Curr Oncol Rep (2015) 17: 36 DOI 10.1007/s11912-015-0463-z
GYNECOLOGIC CANCERS (NS REED, SECTION EDITOR)
When Is It Safe to Omit Surgery in Primary Peritoneal Cancer With Small Volume Disease? Rachel Pounds 1 & Sean Kehoe 2
Published online: 5 June 2015 # Springer Science+Business Media New York 2015
Abstract Primary peritoneal cancer (PPC) is considered a very rare condition, with mesotheliomas deemed the only true PPC when considering the cellular content and embryological derivation of the peritoneum. However, in women, PPC are seen in much greater abundance than that in men and the type of cancer detected is often that of a serous epithelial carcinoma, histologically similar to serous ovarian carcinomas. The management is also similar, i.e. surgery and platin-based chemotherapy. The definition clinically of PPC is that of widespread carcinomatosis with normal-sized ovaries. The carcinomatosis is often extensive, and the only bulk disease may be within the omentum and achieving complete clearance of all disease at primary surgery unlikely. Thus, the concept of using chemotherapy as the main strategy is a reasonable approach and may well be the best single therapeutic option in some patients. This paper reviews the data on PPC and how this approach could be assessed. Keywords Peritoneal cancer . Chemotherapy . Clinical trials
Introduction Primary peritoneal cancer (PPC) is an aggressive malignancy associated with poor outcomes and low survival rates. It This article is part of the Topical Collection on Gynecologic Cancers * Sean Kehoe [email protected]
affects the peritoneal surfaces without, or with minimal, involvement of the ovaries. Occurring almost exclusively in females, it is usually diagnosed in post-menopausal women [1]. It differs from malignant peritoneal mesothelioma, which is known as a ‘pure’ peritoneal cancer, occurring less frequently and predominantly affecting males [2]. PPC has similar histopathological and clinical characteristics to ovarian cancer and is often managed in a similar fashion to ovarian cancer [1, 3]. We undertook a review of recent literature that discusses PPC, surgical intervention and management with chemotherapy and evaluate whether it is safe to ever omit surgery.
Epidemiology PPC is a rare disease, and while the true incidence remains elusive, it has an estimated incidence of one tenth that of ovarian cancer [4••, 5, 6]. It is also thought that 7–15 % of women with ovarian cancer actually have PPC [7]. The incidence of peritoneal carcinoma is changing with time, and indeed over a 200 % increase has been recorded in the USA over a 10-year period, most likely due to the greater use of appropriate definitions in clinical practice. However, this may also be influenced in the future by the relocation reclassification of ‘peritoneal’ to primary fallopian tube carcinomas as discussed later [8]. The crude incidence of peritoneal mesothelioma is 7 per 100,000 in males and 0.8 per 100,000 in females [9], which based on aetiology must be considered the real peritoneal cancer. Survival data is shown in Table 1.
1
City Hospital, Sandwell and West Birmingham Hospitals NHS Trust, Birmingham B18 7Q, UK
Pathology of PPC
2
School of Cancer Studies, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
Several theories exist regarding the pathogenesis of PPC. The coelomic epithelium lining the abdominal cavity, the
Year Type of study
2014 Prospective data collection from Danish Gynaecological cancer database 2005–2013
2015 Literature review
2014 Prospective study from 1991–2013 of peritoneal surface disease treated with CS and HIPEC 2014 Case report
2008 Population-based case-control study
2014 Phase 1 clinical trial of CRS under ALA-PDD plus HIPEC
2013 Retrospective case-control study of PSPC and PSOC, and prognosis compared
2011 Retrospective study of low grade serous PPC
2010 Retrospective case control analysis of risk factors of PPC and EOC
2013 Case report of PPC
Author
Schnack et al. [4••]
Cao et al. [2]
Levine et al. [10]
Jordan et al. [12]
Liu et al. [13]
Chao et al. [14]
Schmeler et al. [15]
Grant et al. [5]
Moccia et al. [3]
Nasser et al. [11]
Overview of included published articles
Table 1
1
N/A
495 EOC, 62 PPC, 1086 controls N/A
53
Extraovarian PPC found in an ovariectomised woman. These cases should be managed similarly to ovarian
Twofold increase in risk of PPC when over 35 years at last pregnancy while EOC risk was reduced. No link between breast cancer or tubal ligation and PPC, while breast cancer increased risk and tubal ligation reduced risk of EOC.
