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Surgery for asymptomatic primary tumour
Evidence review D1
NICE Guideline, No. 151
National Guideline Alliance (UK).
Surgery for the asymptomatic primary tumour in people with metastatic colorectal cancer which cannot be treated with curative intent
This evidence review supports recommendation 1.5.1.
Review question
Does surgery for the asymptomatic primary tumour improve outcomes for people with metastatic colorectal cancer, which cannot be treated with curative intent?
Introduction
Current clinical practice varies regarding whether or not the asymptomatic primary tumour is resected in patients with metastatic colorectal cancer that cannot be treated with curative intent. If not resected an asymptomatic primary tumour might later cause symptoms such as bleeding, obstruction or perforation. At the same time resection of the asymptomatic primary tumour might cause operative and postoperative morbidity and mortality. The aim of this review is to examine the effect of resecting the primary tumour compared to not resecting the primary tumour on survival, quality of life and rate of complications.
Summary of the protocol
Please see Table 1 for a summary of the population, intervention, comparison and outcomes (PICO) characteristics of this review.
Table 1
Summary of the protocol (PICO table).
For further details see the review protocol in appendix A.
Methods and process
This evidence review was developed using the methods and process described in Developing NICE guidelines: the manual 2014. Methods specific to this review question are described in the review protocol in appendix A.
Declarations of interest were recorded according to NICE’s 2014 conflicts of interest policy until 31 March 2018. From 1 April 2018, declarations of interest were recorded according to NICE’s 2018 conflicts of interest policy. Those interests declared until April 2018 were reclassified according to NICE’s 2018 conflicts of interest policy (see Register of Interests).
Clinical evidence
Included studies
Thirteen retrospective cohort studies were included in this evidence review (Ahmed 2015; Alawadi 2017; Benoist 2005; Galizia 2008; He 2016; Matsumoto 2014; Michel 2004; Miyamoto 2014; Ruo 2003; Samalavicius 2018; Seo 2010; Yun 2014; Zhang 2017).
The included studies are summarised in Table 2.
The studies compared surgery of the asymptomatic primary tumour to no resection. Most patients, if not all, in both arms received chemotherapy in all of the studies included in this review.
See the literature search strategy in appendix B and study selection flow chart in appendix C.
Excluded studies
Studies not included in this review with reasons for their exclusions are provided in appendix K.
Summary of clinical studies included in the evidence review
Summaries of the studies that were included in this review are presented in Table 2.
Table 2
Summary of included studies.
See the full evidence tables in appendix D and the forest plots in appendix E.
Quality assessment of clinical outcomes included in the evidence review
See the clinical evidence profiles in appendix F.
Economic evidence
Included studies
A systematic review of the economic literature was conducted but no economic studies were identified which were applicable to this review question.
Excluded studies
A global search of economic evidence was undertaken for all review questions in this guideline. See Supplement 2 for further information.
Economic model
No economic modelling was undertaken for this review because the committee agreed that other topics were higher priorities for economic evaluation.
Evidence statements
Clinical evidence statements
Critical outcomes
Overall survival
- Low quality evidence from 6 retrospective cohort studies (N=7848; median follow-up 1.3 to 6.4 years) showed that resecting the asymptomatic primary tumour produces a clinically important benefit in overall survival compared to not resecting the asymptomatic primary tumour in people with metastatic colorectal cancer not treatable with curative intent.
- Very low quality evidence from 1 retrospective cohort study (N=230) showed that resecting the asymptomatic primary tumour produces a clinically important benefit in 2 year overall survival compared to not resecting the asymptomatic primary tumour in people with metastatic colorectal cancer not treatable with curative intent.
- Very low quality evidence from 1 retrospective cohort study (N=226) showed no clinically important difference in overall survival at 5 years between people with metastatic colorectal cancer not treatable with curative intent who underwent resection of the asymptomatic primary tumour and those who did not.
