Prognostic Significance Of Pathological Response Research Articles

Improved Event-Free Survival After Complete or Major Pathologic Response in Patients With Resectable NSCLC Treated With Neoadjuvant Chemoimmunotherapy Regardless of Adjuvant Treatment: A Systematic Review and Individual Patient Data Meta-Analysis

IntroductionNeoadjuvant chemoimmunotherapy has reshaped the treatment landscape for resectable NSCLC, yet the prognostic significance of pathologic response remains unclear. We conducted a systematic review and individual patient data (IPD) meta-analysis to evaluate the impact of achieving pathologic complete response (pCR) or major pathologic response (MPR) on event-free survival (EFS) and assessed the influence of adjuvant immunotherapy. MethodsWe performed an IPD meta-analysis of prospective clinical trials on neoadjuvant or perioperative anti–programmed death-ligand 1 in combination with platinum-based chemotherapy in patients with resectable NSCLC. The IPD was extracted from Kaplan-Meier curves for pCR and/or MPR from the included studies. Survival outcomes were compared between patients achieving pCR or MPR and those who did not, considering both intention-to-treat and resected populations. ResultsAchieving pCR or MPR was associated with improved EFS in the intention-to-treat population (pCR, hazard ratio = 0.13; MPR, hazard ratio = 0.18, respectively) with a 24 months EFS rate of 94% and 88% for patients who achieved pCR and MPR, respectively. Independently from pCR status, patients who were treated in an experimental arm that included adjuvant immunotherapy had similar EFS. ConclusionsOur study reported a strong EFS improvement in patients who achieved either pCR or MPR after neoadjuvant chemoimmunotherapy. The use of adjuvant immunotherapy after tumor resection was not associated with improved EFS.

Comparison of the predictive value of pathological response at primary tumor and lymph node status after neoadjuvant chemotherapy in locally advanced gastric cancer.

Preoperative chemotherapy has been increasingly used in locally advanced gastric cancer (LAGC). However, the prognostic factors are still insufficient. This study aimed to investigate the prognostic significance of pathological response of the primary tumor to neoadjuvant chemotherapy (NACT) and the lymph node status after NACT. Data from 160 patients with LAGC treated with NACT followed by gastrectomy and met the inclusion criteria between March 2016 and December 2019 were retrospectively reviewed. Pathological evaluation after NACT was based on the grade of pathological response of the primary tumor and the status of lymph node. Survival curves for overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method, and the log-rank test was used to compare survival difference. Univariate and multivariate analyses for prognostic factors were based on the Cox regression. Among 160 selected cases, 90 had pathological response (PR), while 70 had no pathological response (nPR) to NACT. Smaller tumor size was presented in PR group, which also had lower level of signet ring cell features, compared to nPR group (all p < 0.05). Based on the status of lymph nodes, nodal status (-) group showed smaller tumor size, lower depth of tumor invasion, better differentiated degree, lower level of signet ring cell features, lower rate of lymphatic and venous invasion and less advanced ypTNM stage (all p < 0.05). Survival was equivalent between PR and nPR group (all p > 0.05), while patients with no lymph node metastasis had better DFS than that with lymph node metastasis (HR 0.301, 95% CI 0.194-0.468, p = 0.002). Multivariable Cox regression analysis identified that lymph node status after NACT was an independent prognostic factor associated with survival (OS: hazard ratio 1.756, 95% CI 1.114-3.278, p = 0.029; DFS: hazard ratio 1.901, 95% CI 1.331-3.093, p = 0.012). Lymph node status is a potential independent prognostic factor for LAGC patients treated with NACT and may be more efficient than pathological response in primary tumor.

Neoadjuvant chemotherapy for high-risk intrahepatic cholangiocarcinoma – does pathologic response mean better outcomes?

