Predictive Value of Pathological Features for Progression after Radical Prostatectomy

Ravery, V.; Boccon-Gibod, L; Meulemans, A.; Dauge-Geffroy, M.-C.; Toublanc, M.; Boccon‐Gibod, Liliane

doi:10.1159/000475379

Cited by 54 publications

(17 citation statements)

References 11 publications

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“…Although a number of studies have found that PNI predicts BCR on univariable analysis, [7][8][9][10][11][12][13][14][15] only two studies have reported PNI as a significant predictor on multivariable analysis. 8,13 Both of these studies examined relatively small cohorts of fewer than 250 participants.…”

Section: Discussionmentioning

confidence: 99%

Does perineural invasion in a radical prostatectomy specimen predict biochemical recurrence in men with prostate cancer?

Reeves

Hovens

Harewood

et al. 2015

CUAJ

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Introduction: The ability of perineural invasion (PNI) in radical prostatectomy (RP) specimens to predict biochemical recurrence (BCR) is unclear. This study investigates this controversial question in a large cohort. Methods: A retrospective analysis was undertaken of prospectively collected data from 1497 men who underwent RP (no neoadjuvant therapy) for clinically localized prostate cancer. The association of PNI at RP with other clinicopathological parameters was evaluated. The correlation of clinicopathological factors and BCR (defined as prostate-specific antigen [PSA] >0.2 ng/mL) was investigated with univariable and multivariable Cox regression analysis in 1159 men. Results: PNI-positive patients were significantly more likely to have a higher RP Gleason score, pT3 disease, positive surgical margins, and greater cancer volume (p < 0.0005). The presence of PNI significantly correlated with BCR on univariable (hazard ratio 2.30, 95% confidence interval 1.50-3.55, p < 0.0005), but not multivariable analysis (p = 0.602). On multivariable Cox regression analysis the only independent prognostic factors were preoperative PSA, RP Gleason score, pT-stage, and positive surgical margin status. These findings are limited by a relatively short follow-up time and retrospective study design. Conclusions: PNI at RP is not an independent predictor of BCR. Therefore, routine reporting of PNI is not indicated. Future research should be targeted at the biology of PNI to increase the understanding of its role in prostate cancer progression.

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Section: Discussionmentioning

confidence: 99%

Does perineural invasion in a radical prostatectomy specimen predict biochemical recurrence in men with prostate cancer?

Reeves

Hovens

Harewood

et al. 2015

CUAJ

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“…However, the most common interaction between nerves and prostate epithelium during tumorigenesis is PNI. The biological and clinical significance of PNI in prostate cancer has been the subject of intense debate (15)(16)(17)(18). Numerous other authors have reported varying degrees of clinical prognostic significance for PNI (15, 17, 19 -23).…”

Section: Discussionmentioning

confidence: 99%

Growth and Survival Mechanisms Associated with Perineural Invasion in Prostate Cancer

Ayala

Dai²,

Ittmann³

et al. 2004

Cancer Research

213

149

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Perineural invasion (PNI) is the major mechanism of prostate cancer spread outside the prostate. Apoptotic and proliferation indices were determined in PNI cells using the PNI in vitro model and human PNI in tissue microarrays. RNA was extracted from the PNI model and controls and evaluated by cDNA microarray analysis. Differential expression of candidate genes was confirmed by real-time quantitative PCR, fluorescence, and immunohistochemistry using tissue microarrays. Genistein and BAY 11-7085 were added to the supernatant of cocultures and controls in microchamber cultures. The significance of nuclear factor B (NFB) nuclear translocation in human PNI was analyzed using Kaplan-Meier analysis. An increase in proliferation and a decrease in apoptosis were observed in human PNI cells and the PNI model as compared with controls. Three of 15 genes up-regulated in the cDNA microarray were involved in the apoptosis signaling pathway (NFB), and its downstream targets defender against cell death 1 and PIM-2. The increase was corroborated by real-time quantitative PCR and immunofluorescence. NFB nuclear translocation was seen in the in vitro model and human tissues, where strong nuclear expression was associated with a decrease in recurrence-free survival. Addition of genistein and BAY 11-7085 resulted in a decrease in NFB, PIM-2 and defender against cell death 1 as well as a reversal of the inhibition of apoptosis. This is the first description of a biological mechanism and functional significance of PNI. Cancer cells in a perineural location acquire a survival and growth advantage using a NFB survival pathway. Targeting PNI might help detain local spread of the tumor and influence survival.