- Very low quality evidence from 1 retrospective cohort study (N=194; median 12 follow-up 12 months) showed no clinically important difference in all-cause mortality between people with metastatic colorectal cancer not treatable with curative intent who underwent resection of the asymptomatic primary tumour and those who did not.
Overall quality of life
No evidence was identified to inform this outcome.
Grade 3 or 4 treatment complications
- Low quality evidence from 5 retrospective cohort studies (N=712) showed a clinically important increase in risk of postoperative complications (not all grade 3 or 4 complications) in people with metastatic colorectal cancer not treatable with curative intent who underwent resection of the asymptomatic primary tumour compared to those who did not). The rate of postoperative complications ranged from 18% to 35% in the resection group.
- Very low quality evidence from 2 retrospective cohort studies (N=315) showed a clinically important difference in risk of grade 3 or 4 postoperative complications with metastatic colorectal cancer not treatable with curative intent who underwent resection of the asymptomatic primary tumour compared to those who did not. The rate of grade 3 or 4 postoperative complications was 5% in the resection group and 1.5% in the no resection group (some people in the no resection group later underwent resection of the primary tumour).
Tumour-related complications
- Low quality evidence from 8 retrospective cohort studies (N=1080) showed a clinically important decrease in risk of tumour-related complications requiring surgical treatment in people with metastatic colorectal cancer not treatable with curative intent who underwent resection of the asymptomatic primary tumour (compared to those who did not). The rate of tumour-related complications requiring surgical treatment ranged from 6% to 29% in the no resection group.
- Very low quality evidence from 1 retrospective cohort study (N=227) showed no clinically important difference in risk of tumour-related complications not requiring surgical treatment between people with metastatic colorectal cancer not treatable with curative intent who underwent resection of the asymptomatic primary tumour and those who did not.
Important outcomes
Median survival time
- Very low quality evidence from 9 retrospective cohort studies (N=1419) showed that the median survival time was 1 to 8 months longer in people with metastatic colorectal cancer not treatable with curative intent who underwent resection of the asymptomatic primary tumour compared to those who did not but the differences were mostly not statistically significant. One of the studies (N=194) looked at subgroups according to site of the tumour and reported that for people with left-sided colon cancer who underwent resection of the primary tumour median survival time was significantly longer than for those who did not undergo resection (difference of 8 months) whereas for those with right-sided colon cancer there was no significant difference between the groups (difference of 2 months).
30-day mortality
- Very low quality evidence from 7 retrospective cohort studies (N=992) showed no difference in 30-day mortality between people with metastatic colorectal cancer not treatable with curative intent who underwent resection of the asymptomatic primary tumour and those who did not.
Economic evidence statements
No economic evidence was identified which was applicable to this review question.
The committee’s discussion of the evidence
Interpreting the evidence
Outcomes that matter the most
Overall survival was a critical outcome for decision making because an increase in survival would be a key motivation for resecting an asymptomatic primary tumour when there is also metastatic disease. Treatment and tumour-related complications were also critical outcomes, as the decision about resection should consider the balance between complications due to surgery and future complications caused by the tumour if not resected. Overall quality of life was also a critical outcome because of the impact that treatment decisions might have on patients in general, considering the potential adverse effects that primary tumour resection or no resection might have on the patient.
Median survival time and 90-day mortality were important outcomes for decision making.
The quality of the evidence
Evidence was available for all of the outcomes except quality of life. The quality of the evidence was assessed using GRADE and varied from low to very low quality.
The most common reasons for downgrading the quality of the evidence were methodological limitations affecting the risk of bias, mainly insufficient controlling for potential confounders in the analysis, and imprecision due to small sample sizes and low event rates causing uncertainty in the effect estimate.
As only observational evidence was available, it is important to consider the comparability of the intervention and comparison groups and whether the findings are attributable to the intervention of interest (resection of primary tumour) or to the differences in the populations compared. The baseline characteristics (for example age or performance status, tumour location, number of metastases, tumour differentiation grade, CEA level) differed in many of the studies. Although not consistent across all studies, in some studies the resection group were perhaps “lower risk” as they were younger, had better performance status, their tumour was more often well differentiated, or they had fewer metastases. However, all of the included studies used multivariable analysis to control for differences in baseline characteristics between treatment groups. However, the committee was aware that the adjusted analyses might not sufficiently control for the differences between the groups and this reduced their confidence in the findings.
