Introduction
Tumor markers in ovarian cancer
CA125 in ovarian cancer
Search Strategy and Selection Criteria
Quality Assessment
Epidemiologic Studies on CA125 and Ovarian Cancer Survival
Prechemotherapy Absolute Serum CA125 and Ovarian Cancer Survival
First Author, Year, Study Place | Data Collection | Study Design | Sample Size | Groups being Compared | RR/HR, (95% CI), P-Value | Conclusion | Variables Adjusted for |
---|---|---|---|---|---|---|---|
Markman M, 2006, USA, [37] | NA | Longitudinal study | 101 | ≤ 35 U/ml, > 35-- < 100 U/ml, ≥ 100 U/ml | NA | Reduction in serum CA-125 concentration over the initial 2 cycles of chemotherapy was an independent predictor of survival | NA |
Riedinger JM, 2006, France [38] | 1988 to 1996 | Multicentric retrospective study | 631 | ≤ 230 kU/L & > 230 kU/L | Univariate analysis 0.77 (0.73--0.81), < 0.0001 | Pre-chemotherapy CA125 had a univariate prognostic value for disease free survival and overall survival | NA |
Gronlund B, 2005, Denmark [39] | Dec 1993 to Sep 1998 | Prospective study | 70 | Multiple cutoffs of 35, 65, 132 & 339 U/mL | NA | The pretreatment CA125 level was not found to be significantly associated with survival by any of the cutoffs | FIGO stage, histology, localization of tumor relapse, size of tumor relapse, CASA level |
Gadducci A, 1995, Italy [40] | 1986 to 1992 | Multicentric retrospective study | 225 | < 500 U/ml, ≥ 500 U/ml | NA | Survival was found to be significantly related to serum CA 125 before the third cycle | FIGO stage, tumor grade, residual disease, CA125 half life |
Ron IG, 1994, Israel [41] | Feb 1987 to Dec 1990 | Prospective study | 48 | 35-100 U/ml, 101-299 U/ml, 300-499 U/ml, ≥ 500 U/ml | NA, < 0.0001 | Early response (CA125 normalcy by the end of the second chemotherapeutic course) was a highly significant predictor of disease-free survival at 12 months | Age, FIGO stage, histology, grade, residual tumor, ascites |
Davidson NG, 1991, [42] | Sep 1985 to Sep 1987 | Convenience sample | 55 | < 50 kU/l, 125 ≥ 50 kU/l | NA, < 0.003 | Prechemotherapy CA125 level taken 4 weeks after debulking surgery may predict survival in ovarian cancer patients who undergo chemotherapy treatment | Age, Histology, FIGO stage, tumor grade, residual disease |
Rustin GJ, 1989, U.K. [43] | April 1985 to Feb 1987 | Prospective study | 54 | ≥ 35 U/ml, < 35 U/ml | NA, 0.001 | There was a highly significant relationship between the progression free survival time and the change in CA125 levels just prior to chemotherapy | NA |
van der Burg ME, 1988, Netherland [44] | Sept 1979 to Dec 1983 | Consecutive case series | 85 | ≤ 35 U/ml, 35-60 U/ml, > 60 U/ml | NA | The prechemotherapy level of CA125 on itself is strongly correlated with progression rate and the probability of progression within 3 years | FIGO stage, histology, histological grade, postoperative tumor size |
Postchemotherapy Absolute Serum CA125 and Ovarian Cancer Survival
First Author, Year, Study Place | Data Collection | Study Design | Sample Size | Groups being Compared | RR/HR, (95% CI), P-Value | Conclusion | Variables Adjusted for |
---|---|---|---|---|---|---|---|
Kim HS, 2008, South Korea [45] | Jan 1997 to March 2007 | Retrospective study | 123 | < 10 U/ml, 10--21 U/ml and > 21 U/ml | 2.51(1.06-5.92), 0.027 3.13 (1.14-8.61), < 0.001 | The serum CA125 level after 6 cycles of primary adjuvant paclitaxel/carboplatin chemotherapy may be a good prognostic factor for survival in complete responders | Residual tumor, chemotherapy cycles |
Juretzka MM, 2007, USA [46] | 1984 to 1998 | Retrospective cohort study | 241 | CA125 ≤ 12 U/ml vs > 12 U/ml | 1.41 (1.05--1.91), 0.0248 | CA125 level at the end of primary therapy was a predictor of overall survival and progression free survival | FIGO stage, Histology, grade |
Riedinger JM, 2007, France [47] | 1988 to 1996 | Multicentric retrospective study | 494 | ≤ 35 kU/l, > 35 kU/l | Uni-2.7 (2.2--3.3), < 0.0001 Multi-1.27 (0.94--1.71), NS | CA125 change after first course of chemotherapy was independent prognostic factor for both achievement of pathological complete response and overall survival. | Age, Histology FIGO stage, residual tumor |
