Primary Tumor Resection for Metastatic Colorectal, Gastric and Pancreatic Cancer Patients: In Search of Scientific Evidence to Inform Clinical Practice
Abstract
:Simple Summary
Abstract
1. Introduction
2. Primary Tumor Resection for Metastatic Colorectal Cancer: A Matter of Optimal Timing and Patients’ Selection
2.1. Overview of Available Literature Data
2.2. Ongoing Prospective Trials
2.3. Choosing Wisely: A Tentative Algorithm
3. Surgery on Primary Tumor in Metastatic Gastroesophageal Cancer: Have We Already Got the Answers We Need?
3.1. Overview of Available Literature Data
3.2. Ongoing Prospective Trials
3.3. Putting Data in Context
4. Surgery on Primary Tumor in Metastatic Pancreatic Cancer: Onco-Surgical Fancy or Reasonable Multidisciplinary Approach in Selected Patients?
4.1. Overview of Available Literature Data
4.2. Finding the One in a Billion: Is It Really Possible to Select?
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Study (ClinicalTrials.gov ID) | Phase | Main Inclusion Criteria | Estimated Enrollment | Study Start Date-Status | Primary Endpoint | Secondary Endpoint | Active Comparator | Experimental Arm |
---|---|---|---|---|---|---|---|---|
China, Guangdong (NCT02149784) | 3 | Colon cancer or rectal cancer with at least 12 cm far away from anal verge with unresectable metastases. No evidence of obstruction, bleeding or perforation. Pts must respond to 1st line CT. | 480 | September 2015 Recruiting | 3-years OS | Number of pts with AEs both in surgery group and CT group. | Unresectable mCRC pts responders to CT will continue with CT | Unresectable mCRC pts responders to CT will receive surgical resection of PT |
China, Shanghai (NCT02291744) | 2 | Colon cancer adenocarcinoma. Primary and metastatic tumors exist at the same time, and distant metastases are not resectable. No need of surgery for perforation, bleeding or obstruction. No uncontrollable large pleural or peritoneal effusion. No brain metastases. | 130 | October 2014 Recruiting | TFS | None. | 8 cycles of XELOX | 8 cycles of XELOX plus surgery |
CAIRO4 (NCT01606098) Denmark and Netherlands, multicenter | 3 | Resectable PT in situ (CRC) with unresectable distant metastases. No indication for neo-adjuvant (chemo)radiation. No signs or symptoms PT-related that require immediate intervention (i.e., surgery, stenting, systemic therapy or radiotherapy). No condition preventing the safety or feasibility of resection of the PT (i.e., massive ascites or extensive peritoneal disease). | 360 | July 2012 Active, no longer recruiting | OS | PFS. RR. G3-4 CT-related toxicity. Surgery-related morbidity and mortality. QoL. Interval between randomization and initiation of CT. Cost-benefit analyses. Pts requiring resection of PT in the non-resection arm. | 1st line FP-based CT with bevacizumab | PT resection followed by 1st line FP-based CT with bevacizumab |
GRECCAR 8 (NCT02314182) France, multicenter | 3 | Rectal adenocarcinoma (<15 cm from the anal verge) with few or no symptoms and unresectable synchronous metastasis not amenable to curative treatment. No known unresectable PT (with clear margin > 1 mm) on imaging. No PD under CT (for at least 4 cycles). Assessment of KRAS status. No peritoneal carcinomatosis. | 290 | November 2014 Completed (trial end date: 27 February 2018): no longer recruiting | OS | PFS. QoL. Toxicity of CT. RR. Time to PD. Postoperative morbidity. | Continued systemic CT ± target therapy | Immuno-nutrition, PT resection + systemic CT ± target therapy |
CLIMAT-PRODIGE 30 (NCT02363049) France | 3 | Colon adenocarcinoma (≥15 cm from the anal verge) Uncomplicated PT. No known unresectable PT on imaging. Unresectable synchronous liver metastases. No extra-hepatic metastatic disease. | 278 | July 2014 Recruiting | OS | QoL Postoperative complications. PFS. TTP. Rate of secondary curative resection (R0). | CT ± targeted therapy alone | Surgery followed by CT ± targeted therapy |
Study (Year of Publication) [Ref.] | Design | No. | OS (Months or Survival Rate, %) | HR/OR (95% CI) | Subgroup Analysis: HR (95% CI) or p-Value for OS |