One study in particular was discussed. A retrospective cohort study from the US using data from the National Cancer Data Base was by far the largest study included in the review and provided the most evidence on overall survival, the primary outcome of interest. Their analysis on overall survival, which controlled for baseline differences between the groups, showed a clear benefit for the resection group. However, the study also performed analysis that took into account the proportion of patients undergoing resection in different hospitals. This analysis, which appeared to not have been planned a priori, showed no difference in the relative mortality rate at 3 years. The committee took into account these contradictory results but concluded that regardless of this study the pooled result from the other studies still showed a survival benefit for the resection group. In addition, the committee discussed the relevance of the population in this cohort study. Due to the information available in the National Cancer Data Base it was not possible to ensure that only patients with asymptomatic primary tumours and incurable metastases were included. They did, however, exclude patients who had undergone surgery on the primary tumour within 24 hours of diagnosis (in order to minimise inclusion of patients with symptomatic primary tumours) or surgical treatment on other cancers, including metastectomy (in order to minimise inclusion of patients with curable metastatic disease).
Benefits and harms
Taking into account the quality of the evidence, the committee concluded that resection of the primary tumour should be considered as it may be beneficial, provided that the benefits, harms and options are carefully discussed with the patient. Patients with metastatic disease that cannot be treated with curative intent may receive chemotherapy regardless of the resection of the primary tumour. Resection of the asymptomatic primary tumour could be considered in order to prevent tumour-related symptoms, such as obstruction, perforation, bleeding and pain developing later on. The clinical evidence showed that overall survival was better among people who underwent resection of the asymptomatic primary tumour compared to those who did not. However, there is uncertainty how much longer the patients who have had a resection would survive, with the evidence showing up to median of 8 months longer survival time and other studies showing shorter or no difference.
The evidence also showed that around one fifth of the patients who did not undergo resection of the asymptomatic primary tumour ended up developing symptoms related to the primary tumour that were severe enough to require subsequent surgical treatment. The committee discussed that this could often mean an emergency operation that can have higher risks of complications and stoma. Around one quarter of patients undergoing a resection had some postoperative complications, and around 5% had grade 3 or 4 postoperative complications. There was no difference in 30-day mortality between the groups.
The committee emphasised that the benefits, harms, implications and different treatment options and pathways should be discussed with the patient in order to enable an informed decision when considering the resection of an asymptomatic primary tumour. The committee discussed that it would be beneficial to identify those patients who are at a higher risk of developing symptoms, however, this aspect was not covered by this evidence review.
No evidence was identified on quality of life. This is particularly relevant considering the factors which patients and clinicians will need to consider including the risk of developing cancer related bowel symptoms; risks of surgical intervention including morbidity and mortality; and possible differences in other on-going treatments such as chemotherapy.
Despite the lack of RCT data and the lack of data on quality of life, the committee did not make a research recommendation. The committee was aware of several trials in this context which had failed to recruit and that there are several ongoing trials on the topic that in the future may provide randomised evidence. Most of these trials will also collect evidence on quality of life.
Cost effectiveness and resource use
No economic evidence was identified that addressed this topic.
Resection of the asymptomatic primary tumour may increase costs (in comparison to no resection) but this may be offset, at least partially, by the avoidance of primary tumour related symptoms. The evidence suggests that resection of the primary tumour may improve overall survival and so even if the strategy is more costly it could still be cost-effective in cost per QALY terms.
The recommendation would not be anticipated to have a substantial resource impact as it largely reflects current practice.
