Cancers of the female genital system

13 Cancers of the female genital system




Epithelial ovarian cancer





Pathogenesis and pathology


Most EOCs are high grade (G2/3) serous carcinoma (70%) (HGS). p53 mutation is almost universal (97%) in HGS. Downregulation (rather than mutation) of BRCA1 is also thought to be important in the aetiology of non-heriditary HGS. The following are the different types of EOCs:







Within each histiotype, tumours may be classed as benign, malignant, or of low malignant potential (borderline). Low malignant potential tumours are composed of atypical epithelial proliferation without stromal invasion. They present early and have a low likelihood of recurrence, and are therefore treated with surgery alone.


Primary peritoneal carcinoma or papillary serous carcinoma of the peritoneum is histologically indistinguishable from papillary serous ovarian cancer. Primary peritoneal carcinoma is treated identically to serous papillary ovarian cancer and has similar response rates to chemotherapy.





Investigations and staging


All patients with suspected ovarian cancer should have estimation of serum CA-125 and ultrasound scan of the abdomen +/− transvaginal ultrasound scan. The CA-125 is raised in 50% of patients with stage I disease, and in 90% of stage II–IV. Mucinous tumours often have a normal CA-125. Raised CA-125 is not specific to ovarian cancer. Young patients should also have estimation of germ cell tumour markers (AFP, betaHCG, and LDH).


The risk of malignancy index (RMI) scoring system is used to predict whether a pelvic mass is malignant (Box 13.1). Women with an RMI of >200 should be referred to a specialist centre for further management and surgery. An RMI of >200 has a positive predictive value of 87% and a sensitivity of 88% for diagnosing malignant disease.



To assess operability patients should have a CT of the abdomen and pelvis (Figure 13.1), and a CXR. In patients with a pleural effusion, cytological diagnosis is required to determine if the effusion is malignant.



Patients with ascites without a mass on CT, should have cytological and immunohistochemical analysis, in addition to CA-125, CEA and CA19-9 (p. 287). The immunohistochemical profile of an ovarian tumour is typically CK 7 positive and CK 20 negative. A serum CA125:CEA ratio >25 is strongly suggestive of an ovarian rather than a GI primary.






Management (Figure 13.2)




Early stage disease (stage I and II)





Advanced stage disease (stage III and IV)


Patients with advanced disease may develop medical complications as a result of their cancer, notably thrombosis which has consequences for further management (Box 13.4).




Surgery


The extent of cytoreductive surgery is the most important prognostic factor after stage. The aim of surgery is to achieve a complete macroscopic debulking, or failing this, an ‘optimal debulking’. The definition of ‘optimal debulking’ is visible residual tumour of <1 cm. Studies have shown that patients with residual >2 cm show no improvement in survival over patients without debulking, and are considered incurable. Outcomes according to cytoreductive surgery are shown in Box 13.5. However, even after a complete response 25–50% will recur later.



Meta-analyses suggest that patients with stage IV disease obtain a survival benefit after optimal debulking surgery. Even in patients with liver metastases, studies indicate an improved survival for those in whom optimal extra-hepatic cytoreduction is achieved (27 vs. 8 months). However, more extensive surgery such as hepatic metastatectomies does not appear to improve the survival of patients. Patients with chemotherapy resistant disease have a poor prognosis, even if optimal extra-hepatic cytoreduction is achieved.








Relapse


Despite 70% of patients with advanced disease having a complete clinical response at the end of surgery and chemotherapy (no detectable disease on CT scan and/or normal CA-125), 70% of these will relapse, with a median progression free survival from diagnosis of 16 months. The time from first relapse to death is now around 2 years. There are no studies comparing best supportive care with chemotherapy in relapsed patients, but the recent studies suggest that chemotherapy improves survival.




Treatment (Figure 13.3)


Chemotherapy for relapsed disease is palliative and aims to prevent or treat symptoms in order to improve quality of life and possibly extend survival. In selected cases with a long disease free interval (exceeding 12 or 18 months) and localized relapse, surgery may be an option and long term disease free survival may be possible.



The probability of response to re-treatment with platinum chemotherapy depends upon the interval between the completion of platinum-based first line therapy to the time of relapse, known as the platinum free interval (PFI). A longer PFI is associated with a higher response rate, longer PFS and improved survival.


Disease relapsing >6 months after platinum treatment is considered ‘platinum sensitive’, however this group is subdivided into ‘relatively’ platinum sensitive (PFI 6–12 months) and fully platinum sensitive (PFI >12 months).


Although most of the data about the PFI and its relation to response is taken from first relapse studies, this finding has been extended to second and subsequent relapses. Standard practice is continue re-treating with platinum (or platinum combination) until the patient becomes platinum resistant, regardless of the line of treatment. It has been suggested that the response rate to platinum can be improved by ‘artificially’ extending the platinum free interval by using non-platinum agents, but this has not been proven.









Endometrial cancer





Pathogenesis and pathology


Generally there are two types (type I and II) of endometrial cancer and the characteristics these differ.




Histologic types of endometrial malignancies are as follows:






Mesenchymal tumours include stromal sarcomas, leiomyosarcoma and other types of sarcoma (p. 260, uterine sarcomas). Mixed non-epithelial tumours include carcinosarcomas (previously termed malignant mixed Müllerian tumours).



Diagnosis and staging







Treatment (Figure 13.5)



Stage I disease



Surgery


Total abdominal hysterectomy with bilateral salpingo-oophorectomy (TAH-BSO) and peritoneal washings for cytology is the treatment of choice. Vaginal hysterectomy (LAVH) can be considered in some patients.



Controversy exists over the role of staging lymphadenectomy for stage I endometrial cancer. Grade and myometrial invasion are important determinants of lymph node involvement in stage I cancer. For grade 3 tumours, the risk of lymph node involvement is 15%, and for those with more than image invasion of the myometrium, the risk is approximately 25%. With both these factors, there is a 34% risk of pelvic node involvement, and a 24% risk of aortic node involvement. North American practice is to perform routine bilateral pelvic lymph node dissection (BPLND) with or without para-aortic lymphadenectomy but there is no clear evidence that lymphadenectomy improves survival. The initial results of the ASTEC trial comparing pelvic lymphadenectomy with no lymphadenectomy in mostly stage I disease showed similar survival and progression free survival with both approach and hence the UK practice is to perform lymph node sampling of clinically suspicious nodes only. The rationale being patients with micrometastases will be identifiable as having a high risk of locoregional relapse and these patients can be stratified to receive radiotherapy. Some UK centres perform lymphadenectomy in stage I patients with a high risk of locoregional relapse, and omitting External beam radiotherapy (EBRT) to those with uninvolved nodes.


Staging lymphadenectomy is useful for better risk stratification of stage I patients with high-risk disease and significant co-morbidity, e.g. inflammatory bowel disease which would increase the risk of radiation related morbidity.


Jun 18, 2016 | Posted by in ONCOLOGY | Comments Off on Cancers of the female genital system

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