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“…Also, Tlc tumors were less likely to be advanced than non-Tlc tumors with an elevated PSA level (18% versus 55%; Table 4). Considering the independent prognostic values of pathologic stage [13,18], we should expect that the long-term outcome after radical prostatectomy would be relatively favorable for Tlc tumors as compared with non-Tlc tumors with elevated serum PSA levels. A recent study with limited follow-up indeed showed that Tlc tumors seem to have a more favorable outcome than non-Tlc tumors detected at similar preoperative serum PSA concentrations [7].…”

Section: Discussionmentioning

confidence: 99%

“…The relatively high rate of recurrence after curative treatment such as radical prostatectomy [10,13] warrants the attempt to detect prostate cancer at an earlier stage, thereby improving the chances of curative treatment. On the other hand, it should be noted that the incidence of unsuspected prostate cancer in a number of cystoprostatectomy and autopsy studies is very high (30 60% in men > 50 years old) [9,11,14].…”

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confidence: 99%

Comparison of pathologic characteristics of T1c and non-Tic cancers detected in a population-based screening study, the European randomized study of screening for prostate cancer

et al. 1997

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In recent years the introduction of serum prostate-specific antigen (PSA) determination as a screening tool for early detection of prostate cancer in asymptomatic men has led to a markedly increased detection of prostate cancers that are neither palpable nor visible with transrectal ultrasonography (stage T1c). In this preliminary study we assessed pathologic features and aspects that are indicative of clinical significance in T1c tumors and tumors with palpable or visible lesions (non-T1c tumors). Between June 1994 and December 1995, 51 consecutive radical prostatectomies were performed on screened participants in the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer (ERSPC). After determination of pathologic stage and Gleason score, morphometric analysis was performed to determine tumor volume. Radical prostatectomy specimens were divided into three mutually exclusive subsets: T1c tumors, non-T1c tumors with preoperative PSA levels below 4 ng/ml, and non-T1c tumors with PSA levels equal to or greater than 4 ng/ml. These subsets were compared for differences in the distribution of tumor volume, pathologic stage, and Gleason score. An arbitrarily constructed categorization model was used to assess clinical significance. In all, 17 (33%) of the patients had clinical stage T1c disease. In our categorization mode, 88% of the T1c tumors fit the criteria for clinically significant tumors. T1c tumors, however, were significantly smaller (P < 0.01) and were more likely to be organ-confined (P = 0.01) as compared with non-T1c tumors in patients with an elevated preoperative serum PSA level. In contrast, tumors detected at preoperative PSA levels of < 4 ng/ml had comparably the lowest pathologic stages and tumor volumes in our series. In our categorization model, 42% of these tumors fit the criteria for minimal tumor. This group of radical prostatectomies was therefore most likely to harbor clinically insignificant cancer, a finding that was consistent in two other categorization models derived from earlier reports. T1c tumors comprise a large fraction of the tumors found in population-based screening. As judged by their pathologic characteristics. T1c tumors are clinically significant tumors. The overall low pathologic stage and Gleason score of these tumors make these patients excellent candidates for curative treatment by radical prostatectomy or radiotherapy. In contrast, some concern should be raised on the detection of tumors at low serum PSA levels by means of digital rectal examination and transrectal ultrasound alone, since a substantial proportion of these tumors could be considered clinically insignificant. Long-term follow-up, however, is necessary to substantiate this view.

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Predictive Value of Pathological Features for Progression after Radical Prostatectomy

Cited by 54 publications

References 11 publications

Does perineural invasion in a radical prostatectomy specimen predict biochemical recurrence in men with prostate cancer?

Does perineural invasion in a radical prostatectomy specimen predict biochemical recurrence in men with prostate cancer?

Growth and Survival Mechanisms Associated with Perineural Invasion in Prostate Cancer

Comparison of pathologic characteristics of T1c and non-Tic cancers detected in a population-based screening study, the European randomized study of screening for prostate cancer

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