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Ki67 (MIB-1) as a Prognostic Marker for Clinical Decision Making Before Extended Pleurectomy Decortication in Malignant Pleural Mesothelioma.

ABSTRACT:

Introduction

The role of surgery for early stage malignant pleural mesothelioma (MPM) remains controversial. Current expert opinion is only to treat patients surgically as part of multimodality therapy. It is still challenging to identify patients who will not benefit from surgery. We specifically evaluated tumor-related parameters in combination with clinical parameters to identify prognostic markers for survival.

Methods

Clinical data of 27 consecutive patients with MPM treated with extended pleurectomy and decortication within a multimodality approach were collected and analyzed. Several tumor (immuno-)histopathologic characteristics were determined on resected tumor material, among which MTAP and Ki67 (MIB-1). Univariable and multivariable analyses served to correlate clinical and tumor-related parameters to overall survival (OS) and progression-free survival (PFS).

Results

The median PFS (mPFS) was 15.3, and the median OS (mOS) was 26.5 months. Patients with a Ki67 score greater than 10% had a significantly shorter PFS (mPFS = 8.81 versus 25.35 mo, p = 0.001) and OS (mOS 19.7 versus 44.5 mo, p = 0.002) than those with a Ki67 score less than or equal to 10. Receiver operating characteristic curve analysis for Ki67 revealed an area under the curve of 0.756 with a sensitivity of 90% and specificity of 71% for a cutoff of 10% for Ki67. Patients with loss of MTAP had a significantly shorter mPFS (9 versus 21.1 mo, p = 0.014) and mOS (19.7 versus 42.6 mo, p = 0.047) than those without MTAP loss.

Conclusions

In our study, Ki67 was prognostic for OS and PFS in patients with MPM treated with extended pleurectomy/decortication in a multimodality approach. Determination of Ki67 before surgery combined with specific clinical parameters could assist in clinical decision making by identifying patients, with high Ki67, who are unlikely to benefit from surgery.

SUBMITTER: Belderbos RA

PROVIDER: S-EPMC8474452 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Few studies have focused on quality of life (QoL) after treatment of malignant pleural mesothelioma (MPM). There are still questions as to which surgical procedure, extrapleural pneumonectomy (EPP) or pleurectomy decortication (P/D) is most effective and results in better survival outcomes, involves fewer complications, and results in better QoL. Here we performed a literature review on MPM patients to assess and compare QoL changes after P/D and EPP. METHODS:Research articles concerning QoL after mesothelioma surgery were identified through May 2018 in Medline. For inclusion, studies were 1) cohort or randomized controlled trials (RCT) design, 2) included standardized QoL instruments, 3) reported QoL measurement after surgery, 4) described the type of surgery performed (EPP or P/D), 5) were written in English. Measures of lung function (FEV1, FVC) and measures from the EORTC-C30 were compared 6?months following surgery with preoperative values. RESULTS:QoL data was extracted from 17 articles (14 datasets), encompassing 659 patients (102 EPP, 432 P/D); the available evidence was of low quality. While two studies directly compared QoL between the two surgical procedures, additional data was available from one arm of two RCTs, as the RCTs were not comparing EPP and P/D. The remaining data was reported from observational studies. While QoL was still compromised 6?months following surgery, from the limited and low quality data available it would appear that P/D patients had better QoL than EPP patients across all measures. Physical function, social function and global health were better at follow-up for P/D than for EPP, while other indicators such as pain and cough were similar. Forced Expiratory Volume (FEV1) and Forced Vital Capacity (FVC) were reported in one study only, and were higher at follow-up for P/D compared to EPP. CONCLUSIONS:Although the existing evidence is limited and of low quality, it suggests that P/D patients have better QoL than EPP patients following surgery. QoL outcomes should be factored into the choice of surgical procedure for MPM patients, and the possible effects on lung function and QoL should be discussed with patients when presenting surgical treatment options.

Project description:ObjectiveMalignant pleural mesothelioma (MPM) is a rare and aggressive malignant cancer for which there are poor treatment options. Extrapleural pneumonectomy (EPP) and pleurectomy decortication (P/D) are the two most used surgical procedures in patients with resectable disease. We reviewed the available literature in order to compare the overall survival and postoperative complications of EPP and P/D and to provide evidence for the best procedure in the treatment of MPM.MethodsWe performed a systematic review of the literature, including studies from August 2018 to May 2022. The primary outcome was 5-year overall survival (OS) and the secondary outcomes were 30-day mortality, 90-day mortality and peri-operative complications.ResultsThirteen studies were considered, including a total of 1624 patients treated with EPP and 2147 treated with P/D. The estimated pooled HR showed a significant lower hazard for P/D compared to EPP in terms of OS (HR = 0.76; 95% CI from 0.62 to 0.94; p < 0.001). In 12 studies, the risk for 30-day mortality was lower for patients treated with P/D (RR = 0.49; 95% CI from 0.31 to 0.76; p = <0.01), whereas only five studies reported 90-day mortality, and no statistically significant difference between EPP and P/D was found (RR = 0.71; 95% CI from 0.47 to 1.07; p = 0.10). The OS restricted mean survival time difference meta-analysis (RMSDT) confirms the superior survival of P/D on the EPP, a superiority that increases from 0.54 months at one year to 4.23 at five years. The incidence of postoperative empyema, atrial fibrillation, bleeding and bronchopleural fistula was significantly increased in the EPP group except for prolonged air leakage, which is only characteristic of P/D.ConclusionsUsing two different statistical methods, this meta-analysis suggests that long-term survival after surgical treatment for resectable MPM is greater for patients undergoing P/D. Long-term survival had never been previously analyzed with appropriate tests; on the contrary, our result is consistent with the previous meta-analyses and reinforces the evidence of lower 30-day mortality and the prevalence of postoperative complications in P/D versus EPP patients. The recent introduction of innovative therapeutic schemes, both adjuvant and neoadjuvant therapy, keeps the discussion on surgical strategy open and will require new studies.

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