16 The effect of chemotherapy on lymph node metastases in ovarian cancer

doi:10.1016/S0950-3552(89)80051-3

Baillière's Clinical Obstetrics and Gynaecology

Volume 3, Issue 1, March 1989, Pages 167-171

https://doi.org/10.1016/S0950-3552(89)80051-3 Get rights and content

Summary

Twenty-six patients with ovarian cancer underwent pelvic and para-aortic lymphadenectomy at second-look or third-look surgery after complete chemotherapy. The frequency of positive nodes (65.3%) was the same as that found at primary lymphadenectomy. Patients who had received cisplatin had the same frequency of positive nodes as those who had received a schedule which lacked cisplatin. Node involvement was not associated with tumour residual after primary surgery. Survival was strongly associated with nodal status. A difference in survival among patients who underwent primary lymphadenectomy could not be demonstrated.

Of all gynaecological malignancies, ovarian cancer has the highest rate of positive retroperitoneal nodes. Chemotherapy, even with cisplatin, seems to have no effect on tumour deposits in the nodes. It cannot be assumed that a cure is possible if disease persists in the lymph nodes after chemotherapy, even if the abdomen has been cleared by radical primary surgery. Thus, cytoreduction should encompass the retroperitoneal space, and lymphadenectomy should be an integral component of the operative treatment of ovarian cancer.

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There are more references available in the full text version of this article.

Cited by (54)

