patients receiving chemotherapy only. However, in the lit- mortality 33.3% versus 20%), as recently shown by Kleespies erature, there is no substantial difference between these two et al. This data is even more signic fi ant in patients with treatments. Therefore, it is crucial to undertake new studies metastases involving .75% of the liver volume (posttreatment to evaluate and compare the results in terms of quality of life mortality 50% versus 25%) (Tables 2 and 3). in both groups of patients. Local neoplastic extension is not an independent predictor of survival. In the current study, it was demonstrated that in Disclosure Stage T3 and T4 local extension of the primary tumor, elec- The authors report no conflicts of interest in this work. tive surgery presents no benet fi in terms of survival compared to NOM (posttreatment mortality Stage T3: 30% versus References 16.7% and Stage T4: 28.6% versus 21%) (Tables 2 and 3). 1. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55(2):74–108. Peritoneal carcinomatosis is an independent prognos- 2. Edwards BK, Ward E, Kohler BA, et al. Annual report to the nation on tic factor, and it is also recognized as an important risk the status of cancer, 1975–2006, featuring colorectal cancer trends and factor for obstruction. In the current study, peritoneal impact of interventions (risk factors, screening, and treatment) to reduce future rates. Cancer. 2010;116(3):544–573. carcinomatosis appeared not to influence posttreatment 3. 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Br J Surg. 2005;92(9):1155–1160. cancer. Thorac Cardiovasc Surg. 2005;53(6):358–364. 25. Galizia G, Lieto E, Orditura M, et al. First-line chemotherapy vs 11. Van Cutsem E, Nordlinger B, Cervantes A. Advanced colorectal bowel tumor resection plus chemotherapy for patients with unre- cancer: ESMO clinical practice guidelines for treatment. Ann Oncol. sectable synchronous colorectal hepatic metastases. Arch Surg. 2010;21(Suppl 5):v93–v97. 2008;143(4):352–358. 12. Cirocchi R, Trastulli S, Boselli C, et al. Radiofrequency ablation in the 26. Konyalian VR, Rosing DK, Haukoos JS, et al. The role of primary treatment of liver metastases from colorectal cancer [review]. Cochrane tumour resection in patients with stage IV colorectal cancer. Colorectal Database Syst Rev. 2012;6:CD006317. Dis. 2007;9(5):430–437. 13. McCahill LE, Yothers GA, Sharif S, et al. A phase II trial of 27. Kleespies A, Fuessl KE, Seelinger H, et al. 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Cirocchi R, Trastulli S, Abraha I, et al. Non-resection versus resection 17. Poultsides GA, Servais EL, Saltz LB, et al. Outcome of primary tumor for an asymptomatic primary tumour in patients with unresectable in patients with synchronous stage IV colorectal cancer receiving stage IV colorectal cancer [review]. Cochrane Database Syst Rev. combination chemotherapy without surgery as initial treatment. J Clin 2012;8:CD008997. Oncol. 2009;27(20):3379–3384. 18. Karoui M, Soprani A, Charachon A, et al. Primary chemotherapy with or without colonic stent for management of unresectable stage IV colorectal cancer. Eur J Surg Oncol. 2010;36(1):58–64. 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Surgery in asymptomatic patients with colorectal cancer and unresectable liver metastases: the authors’ experience

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OncoTargets and Therapy Dovepress open access to scientific and medical research Open Access Full Text Article O RIG INAL R ESEARCH Surgery in asymptomatic patients with colorectal cancer and unresectable liver metastases: the authors’ experience Carlo Boselli Purpose: In asymptomatic patients with Stage IV colorectal cancer, the debate continues over the efficacy of primary resection compared to chemotherapy alone. The aim of this study Claudio Renzi was to define the optimal management for asymptomatic patients with colorectal cancer and Alessandro Gemini 1 unresectable liver metastases. Elisa Castellani Patients and methods: Patients receiving elective surgery (n = 17) were compared to patients Stefano Trastulli receiving chemotherapy only (n = 31). Data