Prognostic Significance Of Perineural Invasion Research Articles

Prognostic Significance of Perineural Invasion in Patients with Stage II/III Gastric Cancer Undergoing Radical Surgery.

The prognostic significance of perineural invasion in patients with gastric cancer (GC) is controversial. This study aimed to determine the prognostic value of perineural invasion in patients with stage II/III GC undergoing radical surgery. A total of 1913 patients with stage II/III GC who underwent curative resection between 1994 and 2015 were recruited. Clinicopathological factors, tumor recurrence patterns, disease-free survival, and cancer-specific survival were compared in terms of perineural invasion. The prognostic factors of disease-free survival and cancer-specific survival were determined using univariate and multivariate analyses. Perineural invasion was found in 57.1% of the patients. Age of <65 years, female sex, large tumor size, upper tumor location, total gastrectomy, advanced tumor invasion depth and nodal involvement, greater metastatic to examined lymph node ratio, undifferentiated tumor, and presence of lymphatic or vascular invasion were significantly associated with perineural invasion. The patients with perineural invasion had higher locoregional/peritoneal recurrence rates than those without. Perineural invasion was independently associated with disease-free survival and cancer-specific survival. In conclusion, perineural invasion positivity is associated with aggressive tumor behaviors and higher locoregional/peritoneal recurrence rates in patients with stage II/III GC undergoing curative surgery. It is an independent unfavorable prognostic factor of disease recurrence and cancer-specific survival.

Prognostic impact of perineural invasion in oral cancer: a systematic review.

SUMMARYIntroductionNumerous studies have evaluated the prognostic significance of perineural invasion (PNI) in oral cancer; however, the results are inconclusive.PurposeTo identify the prognostic value of PNI in oral cancer through a metanalysis.MethodsA literature review was carried out, searching the MedLine databases via Pubmed, Scielo, Lilacs, Cochrane and Websco.ResultsA total of 56 studies were included. The results indicate that PNI in oral cancer has an incidence of 28% (95% confidence interval (CI) 24-31%); 5-year survival with relative risk (RR) 0.67 (0.59-0.75); 5-year disease-free survival RR 0.71 (0.68-0.75); locoregional recurrence with RR 2.09 (1.86-2.35).ConclusionsPNI is a negative prognostic factor in oral cancer.

ASO Author Reflections: Prognostic Significance of Perineural Invasion in Upper Tract Urothelial Carcinoma

ASO Author Reflections: Prognostic Significance of Perineural Invasion in Upper Tract Urothelial Carcinoma

The Impact of Nerve Involvement on the Prognosis of Gastric Cancer Patients with Curative Gastrectomy: An International Multicenter Analysis.

Background Several studies have been conducted to investigate the association between the presence of perineural invasion (PNI) and overall survival (OS) of gastric cancer (GC) patients who underwent curative resection, but no consensus has been reached. This study is aimed at determining the prognostic significance of PNI in gastric cancer. Study Design. The data of 2969 patients with gastric cancer and who had undergone curative gastrectomy from 2006 to 2010 in two high-volume hospitals of China and Korea were retrospectively analyzed. PNI positivity was identified when carcinoma cells were found to infiltrate into the perineurium or neural fascicles. The relationships between PNI and other clinicopathological factors were evaluated, and survival analyses were performed. Results The presence of PNI was detected in 1055 of the 2969 patients (35.5%). Nationality, age, tumor location, size of tumor, differentiation of the tumor, pT stage, pN stage, lymphatic invasion, and vascular invasion had been associated with PNI positivity. The mean survival time of patients with and without PNI was 62.5 months and 87.3 months, respectively (P < 0.001). However, the presence of PNI was not an independent prognostic factor for gastric cancer, except for patients in stage III (P = 0.037, hazard ratio: 1.21, 95% confidence interval: 1.01-1.44). Conclusion PNI occurs frequently in patients with gastric cancer, and the incidence of PNI increases with the staging of the tumor. The presence of PNI can provide additional information in predicting the survival outcome for those with stage III tumors.

A Study of Prognostic Significance of Perineural Invasion in Oral Squamous Cell Carcinoma

A Study of Prognostic Significance of Perineural Invasion in Oral Squamous Cell Carcinoma

Prognostic effect of perineural invasion in successive years in patients with locally advanced gastric cancer.