References
Ahmed 2015
Ahmed S, Fields A, Pahwa P, et al. (2015) Surgical Resection of Primary Tumour in Asymptomatic or Minimally Symptomatic Patients with Stage IV Colorectal Cancer: A Canadian Province Experience. Clinical Colorectal Cancer 14(4): e41–e47 [PubMed: 26140732]Alawadi 2017
Alawadi Z, Phatak, U, Hu C, et al. (2017) Comparative effectiveness of primary tumour resection in patients with stage IV colon cancer. Cancer 123(7): 1124–1133 [PMC free article: PMC5288308] [PubMed: 27479827]Benoist 2005
Benoist S, Pautrat K, Mitry E, et al. (2005) Treatment strategy for patients with colorectal cancer and synchronous irresectable liver metastases. British Journal of Surgery 92(9): 1155–60 [PubMed: 16035135]Galizia 2008
Galizia G, Lieto E, Orditura M, et al. (2008) First-line chemotherapy vs bowel tumour resection plus chemotherapy for patients with unresectable synchronous colorectal hepatic metastases. Archives of Surgery 143(4): 352–358 [PubMed: 18427022]He 2016
He W, Rong Y, Jiang C et al. (2016) Palliative primary tumour resection provides survival benefits for the patients with metastatic colorectal cancer and low circulating levels of dehydrogenase and carcinoembryonic antigen. Chinese Journal of Cancer 35(1): 58 [PMC free article: PMC4928252] [PubMed: 27357402]Matsumoto 2014
Matsumoto T, Hasegawa S, Matsumoto S, et al. (2014) Overcoming the challenges of primary tumour management in patients with metastatic colorectal cancer unresectable for cure and an asymptomatic primary tumour. Diseases of the Colon and Rectum 57(6): 679–686 [PubMed: 24807591]Michel 2004
Michel P, Roque I, Di Fiore F, et al. (2004) Colorectal cancer with non-resectable synchronous metastases: Should the primary tumour be resected? Gastroenterologie Clinique et Biologique 28(5): 434–437 [PubMed: 15243315]Miyamoto 2014
Miyamoto Y, Watanabe M, Sakamoto Y, et al. (2014) Evaluation of the necessity of primary tumour resection for synchronous metastatic colorectal cancer. Surgery Today 1–6 [PubMed: 24623012]Ruo 2003
Ruo L, Gougoutas C, Paty P, et al. (2003) Elective bowel resection for incurable stage IV colorectal cancer: Prognostic variables for asymptomatic patients. Journal of the American College of Surgeons 196(5): 722–728 [PubMed: 12742204]Samalavicius 2016
Samalavicius N, Dulskas A, Baltruskeviciene E, et al. (2016) Asymptomatic primary tumour in incurable metastatic colorectal cancer: Is there a role for surgical resection prior to systematic therapy or not? Wideochirurgia I Inne Techniki Maloinwazyjne 11(4): 274–282 [PMC free article: PMC5299087] [PubMed: 28194248]Seo 2010
Seo G, Park J, Yoo S, et al. (2010) Intestinal complications after palliative treatment for asymptomatic patients with unresectable stage IV colorectal cancer. Journal of Surgical Oncology 102(1): 94–99 [PubMed: 20578086]Yun 2014
Yun J, Huh J, Park Y, et al. (2014) The role of palliative resection for asymptomatic primary tumour in patients with unresectable stage IV colorectal cancer. Diseases of the Colon and Rectum 57(9): 1049–1058 [PubMed: 25101600]Zhang 2017
Zhang R, Ma W, Gu Y, et al. (2017) Primary tumour location as a predictor of the benefit of palliative resection for colorectal cancer with unresectable metastasis. World Journal of Surgical Oncology 15(1): 138 [PMC free article: PMC5530936] [PubMed: 28750680]
Appendices
Appendix A. Review protocol
Review protocol for review question: Does surgery for the asymptomatic primary tumour improve outcomes for people with metastatic colorectal cancer, which cannot be treated with curative intent?
Appendix B. Literature search strategies
Literature search strategies for review question: Does surgery for the asymptomatic primary tumour improve outcomes for people with metastatic colorectal cancer, which cannot be treated with curative intent?