concerning patients’ demographics, location of pri- Jacopo Desiderio mary tumor, comorbidities, performance status, Child–Pugh score, extension of liver metastases, Alessia Corsi size of primary, and other secondary locations were collected. Francesco Barberini Results: Thirty-day mortality after chemotherapy was lower than that after surgical resection Roberto Cirocchi (19.3% versus 29.4%; not significant). In patients with .75% hepatic involvement, mortality Alberto Santoro at 1 month was higher after receiving surgical treatment than after chemotherapy alone (50% Amilcare Parisi versus 25%). In patients with ,75% hepatic involvement, 30-day mortality was similar in Adriano Redler both groups (not significant). Thirty-day mortality in patients with Stage T3 was lower in those Giuseppe Noya receiving chemotherapy (16.7% versus 30%; not significant). Overall survival was similar in 1 both groups. The risk of all-cause death after elective surgery (2.1) was significantly higher Department of General and Oncologic Surger y, University of than in patients receiving chemotherapy only (P = 0.035). Perugia, Perugia, Department of Conclusion: This study demonstrated that in palliative treatment of asymptomatic unresect- General Surger y, University of able Stage IV colorectal cancer, the overall risk of death was significantly higher after elective Perugia, St Maria Hospital, Terni, Department of Surgical Sciences, surgery compared to patients receiving chemotherapy alone. However, in the literature, there Sapienza University of Rome, Rome, is no substantial difference between these treatments. New studies are required to better evalu- Department of Digestive Surgery, ate outcomes. St Maria Hospital, Terni, Italy Keywords: large bowel, tumor, inoperable liver replacement, palliative surgery, 30-day mortality Introduction Colorectal cancer (CRC) represents more than 9% of all new cancer cases worldwide, and in 2002, more than 1 million new cases were diagnosed. In the US, the incidence of this malignancy has decreased by 3.0% in men and 2.2% in women in 1998–2006, with a reduction in male mortality of 3.9% in 2002–2006. However, an increased incidence of CRC has occurred in Europe, particularly in the southeastern countries. Among 4,5 patients with newly diagnosed CRC, 20%–30% have liver metastases, 10%–15% Correspondence: Claudio Renzi 6,7 8–10 have peritoneal carcinomatosis, and 10%–25% have lung metastases. St Maria Hospital, Via Tristano di Joannuccio 4, Terni 05100, Italy According to the European Society for Medical Oncology guidelines, hepatectomy Tel +39 744 205 442 for patients with metastatic CRC is to be performed only with curative intent following Fax +39 744 205 111 Email [email protected] the criteria of oncological radicality and if it is indicated that there is enough remnant submit your manuscript | www.dovepress.com OncoTargets and Therapy 2013:6 267–272 Dovepress © 2013 Boselli et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article http://dx.doi.org/10.2147/OTT.S39448 which permits unrestricted noncommercial use, provided the original work is properly cited. Boselli et al Dovepress liver parenchyma following the resection (.30%) and/or in Thirty-one patients (nonoperative group) received the absence of unresectable multivisceral spreading of the chemotherapy alone, leaving the primary tumor in place, 11,12 disease or carcinomatosis. ie, nonoperative management (NOM). In this group, Treatment of advanced stages of CRC, especially in 24 patients received FOLFOX plus bevacizumab as first- patients not eligible for curative surgery, consists of medical line therapy. FOLFOX only was administered to the therapies. The availability of new polychemotherapeutic regi- remaining seven patients who were not able to tolerate the mens (5-u fl orouracil, folinic acid, and oxaliplatin; FOLFOX) combination. Switching to second-line therapy was not in combination with biologic agents (monoclonal antibod- needed. Administration of bevacizumab was suspended at ies such as bevacizumab, cetuximab, and panitumumab) 3 months in six patients because of drug-related toxicity or has markedly improved the median survival of patients worsening of their condition and in two patients because in advanced stages, with no increase in the incidence of disease control was reached. 