The present study evaluates the prognostic significance of perineural invasion (PNI) on 2-year, 5-year, and overall survival in patients undergoing gastrectomy and D2 lymphadenectomy due to locally advanced gastric cancer. Included in the study were 231 patients who underwent surgery between November 2006 and October 2018 due to stage 1B and over locally advanced gastric cancer, whose records were reviewed retrospectively. The variables in the presence or absence of PNI were compared between the two groups with a Chi-square test, a Fisher's exact test, a likelihood ratio, and a Mann-Whitney U test. Overall survival data were evaluated with a Kaplan-Meier test. Prognostic factors were evaluated with a stepwise Cox regression analysis. PNI was identified in 167 (72.3%) of the patients. The 2-year, 5-year, and overall survival rates at the end of the follow-up period were 85.9%, 70.3%, and 64.1% in those without PNI, and 52.7%, 38.3%, and 36.5% in those with PNI, respectively. In a multivariate analysis, PNI appeared to be a significant prognostic factor for 2-year survival (P = 0.04) but had no effect on 5-year and overall survival. Survival was shorter in patients with PNI than in patients without PNI, and PNI had no effect on overall survival, although it was found to be of prognostic significance for 2-year survival.

Prognostic Significance of Perineural Invasion in Node Negative Early Oral Cancer

Garg, Apurva MBBS, MS; Singh, Vaibhav MDS; Dhar, Harsh MBBS, MS, MCh Author Information

Perineural invasion predicts for locoregional failure in patients with oesophageal adenocarcinoma treated with neoadjuvant chemoradiotherapy

AimThe prognostic significance of perineural invasion (PNI) in oesophageal adenocarcinoma (EAC) is unclear. We examined the association of PNI with clinical outcomes in patients treated with neoadjuvant chemoradiotherapy (nCRT) and...

Perineural invasion as a predictive factor for survival outcome in gastric cancer patients: a systematic review and meta-analysis

AimsThe prognostic significance of perineural invasion (PNI) for gastric cancer (GC) patients was under debate. This study aimed to review relevant studies and evaluate the impact of PNI on the...

Multifocal perineural invasion is a better prognosticator than depth of invasion in oral squamous cell carcinoma.

Prognostic significance of perineural invasion (PNI) in oral squamous cell carcinoma (OSCC) characterized as unifocal and multifocal was compared to depth of invasion (DOI) and extranodal extension (ENE). Univariable and multivariable analyses of 861 consecutive patients with OSCC undergoing treatment between 1995 and 2018 were performed, with local failure (LF) and disease-specific mortality (DSS) as the primary endpoints. After adjusting for other adverse histopathological factors and adjuvant therapy, multifocal PNI was associated with a greater risk of LF (P = .01) and DSS (P = 0.02) compared to DOI. The effect of multifocal PNI was comparable to the effect of nodal metastases without ENE (P = 0.02). LF and DSS were not improved by the administration of adjuvant radiotherapy within unifocal or multifocal PNI groups. Multifocal PNI is associated with a greater risk of death in OSCC than DOI. Its effect is comparable to that of nodal metastases (without ENE).

Prognostic significance of perineural invasion in vulvar squamous cell carcinoma.

Background: Perineural invasion (PNI) is closely associated with poor survival in several types of malignant tumours, but whether this is true in vulvar squamous cell carcinoma (VSCC) is unclear. The aims of this study were to determine the prognostic significance of PNI in patients with VSCC.Patients and methods: We retrospectively analysed clinico-pathological data on 105 patients with VSCC (stages IB-IV) treated surgically at our medical center between 2005 and 2015.Results: PNI was detected in 30 (28.6%) patients, and it was significantly associated with well-known clinical risk factors: large tumour size, depth of invasion, lymphatic vascular space invasion (LVSI), and intra- or extra-nodal spread. Significantly greater proportions of patients with PNI received adjuvant therapy after surgery (P=0.001) or showed local recurrence (P=0.002). Multivariable analysis indicated that risk factors for disease-free survival were tumour size (HR 3.02, 95%CI 1.75–7.75), LVSI (HR 4.82, 95%CI 1.36–17.07), depth of invasion (HR 3.11, 95%CI 1.50–6.44), lymph node metastasis (HR 3.15, 95%CI 1.14–8.96) and positive or close surgical margins (HR 4.86, 95%CI 1.67–14.19). The latter three variables were also risk factors for overall survival. PNI was associated with significantly shorter disease-free survival (DFS) (P=0.020) and overall survival (OS) (P=0.017) based on the log-rank test. Among patients who received adjuvant treatment, Kaplan-Meier curves indicated no significant differences between PNI-positive or -negative subgroups in disease-free survival (P=0.085) or overall survival (P=0.061). Based on multivariable analysis of all patients, PNI was not a significant risk factor for either type of survival .Conclusion: PNI in VSCC is associated with significantly shorter disease-free and overall survival, though it appears to be a weak independent predictor of worse prognosis. Combining PNI with other risk factors may be useful for predicting whether postoperative adjuvant therapy will be needed.

