Secondary Cytoreduction Research Articles

Tertiary cytoreduction for recurrent ovarian carcinoma: An updated and expanded analysis

ObjectiveWe sought to describe clinicopathologic and surgical factors associated with oncologic outcomes in patients undergoing tertiary cytoreduction and to present a clinical model to identify patients with high-grade serous ovarian cancer (HGSOC) who may benefit most from tertiary cytoreduction. MethodsWe retrospectively identified patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who underwent tertiary cytoreduction at our institution from 1/1/1990–1/1/2019. Kaplan-Meier curves were used to estimate survival and compared using the log-rank test. Cox-proportional hazards regression was used to detect variables associated with survival. ResultsOf 114 patients who met inclusion criteria, 79 (69.2%) had high-grade serous tumors. Of patients with available genetic testing (n = 66), 22 (33%) harbored germline or somatic BRCA mutations. Fifty-eight women (50.9%) died of disease. Complete gross resection (CGR) at tertiary cytoreduction, treatment-free interval (TFI), and platinum sensitivity were all significantly associated with disease-specific survival (DSS) and maintained significance on multivariate analysis (HR 3.71, 95% CI: 1.59–8.70; HR 0.49, 95% CI: 0.28–0.85; and HR 2.94, 95% CI: 1.22–7.07, respectively). Postoperative treatment was not associated with a survival difference. Patients with HGSOC and a single site of recurrence who were ≥2 years from secondary cytoreduction had the longest survival after tertiary cytoreduction (median DSS, 79.5 months). ConclusionsProper patient selection for tertiary cytoreduction is essential. Those who achieve CGR likely derive the greatest benefit from tertiary surgery. Platinum sensitivity and prolonged TFI are also associated with improved DSS. Patients with HGSOC and single-site recurrence who were ≥2 years out from secondary cytoreduction had the longest DSS.

Improving the prediction of surgical outcome at secondary cytoreduction in patients with ovarian cancer: Results from retrospective part of HELP-ER study NOGGO TR2/ENGOT OV47-TR.

5558 Background: Complete resection at secondary cytoreductive surgery is associated with prolonged progression free and overall survival for patients with relapsed ovarian cancer. Secondary cytoreductive surgery has no impact on survival rates, if macroscopically tumor clearance cannot be achieved. Therefore, in order to avoid unnecessary perioperative morbidity and mortality, selection of patients who will undergo secondary tumor debulking is crucial. This study aims to improve upon the contemporary Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) score by including additional clinical variables like circulating HE4 and CA125 levels to predict surgical outcome at secondary cytoreduction. Methods: A total of 90 patients underwent secondary cytoreductive surgery and were retrospectively assigned a positive AGO score. Of those patients, 62 (68.9%) achieved optimal surgical outcome at secondary debulking with 28 (31.1%) patients retaining residual tumor mass ( > 0mm). Utilizing clinical variables including circulating HE4 and CA125 levels, we implemented a machine learning workflow to predict suboptimal surgical outcome in patients despite a positive AGO score. Results: We elucidated significantly lower levels of circulating HE4 (p = 0.0038) in patients with optimal surgical outcome compared to patients that retain macroscopic residual tumor at secondary cytoreductive surgery. Moreover, machine learning algorithms trained on clinical variables (e.g. serum HE4 level, serum CA125 level, age, Risk of Ovarian Malignancy Algorithmus (ROMA) score and occurrence of peritoneal carcinomatosis) achieved a mean area under the curve (AUC) of 78.4% based on 100 consecutive executions with randomized training and test sets. Conclusions: The application of machine learning allows to further improve the prediction of patients with high likelihood of achieving optimal surgical outcome at secondary cytoreduction. In turn, it might identify patients that would benefit from amplified treatment efforts. However, machine learning relies on large amounts of data to account for biological and clinical variation and produce predictions of sufficient/adequate quality. Given this limitation, we would validate this data within the prospective multicentric cohort of patients collected within NOGGO/ENGOT HELP_ER Trial.