13–16 complications. Age, comorbidities, and performance status, and the risk of In a retrospective study, 93% of patients with Stage IV complications (obstruction and perforation) were the criteria CRC on chemotherapy did not develop complications related used to choose between the resection of the primary tumor and to the primary tumor. In patients with obstructive tumor, the NOM (Table 1). Thirty-day overall mortality and overall sur- use of stents allowed them to be quickly started on systemic vival were the primary and secondary endpoints assessed. 18,19 chemotherapy. Nevertheless, in asymptomatic patients Statistics on the clinical characteristics of patients were with Stage IV CRC, the debate continues over the efficacy calculated by Fisher’s exact test for 2 × 2 comparisons and by of primary neoplasia resection compared to chemotherapy Pearson’s Chi-squared test for comparisons greater than 2 × 2 alone. (95% confidence interval, α = 0.05). A multivariate analysis The aim of this study was to determine if there was any for 30-day mortality and overall survival was performed by improvement in overall survival and a reduction of posttreat- Cox logistic regression. ment mortality after resection of the primary tumor, with The mean age of the patients was lower in the opera- respect to nonoperative treatment in patients with Stage IV tive group (Table 1). Local extension of the disease was CRC and unresectable liver metastases. Table 1 Clinical characteristics of the patients according to Patients and methods treatment Data on patients with synchronous unresectable liver metas- Clinical characteristic Elective NOM P tases from CRC who consecutively underwent palliative surgery therapy between January 2010 and December 2011 were Average age (range), years 70 (54–84) 73 (60–87) retrospectively reviewed. Among patients with rectal cancer, Primary tumor localization Right colon 4 (23.5%) 7 (22.6%) 0.22 only those with intraperitoneal localization were selected Left colon 7 (41.4%) 6 (19.4%) because extraperitoneal rectal cancer with unresectable liver Rectosigmoid colon 6 (35.3%) 18 (58%) metastases is best treated with chemotherapy and radiation Number of comorbidities therapy as an effective palliative treatment. None of the 0 4 (23.5%) 7 (22.6%) 0.60 1 9 (52.9%) 11 (35.5%) 48 patients included in this multicentric study had bowel 2 3 (17.6%) 10 (32.2%) obstruction, bleeding, or perforation. 3 1 (6%) 3 (9.7%) Seventeen patients (operative group) underwent elec- Performance status tive palliative surgery consisting of colonic resection, 14 of ASA I/ECOG 0 6 (35.3%) 7 (22.6%) 0.60 ASA II/ECOG 1 8 (47.1%) 16 (51.6%) whom had open surgery by median laparotomy, two with ASA III/ECOG 2 3 (17.6%) 8 (25.8%) primary tumor in rectosigmoid colon underwent laparoscopic Child before treatment colorectal dissection followed by suprapubic laparotomy in A 11 (64.7%) 14 (45.2%) 0.24 which total mesorectal excision and colorectal anastomosis B 6 (35.3%) 17 (54.8%) Hepatic parenchyma replaced by metastases were performed, and one with right CRC had laparoscopic 9 (53%) 13 (42%) 0.51 ,50% exploration followed by total laparotomic right colectomy due 50%–75% 6 (35%) 10 (32%) to local extension of the disease. Seven of the patients who .75% 2 (12%) 8 (26%) underwent elective surgery had neoplastic stenosis; however, Abbreviations: ASA, American Society of Anesthesiologists; ECOG, Eastern despite this, obstinate constipation was reported. Cooperative Oncology Group; NOM, nonoperative management. submit your manuscript | www.dovepress.com OncoTargets and Therapy 2013:6 Dovepress Dovepress Palliative surgery in metastatic colorectal cancer determined by computed tomography scan and pathological mortality since the difference between the two groups was examination in the operative group, and by computed tomog- minimal (2/7 versus 4/19 for elective surgery and NOM, raphy scan only in the NOM group (Table 1). respectively) (Tables 2 and 3). Secondary