Badulescu F, 2005, Romania [48] | 2000 to 2002 | Prospective study | 40 | NA | NA, < 0.05 | The response evaluation criteria based on the blood levels variations of CA125 antigen are a better instrument for the estimation of the compared prognosis with the RECIST criteria | Age, FIGO stage, RECIST criteria |
Van Dalen A, 2000, Europe [5] | 1994 to 1997 | Prospective multicentric study | 213 | ≤ 25 kU/L, > 25 kU/L | 5.6 (2.65--11.90), < 0.0001 | CA125 level of 25 kU/L on completion of three courses of chemotherapy is a good indicator of 2-year overall survival | FIGO stage, Histology, grade, TPS levels |
Ron IG, 1994, Israel [41] | Feb 1987 to Dec 1990 | Prospective study | 48 | ≤ 35 U/ml, > 35 U/ml | NA, < 0.0001 | Patients with CA125 below 35 U/ml after 2 courses had a significantly longer median and disease-free survival than those whose CA125 dropped to normal after the third or a later cycle | Age, FIGO stage, histology, grade, residual tumor, ascites, prechemotherapy CA125 |
Fisken J, 1993, UK [49] | NA | Retrospective study | 58 | 4 quartiles < 55 U/ml, 58-221 U/ml, 228-434 U/ml, > 450 U/ml | < 0.0005 | CA125 was a highly significant predictor of both progression free and overall survival after the first cycle and throughout primary chemotherapy | Residual disease, age, tumor grade, performance status, ascites |
Redman CW, 1990, U.K. [50] | March 1986 to March 1988 | Consecutive case series | 50 | ≤ 35 U/ml, > 35 U/ml | NA, 0.0009 | Serum CA125 after two courses gave the greatest discrimination between patients alive at 12 months and those who did not survive that long | Age, FIGO stage, histology, grade, residual disease |
Absolute Serum CA125 during Chemotherapy and Ovarian Cancer Survival
First Author, Year, Study Place | Data Collection | Study Design | Sample Size | Groups being Compared | RR/HR, (95% CI), P-Value | Conclusion | Variables Adjusted for |
---|---|---|---|---|---|---|---|
Colakovic S, 2000, Yugoslavia [51] | NA | Retrospective study | 222 | ≤ 35 U/ml & > 35 U/ml | < 0.0001 | The time needed for normalization of CA125 levels can divide patients into good and poor prognostic groups early during chemotherapy | Therapeutic response Karnofsky index, residual disease, tumor grade, CA125 half-life, CA125 kinetics |
Gadducci A, 1995, Italy [40] | 1986 to 1992 | Multicentric retrospective study | 225 | < 35 U/ml & > 35 U/ml before the third cycle of chemotherapy | NA | Serum CA125 half-life during early chemotherapy was an independent prognostic factor for both the achievement of a pathological complete response and the survival of patients with advanced epithelial ovarian cancer | FIGO stage, tumor grade, size of residual disease, serum CA125 before the first cycle of chemotherapy & serum CA125 half life |
Yedema CA, 1993, Netherlands [52] | July 1984 to Dec 1990 | Retrospective study | 60 | ≤ 35 U/ml & > 35 U/ml | 5.60 (1.16-27.1), 0.03 | There was a significant co relationship between serum CA125 levels after three courses of chemotherapy and survival in ovarian cancer. | Stage, histology, grade, tumor rest |
Preoperative Absolute Serum CA125 and Ovarian Cancer Survival
First Author, Year, Study Place | Data Collection | Study Design | Sample Size | Groups being Compared | RR/HR, (95% CI), P-Value | Conclusion | Variables Adjusted for |
---|---|---|---|---|---|---|---|
Osman N, 2008, Limerick [53] | Jan 2001 to Dec 2005 | Retrospective study | 75 | ≤ 500 u/ml, > 500 u/ml | NA, 0.85 | The preoperative CA125 level did not correlate significantly with stage, tumor grade or survival | Age, histology, FIGO stage, grade |
Petri A, 2006, Denmark [54] | Dec 1994 to May 1999 | Retrospective study | 118 | < 65 U/mL, ≥ 65 U/mL | 3.4 (1.2--9.6), 0.01 | Patients with stage I EOC and preoperative serum CA125 levels < 65 U/mL had a significantly longer survival compared to those with serum CA125 ≥ 65 U/mL | Age, histology FIGO substage, grade, chemotherapy |