Phase II consolidation trial with anti-Lewis-Y monoclonal antibody (hu3S193) in platinum-sensitive ovarian cancer after a second remission

ObjectiveTo investigate the efficacy and safety of hu3S193, a humanized anti-Lewis-Y monoclonal antibody, as a consolidation strategy in patients with platinum-sensitive recurrent epithelial ovarian cancer who achieved a second complete...

Update on the secondary cytoreduction in platinum-sensitive recurrent ovarian cancer: a narrative review.

The ovarian cancer recurrence occurs in 75% of patients with advanced FIGO stage, and its treatment is a challenge for the oncologist in gynecology. The standard treatment of recurrent ovarian cancer (ROC) usually includes intravenous chemotherapy according to platinum sensitivity. Furthermore, maintenance treatment with target therapies [e.g., anti-angiogenic drug or PARP inhibitors (PARPi)], should be provided if not precedently administrated. In this scenario, secondary cytoreductive surgery (SCS) remains a practical but controversial option for platinum-sensitive ROC (PSROC). So far, several retrospective series and a Cochrane meta-analysis had concluded that SCS could determine better survival outcomes in ROC with favorable prognostic characteristics, such as the presence of a single anatomical site of recurrence, or when patients are accurately selected for surgery based on complete resection’s predictive models. Recently, three randomized clinical trials (RCTs) investigated the role of SCS in PSROC patients selected with different criteria. All the three RCTs showed a significant statistical advantage in progression-free survival (PFS) in the SCS group, with an even more significant difference in patients with complete cytoreduction (about 7-month PFS increased). Data on overall survival (OS) are different in the two completed trials. The GOG213 study has documented a longer OS of PSROC patients who received chemotherapy alone compared to surgery plus chemotherapy. Contrarily, the DESKTOP III trial showed 7.7 months of increased OS in the surgery group vs. chemotherapy alone, with a more difference in the complete tumor cytoreduction (CTC) group (12 months). These RCTs thereby suggest that undergoing complete cytoreduction may not be the only key and that the disease biology may also matter. Few recent retrospective series investigated the role of SCS according to BRCA mutation status and the effect of SCS in patients receiving emerging PARPi. A consequence of the developments in SCS and knowledge of different molecular pathways influencing the recurrent disease is that the future research objective should be to individualize and personalize the surgical approach.

The role of secondary cytoreduction in recurrent, platinum-sensitive ovarian cancer: what do the trials tell us?

The role of secondary cytoreduction in recurrent, platinum-sensitive ovarian cancer: what do the trials tell us?

Role of CA-125 in achieving optimal secondary cytoreduction

Objective: Our purpose was to investigate the role of routine utilization of CA-125 in the diagnosis and treatment of recurrent ovarian cancer, with particular attention to surgical outcomes of secondary cytoreductive surgery (SCS).

Secondary cytoreduction in relapsed serous ovarian cancer: Who really benefits?

Objective: The aim of this study was to determine the potential survival benefit of secondary cytoreductive surgery (SCS) in relapsed serous ovarian cancer (SOC) and to set up a predictive model for the beneficiaries.

Laparotomy vs. minimally invasive surgery for ovarian cancer recurrence: a systematic review.