The perineural invasion paradox: Is perineural invasion an independent prognostic indicator of biochemical recurrence risk in patients with pT2N0 prostate cancer?

6 Background: Perineural invasion is a histologic feature present in approximately 19% of patients with prostate cancer. The prognostic significance of perineural invasion is controversial with recent studies yielding contradictory results. This study aims to assess whether perineural invasion on surgical pathology of patients with pT2N0 disease is an independent prognostic indicator of the risk of biochemical recurrence. Methods: We identified 201 patients with non-metastatic pT2N0 prostate cancer at our institution between 1/1/2008-12/31/2014. We reviewed the electronic medical record of these patients and identified whether the patient had biochemical recurrence (defined as PSA &gt; 0.2 after surgery). A multivariable analysis was then performed using clinical and histological data for each patient to assess the association between perineural invasion and biochemical recurrence. Results: Of the 201 patients identified, 68.1% (137/201) had perineural invasion and 14% (28/201) had biochemical recurrence. Perineural invasion was associated with pT2c disease (p &lt; 0.001), an increased number of positive cores on biopsy (p &lt; 0.001), and a higher surgical Gleason score (p &lt; 0.001). 19% of patients with perineural invasion had disease recurrence compared to 3.1% without perineural invasion (p = 0.001, Hazard ratio of 6.2). After performing a multivariable analysis and accounting for pathologic tumor staging and Gleason score, perineural invasion had a trend towards a significant association with recurrence (p = 0.085, Hazard ratio of 3.2). Conclusions: Perineural invasion may be an indicator of unfavorable histology such as a high Gleason score or more widespread disease rather than an independent prognostic indicator of the risk of biochemical recurrence.

Prognostic significance of perineural invasion in laryngeal cancer

Introduction: Perineural invasion (PNI) may be an independent risk factor for lymph node metastasis in laryngeal cancer, impacting on decreased survival, increased rates of locoregional recurrence, and shortening the period for recurrence. Objective: To evaluate the prognostic significance of PNI in laryngeal cancer. Materials and Methods: This is a retrospective study, with review of anatomopathological material of patients with laryngeal cancer surgically treated from March 2009 to May 2016. The presence of PNI is related to the oncological results. Results: Of the 69 patients studied, four presented PNI in the review of the slides, one of which presented local recurrence and two, regional relapse. Conclusion: The finding of PNI was 5.8%.

Defining the Prevalence and Prognostic Value of Perineural Invasion and Angiolymphatic Invasion in Human Papillomavirus–Positive Oropharyngeal Carcinoma

Importance Recently, the American Joint Committee on Cancer (AJCC) updated its staging system for human papillomavirus (HPV)–positive oropharyngeal squamous cell carcinoma (OPSCC). The prognostic significance of perineural invasion (PNI) and angiolymphatic invasion (ALI) within this staging system is unknown. Objective To examine the prevalence and prognostic significance of PNI and ALI in HPV-positive OPSCC. Design, Setting, and Participants A retrospective review was performed of all patients with HPV-positive OPSCC treated surgically at the University of Pittsburgh Medical Center from January 1, 1980, through December 31, 2015, with at least 1 year of follow-up or death within 1 year. Interventions Surgical treatment of HPV-positive OPSCC. Main Outcomes and Measures The prevalence of PNI and ALI was determined from review of pathologic data, and Kaplan-Meier curves were generated for overall survival and disease-free survival when stratified by the presence of PNI and ALI. Multivariate analysis was performed using a Cox proportional hazards regression model. Results A total of 201 patients met the inclusion criteria (mean [SD] age, 57.4 [9.0] years; 79.6% [3.0%] male, and 20.4% [3.0%] female). Perineural invasion was identified in 32 of 201 primary specimens (15.9%), whereas ALI was identified in 74 of 201 primary specimens (36.8%). Both were significantly associated with increasing T stage. On multivariate analysis, the presence of at least 1 risk factor was significantly associated with overall and disease-free survival (overall hazard ratio, 2.78; 95% CI, 1.15-6.76; disease-free survival hazard ratio, 3.10; 95% CI, 1.17-8.23). Among patients classified as having stage II disease according to the eighth edition of the AJCC manual, the presence of at least 1 risk factor was associated with worse overall survival (hazard ratio, 11.7; 95% CI, 1.2-111.7). Conclusions and Relevance Both PNI and ALI were commonly found in HPV-positive OPSCC, with increasing prevalence as T stage increased. The presence of at least 1 risk factor was associated with worse overall and disease-free survival. Specifically, among patients classified as having stage II disease according to the eighth edition of the AJCC manual, the presence of ALI or PNI may suggest a poorer prognosis.