Cooper BC, 2002, USA [55] | 1990 to 1996 | Retrospective study | 142 | < 160, 160--399, 400--924, 925--2399, 2400 U/mL | GI-Reference, GII-2, GIII-1.5, GIV-4, GV-2, 0.03 (for trend) | There was a significant association between CA125 levels and disease-specific survival | Age, histology FIGO stage, grade, ascites, and optimal cytoreduction |
Buller R, 1996, USA [56] | 1987 to 1982 | Retrospective study | 126 | ≤ 500 U/ml, > 500 U/ml, ≤ 3000 U/ml, > 3000 U/ml | I-HR-NA, 0.48 II-HR-NA, 0.65 | Preoperative CA125 levels did not predict survival advantage over a range of cut points (400 to 3000 U/ml) | Age, histology, FIGO stage, tumor grade, residual disease, time to initial chemotherapy |
Geisler JP, 1996, USA [57] | NA | Consecutive case series | 82 | NA | NA, 0.047 | In epithelial ovarian carcinoma, high preoperative serum levels of CA125 predict decreased length of survival | Histology FIGO substage, grade |
Gadducci A, 1995, Italy [40] | 1986 to 1992 | Multicentric retrospective study | 225 | ≥ 500 U/ml, < 500 U/ml | NA | Serum CA125 half-life during early chemotherapy was an independent prognostic factor for survival | FIGO stage, tumor grade, size of residual disease & serum CA125 half life |
Nagele F, 1995, Austria [58] | Jan 1984 to June 1993 | Retrospective study | 201 | < 65 U/mL, ≥ 65 U/mL | Uni-7.45 (2.83-19.65), < 0.001 Multi-6.37 (2.39-16.97), < 0.001 | Preoperative CA125 was the most powerful prognostic factor for survival | Age, FIGO substage, grade, |
Makar AP, 1992, Norway [59] | 1983 to 1990 | Prospective study | 200 | ≤ 150 U/ml, > 150 U/ml | NA, 0.035 | Preoperative CA125 did not appear to be of any prognostic value in epithelial ovarian cancer | NA |
Sevelda P, 1989, Austria [60] | NA | Prospective study | 163 | ≥ 35 U/ml, < 35 U/ml | NA, 0.13 | Preoperative CA125 was not a predictor of survival | Histologic grade, FOGO stage, residual tumor |
Moebus V, 1988, Germany [61] | NA | Convenience sample | 202 | ≥ 65 U/ml, < 65 U/ml | NA, 0.005 | Significantly longer survival was noted for patients with preoperative values below 65 U/ml than for those with values above 65 U/ml | NA |
Cruickshank D, 1987, Aberdeen [62] | NA | Prospective study | 52 | ≥ 35 U/ml, < 35 U/ml | NA | No correlation was found between CA125 concentration and survival | NA |
Postoperative Absolute Serum CA125 and Ovarian Cancer Survival
First Author, Year, Study Place | Data Collection | Study Design | Sample Size | Groups being Compared | RR/HR, (95% CI), P-Value | Conclusion | Variables Adjusted for |
---|---|---|---|---|---|---|---|
Osman N, 2008, Limerick [53] | Jan 2001 to Dec 2005 | Retrospective study | 68 | ≤ 500 U/ml, > 500 U/ml | NA, < 0.01 | The postoperative CA125 correlated to FIGO stage, tumor grade and overall survival. Reduced survival was noted with increasing age at the time of surgery and bulk of the residual disease postoperatively. | Age, histology, FIGO stage, grade |
Munstedt K, 1997, Germany [63] | 1987 to 1994 | Retrospective study | 85 | < 60 U/ml, > 60 U/ml, > 480 U/ml | NA | Serum CA125 levels within 4 weeks of operation were of no significant value as indicators of overall survival | Age, FIGO stage, histology, grades |
Makar AP, 1992, Norway [59] | 1983 to 1990 | Prospective study | 487 | ≤ 35 U/ml, 36-65 U/ml, > 65 U/ml | I-1.00, (Reference), II- 1.56 (0.82-2.80), NS, III- 2.40 (1.42-4.06), 0.0008 | In patients without residual disease after primary surgery, histologic type, postoperative CA125 level with 35 U/mL as the cutoff value, and tumor grade were independent prognostic factors for survival | Size of residual disease, histology, FIGO stage, tumor grade |
Sevelda P, 1989, Austria [60] | NA | Prospective study | 132 | ≥ 35 U/ml, < 35 U/ml | NA, 0.0006 | Postoperative CA125 was the strongest independent prognostic factor for survival | Histologic grade, FOGO stage, residual tumor |
Moebus V, 1988, Germany [61] | NA | Convenience sample | 165 | ≥ 65 U/ml, < 65 U/ml | NA, 0.001 | Significantly longer survival was noted for patients with postoperative values below 65 U/ml than for those patients with postoperative values above 65 U/ml | NA |