BackgroundThe role of neoadjuvant chemotherapy (NAC) in the management of intrahepatic cholangiocarcinoma (ICC) remains unknown. We sought to evaluate our experience treating high-risk ICC with NAC and to determine the prognostic significance of pathologic response. MethodsPatients with ICC treated with NAC and surgery were analyzed using a prospectively maintained database. Pathologic response was graded by a blinded pathologist. Clinicopathologic/treatment variables were evaluated for associations with survival. ResultsAmong 45 patients who received NAC followed by hepatectomy for high-risk ICC, 32(71%) were considered stage III, and 6(13%) were considered stage IV at time of diagnosis. Major response was identified in 39% of cases, including 2 with pathologic complete response. Patients with major response had a longer median NAC duration than patients with minor response (6 vs 4cycles, P=0.02). Regimen (gemcitabine/cisplatin vs gemcitabine/cisplatin/nab-paclitaxel) was not associated with response rate. Median recurrence-free (RFS) and overall survival (OS) were 11 and 45 months. Pathologic response was not associated with improved survival. ConclusionPathologic response to NAC was not associated with survival in this highly selected cohort. Nonetheless, the extended OS experienced by these high-risk patients is encouraging and suggests that NAC may help select patients who stand to benefit from aggressive resection.

Evaluation of the prognostic impact of pathologic response to preoperative chemotherapy using Mandard’s Tumor Regression Grade (TRG) in gastric adenocarcinoma

BackgroundPerioperative chemotherapy is the gold standard in gastric cancer management. The prognostic significance of pathological response has been investigated in many malignancies, using Tumor Regression Grade (TRG). Its prognostic value in gastric cancer remains poorly known. AimsThis study aimed to assess the prognostic value of pathological response to chemotherapy, using Mandard’s TRG in gastric cancer, and to identify factors predictive of response to chemotherapy. MethodsWe retrospectively identified patients with gastric adenocarcinoma from two institutional surgical databases, with preoperative chemotherapy and subsequent gastrectomy. Pathological response was centrally reviewed using Mandard’s TRG. ResultsFrom 325 patients resected from a gastric cancer between 1997 and 2016, 109 underwent a preoperative chemotherapy. 42% were pathologic responders (TRG1-3) and 58% non-responders (TRG4-5). Five-years overall survival (OS) was 35% for non-responders, and 73% for responders (p = 0,006). Five-years disease-free survival (DFS) was 34% for non-responders and 65% for responders (p = 0,013). In multivariate analysis, pathological response was an independent prognostic factor of poor OS: HR = 2.736 (CI95% = 1.335–5.608; p = 0.006) and DFS: HR = 2.241 (CI95% = 1.130–4.446; p = 0.021). ConclusionTRG after preoperative chemotherapy is an important prognostic factor in patients resected for a gastric adenocarcinoma. Further studies should be performed to evaluate if adjuvant therapy should be adapted to pathological response.

Prognostic significance of pathological response to preoperative chemoradiotherapy in patients with locally advanced rectal cancer.

Preoperative chemoradiotherapy (CRT) is widely used in the treatment of locally advanced rectal cancer (LARC). Pathological response to CRT has been shown to be a potential prognostic predictor in rectal cancer patients. The aim of this study was to determine the prognostic significance of pathological response to preoperative CRT in LARC patients. Thirty-two patients with LARC were retrospectively analyzed to determine the relationships of pathological response and clinicopathological characteristics to survival outcomes. Patients received CRT with tegafur/uracil and leucovorin. Radiotherapy was administered in fractions of 1.8 Gy/day and 5 days per week. The total dose of radiation delivered was 45 Gy. All patients underwent total mesorectal excision with lymph node dissections after CRT, and resected specimens were examined pathologically. Four patients showed pathological complete response, 14 showed good response, and 14 showed poor response. Pathological complete or good response was associated with longer survival (P = 0.041). Clinicopathological factors excluding gender were not correlated with outcome. No factor was associated with recurrence. Pathological response to preoperative CRT may be a useful prognostic predictor in patients with LARC.

Does pathological response after transarterial chemoembolization for hepatocellular carcinoma in cirrhotic patients with cirrhosis predict outcome after liver resection or transplantation?