Similar progression-free survival, shorter overall survival. PFS 12 months (95 % CI 7.3–16.7) PSPC older patients and with more high-grade for PSPC, 16.7 months (12.9–20.4). tumours. OS 62 months (95 % CI 19.6–104.4) in PSPC, 77.5 (69.7–85.2) in PSOC. 5-year PFS 16 %, 5-year OS 69 % Low-grade serous PPC has higher rates of persistent disease at completion of primary treatment and a longer survival than previous data of high-grade serious ovarian and PPC. Low-grade PPC is associated with increased age, increased BMI, reduced CA125 at diagnosis and increased rate of smoking compared to low-grade ovarian carcinoma. There was increased resistance to paclitaxel and carboplatin than high-grade serious carcinoma.
38 PSPC, 53 PSOC
ALA-PDD gives high sensitivity and specificity in detecting peritoneal metastasis. CRS under ALA-PDD and HIPEC is a safe and feasible treatment of PC
N/A
Hormonal contraception reduced risk of all three cancer types. Parous women had increased risk of PPC while parity reduced risk in ovarian and fallopian tube cancer. Obesity doubled the risk of PPC while no link between BMI and ovarian/fallopian tube malignancy was found
N/A
20 (16 ovarian, 4 PPC)
627 ovarian cancer, 129 PPC, 45 fallopian tube cancer, 1508 controls
The fallopian tube is the likely source of a proportion of PPSCs, with STIC as a precursor explaining many features of PPSC.
N/A
Cytoreductive surgery and HIPEC have improved outcomes and long-term survival is possible
27.1 months median survival for mesothelioma, 28.5 ovary
1000 total patients, 72 with mesothelioma, 69 with ovarian cancer 1 PPC
PPC has lower overall and median survival, increased post-operative carcinosis, reduced lymphadenectomy and reduced macro-radical surgery compared to POC. PPC is associated with significantly higher age at diagnosis than POC and higher median age at menarche. Oopherectomy/salpingectomy is associated with increased PPC than POC.
5-year survival in MPM is 39–91.3 %, Unresectable MPM tumours can be treated with combined 31.5–50.9 % in peritoneal carcinoma. chemotherapy, radiotherapy and immunotherapy. CRS and HIPEC can be used as the standard treatment in certain patients with MPM with elevated survival.
25.7 (95 % CI 21.3–30.1) months for PPC stage III and IV (median survival)
268 PPC, 1443 POC, 171 PFC
Main Findings
N/A
Survival
No. cases
36 Page 2 of 9 Curr Oncol Rep (2015) 17: 36
Median survival 29–78 months for first line HIPEC treatment in advanced ovarian cancer, 8–61 months for HIPEC in recurrent ovarian cancer. 5-year survival for CRS only is 17–42 %, CRS with HIPEC is 58–68 %.
2014
Bakrin et al. [22]
N/A
5-year overall survival 57.4 %. 1 year, 93.6 %, 3 year 71.5 %.
2013 Retrospective multicentre review of 36 cytoreductive surgery and HIPEC in PPSC
Bakrin et al. [21]
HPIC associated with complete CRS gives encouraging survival and morbidity data in PC of ovarian origin. Prognostic factors are PCI value and the possibility of complete CRS
Optimal cytoreductoin in 89 %; cytoreductive surgery and HIPEC may achieve long-term survival in PPSC. Peritoneal cancer index was only a factor to give a prognostic value.
Optimal cytoreductive surgery rate after NACT was 79.3. NACT plus cytoreductive surgery after laparoscopic diagnosis is effective PPC treatment. Mean survival was increased when optimal cytoreduction is achieved. Mean OS 46 months, median OS 48 months
29
2012 Retrospective review of PPC patients undergoing NACT, cytoreductive surgery and adjuvant chemotherapy.
Yang et al. [20]
PPC has a similar initial response but is associated with increased platinum resistance and reduced survival.
Six cycles of neoadjuvant carboplatin and paclitaxel was safe and effective, complications not increased in those unsuitable for PDS. Overall survival is higher than those who underwent ID surgery.