Databases: Embase/Medline
Last searched on: 12/02/2019
| # | Search |
|---|---|
| 1 | (exp colorectal cancer/ or exp colon tumour/ or exp rectum tumour/) use emez |
| 2 | exp colorectal neoplasms/ use ppez |
| 3 | ((colorect* or colo rect* or colon or colonic or rectal or rectum) adj3 (adenocarcinoma* or cancer* or carcinoma* or malignan* or neoplas* or oncolog* or tumo?r*)).tw. |
| 4 | or/1-3 |
| 5 | metastasis/ use emez |
| 6 | neoplasm metastasis/ use ppez |
| 7 | (stage IV or stage 4 or advanc*).tw. |
| 8 | ((unresect* or inopera* or untreat* or incurable*) adj3 (cancer* or tumo?r or metasta*)).tw. |
| 9 | or/5-8 |
| 10 | 4 and 9 |
| 11 | (exp Surgery, Computer-Assisted/ or exp Dissection/ or Endoscopic Mucosal Resection/ or exp Laparoscopy/ or exp Minimally Invasive Surgical Procedures/ or exp Surgical Procedures, Operative/ or exp Transanal Endoscopic Surgery/) use ppez |
| 12 | (exp computer assisted surgery/ or dissection/ or endoscopic polypectomy/ or exp endoscopic surgery/ or exp excision/ or laparoscopic surgery/ or exp minimally invasive surgery/ or exp rectum resection/ or exp surgery/ or exp transanal endoscopic surgery/) use emez |
| 13 | (dissect* or endoscop* or EMR or ESD or excis* or laparoscop* or operat* or resect* or surger* or surgic* or TAE or TAMIS or TART or TaTME or TEM or TEMS or TME).tw. |
| 14 | or/11-13 |
| 15 | primary tumour/ use emez |
| 16 | (primary adj2 tumo?r).tw. |
| 17 | or/15-16 |
| 18 | 14 and 17 |
| 19 | 10 and 18 |
| 20 | limit 19 to (yr=“1998 - current” and english language) |
| 21 | Letter/ use ppez |
| 22 | letter.pt. or letter/ use emez |
| 23 | note.pt. |
| 24 | editorial.pt. |
| 25 | Editorial/ use ppez |
| 26 | News/ use ppez |
| 27 | exp Historical Article/ use ppez |
| 28 | Anecdotes as Topic/ use ppez |
| 29 | Comment/ use ppez |
| 30 | Case Report/ use ppez |
| 31 | case report/ or case study/ use emez |
| 32 | (letter or comment*).ti. |
| 33 | or/21-32 |
| 34 | randomized controlled trial/ use ppez |
| 35 | randomized controlled trial/ use emez |
| 36 | random*.ti,ab. |
| 37 | or/34-36 |
| 38 | 33 not 37 |
| 39 | animals/ not humans/ use ppez |
| 40 | animal/ not human/ use emez |
| 41 | nonhuman/ use emez |
| 42 | exp Animals, Laboratory/ use ppez |
| 43 | exp Animal Experimentation/ use ppez |
| 44 | exp Animal Experiment/ use emez |
| 45 | exp Experimental Animal/ use emez |
| 46 | exp Models, Animal/ use ppez |
| 47 | animal model/ use emez |
| 48 | exp Rodentia/ use ppez |
| 49 | exp Rodent/ use emez |
| 50 | (rat or rats or mouse or mice).ti. |
| 51 | or/38-50 |
| 52 | 20 not 51 |
| 53 | remove duplicates from 52 |
Databases: Cochrane Library
Last searched on: 12/02/2019
| # | Search |
|---|---|
| 1 | MeSH descriptor: [Colorectal Neoplasms] explode all trees |
| 2 | ((colorect* or colo rect* or colon or colonic or rectal or rectum) near/3 (adenocarcinoma* or cancer* or carcinoma* or malignan* or neoplas* or oncolog* or tumo?r*)):ti,ab,kw |
| 3 | #1 or #2 |
| 4 | MeSH descriptor: [Neoplasm Metastasis] this term only |
| 5 | (stage IV or stage 4 or advanc*):ti,ab,kw |
| 6 | ((unresect* or inopera* or untreat* or incurable*) near/3 (cancer* or tumo?r or metasta*)):ti,ab,kw |
| 7 | {or #4-#6} |
| 8 | MeSH descriptor: [Surgery, Computer-Assisted] explode all trees |
| 9 | MeSH descriptor: [Dissection] explode all trees |
| 10 | MeSH descriptor: [Endoscopic Mucosal Resection] this term only |
| 11 | MeSH descriptor: [Laparoscopy] explode all trees |
| 12 | MeSH descriptor: [Minimally Invasive Surgical Procedures] explode all trees |