localizations in addition to hepatic replace- Results ment did not affect 30-day mortality. The two groups were Overall mortality within 30 days of commencing palliative not comparable because not all patients presented extrahe- chemotherapy was lower than that of surgical resection (five patic metastases (Tables 2 and 3). versus six), even though this outcome was not statistically Of the patients who underwent elective surgery, eleven signic fi ant. In the operative group, three patients died of liver started palliative chemotherapy (six received FOLFOX plus failure presenting hepatorenal syndrome, two patients died of bevacizumab and v fi e received FOLFOX only) and six died of heart failure, and six patients had postoperative complications disease or complications before starting it. The mean interval (three wound infections, one urinary tract infection, and two between surgery and starting postoperative chemotherapy with bronchopneumonia). Of the six patients who received was 5 weeks. chemotherapy only, four died of hepatorenal syndrome and The mean and median follow-up was 8 months and two died of heart failure. 7 months, respectively. The mean and median overall sur- In patients with .75% of the parenchyma replaced vival of the patients receiving elective surgery was 6 months by metastases, mortality after treatment was found to be and 4 months, respectively. For the patients who under- 50% if on elective surgery and 25% if on chemotherapy went palliative chemotherapy only, the mean and median alone. The reported difference between the two groups overall survival was 7 months and 5 months, respectively. of patients for ,75% hepatic involvement of the volume The 1-year overall survival rate was 17.6% versus 19.4% was minimal (50%–75%: 2/6 versus 2/10 and ,50%: 2/9 for elective surgery and chemotherapy alone, respectively versus 2/13 for elective surgery and NOM, respectively) (Figure 1). (Tables 2 and 3). Multivariate analysis of the data demonstrated that there Thirty-day mortality in patients with Stage T3 was lower were no statistically significant differences in 30-day mortal - in the group receiving chemotherapy, although this outcome ity. On the other hand, data analysis using the Cox regression was not statistically significant (3/10 versus 2/12 for elective model demonstrated that the risk of all-cause death was sig- surgery and NOM, respectively). In patients with Stage T4, nificantly higher after elective surgery (2.1; 95% confidence local extension of the tumor did not appear to affect 30-day interval 1.06–4.5; P = 0.035; adjusted to liver replacement Table 2 Factors affecting 30-day overall mortality and overall survival after elective surgery Patient Overall survival from the Hepatic Local Lung Peritoneal (by date) start of therapy (months) involvement extension (T) metastases metastases 1 1 ,50% 4 x x 2 2 50%–75% 4 x 3 9 3 x ,50% 4 1 50%–75% 3 x 5 8 4 ,50% 6 15 ,50% 3 7 3 3 x x ,50% 8 4 50%–75% 3 9 1 50%–75% 4 x 10 20* ,50% 3 11 1 3 .75% 12 10 3 ,50% 13 3 .75% 4 14 12 3 ,50% 15 4 50%–75% 4 x 16 1 ,50% 4 x 17 6 50%–75% 3 Note: *Alive October 2012. Abbreviations: X, positive; –, negative. submit your manuscript | www.dovepress.com OncoTargets and Therapy 2013:6 Dovepress Boselli et al Dovepress Table 3 Factors affecting 30-day overall mortality and overall survival after nonoperative management Patient Overall survival from the Hepatic Local Lung Peritoneal (by date) start of therapy (months) involvement extension (T) metastases metastases 1 11 ,50% 3 2 1 50%–75% 4 x x 3 22 ,50% 4 4 7 3 x .75% 5 4 4 x .75% 6 11 4 ,50% 7 3 .75% 4 x x 8 12 4 ,50% 9 4 50%–75% 3 x 10 1 3 x .75% 11 8 4 ,50% 12 6 3 x ,50% 13 2 .75% 4 x 14 1 50%–75% 3 x 15 16 ,50% 3 16 5 4 x .75% 17 19* 3 ,50% 18 1 50%–75% 4 x 19 4 50%–75% 4 x 20 13 3 ,50% 21 5 50%–75% 4 x 22 1 4 .75% 23 3 50%–75% 3 x 24 8 4 ,50% 25 2 .75% 4 x 26 10 4 ,50% 27 3 50%–75% 4 x x 28 12* 3 ,50% 29 1 50%–75% 4 x 30 4 50%–75% 4 x 31 7 3 x ,50% Note: *Alive October 2012. Abbreviations: X, positive; –, negative. and other metastases) compared to patients receiving che- to Galizia et al, this occurrence may be balanced by a better