Median OS 42 months (95 % CI 20–64) in PPC, 67 (48–86) in EOC. Median PFS 17 months (95 % CI 14–20) in PPC, 25 (21–30) in EOC
Median overall survival 37.5 months, mean OS 36.8 months (95 % CI 32–41)
2010 Systematic review of SPPC
Pentheroudakis et al. [18]
43 PPC, 129 EOC
Similar overall survival between PPC and OSC suggests management would be similar. Survival increased when CA125 normalises during or after treatment. Debulking surgery plus paclitaxel/carboplatin chemotherapy may give most effective treatment. CA125 after surgery can be a prognostic factor for OS and PFS in PPC.
72 ovarian, 10 PPC
2008 Retrospective study of chemotherapy response and survival in PPC and EOC
Eisenhauer et al. [17]
22 PPC, 55 OSC
Prognostic factors include ECOG performance status 0 and optimal cytoreduction. Platinum/taxane chemotherapy was an effective treatment combination. IP treatment believed to improve survival.
Da Costa Miranda et al. [19] 2015 Retrospective review of platinum-based NACT in PPC, tubal carcinoma and EOC
2012 Retrospective review of PPC and OSC patients treated with paclitaxel and carboplatin after exploratory laparotomy.
Kawaguchi et al. [16]
Median survival 41 months in paclitaxel/carboplatin group, 70.3 in paclitaxel/cisplatin group. Median progression-free survival was 15.6 and 37.8 months, respectively. Median overall survival 26.5 months (95 % CI 14.6–38;3) in PPC, 38.8 months (23.8–53.7) in OSC. Median PFS 12.7 months (6.3–19.1) in PPC, 15.9 (13.3–18.5) in OSC.
79 PPC
malignancy but reported separately. Early diagnosis and treatment can result in long-term disease-free survival.
Main Findings
Reduced survival by 2–6 months compared to ovarian cancer despite optimal cytoreduction, increased HER2 over expression in PPC than ovarian cancer, SPPC is more frequently multifocal than ovarian cancer, affected older patients
2014 Retrospective review of PPC characteristics and prognosis, and the effectiveness and toxicity of platinum/taxane chemotherapy
Unal et al. [1]
Survival
No. cases
579
Year Type of study
Author
Table 1 (continued)
Curr Oncol Rep (2015) 17: 36 Page 3 of 9 36
2013 Retrospective analysis of PPC and the frequency of serous tubal in situ carcinoma (STIC) and its precursor lesions. 2014 Retrospective analysis of patients with ovarian cancer who underwent NACT and interval debulking surgery. 2001 Retrospectivematched case comparison study
Horn et al. [23••]
2012 Retrospective study of ovarian, fallopian tube and PPC, the surgery undertaken and outcomes
2009 Analysis of US cancer registers from 1995–2004 for ovarian, fallopian tube and peritoneal cancers
Luycxk et al. [25]
Goodman et al. [8]
Halperin et al. [6]
Colon et al. [24]
Year Type of study
Author
Table 1 (continued)
Complete cytoreductive surgery in 71 % of all patients. After neoadjuvant therapy, the rate of complete debulking surgery was higher (74 %) compared to primary cytoreductive surgery (65 %). In those with complete cytoreduction, DFS was better when surgery is given before chemotherapy than those having chemotherapy first. Similar incidence patterns for all three malignancies suggest a common molecular pathogenesis. White women had highest incidence rates. PPC was diagnosed at later ages and more advanced stages. Ovarian cancer was declining while fallopian tube and peritoneal cancers were increasing.
Median DFS was 17.9 months, but median OS was not reached
N/A
112,541 ovarian cancers, 6458 peritoneal cancers, 3479 fallopian tube cancers
PPSPC associated with earlier menarche, higher number of births, increased abdominal distension, increased incidence of ascites and reduced incidence of a palpable mass at presentation, increased incidence of minimal disease on exploratory laparotomy and increase in prevalence compared to OSPC
STIC can persist despite NACT and have similar immunohistochemical features to untreated lesions
527
N/A
14
The precursors STIC was found in 21.7 % and p53 in 19.6 % of PSPC. There may be two carcinogenesis pathways within PPC.