---|---|---|---|---|---|
Sun J. et al. (2013) [72] | Meta-analysis (published data) | 3003 | Weighted average of median OS: Gastrectomy: 14.96 Control: 7.07 | 0.56 (0.39–0.80) | Peritoneum: 0.76 (0.63–0.92) Liver: 0.41 (0.30–0.55) Lymph node: 0.36 (0.23–0.59) |
Lasithiotakis K. et al. (2014) [73] | Meta-analysis (published data) | 2911 | 1-year OS: Gastrectomy: 50% (weighted mean) Non-resectional surgery: 10% Control: 39% | 2.6 (1.7–4.2) 4.9 (3.2–7.5) | Not reported |
Yazici O. et al. (2016) | Retrospective | 488 | Median OS: Gastrectomy: 14 Control: 9 | 0.52 (0.38–0.71) | Peritoneum: p < 0.001 Visceral metastases: p < 0.001 |
Fornaro L. et al. (2017) [74] | Retrospective | 513 | Median OS: Gastrectomy: 18.7 Control: 13.5 | 0.620 (0.487–0.790) | Peritoneum: 0.52 (0.35–0.77) Liver: 0.71 (0.48–1.06) |
Hsu J.T. et al. (2017) | Retrospective | 333 | Median OS: Gastrectomy + metastasectomy: 7.7 Non-resective procedures: 4.9 | p < 0.001 | Age (> vs. ≤58 years): 1.47 (1.01–2.13) Albumin (> vs. ≤3 g/dL): 1.93 (1.24–3.00) N1/N0: 0.83 (0.33–2.10) Adjuvant CT (no vs. yes): 1.68 (1.19–2.38) |
Warschkow R. et al. (2018) [75] | Retrospective population-based cohort | 7026 | Median OS: Primary tumor resection + CT: 13.9 CT: 79 | 0.60 (0.56–0.64) | Lymph node: 0.52 (0.41–0.66) Peritoneum: 0.66 (0.53–0.83) |
Picado O. et al. (2018) [76] | Retrospective population-based cohort | 3175 | Median OS: Gastrectomy with perioperative CT: 16 CT: 9.7 | 0.53 (0.44–0.63) | African American: 0.81 (0.71–0.91) Non-academic program: 1.23 (1.13–1.33) Overlapping lesion: 1.23 (1.11–1.37) Moderately differentiated: 1.18 (0.90–1.56) |
Kamarajah S.K. et al. (2021) [77] | Retrospective population-based cohort | 19,411 | Median OS: No treatment: 1.8 CT: 9.5 Gastrectomy: 12.8 | 0.76 (0.71–0.81) vs. CT | N0: 0.66 (0.56–0.77) N1: 0.65 (0.56–0.76) N2: 0.80 (0.64–1.00 N3: 0.76 (0.60–0.97) Liver: 0.82 (0.72–0.93) Peritoneum: 0.59 (0.37–0.95) Lung: 1.07 (0.78–1.69) Bone: 0.56 (0.36–0.89) |
Park J.Y. et al. (2021) | Retrospective | 148 | Median OS: Palliative gastrectomy: 28.4 Non-resection: 7.7 | p < 0.001 | Not reported |
Fujitani K. et al. (2016) [78] | Randomized phase III | 175 | Median OS: Gastrectomy + CT: 14.3 CT: 16.6 | 1.09 (0·78–1·52) | N0-1: 1.79 (1.14–2.83) Upper-third tumors: 2.23 (1.14–4.37) |
Al-Batran S.E. et al. (2017) [79] | Phase II (subgroup analysis) | 60 | Median OS: Gastrectomy + metastasectomy: 31.3 months Control: 15.9 months | Not reported | Not reported |
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Fanotto, V.; Salani, F.; Vivaldi, C.; Scartozzi, M.; Ribero, D.; Puzzoni, M.; Montagnani, F.; Leone, F.; Vasile, E.; Bencivenga, M.; et al. Primary Tumor Resection for Metastatic Colorectal, Gastric and Pancreatic Cancer Patients: In Search of Scientific Evidence to Inform Clinical Practice. Cancers 2023, 15, 900. https://doi.org/10.3390/cancers15030900
Fanotto V, Salani F, Vivaldi C, Scartozzi M, Ribero D, Puzzoni M, Montagnani F, Leone F, Vasile E, Bencivenga M, et al. Primary Tumor Resection for Metastatic Colorectal, Gastric and Pancreatic Cancer Patients: In Search of Scientific Evidence to Inform Clinical Practice. Cancers. 2023; 15(3):900. https://doi.org/10.3390/cancers15030900
Chicago/Turabian StyleFanotto, Valentina, Francesca Salani, Caterina Vivaldi, Mario Scartozzi, Dario Ribero, Marco Puzzoni, Francesco Montagnani, Francesco Leone, Enrico Vasile, Maria Bencivenga, and et al. 2023. "Primary Tumor Resection for Metastatic Colorectal, Gastric and Pancreatic Cancer Patients: In Search of Scientific Evidence to Inform Clinical Practice" Cancers 15, no. 3: 900. https://doi.org/10.3390/cancers15030900
APA StyleFanotto, V., Salani, F., Vivaldi, C., Scartozzi, M., Ribero, D., Puzzoni, M., Montagnani, F., Leone, F., Vasile, E., Bencivenga, M., De Manzoni, G., Basile, D., Fornaro, L., Masi, G., & Aprile, G. (2023). Primary Tumor Resection for Metastatic Colorectal, Gastric and Pancreatic Cancer Patients: In Search of Scientific Evidence to Inform Clinical Practice. Cancers, 15(3), 900. https://doi.org/10.3390/cancers15030900