Serum CA125 Half-life and Ovarian Cancer Survival
First Author, Year, Study Place | Data Collection | Study Design | Sample Size | Groups being Compared | RR/HR, (95% CI), P-Value | Conclusion | Variables Adjusted for |
---|---|---|---|---|---|---|---|
Riedinger JM, 2008, France [64] | 1996 to 2000 | Multicentric Retrospective study | 130 | Non-assessable, ≤ 14 days and mono-exponential decay, ≤ 14 days and bi-exponential decay, > 14 days | NA | The CA125 group classification was found to be an independent prognostic factor only for DFS | CA125 nadir, chemotherapy courses, residual tumor |
Riedinger JM, 2006, France [38] | 1988 to 1996 | Multicentric Retrospective study | 553 | ≤ 14 days, > 14 days | 2.04 (1.58-2.63), < 0.0001 | Among well-established prognostic factors in ovarian cancers, CA125 half-life and nadir concentration bear a strong and independent prognostic value | FIGO stage, residual tumor, age, CA125 nadir |
Gadducci A, 2004, Italy [65] | 1996 to 2002 | Retrospective study | 71 | ≤ 14 days, > 14 days | 3.11 (1.22--7.98), 0.0181 | Serum CA125 half-life was an independent prognostic factor for the chance of achieving a complete response to treatment as well as for progression-free survival and overall survival | Age, Histology FIGO stage, Residual disease, chemotherapy regimen, CA125 percentage reduction after the first cycle of chemotherapy |
Colakovic S, 2000, Yugoslavia [51] | NA | Retrospective study | 222 | < 20 days, > 20 days | NA, 0.007 | CA125 half life can divide patients into good and poor prognostic groups early during chemotherapy | Therapeutic response Karnofsky index, residual disease, tumor grade, CA125 kinetics |
Munstedt K, 1997, Germany [63] | 1987 to 1994 | Retrospective study | 85 | < 20 days, > 20 days | 0.6184 | Serum CA125 half-life did not have any significant correlation with survival | Age, FIGO stage, Histology, grades |
Gadducci A, 1995, Italy [40] | 1986 to 1992 | Multicentric Retrospective study | 225 | < 25 days, ≥ 25 days | 2.13 (1.23-3.68), 0.0073 | Serum CA125 half-life during early chemotherapy was an independent prognostic factor for both achievement of a pathological complete response and survival | FIGO stage, Tumor grade, size of residual disease, CA125 level |
Rosman M, 1994, Connecticut [66] | June 1985 to July 1989 | Retrospective study | 51 | ≤ 12 days, > 12 days | 3.6 (1.8-7.4), < 0.001 | In those patients in whom residual small volume disease after primary surgery indicates a good prognosis, minimum CA125 and CA125 t1/2 during chemotherapy can further categorize patients into favourable and unfavourable prognostic groups | FIGO stage, tumor grade, residual disease, CA125 |
Yedema C A, 1993, Netherlands [52] | July 1984 to Dec 1990 | Retrospective study | 60 | ≤ 20 days, > 20 days | 9.17 (1.49-56.3), 0.01 | CA125 half-life provides an independent prognostic factor for survival in stage III-IV patients early in the course of therapy | Stage, histology, grade, tumor rest |
Hogberg T, 1990, Sweden [67] | 1984-1987 | Prospective study | 72 | ≤ 8 days, 8 - ≤ 12 days, 12 < - ≤ 16 days, > 16 days | NA, 0.003 | The patients with a short serum CA125 half-life had a significantly better probability of survival | Age, histology FIGO stage, residual tumor, grade |
Hunter VJ, 1990, Durham [68] | March 1984 to Jan 1989 | Prospective study | 54 | ≤ 20 days, > 20 days | NA, < 0.015 | Overall survival was significantly greater in patients with a CA125 half life ≤ 20 days | NA |
Hawkins RE, 1989, London [69] | NA | Prospective study | 29 | < 20 days, 20-40 days, > 40 days | 3.7 (0.7-20.1), 0.001; 27.8 (4.0-193), 0.001 | CA125 half life was independent prognostic indicator for survival | Residual tumor, stage, ascites |
van der Burg ME, 1988, Netherlands [44] | Sept 1979 to Dec 1983 | Consecutive case series | 85 | < 20 days, ≥ 20 days | NA | The half-life of CA125 appeared to be significantly and independently correlated with progression rate and progression-free survival | FIGO stage, histology, histological grade, postoperative tumor size |