Median survival in PPSPC was 17 months, OSPC 40 months
N/A
46
Main Findings
28 PPSPC, 35 OSPC
Survival
No. cases
36 Page 4 of 9 Curr Oncol Rep (2015) 17: 36
Curr Oncol Rep (2015) 17: 36
peritoneal mesothelium, and that lining the ovaries, the germinal epithelium, have the same embryonic origin. Due to this, it is thought that PPC can develop when these cells undergo neoplastic transformation. It is hypothesised that the mesothelium and epithelium respond similarly to oncogenic stimuli creating a ‘field effect’ due to either a tumour from the ovarian surface spreading throughout the peritoneum or due to a multifocal malignant transformation. An alternative theory is that both ovarian and peritoneal neoplasms both originate primarily from the fallopian tube [3, 12, 15, 20, 23••]. The evidence from the examination of fallopian tubes removed in BRCA carrier patients undergoing prophylactic surgery indicates the fallopian tubes as a major source of these cancers, known as serous tubal intraepithelial carcinoma (STIC). Equally, robust animal models investigating fallopian tube cancers and PPC development support the fact that the FT is a major source of the high-grade serous intra-abdominal tumours, which includes ovarian cancers. However, in PPCs, in only 50 % of cases to date has STIC been detected, which may be an issue related to the advanced disease status at presentation, whereby the pre-invasive element is not physically detectable or may be a real fact in that the PPC is more of a ‘field’ effect and thus a real phenomenon, a concept best not excluded until evidence proves otherwise. The most frequent mutation in high-grade serous carcinoma occurs in the tumour suppressor gene p53. Identical mutations in p53 have been found in both fallopian tube malignancies and in distant PPC lesions. This indicates that the two tumours are linked and that the fallopian tube malignancy may be the source of serous PPC [11, 24]. Both hypotheses may explain the origins of PPC. Mesothelioma presents similarly to PPC but is mainly caused by asbestos exposure, radiation and simian virus 40 (SV40) [2].
Diagnosis By the nature of staging, PPC usually presents at an advanced stage, typically FIGO stage three or four [4••]. At diagnosis, this is mainly due to PPC presenting with widespread peritoneal disease without a predominant pelvic or ovarian mass, though encountering an omental ‘cake’ is common. The diagnosis of peritoneal cancer can be made in two ways depending on definitions. Firstly with imaging evidence of ‘normal ovaries’ (which in the post-menopausal state may be defined as
GYNECOLOGIC CANCERS (NS REED, SECTION EDITOR)
When Is It Safe to Omit Surgery in Primary Peritoneal Cancer With Small Volume Disease? Rachel Pounds 1 & Sean Kehoe 2
Published online: 5 June 2015 # Springer Science+Business Media New York 2015
Abstract Primary peritoneal cancer (PPC) is considered a very rare condition, with mesotheliomas deemed the only true PPC when considering the cellular content and embryological derivation of the peritoneum. However, in women, PPC are seen in much greater abundance than that in men and the type of cancer detected is often that of a serous epithelial carcinoma, histologically similar to serous ovarian carcinomas. The management is also similar, i.e. surgery and platin-based chemotherapy. The definition clinically of PPC is that of widespread carcinomatosis with normal-sized ovaries. The carcinomatosis is often extensive, and the only bulk disease may be within the omentum and achieving complete clearance of all disease at primary surgery unlikely. Thus, the concept of using chemotherapy as the main strategy is a reasonable approach and may well be the best single therapeutic option in some patients. This paper reviews the data on PPC and how this approach could be assessed. Keywords Peritoneal cancer . Chemotherapy . Clinical trials
Introduction Primary peritoneal cancer (PPC) is an aggressive malignancy associated with poor outcomes and low survival rates. It This article is part of the Topical Collection on Gynecologic Cancers * Sean Kehoe [email protected]
affects the peritoneal surfaces without, or with minimal, involvement of the ovaries. Occurring almost exclusively in females, it is usually diagnosed in post-menopausal women [1]. It differs from malignant peritoneal mesothelioma, which is known as a ‘pure’ peritoneal cancer, occurring less frequently and predominantly affecting males [2]. PPC has similar histopathological and clinical characteristics to ovarian cancer and is often managed in a similar fashion to ovarian cancer [1, 3]. We undertook a review of recent literature that discusses PPC, surgical intervention and management with chemotherapy and evaluate whether it is safe to ever omit surgery.