Perineural invasion by prostate cancer on MR/US fusion targeted biopsy is associated with extraprostatic extension and early biochemical recurrence after radical prostatectomy

In recent years, multiparametric magnetic resonance imaging and magnetic resonance/ultrasound fusion targeted biopsy (TB) have become more widely adopted to aid in prostate cancer (PCa) detection. Previously, TB has been found to increase the yield of clinically significant PCa and is more likely to sample the index tumor compared with traditional 12-core extended sextant biopsies. Currently, the prognostic significance of perineural invasion (PNI) when identified on TB (PNI-TB) is unknown. We identified 95 men at 2 tertiary referral centers who underwent TB followed by radical prostatectomy between January 2014 and January 2017. Clinical, radiological, and pathological variables were retrospectively reviewed. PNI was identified on TB in 27 of 95 (28.4%) patients. On multivariable logistic regression, independent predictors of extraprostatic extension were prostate-specific antigen, TB maximum % core involvement, and PNI-TB (all P<.05). Furthermore, Kaplan-Meier analysis demonstrated that PNI-TB was associated with early biochemical recurrence events within 12 months after prostatectomy (log-rank P=.049). Given the increasing adoption of TB for PCa detection in clinical practice, PNI-TB may be useful for PCa risk stratification.

Clinical and prognostic significance of perineural invasion in gastric cancer: A single center experience

Clinical and prognostic significance of perineural invasion in gastric cancer: A single center experience

Influence of perineural invasion in predicting overall survival and disease-free survival in patients With locally advanced gastric cancer

BackgroundThe aim of the present study was to evaluate the prognostic significance of perineural invasion (PNI) in locally advanced gastric cancer patients who underwent D2 gastrectomy and adjuvant chemotherapy. MethodsThe records of a series of 103 patients undergoing D2 gastrectomy with curative intent combined with adjuvant chemotherapy from January 2004 to December 2014 were retrospectively reviewed. ResultsPNI was positive in 47 (45.6%) specimens. The 1-, 3-, and 5-year overall survival rates were 81%, 55%, and 42%, respectively. The 1-, 3-, and 5-year disease-free survival (DFS) rates were 76%, 57%, and 49%, respectively. A multivariate analysis showed that age number of positive lymph nodes, T stage, and PNI were independently associated with overall survival. Regarding DFS, the multivariate analysis showed that only PNI was independently associated with DFS. ConclusionsPNI and T stage and positive lymph nodes are independent markers of poor prognosis in patients with gastric cancer. PNI should be incorporated in the postoperative staging system for planning follow-up after surgery and in our opinion to propose more aggressive postoperative therapies in PNI-positive patients.

The prognostic significance of perineural invasion in patients with esophageal adenocarcinoma treated with neoadjuvant chemoradiotherapy.

