The impact of prostate cancer upgrading and upstaging on biochemical recurrence and cancer-specific survival

Abstract Significant numbers of prostate cancer (PCa) patients experience tumour upgrading and upstaging between prostate biopsy and radical prostatectomy (RP) specimens. The aim of our study was to investigate the role of grade and stage increase on surgical and oncological outcomes.Methods Upgrading and upstaging rates were analysed in 676 treatment-naïve PCa patients who underwent RP with subsequent follow-up. Positive surgical margin (PSM), biochemical recurrence (BCR), overall (OS) and cancer specific survival (CSS) were analysed according to upgrading and upstaging.Results Upgrading was observed in 29% and upstaging in 22% of PCa patients. Patients undergoing upgrading or upstaging were 1.5-times more likely to have a PSM on RP pathology. Both upgrading and upstaging were associated with increased risk for BCR: 1.8 and 2.1-times, respectively. Mean time to BCR after RP was 2.1 years in upgraded cases and 2.7 years in patients with no upgrading (p < 0.001), while mean time to BCR was 1.9 years in upstaged and 2.8 years in non-upstaged cases (p < 0.001). Grade and stage increase after RP were associated with inferior ten-year CSS rates: 78% vs. 96% for upgrading (p = 0.002) and 77% vs. 95% for upstaging (p = 0.001).Conclusions Currently used risk stratification models are associated with a substantial number of misdiagnosis. Pathological upgrading and upstaging have been associated with inferior surgical results, substantial higher risk of BCR and inferior rates of important oncological outcomes, what should be considered when counselling PCa patients at the time of diagnosis or after definitive therapy.

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The Impact of Prostate Cancer Upgrading and Upstaging on Biochemical Recurrence and Cancer-Specific Survival

Medicina ◽

10.3390/medicina56020061 ◽

2020 ◽

Vol 56 (2) ◽

pp. 61

Author(s):

Arnas Bakavičius ◽

Mingailė Drevinskaitė ◽

Kristina Daniūnaitė ◽

Marija Barisienė ◽

Sonata Jarmalaitė ◽

...

Keyword(s):

Prostate Cancer ◽

Biochemical Recurrence ◽

Surgical Margin ◽

Positive Surgical Margin ◽

Cancer Specific Survival ◽

Oncological Outcomes ◽

Increased Risk ◽

Definitive Therapy ◽

The Impact ◽

Mean Time

Background and Objectives: Significant numbers of prostate cancer (PCa) patients experience tumour upgrading and upstaging between prostate biopsy and radical prostatectomy (RP) specimens. The aim of our study was to investigate the role of grade and stage increase on surgical and oncological outcomes. Materials and Methods: Upgrading and upstaging rates were analysed in 676 treatment-naïve PCa patients who underwent RP with subsequent follow-up. Positive surgical margin (PSM), biochemical recurrence (BCR), metastasis-free survival (MFS), overall (OS) and cancer specific survival (CSS) were analysed according to upgrading and upstaging. Results: Upgrading was observed in 29% and upstaging in 22% of PCa patients. Patients undergoing upgrading or upstaging were 1.5 times more likely to have a PSM on RP pathology. Both upgrading and upstaging were associated with increased risk for BCR: 1.8 and 2.1 times, respectively. Mean time to BCR after RP was 2.1 years in upgraded cases and 2.7 years in patients with no upgrading (p < 0.001), while mean time to BCR was 1.9 years in upstaged and 2.8 years in non-upstaged cases (p < 0.001). Grade and stage increase after RP were associated with inferior MFS rates and ten-year CSS: 89% vs. 98% for upgrading (p = 0.039) and 87% vs. 98% for upstaging (p = 0.008). Conclusions: Currently used risk stratification models are associated with substantial misdiagnosis. Pathological upgrading and upstaging have been associated with inferior surgical results, substantial higher risk of BCR and inferior rates of important oncological outcomes, which should be considered when counselling PCa patients at the time of diagnosis or after definitive therapy.