Epidemiology PPC is a rare disease, and while the true incidence remains elusive, it has an estimated incidence of one tenth that of ovarian cancer [4••, 5, 6]. It is also thought that 7–15 % of women with ovarian cancer actually have PPC [7]. The incidence of peritoneal carcinoma is changing with time, and indeed over a 200 % increase has been recorded in the USA over a 10-year period, most likely due to the greater use of appropriate definitions in clinical practice. However, this may also be influenced in the future by the relocation reclassification of ‘peritoneal’ to primary fallopian tube carcinomas as discussed later [8]. The crude incidence of peritoneal mesothelioma is 7 per 100,000 in males and 0.8 per 100,000 in females [9], which based on aetiology must be considered the real peritoneal cancer. Survival data is shown in Table 1.
1
City Hospital, Sandwell and West Birmingham Hospitals NHS Trust, Birmingham B18 7Q, UK
Pathology of PPC
2
School of Cancer Studies, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
Several theories exist regarding the pathogenesis of PPC. The coelomic epithelium lining the abdominal cavity, the
Year Type of study
2014 Prospective data collection from Danish Gynaecological cancer database 2005–2013
2015 Literature review
2014 Prospective study from 1991–2013 of peritoneal surface disease treated with CS and HIPEC 2014 Case report
2008 Population-based case-control study
2014 Phase 1 clinical trial of CRS under ALA-PDD plus HIPEC
2013 Retrospective case-control study of PSPC and PSOC, and prognosis compared
2011 Retrospective study of low grade serous PPC
2010 Retrospective case control analysis of risk factors of PPC and EOC
2013 Case report of PPC
Author
Schnack et al. [4••]
Cao et al. [2]
Levine et al. [10]
Jordan et al. [12]
Liu et al. [13]
Chao et al. [14]
Schmeler et al. [15]
Grant et al. [5]
Moccia et al. [3]
Nasser et al. [11]
Overview of included published articles
Table 1
1
N/A
495 EOC, 62 PPC, 1086 controls N/A
53
Extraovarian PPC found in an ovariectomised woman. These cases should be managed similarly to ovarian
Twofold increase in risk of PPC when over 35 years at last pregnancy while EOC risk was reduced. No link between breast cancer or tubal ligation and PPC, while breast cancer increased risk and tubal ligation reduced risk of EOC.
Similar progression-free survival, shorter overall survival. PFS 12 months (95 % CI 7.3–16.7) PSPC older patients and with more high-grade for PSPC, 16.7 months (12.9–20.4). tumours. OS 62 months (95 % CI 19.6–104.4) in PSPC, 77.5 (69.7–85.2) in PSOC. 5-year PFS 16 %, 5-year OS 69 % Low-grade serous PPC has higher rates of persistent disease at completion of primary treatment and a longer survival than previous data of high-grade serious ovarian and PPC. Low-grade PPC is associated with increased age, increased BMI, reduced CA125 at diagnosis and increased rate of smoking compared to low-grade ovarian carcinoma. There was increased resistance to paclitaxel and carboplatin than high-grade serious carcinoma.
38 PSPC, 53 PSOC
ALA-PDD gives high sensitivity and specificity in detecting peritoneal metastasis. CRS under ALA-PDD and HIPEC is a safe and feasible treatment of PC
N/A
Hormonal contraception reduced risk of all three cancer types. Parous women had increased risk of PPC while parity reduced risk in ovarian and fallopian tube cancer. Obesity doubled the risk of PPC while no link between BMI and ovarian/fallopian tube malignancy was found
N/A
20 (16 ovarian, 4 PPC)
627 ovarian cancer, 129 PPC, 45 fallopian tube cancer, 1508 controls
The fallopian tube is the likely source of a proportion of PPSCs, with STIC as a precursor explaining many features of PPSC.
N/A
Cytoreductive surgery and HIPEC have improved outcomes and long-term survival is possible
27.1 months median survival for mesothelioma, 28.5 ovary
1000 total patients, 72 with mesothelioma, 69 with ovarian cancer 1 PPC
PPC has lower overall and median survival, increased post-operative carcinosis, reduced lymphadenectomy and reduced macro-radical surgery compared to POC. PPC is associated with significantly higher age at diagnosis than POC and higher median age at menarche. Oopherectomy/salpingectomy is associated with increased PPC than POC.