Neo-adjuvant chemotherapy does not reduce surgical complexity nor the accuracy of intra-operative visual assessment of disease in advanced ovarian cancer
2023, European Journal of Surgical Oncology
Compare the surgical complexity and histological accuracy of visual inspection of disease in patients undergoing primary debulking (PDS) versus delayed debulking surgery (DDS) following neo-adjuvant chemotherapy (NACT) for advanced ovarian cancer (AOC).
All patients undergoing PDS or DDS for stage III / IV AOC at a UK cancer centre between January 2014–October 2021 were included. Retrospective data was collected accessing an electronic gynaecological oncology database, operation and histology records. Comparative frequencies of surgical procedures performed were calculated for primary versus delayed cohorts; and correlation between intra-operative suspicion of disease and specimen histology at PDS and DDS compared.
N=232. PDS was performed in 45.3% and DDS in 54.7% of patients; achieving complete cytoreduction in 77.2%. Appendicectomy, pelvic and para-aortic nodal dissection were undertaken significantly more often at primary surgery; whilst right diaphragm stripping, pelvic peritonectomy, splenectomy and cholecystectomy were more likely following NACT. We found no variation in bowel resection rates between cohorts. For the majority of specimens, there was no difference in correlation between intra-operative suspicion of disease and final histopathology – with a significantly lower positive predictive value for visual assessment demonstrated only for liver capsule and pelvic peritoneum at DDS.
NACT does not appear to reduce the complexity of surgery, including rates of bowel resection; nor accuracy of intra-operative visual assessment of disease. We therefore caution against both deferring to NACT to facilitate less radical delayed debulking; and any presumption that macroscopically abnormal tissue at DDS may represent inert post-NACT ‘burn-out’, mitigating indication for excision. We instead suggest reservation of the neo-adjuvant pathway for patients with poor PS and radiologically-confirmed surgical stopping points; and advocate equivalent and maximal cytoreductive effort to remove all visibly abnormal tissue in both the upfront and delayed surgical settings.
Survival outcomes of ovarian cancer patients treated with secondary cytoreductive surgery for isolated lymph node recurrence: A systematic review of the literature
2019, International Journal of Surgery
Citation Excerpt :
In 2004 Morice et al. observed that lymph node metastases tend to be chemoresistant and this may partially explain the results of this systematic review [27]. An earlier report also suggested that platinum based chemotherapy has a small effect on lymph node tumour deposits [28]. Given this information, one could, assume that lymphadenectomy could improve survival outcomes of patients with ILNR by simply removing the chemoresistant residual disease.
Isolated lymph node recurrence (ILNR) is present in 12–37% of recurrences in ovarian cancer patients. Although several studies have investigated the impact of secondary cytoreduction in these cases, consensus still lacks concerning their optimal management. The purpose of the present review is to investigate whether secondary cytoreduction benefits patients with ILNR in terms of overall survival (OS) and post-relapse survival (PRS).
The present systematic review was designed using the PRISMA and AMSTAR guidelines and has been registered with PROSPERO (CRD42019122854). We searched Medline, Scopus, Clinicaltrials.gov, EMBASE, Cochrane Central Register of Controlled Trials CENTRAL and Google Scholar databases from inception until February 2019.
Overall, eight studies where included that recruited a total number of 479 women. Current evidence suggests that ILNR in EOC patients should be clearly distinguished from recurrences in other sites (including peritoneal and parenchymal) as their course seems to be less aggressive. Furthermore, the implementation of secondary cytoreduction as an adjunct to standard chemotherapy should be taken into consideration in this specific group of patients as the PRS may easily reach and even extend beyond 5 years. Prolonged survival (>110 months) may be seen as a realistic target for a significant number of these patients when systematic lymphadenectomy is performed.
The findings of our review suggest that patients with ILNR should be treated with a combined surgical and chemotherapeutic approach to optimize survival outcomes. However, further studies are needed to reach firm conclusions as current evidence is based in low quality studies.
The role of pelvic and aortic lymphadenectomy at second look surgery in apparent early stage ovarian cancer after inadequate surgical staging followed by adjuvant chemotherapy
2014, Gynecologic Oncology
Citation Excerpt :
Second look surgery for ovarian cancer was introduced in clinical practice to accurately assess the pathological response in women with apparent clinical complete response to first line chemotherapy, to perform a debulking of persistent disease and to select women who might benefit from a second line chemotherapeutic treatment [14–18,28]. In this context SAPL at second look surgery was generally performed to remove eventual resistant clones of tumor cells in the pelvic or aortic nodes, undetectable by clinical evaluation or palpation or by imaging [27–30]. Only limited data on the value of lymphadenectomy at second look surgery are available, showing that the risk of nodal involvement is mainly related with stage, presence of residual tumor at primary surgery and persistent peritoneal tumor at second look [19–21].
Systematic aortic and pelvic lymphadenectomy (SAPL) is a milestone procedure in the treatment of early stage ovarian cancer. It defines staging and prognosis and helps in tailoring adjuvant chemotherapy. Only limited data are available about SAPL at second look surgery in patients with apparent early stage ovarian cancer who underwent inadequate surgical staging and adjuvant platinum based chemotherapy.
From January 1991 through January 2013, 66 patients with International Federation of Gynecology and Obstetrics (FIGO) stage IA–IIA epithelial ovarian carcinoma suboptimally surgically staged and treated with adjuvant chemotherapy, were referred to our center and underwent second look surgery including SAPL.
Twenty-two women underwent bilateral and 44 unilateral SAPL. A total of 2168 nodes were removed and analyzed. The median number of lymph nodes dissected was 29 (range 14–73); in particular it was 29 (range 14–60) in case of unilateral and 37 (range 17–73) in case of bilateral SAPL. Only one woman had nodal metastasis (1.5%). After a median follow-up of 78 months, 10 women (15.2%) relapsed and 5 (7.6%) died of progressive disease. The 5-year disease-free survival and overall survival are 91.7% and 96%.
The risk of nodal metastases in stage I–IIA unstaged ovarian cancer after adjuvant chemotherapy is negligible. Our study suggests that SAPL at second look is not indicated in this subset of women.
Prognostic factors for and prognostic value of mesenteric lymph node involvement in advanced-stage ovarian cancer
2012, European Journal of Surgical Oncology