To investigate the prognostic significance of pathologic response (PR) after transarterial chemoembolization (TACE) in cirrhotic patients resected or transplanted for hepatocellular carcinoma (HCC), and to identify predictors of complete pathologic response (CPR). Between 1990 and 2010, 373 consecutive cirrhotic patients with HCC were treated by TACE followed by either liver resection (LR:184 patients) or liver transplantation (LT:189 patients). The PR was evaluated as the mean percentage of non-viable tumor area within each tumor. CPR was defined as the absence of any viable tumor area in all the present nodules. A total of 59 (32%) and 37 (20%) patients had CPR after LR and LT, respectively. Five-year overall survival (OS) was higher in patients with CPR compared to those without, after LR (58% vs. 34%; p=0.0006) and tends to be higher after LT (84% vs. 65%; p=0.09). The 5-year recurrence-free survival (RFS) rates were significantly higher in both groups (24% vs. 13% after LR; p=0.008 and 94% vs. 73% after LT, p=0.007). A cut-off value of >90% necrosis emerged as an impacting factor on patient survival after LR or LT. On multivariate analysis stratified on the type of procedure (LR or LT), PR >90% remained an independent factor of better OS and RFS. Independent factors associated with CPR were: a maximal tumor size <30 mm (RR 2.17 [1.27-3.74]), a single tumor (RR 6.08 [3.29-12.07]), and an preoperative AFP<100 ng/ml (see results section) (RR 3.99 [1.63-11.98]). The probability to achieve a CPR ranged from 2% in the absence of any factors to 48% in the presence of all factors. In cirrhotic patients with HCC, a complete or nearly complete PR improves long-term survival after LR and LT independently of other pathological factors. This underlines the importance of neoadjuvant treatment to obtain a significant decrease of active tumor load.

Prognostic significance of pathological response after neoadjuvant chemotherapy or chemoradiation for locally advanced cervical carcinoma

BackgroundCisplatin-based chemoradiation is the standard of care for locally advanced cervical cancer patients; however, neoadjuvant modalities are currently being tested. Neoadjuvant studies in several tumor types have underscored the prognostic significance of pathological response for survival; however there is a paucity of studies in cervical cancer investigating this issue.MethodsFour cohorts of patients with locally advanced cervical carcinoma (stages IB2-IIIB); included prospectively in phase II protocols of either neoadjuvant chemotherapy with 1) cisplatin-gemcitabine, 2) oxaliplatin-gemcitabine, 3) carboplatin-paclitaxel or 4) chemoradiation with cisplatin or cisplatin-gemcitabine followed by radical hysterectomy were analyzed for pathological response and survival.ResultsOne-hundred and fifty three (86%) of the 178 patients treated within these trials, underwent radical hysterectomy and were analyzed. Overall, the mean age was 44.7 and almost two-thirds were FIGO stage IIB. Pathological response rates were as follows: Complete (pCR) in 60 cases (39.2%), Near-complete (p-Near-CR) in 24 (15.6 %) and partial (pPR) in 69 cases (45.1%). A higher proportion rate of pCR was observed in patients treated with chemoradiotherapy (with cisplatin [19/40, 47.5%]; or with cisplatin-gemcitabine [24/41, 58.5%] compared with patients receiving only chemotherapy, 6/23 (26%), 3/8 (37.5%) and 8/41 (19.5%) for cisplatin-gemcitabine, oxaliplatin-gemcitabine and carboplatin-paclitaxel respectively [p = 0.0001]). A total of 29 relapses (18.9%) were documented. The pathological response was the only factor influencing on relapse, since only 4/60 (6.6%) patients with pCR relapsed, compared with 25/93 (26.8%) patients with viable tumor, either pNear-CR or pPR (p = 0.001). Overall survival was 98.3% in patients with pCR versus 83% for patients with either pNear-CR or pPR (p = 0.009).ConclusionComplete pathological response but no Near-complete and partial responses is associated with longer survival in cervical cancer patients treated with neoadjuvant chemotherapy or chemoradiotherapy.