5-year survival in MPM is 39–91.3 %, Unresectable MPM tumours can be treated with combined 31.5–50.9 % in peritoneal carcinoma. chemotherapy, radiotherapy and immunotherapy. CRS and HIPEC can be used as the standard treatment in certain patients with MPM with elevated survival.
25.7 (95 % CI 21.3–30.1) months for PPC stage III and IV (median survival)
268 PPC, 1443 POC, 171 PFC
Main Findings
N/A
Survival
No. cases
36 Page 2 of 9 Curr Oncol Rep (2015) 17: 36
Median survival 29–78 months for first line HIPEC treatment in advanced ovarian cancer, 8–61 months for HIPEC in recurrent ovarian cancer. 5-year survival for CRS only is 17–42 %, CRS with HIPEC is 58–68 %.
2014
Bakrin et al. [22]
N/A
5-year overall survival 57.4 %. 1 year, 93.6 %, 3 year 71.5 %.
2013 Retrospective multicentre review of 36 cytoreductive surgery and HIPEC in PPSC
Bakrin et al. [21]
HPIC associated with complete CRS gives encouraging survival and morbidity data in PC of ovarian origin. Prognostic factors are PCI value and the possibility of complete CRS
Optimal cytoreductoin in 89 %; cytoreductive surgery and HIPEC may achieve long-term survival in PPSC. Peritoneal cancer index was only a factor to give a prognostic value.
Optimal cytoreductive surgery rate after NACT was 79.3. NACT plus cytoreductive surgery after laparoscopic diagnosis is effective PPC treatment. Mean survival was increased when optimal cytoreduction is achieved. Mean OS 46 months, median OS 48 months
29
2012 Retrospective review of PPC patients undergoing NACT, cytoreductive surgery and adjuvant chemotherapy.
Yang et al. [20]
PPC has a similar initial response but is associated with increased platinum resistance and reduced survival.
Six cycles of neoadjuvant carboplatin and paclitaxel was safe and effective, complications not increased in those unsuitable for PDS. Overall survival is higher than those who underwent ID surgery.
Median OS 42 months (95 % CI 20–64) in PPC, 67 (48–86) in EOC. Median PFS 17 months (95 % CI 14–20) in PPC, 25 (21–30) in EOC
Median overall survival 37.5 months, mean OS 36.8 months (95 % CI 32–41)
2010 Systematic review of SPPC
Pentheroudakis et al. [18]
43 PPC, 129 EOC
Similar overall survival between PPC and OSC suggests management would be similar. Survival increased when CA125 normalises during or after treatment. Debulking surgery plus paclitaxel/carboplatin chemotherapy may give most effective treatment. CA125 after surgery can be a prognostic factor for OS and PFS in PPC.
72 ovarian, 10 PPC
2008 Retrospective study of chemotherapy response and survival in PPC and EOC
Eisenhauer et al. [17]
22 PPC, 55 OSC
Prognostic factors include ECOG performance status 0 and optimal cytoreduction. Platinum/taxane chemotherapy was an effective treatment combination. IP treatment believed to improve survival.
Da Costa Miranda et al. [19] 2015 Retrospective review of platinum-based NACT in PPC, tubal carcinoma and EOC
2012 Retrospective review of PPC and OSC patients treated with paclitaxel and carboplatin after exploratory laparotomy.
Kawaguchi et al. [16]
Median survival 41 months in paclitaxel/carboplatin group, 70.3 in paclitaxel/cisplatin group. Median progression-free survival was 15.6 and 37.8 months, respectively. Median overall survival 26.5 months (95 % CI 14.6–38;3) in PPC, 38.8 months (23.8–53.7) in OSC. Median PFS 12.7 months (6.3–19.1) in PPC, 15.9 (13.3–18.5) in OSC.
79 PPC
malignancy but reported separately. Early diagnosis and treatment can result in long-term disease-free survival.