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Obesity and metabolic syndrome correlate with a higher risk of biochemical recurrence in high risk and intermediate risk prostate cancer patients who underwent robotic-assisted laparoscopic prostatectomy.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.5580 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 5580-5580

Author(s):

Shifeng Mao ◽

Ralph Miller ◽

John Lyne ◽

Jeffrey Cohen ◽

Arash Samiei

Keyword(s):

Prostate Cancer ◽

Metabolic Syndrome ◽

Biochemical Recurrence ◽

Surgical Margin ◽

Positive Surgical Margin ◽

Obese Patients ◽

Robotic Assisted ◽

Laparoscopic Prostatectomy ◽

Increased Risk ◽

Significant Difference

5580 Background: Obesity and metabolic syndrome (MS) is prevalent in our society, and have been linked to a higher incidence of prostate cancer (PCa). The relationship of obesity or MS and cancer control has yielded mixed results in previous studies. We examined the correlation between the incidence of biochemical recurrence (BCR) with MS and BMI in a cohort of patients with PCa who underwent robotic-assisted laparoscopic prostatectomy (RALP). Methods: A retrospective study of patients who underwent RALP at a single center from 2007 to 2015 was conducted. Parameters including preoperative BMI, fasting glucose, lipid profile, blood pressure, PSA, Gleason score, pathologic stage, time to BCR, and surgical margin status were analyzed. Patients were categorized in high (HR), intermediate (IR), and low-risk (LR) groups based on the National Comprehensive Cancer Network (NCCN) guidelines. WHO classification was used for MS criteria, and BCR was defined as two consecutive postoperative PSA volume of ≥ 0.2 ng/mL. Obesity is defined as BMI ≥30 kg/m2. Results: A total of 726 patients with 189 in HR, 471 in IR and 66 patients in LR groups were included in this study with the median age of 59 (interquartile range [IQR] 55-64) years old. The median follow-up from surgery was 38 (IQR 22-46) months. More obese patients were found in the HR group compared to IR/LR group (46.5% vs. 33.1%, p<0.01). There were also more patients with MS in the HR group compared to IR/LR group (36.5% vs. 12.0%, p<0.01). Obese patients had a higher rate of BCR across risk groups in comparison to non-obese patients 32.1% vs. 15.4% (P<0.001), specifically 68% vs. 40%(p<0.01) in HR group and 21.3% vs. 12.7% (p=0.035) in the IR group. Similarly, patients with MS had a higher rate of BCR in HR and IR groups in comparison to the patients without MS, 39.1% vs. 18.7% (P<0.01); specifically, 67.7% vs. 42.2% (p<0.01) in HR and 29% vs. 11.6% (p<0.01) in the IR group. No correlation between MS or obesity and BCR was observed in LR group. There was no statistically significant difference in the positive surgical margin rate between obese and non-obese cohorts in each risk group. Conclusions: Among HR and IR-PCa patietns who underwent RALP, both obesity and MS correlate with increased risk of BCR. There were significantly more obesity and MS in HR-PCa patients, suggesting a potential pathophysiologic interplay between obesity or MS and cancer progression.

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The impact of DNA methylation on the identification of recurrent prostate cancer

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.21086 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 21086-21086

Author(s):

J. J. Alumkal ◽

Z. Zhang ◽

E. B. Humphreys ◽

C. Bennett ◽

L. A. Mangold ◽

...

Keyword(s):