The objective of the present review is to thoroughly investigate the role of minimally invasive surgery (MIS) in the setting of secondary cytoreduction for ovarian cancer recurrence, comparing this approach to traditional open surgery. PubMed, ClinicalTrials.gov, Scopus and Web of Science databases (between 1st January 1989 and 1st January 2020), have been systematically queried to identify all articles reporting either laparoscopic or robotic-assisted secondary surgical cytoreduction for recurrent ovarian cancer. We also manually searched the reference lists of the identified studies. Only English language papers were considered. Two independent reviewers screened and identified the reports. A sub-analysis was performed including studies comparing MIS vs. open abdominal secondary cytoreduction. A total of 617 articles were considered. Among them, we included 12 retrospective studies on minimally invasive secondary cytoreduction, enrolling 372 patients (260 of whom were submitted to whether robotics or laparosopy). Three studies compared 69 patients who underwent MIS vs. 112 cases of open abdominal secondary cytoreduction. Other 9 articles described a total of 191 patients who had minimally invasive secondary cytoreduction for recurrent ovarian cancer without a comparative arm. The quality of the evidence was low. The decision regarding the use of MIS was left to surgeon's discretion; in general, the candidates to MIS were selected patients with single-site disease or few localizations of relapse. Compared to open surgery, MIS was associated with significantly lower blood loss, shorter hospital stay and less postoperative complications; the rate of complete cytoreduction to residual tumor =0 was 95.5% in MIS cases vs. 87.5% in laparotomy cases. The risk of complications was generally low. Disease-free and overall survival were comparable between groups. There is no consensus on the criteria to select patients for laparoscopic or robotic secondary cytoreduction. Intra-operative ultrasound has been proposed as a possible tool to better identify the site of recurrence and for confirmation of complete resection of disease. In conclusion, MIS is an option in selected patients with recurrent ovarian cancer, provided there is no widespread disease. Selection of patients appears of utmost importance to obtain satisfactory survival outcomes.

Surgery vs. chemotherapy for ovarian cancer recurrence: what is the best treatment option.

Nowadays, the best treatment option for ovarian cancer recurrence is often subjective, can vary in the different centers and depend on personal experience. Arbeitsgemeinschaft Gynaekologische Onkologie (AGO)-DESKTOP studies have identified a population of patients who could benefit from secondary surgery. The results of the Gynecologic Oncology Group (GOG)-0213 study were recently published, which showed no advantage in terms of overall survival (OS) in patients with platinum-sensitive recurrent epithelial ovarian undergoing secondary cytoreductive surgery (SCS) compared to chemotherapy alone. Aim of this narrative review is to summarize the best aspects that can make ovarian cancer recurrence patients suitable for SCS. A narrative review analyzing all the literature of the past 30 years has been performed. PubMed, Scopus, Web of Science and Ovid MEDLINE were used for research. All non-English-language articles have been excluded. The following keywords were searched: 'recurrent ovarian cancer', 'secondary surgery', 'secondary cytoreductive surgery', 'platinum-sensitive ovarian cancer', 'platinum-resistant ovarian cancer'. We divided eligible patients for secondary cytoreduction in relation to the following factors: platinum-sensitivity, AGO-score or Tian model, unresectable lesions, surgical generic contraindication, woman's personal choice. The selection of truly suitable patients for surgery seems an essential requirement for the patient's best therapeutic choice. In case of absent post-surgical residual tumor, good performance status, single recurrence, and platinum-sensitive ovarian recurrence, surgery could be performed.

Hyperthermic intraperitoneal chemotherapy (HIPEC) for ovarian cancer recurrence: systematic review and meta-analysis.

Ovarian cancer is the first cause of death among gynecological malignancies with a high incidence of recurrence. Different treatment options are suitable to prolong the survival rate of these patients. Over the last years, one of the most intriguing methods, adopted in different oncologic centers worldwide, is the hyperthermic intraperitoneal chemotherapy (HIPEC). A meta-analysis was performed to value the role of HIPEC for ovarian cancer recurrence. Search strategy was conducted with a combination of the following keywords: "ovarian recurrence, ovarian cancer recurrence, peritoneal cancer recurrence, ovarian recurrence AND HIPEC, secondary cytoreduction HIPEC". Seven studies were selected for analysis. In women with recurrent ovarian cancer (ROC), the use of HIPEC in addition to cytoreductive surgery and chemotherapy significantly improved 1-year overall survival (OS) when compared to protocols without HIPEC (OR 2.42; 95% CI, 1.06-5.56; P=0.04; I2=4%). The improvement in OS was maintained significant also after 2, 3 and 5 years respectively (OR 3.33; 95% CI, 1.81-6.10; P<0.01; I2=0%), (OR 4.22; 95% CI, 2.07-8.60; P<0.01; I2=52%), (OR 5.17; 95% CI, 1.40-19.09; P=0.01; I2=82%). HIPEC seems to have an effective role to prolong survival in patients affected by ROC.