146 Background: Perineural invasion (PNI) is the process of neoplastic invasion of nerves. PNI has been reported as a prognostic indicator in malignancies of the pancreas, stomach, colon, rectum, prostate, head and neck, and biliary tract. However, studies examining the prognostic significance of PNI in esophageal cancer have shown inconsistent results. Analyses in patients with esophageal adenocarcinoma (EAC) have alternatively shown PNI to be a significant and a nonsignificant predictor of OS and DFS in both univariate and multivariate analysis. The majority of these studies analyzed patients who had not received any preoperative therapy. We sought to identify the prognostic significance of PNI in patients with EAC treated with neoadjuvant chemoradiotherapy (nCRT). Methods: We performed a retrospective analysis of 108 patients treated with nCRT and surgery for EAC at The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute from 1996-2015. The final analysis identified 73 patients with data on PNI. We evaluated the association of PNI with disease-free survival (DFS), loco-regional progression-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS) using log-rank and Cox proportional hazard modeling. Results: Of 73 patients, 17 patients (23%) had PNI and 56 patients (77%) did not have PNI at the time of surgery. The median follow-up was 15.3 months (range 5.8 to 179.3 months). The median DFS was 12.4 months for PNI+ and 36.4 months for PNI- (p = 0.042). The median LRFS was 48.2 months for PNI+ and median not reached for PNI- (p = 0.003). We did not detect a significant association between the presence of PNI and worse OS or DMFS. In a multivariate model including age, sex, gastric involvement, biopsy grade, presence of pathologic complete response, and pathologic N stage, PNI remained a significant independent predictor of LRFS (HR 0.37, 95% CI 0.14 to 1, p = 0.05). Conclusions: In patients with esophageal adenocarcinoma treated with neoadjuvant chemoradiotherapy, PNI discovered at the time of surgery is significantly associated with worse DFS and LRFS.

Prognostic Value of Perineural Invasion in Esophageal and Esophagogastric Junction Carcinoma: A Meta-Analysis.

Objective. Here we aimed to clarify the prognostic significance of perineural invasion (PNI) in esophageal and esophagogastric junction (EGJ) carcinoma. Methods. A comprehensive literature search for relevant reports published up to July 2015 was performed using Pubmed and Embase databases. The pooled HR and 95% CI for overall survival (OS) and disease-free survival (DFS) were used to assess the prognostic value. The association of PNI with pathological characteristics was evaluated by OR and 95% CI. Results. A total of 13 cohorts were retrieved, covering 2770 patients treated by surgery. The cumulative analysis revealed a statistical correlation between PNI and poor OS (HR = 1.76, 95% CI: 1.54–2.20, and P < 0.00001), as well as poor DFS (HR = 1.96, 95% CI: 1.42–2.71, and P < 0.001). Moreover, analysis of 1475 patients showed improved PNI in T3 + T4 (OR = 0.39, 95% CI: 0.21–0.70, and P = 0.002), N+ (OR = 0.52, 95% CI: 0.40–0.69, and P < 0.00001), and G3 + G4 (OR = 0.66, 95% CI: 0.48–0.90, and P = 0.008) patients compared with T1 + T2, N−, and G1 + G2 ones, respectively. No significant heterogeneity was found between the studies. Conclusions. PNI is an adverse prognostic biomarker in esophageal and EGJ carcinoma. Moreover, PNI implies advanced T, N stage and poor cell differentiation.

Prognostic significance of perineural invasion in localized prostate cancer.

30 Background: While perineural invasion (PNI) has been associated with poorer clinical outcomes in prostate cancer patients, it is not well defined as a predictor of long-term endpoints in newly diagnosed prostate cancer. Therefore, we evaluated the role of PNI as a prognostic marker in patients with localized prostate cancer who underwent surgery or radiation. Methods: We analyzed a prospectively collected cohort of 5,034 consecutive patients with localized prostate cancer treated with surgery (n = 4,207) or radiation (n = 827) at University of Michigan from 1994-2013. The primary outcome measured was metastasis-free survival, with secondary outcomes of PSA-recurrence free survival and overall survival (OS). Covariates included age, treatment year, race, comorbidity index, pre-treatment PSA, Gleason score, and T-stage. Survival analysis was estimated using the Kaplan-Meir method, and multivariable analysis was performed using a Cox proportional hazards model. Results: 22.6% of surgery patients and 37.5% of radiation patients had PNI. 169 patients developed metastasis a median of 44 months (IQR 21-83 months) after primary therapy. In the combined cohort, PNI was a predictor of metastasis and PSA recurrence, but not OS (Table 1). For surgery, PNI was a predictor of metastasis, PSA recurrence, and OS. For radiation, PNI was a predictor of metastasis and PSA recurrence, but not OS. Conclusions: PNI is an independent predictor of long-term outcomes in newly diagnosed prostate cancer patients regardless of subsequent therapy. These data support the importance of PNI as a key factor denoting potentially aggressive prostate cancer and importing a significant increase in the likelihood of eventual metastatic progression. [Table: see text]