motherapy only (Tables 2 and 3). response rate to chemotherapy in selected patients before Overall the two groups showed similar performance primary tumor debulking. The current analysis doesn’t status. The difference between the two groups was greatest suggest that primary tumor resection is a safe and effective for American Society of Anesthesiologists I/ Eastern Coop- treatment of asymptomatic patients with Stage IV CRC when erative Oncology Group 0 (Table 1). Furthermore, patients not radically resectable. undergoing surgery had a better hepatic function since they Liver tumor burden has been recognized as an indepen- had a smaller metastatic liver replacement than those receiv- dent risk factor for poor outcome, regardless of therapy. ing chemotherapy alone (Table 1). Thus, patients with extensive (.75%) hepatic tumor involve- ment carry an extremely unfavorable prognosis. Hepatic Discussion parenchymal replacement is significantly related to survival. Resection of the primary tumor is necessary for patients with Hepatic tumor burden . 50% is related to poor overall complications, whereas chemoradiotherapy in combination survival. Bilobar liver involvement is related with an even with targeted agents appears safe and seems a suitable alter- greater unfavorable prognosis. native for patients without complications. After resection In palliative treatment of uncomplicated patients of the primary tumor, adjuvant therapy should be promptly affected by CRC with unresectable liver metastases, undertaken as a delay may decrease its efficacy. According chemoradiotherapy combined with biological agents is submit your manuscript | www.dovepress.com OncoTargets and Therapy 2013:6 Dovepress Dovepress Palliative surgery in metastatic colorectal cancer 1.00 0.75 0.50 0.25 0.00 0 5 10 15 20 Months Chemotherapy Surgery Figure 1 Kaplan–Meier survival curves according to treatment. a suitable alternative to surgical resection of the primary no significant difference in 30-day mortality and overall sur - tumor. vival was found between the two groups of patients. Asymptomatic patients with a liver metastasis involving ,50% of the parenchyma, when undergoing resection of the Conclusion primary tumor, display a survival rate similar to patients on This study shows that in palliative treatment of asymptom- chemotherapy alone (Tables 2 and 3). In asymptomatic patients atic unresectable Stage IV CRC, the risk of all-cause death with a replaced liver volume of 50%–75%, surgery showed was significantly higher after elective surgery compared to no benet fi s in terms of survival over NOM (posttreatment patients receiving chemotherapy only. However, in the lit- mortality 33.3% versus 20%), as recently shown by Kleespies erature, there is no substantial difference between these two et al. This data is even more signic fi ant in patients with treatments. Therefore, it is crucial to undertake new studies metastases involving .75% of the liver volume (posttreatment to evaluate and compare the results in terms of quality of life mortality 50% versus 25%) (Tables 2 and 3). in both groups of patients. Local neoplastic extension is not an independent predictor of survival. In the current study, it was demonstrated that in Disclosure Stage T3 and T4 local extension of the primary tumor, elec- The authors report no conflicts of interest in this work. tive surgery presents no benet fi in terms of survival compared to NOM (posttreatment mortality Stage T3: 30% versus References 16.7% and Stage T4: 28.6% versus 21%) (Tables 2 and 3). 1. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55(2):74–108. Peritoneal carcinomatosis is an independent prognos- 2. Edwards BK, Ward E, Kohler BA, et al. Annual report to the nation on tic factor, and it is also recognized as an important risk the status of cancer, 1975–2006, featuring colorectal cancer trends and factor for obstruction. In the current study, peritoneal impact of interventions (risk factors, screening, and treatment) to reduce future rates. Cancer. 2010;116(3):544–573. carcinomatosis appeared not to influence posttreatment 3. 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