Main Findings
Reduced survival by 2–6 months compared to ovarian cancer despite optimal cytoreduction, increased HER2 over expression in PPC than ovarian cancer, SPPC is more frequently multifocal than ovarian cancer, affected older patients
2014 Retrospective review of PPC characteristics and prognosis, and the effectiveness and toxicity of platinum/taxane chemotherapy
Unal et al. [1]
Survival
No. cases
579
Year Type of study
Author
Table 1 (continued)
Curr Oncol Rep (2015) 17: 36 Page 3 of 9 36
2013 Retrospective analysis of PPC and the frequency of serous tubal in situ carcinoma (STIC) and its precursor lesions. 2014 Retrospective analysis of patients with ovarian cancer who underwent NACT and interval debulking surgery. 2001 Retrospectivematched case comparison study
Horn et al. [23••]
2012 Retrospective study of ovarian, fallopian tube and PPC, the surgery undertaken and outcomes
2009 Analysis of US cancer registers from 1995–2004 for ovarian, fallopian tube and peritoneal cancers
Luycxk et al. [25]
Goodman et al. [8]
Halperin et al. [6]
Colon et al. [24]
Year Type of study
Author
Table 1 (continued)
Complete cytoreductive surgery in 71 % of all patients. After neoadjuvant therapy, the rate of complete debulking surgery was higher (74 %) compared to primary cytoreductive surgery (65 %). In those with complete cytoreduction, DFS was better when surgery is given before chemotherapy than those having chemotherapy first. Similar incidence patterns for all three malignancies suggest a common molecular pathogenesis. White women had highest incidence rates. PPC was diagnosed at later ages and more advanced stages. Ovarian cancer was declining while fallopian tube and peritoneal cancers were increasing.
Median DFS was 17.9 months, but median OS was not reached
N/A
112,541 ovarian cancers, 6458 peritoneal cancers, 3479 fallopian tube cancers
PPSPC associated with earlier menarche, higher number of births, increased abdominal distension, increased incidence of ascites and reduced incidence of a palpable mass at presentation, increased incidence of minimal disease on exploratory laparotomy and increase in prevalence compared to OSPC
STIC can persist despite NACT and have similar immunohistochemical features to untreated lesions
527
N/A
14
The precursors STIC was found in 21.7 % and p53 in 19.6 % of PSPC. There may be two carcinogenesis pathways within PPC.
Median survival in PPSPC was 17 months, OSPC 40 months
N/A
46
Main Findings
28 PPSPC, 35 OSPC
Survival
No. cases
36 Page 4 of 9 Curr Oncol Rep (2015) 17: 36
Curr Oncol Rep (2015) 17: 36
peritoneal mesothelium, and that lining the ovaries, the germinal epithelium, have the same embryonic origin. Due to this, it is thought that PPC can develop when these cells undergo neoplastic transformation. It is hypothesised that the mesothelium and epithelium respond similarly to oncogenic stimuli creating a ‘field effect’ due to either a tumour from the ovarian surface spreading throughout the peritoneum or due to a multifocal malignant transformation. An alternative theory is that both ovarian and peritoneal neoplasms both originate primarily from the fallopian tube [3, 12, 15, 20, 23••]. The evidence from the examination of fallopian tubes removed in BRCA carrier patients undergoing prophylactic surgery indicates the fallopian tubes as a major source of these cancers, known as serous tubal intraepithelial carcinoma (STIC). Equally, robust animal models investigating fallopian tube cancers and PPC development support the fact that the FT is a major source of the high-grade serous intra-abdominal tumours, which includes ovarian cancers. However, in PPCs, in only 50 % of cases to date has STIC been detected, which may be an issue related to the advanced disease status at presentation, whereby the pre-invasive element is not physically detectable or may be a real fact in that the PPC is more of a ‘field’ effect and thus a real phenomenon, a concept best not excluded until evidence proves otherwise. The most frequent mutation in high-grade serous carcinoma occurs in the tumour suppressor gene p53. Identical mutations in p53 have been found in both fallopian tube malignancies and in distant PPC lesions. This indicates that the two tumours are linked and that the fallopian tube malignancy may be the source of serous PPC [11, 24]. Both hypotheses may explain the origins of PPC. Mesothelioma presents similarly to PPC but is mainly caused by asbestos exposure, radiation and simian virus 40 (SV40) [2].
Diagnosis By the nature of staging, PPC usually presents at an advanced stage, typically FIGO stage three or four [4••]. At diagnosis, this is mainly due to PPC presenting with widespread peritoneal disease without a predominant pelvic or ovarian mass, though encountering an omental ‘cake’ is common. The diagnosis of peritoneal cancer can be made in two ways depending on definitions. Firstly with imaging evidence of ‘normal ovaries’ (which in the post-menopausal state may be defined as