Citation Excerpt :
This is probably unlikely since the rate of positive mesenteric nodes was similar in patients treated initially or after neoadjuvant chemotherapy (Table 1). Furthermore, other reports suggest that the rate of nodal involvement is similar whether patients receive chemotherapy or not before debulking surgery.20–26 Whatever the factors likely to influence the risk of mesenteric node involvement, should such a discovery modify the preoperative strategy, as suggested in the conclusion of the papers reported by O’Hanlan et al. and Silani et al.15,17 ?
To determine the prognosis of and prognostic factors for mesenteric node involvement in patients undergoing a bowel resection at the time of debulking surgery for primary treatment of advanced-stage ovarian cancer (ASOC).
A retrospective review of patients treated between 2005 and 2008 for ASOC and undergoing initial and interval debulking surgery with bowel resection (whatever the bowel segment). The characteristics and prognostic impact of mesenteric node involvement were studied.
During the study period, 52 patients underwent debulking surgery for ASOC with bowel resection. Eighteen and 34 patients underwent initial or interval debulking surgery respectively. The most frequent site of the bowel resection was the rectosigmoid colon (38 patients; 73%) and 12 patients had resection of at least 2 intestinal segments. All patients had a complete macroscopic resection of peritoneal disease. Nineteen patients (37%) had mesenteric node involvement with a median of 4 involved nodes (range, 1–12). The degree of involvement of the intestinal wall and retroperitoneal node involvement (pelvic or para-aortic) had no impact on the risk of mesenteric node involvement. Overall survival and the location of recurrent disease were similar in patients with or without spread to mesenteric nodes.
This study suggests that mesenteric node involvement is frequent in patients undergoing bowel resection in ASOC. Such spread does not appear to have an impact on patient survival. Modifying peroperative (particularly the extent of the mesocolon resection) or postoperative management is therefore unnecessary.
The clinical outcome of epithelial ovarian cancer patients with apparently isolated lymph node recurrence: A multicenter retrospective Italian study
2010, Gynecologic Oncology
Citation Excerpt :
For instance in the series of Blanchard et al. [21], the treatment of 20 patients with isolated nodal recurrence consisted of chemotherapy alone in 8 patients, surgery followed by chemotherapy in 5, chemo-radiation in 2, surgery alone in 2, irradiation alone in 2 and surgery followed by irradiation in one patient. A complete response to chemotherapy was obtained in 55% of the patients, which contradicted previous studies suggesting that nodal metastases from epithelial ovarian cancer are chemo-resistant lesions [30–34]. Some authors have recommended radiotherapy (45–60 Gy), but it might not be effective in treating bulky nodes [21,35].
To assess the clinical outcome of epithelial ovarian cancer patients who developed an apparently isolated lymph node recurrence after primary therapy.
The authors retrospectively assessed 69 patients with epithelial ovarian cancer who were clinically or pathologically free of disease after primary therapy and who subsequently developed an apparently isolated lymph node recurrence. The median follow-up of survivors was 74.5 months.
Median age was 58 years, FIGO stage was III–IV in 52 (75%) patients, residual disease after primary surgery was > 1 cm in 36 (52%), first-line chemotherapy consisted of paclitaxel-/platinum-based chemotherapy in 44 (64%), time to recurrence was > 12 months in 43 (62%), recurrence was pelvic and/or para-aortic in 41 (59%), and treatment at recurrence consisted of chemotherapy alone in 44 (64%), surgery plus chemotherapy in 22 (32%), surgery alone in one patient, surgery plus irradiation in one, and irradiation alone in one patient. Survival after recurrence was significantly related to the type of treatment (chemotherapy alone versus surgery plus chemotherapy, median: 20.8 months versus not reached, p = 0.0002), and patient age (> 58 versus < 58 years, median: 26.8 versus 44.0 months, p = 0.02). Overall survival was significantly related to the type of treatment (chemotherapy alone versus surgery plus chemotherapy, median: 45.4 months versus not reached, p = 0.0001), patient age (> 58 versus < 58 years, median: 45.4 versus 62.9 months, p = 0.03) and time to recurrence (< 12 months versus > 12 months, median: 45.4 versus 66.9 months, p = 0.01). Cox model showed that treatment at recurrence was the strongest independent prognostic variable for both survival after recurrence (hazard ratio [HR] = 0.277, p = 0.0003) and overall survival (HR = 0.249, p = 0.0002).
Patients who underwent surgery plus chemotherapy had a 72% reduction in the risk of death after recurrence and a 75% reduction in the risk of death after initial diagnosis when compared with those treated with chemotherapy alone. Secondary cytoreductive surgery appears to be able to prolong survival in epithelial ovarian cancer patients with apparently isolated lymph node recurrence.
Role of complete lymphadenectomy in endometrioid uterine cancer
2007, Lancet Oncology
Citation Excerpt :
Additionally, an extensive lymph-node resection could lead to an improvement in survival by removing micrometastatic or macrometastatic disease within the lymph nodes, which might become resistant to chemotherapy. Previous studies on patients with ovarian cancer who underwent chemotherapy followed by postchemotherapy surgical restaging showed that 33·3–65·3% of patients with advanced-stage disease had residual disease in the retroperitoneal lymph nodes.78,79 This finding suggests that chemotherapy has a minimum effect on tumour deposits in the lymph nodes.
Although surgical pathological staging is the standard of care for uterine carcinoma, the benefits of a complete lymphadenectomy remain controversial. Evidence suggests that this procedure provides prognostic information and directs the use of appropriate adjuvant treatment in patients who are node-positive. Furthermore, it eliminates the need for adjuvant treatment in low-risk patients with negative nodes and no extrauterine spread of disease. Although the complications associated with this procedure raise the question as to whether all low-risk patients need a complete lymphadenectomy, the limitations of preoperative and intraoperative pathological analyses mean that lymphadenectomy in low-risk patients might still have merit. Future advances are warranted to enhance preoperative radiological and intraoperative pathological assessment to establish the risk of nodal disease. In this review, we assess the evidence on the prognostic and therapeutic benefits of a complete versus selective lymphadenectomy. Moreover, we discuss the complications associated with lymphadenectomy and identify subsets of low-risk patients who might not need to undergo this procedure.

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16 The effect of chemotherapy on lymph node metastases in ovarian cancer

Summary

American Journal of Obstetrics and Gynecology

Gynecologic Oncology