THE VALUE OF CYTOREDUCTIVE SURGERY FOR ISOLATED LYMPH NODE RECURRENCE OF OVARIAN CANCER

The purpose of the study was to undertake a systematic literature review regarding the role of cytoreductive surgery in treatment of recurrent ovarian cancer, as well as to summarize available data on various current studies and estimate indications for secondary cytoreduction in recurrent ovarian cancer with isolated lymph node involvement.Material and Methods. The search for relevant sources was carried out in PubMed, Gynecol Oncol, Medline, NCCN, Elibrary systems; publications were included from January 2006 up to March 2019. Of the 87 studies found, 26 were used to write a systematic review.Results. Ovarian cancer (OC) remains the leading cause of death from gynecological cancer. The initial treatment for IC-IV stages of OC includes surgical cytoreduction followed by platinum-containing chemotherapy. The best outcomes are observed in patients, in whom complete cytoreduction has been achieved. Despite this fact, most patients develop relapses and the 5-year survival rate is about 30 %. The frequency of lymph node involvement in patients with recurrent OC is not reliably known; isolated lymph node recurrence is reported to occur in 5–32 % of patients. To date, the problem regarding the extent of lymph node dissection in treatment of OC recurrence is still unsolved. In our paper we review the available data concerning the role of secondary cytoreductive surgery for isolated lymph node recurrence of ovarian cancer.Conclusion. Isolated lymph node recurrence of ovarian cancer may indicate a more favorable prognosis and has a less aggressive pattern of OC relapse. The role of secondary cytoreduction in this context is not fully understood, but this category of patients may be one of the most suitable for surgical treatment of ovarian cancer recurrence.

The value of secondary neoadjuvant chemotherapy in platinum-sensitive recurrent ovarian cancer: a case-control study post GOG-0213 trial

BackgroundThe prognostic value and optimal resection outcome related factors of the secondary cytoreduction surgery (SCR) in Platinum-sensitive recurrent ovarian cancer (PSOC) patients were still in doubt. The present retrospective study aims to determine the relationship between the objective response of secondary neo-adjuvant chemotherapy (SNAC) and the resection outcome of SCR.MethodsData were reviewed from 142 type II PSOCs who underwent SCR in Jiangsu Institute of Cancer Research between 1996 and 2016. Among them, 55 cases received preliminary Platinum based SNAC before SCR. Logistic regression analysis was used to explore optimal SCR related factors. Cox proportional hazards model and log-rank test were used to assess the associations between the survival durations and covariates.ResultsOptimal initial CRS (p = 0.02), disappearance of ascites after SNAC (p = 0.04) recurrent status (p = 0.02) and longer Platinum-free interval (p = 0.01) were the independent indicators of optimal SCR. Optimal SCR was associated with time to progression (TTP) but not overall survival (OS) (p = 0.04 and p = 0.41). The TTP and OS of PSOCs underwent SNAC were similar to those patients underwent SCR (p = 0.71, and p = 0.77, respectively) directly.ConclusionsSNAC might be another choice for PSOCs were not suitable for directly SCR. Optimal SCR had survival benefit in PSOCs whenever underwent SNAC or not.