Nadir Serum CA125 and Ovarian Cancer Survival
First Author, Year, Study Place | Data Collection | Study Design | Sample Size | Groups being Compared | RR/HR, (95% CI), P-Value | Conclusion | Variables Adjusted for |
---|---|---|---|---|---|---|---|
Riedinger JM, 2008, France [64] | 1996 to 2000 | Multicentric Retrospective study | 130 | ≤ 20 kU/L, > 20 kU/L | 4.18 (2.65-6.62), < 0.0001 | Nadir concentration, residual tumor volume and number of chemotherapy courses were found to be independent prognostic factors for disease free survival and overall survival | Chemotherapy courses, residual tumor |
Riedinger JM, 2006, France [38] | 1988 to 1996 | Multicentric retrospective study | 631 | ≤ 20 kU/L, > 20 kU/L | 1.65 (1.28-2.12), < 0.0001 | CA125 half life and nadir concentration are powerful independent prognostic factors. CA125 nadir concentration and time to nadir all had a univariate prognostic value for disease free survival and overall survival | Age, FIGO stage, residual tumor, CA125 half life |
Crawford SM, 2005, [8] | 1988 to 2000 | Retrospective study | 79 | ≤ 10 U/ml, 11--20 U/ml, 21--30 U/ml | NA, < 0.001 | The nadir group was the only predictor of overall survival that remained very highly significant (P < 0.001) after the effect of the other factors was allowed for | Type of chemotherapy, CA125 level at course three |
Gard GB, 1994, Australia [70] | 1985 to 1991 | Retrospective study | 223 | > 35 U/ml, 15-35 U/ml, < 15 U/ml | Uni- 3.23 (2.62-3.99), < 0.0001 Multi-0.85 (0.54-1.33), 0.476 | The initial CA125 level and nadir CA125 level, although significant when considered alone, were not significant independent variables | Tumor types, FIGO stage, residual disease, CA125 |
Time to Reach CA125 Nadir and Ovarian Cancer Survival
First Author, Year, Study Place | Data Collection | Study Design | Sample Size | Groups being Compared | RR/HR, (95% CI), P-Value | Conclusion | Variables Adjusted for |
---|---|---|---|---|---|---|---|
Riedinger J M, 2006, France [38] | 1988 to 1996 | Multicentric retrospective study | 553 | ≤ 72 days, > 72 days | Univariate analysis 0.67 (0.63--0.71) < 0.0001 | CA125 nadir concentration and time to nadir all had a univariate prognostic value for disease free survival and overall survival. In Cox models, nadir concentration was the most powerful prognostic factors for disease free survival | NA |
Frasci G, 1996, Italy [71] | 1985 to 1990 | Consecutive case series | 54 | ≤ 1 month, > 1 months | 0.009 | Survival of patients with advanced ovarian cancer could be accurately predicted by considering some pretreatment variables and time to CA125 normalization together, without performing second look laparotomy | Residual tumor burden after surgery, Eastern Cooperative Oncology Group (ECOG) performance status |
CA125 Area under the Curve (AUC) and Ovarian Cancer Survival
Longitudinal Serum CA125 and Ovarian Cancer Survival
First Author, Year, Study Place | Data Collection | Study Design | Sample Size | Groups being Compared | RR/HR, (95% CI), P-Value | Conclusion | Variables Adjusted for |
---|---|---|---|---|---|---|---|
Riedinger JM, 2007, France [47] | 1988 to 1996 | Multicentric study | 494 | ≥ 75% decrease, < 75% decrease or increase | Univariate- 1.92 (1.34--2.74), < 0.0001 3.08 (2.10--4.50), < 0.0001 Multivariate-0.90 (0.59--1.39), NS 0.97 (0.59--1.59), NS | The CA125 change after first course of CT was independent prognostic factors for both achievement of pathological complete response and overall survival. | Age, Histology FIGO stage, Residual tumor |
Markman M, 2006, USA [37] | NA | Longitudinal study | 291 | I > 100, ≤ 35 u/ml II 36--99, ≤ 35 u/ml III > 100, 36--99 u/ml | I - 3.0 (1.7--8.6), 0.0001 II - 1.6 (0.9--2.8), 0.09 III-1.8 (1.0--3.5), 0.07 | While pretreatment CA125 values did not correlate with survival, the concentration of CA125 8 weeks after initiation of therapy was a powerful independent prognostic factor. | Age, performance status, disease stage, measurable disease, treatment, tumor necrosis, stromal sclerosis |