| 13 | MeSH descriptor: [Surgical Procedures, Operative] explode all trees |
| 14 | MeSH descriptor: [Transanal Endoscopic Surgery] explode all trees |
| 15 | (dissect* or endoscop* or EMR or ESD or excis* or laparoscop* or operat* or resect* or surger* or surgic* or TAE or TAMIS or TART or TaTME or TEM or TEMS or TME):ti,ab,kw |
| 16 | {or #8-#15} |
| 17 | MeSH descriptor: [Neoplasms, Unknown Primary] explode all trees |
| 18 | (primary near/2 tumo?r):ti,ab,kw |
| 19 | {or #17-#18} |
| 20 | #3 and #7 |
| 21 | #16 and #19 |
| 22 | #20 and #21 Publication Year from 1998 to 2018 |
Appendix C. Clinical evidence study selection
Clinical study selection for: Does surgery for the asymptomatic primary tumour improve outcomes for people with metastatic colorectal cancer, which cannot be treated with curative intent?
Appendix D. Clinical evidence tables
Clinical evidence tables for review question: Does surgery for the asymptomatic primary tumour improve outcomes for people with metastatic colorectal cancer, which cannot be treated with curative intent?
Table 4. Clinical evidence tables (PDF, 616K)
Appendix E. Forest plots
Forest plots for review question: Does surgery for the asymptomatic primary tumour improve outcomes for people with metastatic colorectal cancer, which cannot be treated with curative intent?
Figure 6. Resection versus no resection for asymptomatic primary tumour – 30-day mortality
Appendix F. GRADE tables
GRADE tables for review question: Does surgery for the asymptomatic primary tumour improve outcomes for people with metastatic colorectal cancer, which cannot be treated with curative intent?
Appendix G. Economic evidence study selection
Economic evidence study selection for review question: Does surgery for the asymptomatic primary tumour improve outcomes for people with metastatic colorectal cancer, which cannot be treated with curative intent?
A global search of economic evidence was undertaken for all review questions in this guideline. See Supplement 2 for further information.
Appendix H. Economic evidence tables
Economic evidence tables for review question: Does surgery for the asymptomatic primary tumour improve outcomes for people with metastatic colorectal cancer, which cannot be treated with curative intent?
No economic evidence was identified which was applicable to this review question.
Appendix I. Economic evidence profiles
Economic evidence profiles for review question: Does surgery for the asymptomatic primary tumour improve outcomes for people with metastatic colorectal cancer, which cannot be treated with curative intent?
No economic evidence was identified which was applicable to this review question.
Appendix J. Economic analysis
Economic evidence analysis for review question: Does surgery for the asymptomatic primary tumour improve outcomes for people with metastatic colorectal cancer, which cannot be treated with curative intent?
No economic analysis was conducted for this review question. 6
Appendix K. Excluded studies
Excluded clinical studies for review question: Does surgery for the asymptomatic primary tumour improve outcomes for people with metastatic colorectal cancer, which cannot be treated with curative intent?
Appendix L. Research recommendations
Research recommendations for review question: Does surgery for the asymptomatic primary tumour improve outcomes for people with metastatic colorectal cancer, which cannot be treated with curative
No research recommendations were made for this review question.