CRS + HIPEC in stage IIIc epithelial ovarian cancer and comparison of oncological outcome only with CRS and IV chemotherapy and CRS + IP chemotherapy.

e18054 Background: Our study aims to describe role of CRS &amp; HIPEC in stage IIIC epithelial ovarian malignancy &amp; compare the oncological outcome (DFS &amp; OS) of extensive CRS+ HIPEC in comparison with CRS &amp; IV chemotherapy &amp; CRS + IP chemotherapy. Methods: Patients diagnosed of stage IIIc EOC underwent extensive CRS + HIPEC. All data prospectively entered in the HIPEC registry was analysed. Outcome of CRS &amp; IV group (n = 50), CRS + IP group (n = 60) operated around same period was compared with the CRS &amp; HIPEC group. Results: Out of 135 patients, upfront, interval and secondary cytoreduction plus HIPEC was done in 29.6%, 44.4% &amp; 25.9% &amp; mean PCI was 14.1, 9.6 &amp; 13.0 respectively. Multi-visceral resection, diaphragmatic resection &amp; bowel resection was required in 12.7%, 50% &amp; 41.8% respectively. Overall G3- G5 morbidity was seen in 25.4% with major being electrolyte imbalance 16.3%, hematological 12.7% &amp; surgical 11.8%. Mean ICU &amp; hospital stay 1.5 &amp; 11 days respectively. Overall 30 day mortality was 4.5%. With a median follow up of 42 months DFS was 30, 33 &amp; 16 months and OS was 70%, 67% &amp; 51% at 4 year for upfront, interval and the recurrent settings respectively. Detailed description presented in Table. Most of the recurrences in CRS &amp; IV group were in peritoneum whereas the other two groups had lesser peritoneal &amp; systemic recurrence. Conclusions: Optimal cytoreduction &amp; some form of IP therapy is needed to improve outcomes. CRS+ HIPEC is feasible in all groups of ovarian cancer with acceptable morbidity &amp; mortality. However the role of single HIPEC in comparison to 6 cycles of IP chemotherapy needs to be evaluated with a well-designed multi-institutional randomised study. [Table: see text]

Positron Emission Tomography/Computed Tomography in Platinum-sensitive Recurrent Ovarian Cancer: A Single-center Italian Study.

To assess the correlation between contrast-enhanced computed tomography (CE-CT) and positron-emission tomography (PET)/CT results and surgical and pathological findings in patients with recurrent platinum-sensitive ovarian cancer who underwent secondary cytoreduction. 18F-fluorodeoxyglucose (18F-FDG) PET/CT with/without CE-CT were performed before 56 cytoreductive surgeries in 49 patients with suspicious recurrent ovarian cancer. 18F-FDG PET/CT showed higher sensitivity and diagnostic accuracy compared with CE-CT for both the whole series (100% versus 90.6%, respectively, and 97.8% versus 85.3%), and the 24 cases in which both examinations were performed (100% versus 87.0% and, respectively, 95.8% versus 83.3%). The addition of CE-CT to 18F-FDG PET/CT did not improve its diagnostic reliability. 18F-FDG PET/CT appears to be the more reliable imaging technique for the evaluation of patients with suspicious recurrent ovarian cancer, and for the selection of those more suitable for secondary cytoreductive surgery.

Secondary Surgical Cytoreduction for Recurrent Ovarian Cancer

(Abstracted from N Engl J Med 2019;381:1929–1939) The National Comprehensive Cancer Network recommends secondary cytoreduction for ovarian cancer patients with recurrent disease who have received no treatment for a period of 6 months following a complete response from prior chemotherapy. Retrospective reviews and meta-analyses have shown the most benefit from this operation in those with platinum-sensitive disease and those with little or no postoperative residual disease.

Multivisceral Resection in the Surgical Treatment of Ovarian Cancer: Our Experience

Background: Surgical treatment of advanced ovarian cancer can be performed according to different surgical approaches: -Primary cytoreduction (PC); -Interval surgery (IS) after neoadiuvant chemotherapy (NACT); -Secondary and Tertiary cytoreduction to treat cancer recurrence.

Maintenance Therapy in the Treatment of Recurrent Epithelial Ovarian Cancer.