Final
Evidence reviews
Developed by the National Guideline Alliance part of the Royal College of Obstetricians and Gynaecologists
Disclaimer: The recommendations in this guideline represent the view of NICE, arrived at after careful consideration of the evidence available. When exercising their judgement, professionals are expected to take this guideline fully into account, alongside the individual needs, preferences and values of their patients or service users. The recommendations in this guideline are not mandatory and the guideline does not override the responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or their carer or guardian.
Local commissioners and/or providers have a responsibility to enable the guideline to be applied when individual health professionals and their patients or service users wish to use it. They should do so in the context of local and national priorities for funding and developing services, and in light of their duties to have due regard to the need to eliminate unlawful discrimination, to advance equality of opportunity and to reduce health inequalities. Nothing in this guideline should be interpreted in a way that would be inconsistent with compliance with those duties.
NICE guidelines cover health and care in England. Decisions on how they apply in other UK countries are made by ministers in the Welsh Government, Scottish Government, and Northern Ireland Executive. All NICE guidance is subject to regular review and may be updated or withdrawn.
- Review Non-resection versus resection for an asymptomatic primary tumour in patients with unresectable stage IV colorectal cancer.[Cochrane Database Syst Rev. 2012]Review Non-resection versus resection for an asymptomatic primary tumour in patients with unresectable stage IV colorectal cancer.Cirocchi R, Trastulli S, Abraha I, Vettoretto N, Boselli C, Montedori A, Parisi A, Noya G, Platell C. Cochrane Database Syst Rev. 2012 Aug 15; (8):CD008997. Epub 2012 Aug 15.
- Elective bowel resection for incurable stage IV colorectal cancer: prognostic variables for asymptomatic patients.[J Am Coll Surg. 2003]Elective bowel resection for incurable stage IV colorectal cancer: prognostic variables for asymptomatic patients.Ruo L, Gougoutas C, Paty PB, Guillem JG, Cohen AM, Wong WD. J Am Coll Surg. 2003 May; 196(5):722-8.
- Aspects of survival from colorectal cancer in Denmark.[Dan Med J. 2012]Aspects of survival from colorectal cancer in Denmark.Iversen LH. Dan Med J. 2012 Apr; 59(4):B4428.
- Review Survival and symptomatic benefit from palliative primary tumor resection in patients with metastatic colorectal cancer: a review.[Int J Colorectal Dis. 2008]Review Survival and symptomatic benefit from palliative primary tumor resection in patients with metastatic colorectal cancer: a review.Eisenberger A, Whelan RL, Neugut AI. Int J Colorectal Dis. 2008 Jun; 23(6):559-68. Epub 2008 Mar 11.
- Meta-analysis of outcomes following resection of the primary tumour in patients presenting with metastatic colorectal cancer.[Br J Surg. 2018]Meta-analysis of outcomes following resection of the primary tumour in patients presenting with metastatic colorectal cancer.Nitsche U, Stöß C, Stecher L, Wilhelm D, Friess H, Ceyhan GO. Br J Surg. 2018 Jun; 105(7):784-796. Epub 2017 Oct 31.
- Surgery for asymptomatic primary tumourSurgery for asymptomatic primary tumour
- Optimal combination and sequence of treatments in patients presenting with metas...Optimal combination and sequence of treatments in patients presenting with metastatic colorectal cancer in the liver not amenable to treatment with curative intent
- Use of molecular biomarkers to guide systemic therapyUse of molecular biomarkers to guide systemic therapy
- Homo sapiens Rho GTPase activating protein 25 (ARHGAP25), transcript variant 5, ...Homo sapiens Rho GTPase activating protein 25 (ARHGAP25), transcript variant 5, mRNAgi|1423310397|ref|NM_001364819.1|Nucleotide
- Proteus anguinus mitochondrion, complete genomeProteus anguinus mitochondrion, complete genomegi|575669328|ref|NC_023342.1||gnl|N ENOMES|35428Nucleotide
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