A diagnosis of recurrent epithelial ovarian cancer carries with it a very poor prognosis despite aggressive chemotherapy with or without secondary surgical cytoreduction. Recently, maintenance treatment after second-line chemotherapy has gained momentum given promising results of antiangiogenics and PARP inhibitors used in this setting. When used appropriately, these agents may provide a meaningful survival benefit with minimal effects on quality of life. This paper reveals the current literature evaluating the use of maintenance therapy in the recurrent setting for the epithelial ovarian, fallopian tube, or primary peritoneal cancers.

Does sites of recurrence impact survival in secondary cytoreduction surgery for recurrent epithelial ovarian cancer?

Outcomes of secondary cytoreduction surgery (SCS) were evaluated for morbidity, progression free survival (PFS) and overall survival (OS) and factors influencing results were explored. Retrospective analysis of all cases of SCS for epithelial ovarian cancer (EOC) was performed from October 2010 to December 2017. 62 patients were prospectively identified as candidates for SCS and 57 underwent SCS. 20(35%) patients required bowel resection/s, 24(42%) had nodal resections and 11(19%) had extensive upper abdominal surgery. 51(89%) achieved complete cytoreduction. After a median follow-up of 30 months (range 9–95 months), median PFS was 32 months (CI 17–76 months) and median OS has not reached. Seventeen patients have died and 32 have progressed. Three patients had Clavien-Dindo grade-3 and two had grade-4 morbidity. Patients who had multi-site recurrence had shorter median PFS (p = 0.04) and patients who required bowel resections had lower median OS (p = 0.009) compared to rest of the cohort.IMPACT STATEMENTWhat is already known on this subject? Retrospective studies have confirmed survival advantage for recurrence in epithelial ovarian cancer and recommend SCS for carefully selected patients. This finding is being evaluated in randomised control trials currently.What do the results of this study add? This study presents excellent results for survival outcomes after SCS and highlights importance of careful selection of patients with a goal to achieve complete cytoreduction. In addition, for the first time in literature, this study also explores various factors that may influence results and finds that there are no differences in survival outcomes whether these patients had early stage or advanced stage disease earlier. Patients who have multisite recurrence tend to have shorter PFS but no difference were noted for overall survival. Patients who have recurrence in bowels necessitating resection/s have a shorter median OS compared to rest of cohorts, however, still achieving a good survival time.What are the implications of these findings for clinical practice and/or further research? These findings will raise awareness for the clinicians and patients while discussing surgical outcomes and would set an achievable standard to improve cancer services. The pattern of recurrence and associated outcomes also point towards difference in biological nature of recurrent disease and could provide an opportunity for scientists to study the biological makeup of these recurrent tumours.

Severe metabolic acidosis secondary to iatrogenic hyperglycaemia in secondary cytoreduction and hyperthermic intraperitoneal chemotherapy (HiPEC).

Severe metabolic acidosis secondary to iatrogenic hyperglycaemia in secondary cytoreduction and hyperthermic intraperitoneal chemotherapy (HiPEC).

Extended Pelvic Resections as Part of Secondary Cytoreduction for Relapsed Ovarian Adenocarcinoma.

Ovarian cancer presents an aggressive tumor biology, a significant number of patients experiencing recurrent disease. The aim of this study was to examine the feasibility and effectiveness of secondary debulking surgery for relapsed ovarian cancer. Between 2014 and 2018, debulking surgery for relapsed ovarian cancer was performed in 40 cases. Debulking surgery to no residual disease was achieved in 31 cases; among the remaining cases, an R1 resection was feasible in six cases, while in the remaining three cases an R2 resection was performed. The most commonly performed visceral resections were represented by rectosigmoidian resection, right colon resection, total or partial cystectomy and unilateral or bilateral ureteral resection. The early postoperative morbidity rate was 32.5% while the postoperative mortality rate was 2.5%. Extended pelvic resections are feasible in patients with relapsed ovarian cancer and might be performed with acceptable rates of postoperative complications.