Prostate Cancer ◽

Dna Methylation ◽

Radical Prostatectomy ◽

Biochemical Recurrence ◽

Methylation Status ◽

Surgical Margin ◽

Multivariable Logistic Regression Analysis ◽

Tissue Samples ◽

Increased Risk ◽

The Impact

21086 Purpose: Biochemical (PSA) recurrence of prostate cancer following radical prostatectomy remains a major problem. Better biomarkers are needed to identify high and low-risk patients. DNA methylation of promoter regions leads to gene silencing in many cancers. In this study, we assessed the impact of changes in DNA methylation on biochemical recurrence in men with prostate cancer. Methods: We examined the methylation status of fifteen genes using MSP (Methylation Specific PCR) on tissue samples from 151 patients with clinically localized prostate cancer for whom at least five years of follow-up after prostatectomy was available. Results: In a multivariable logistic regression analysis, extra capsular penetration, high Gleason score, and involvement of the lymph nodes, seminal vesicles, or surgical margin were associated with an increased risk of recurrence. In addition, samples with methylation of 2 specific genes involved in cell-cell adhesion and apoptosis were associated with biochemical recurrence with an odds ratio of 5.64 (95% CI=1.47–21.7, p=0.012) compared to samples without methylation of both of these genes. The methylation status of these 2 genes had a higher sensitivity (72.3%; 95% CI=57–84.4%) for detecting recurrences than all the clinico-pathological variables (p<0.02) except extra-capsular penetration (p=0.346). The methylation status of these 2 genes had a similar negative predictive value (79.0%; 95% CI=66.8–88.3%) as the individual clinico-pathological variables examined. Conclusion: DNA Methylation of specific genes is independently associated with an increased risk of biochemical recurrence after radical prostatectomy even one considers the prognostic clinico-pathologic variables used in the clinic today. Our findings should be validated on another larger group of patients with prostate cancer who have undergone radical prosatetectomies. No significant financial relationships to disclose.

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Elevated Expression of Glycerol-3-Phosphate Phosphatase as a Biomarker of Poor Prognosis and Aggressive Prostate Cancer

Cancers ◽

10.3390/cancers13061273 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1273

Author(s):

Mohamed Amine Lounis ◽

Veronique Ouellet ◽

Benjamin Péant ◽

Christine Caron ◽

Zhenhong Li ◽

...

Keyword(s):

Prostate Cancer ◽

Bone Metastasis ◽

Biochemical Recurrence ◽

Poor Prognosis ◽

Cox Regression ◽

Specific Antigen ◽

Metabolic Stress ◽

Cancer Specific Survival ◽

High Risk Prostate Cancer ◽

Increased Risk

The limitations of the biomarker prostate-specific antigen (PSA) necessitate the pursuit of biomarkers capable of better identifying high-risk prostate cancer (PC) patients in order to improve their therapeutic management and outcomes. Aggressive prostate tumors characteristically exhibit high rates of glycolysis and lipogenesis. Glycerol 3-phosphate phosphatase (G3PP), also known as phosphoglycolate phosphatase (PGP), is a recently identified mammalian enzyme, shown to play a role in the regulation of glucose metabolism, lipogenesis, lipolysis, and cellular nutrient-excess detoxification. We hypothesized that G3PP may relieve metabolic stress in cancer cells and assessed the association of its expression with PC patient prognosis. Using immunohistochemical staining, we assessed the epithelial expression of G3PP in two different radical prostatectomy (RP) cohorts with a total of 1797 patients, for whom information on biochemical recurrence (BCR), metastasis, and mortality was available. The association between biomarker expression, biochemical recurrence (BCR), bone metastasis, and prostate cancer-specific survival was established using log-rank and multivariable Cox regression analyses. High expression of G3PP in PC epithelial cells is associated with an increased risk of BCR, bone metastasis, and PC-specific mortality. Multivariate analysis revealed high G3PP expression in tumors as an independent predictor of BCR and bone metastasis development. High G3PP expression in tumors from patients eligible for prostatectomies is a new and independent prognostic biomarker of poor prognosis and aggressive PC for recurrence, bone metastasis, and mortality.

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Impact of positive surgical margin on biochemical recurrence in localized prostate cancer

Prostate International ◽

10.1016/j.prnil.2020.12.004 ◽

2021 ◽

Author(s):

Wonchul Lee ◽

Bumjin Lim ◽

Yoon Soo Kyung ◽

Choung-Soo Kim

Keyword(s):

Prostate Cancer ◽

Biochemical Recurrence ◽

Surgical Margin ◽

Localized Prostate Cancer ◽

Positive Surgical Margin

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874 The impact of prostate weight and a nerve-sparing operation on the positive surgical margin rate in organ confined prostate cancer in patients undergoing a robotic assisted radical prostatectomy

European Urology Supplements ◽

10.1016/s1569-9056(12)60871-9 ◽

2012 ◽

Vol 11 (1) ◽

pp. e874-e874a

Author(s):

Z. Bütow ◽

C.H. Ohlmann ◽

J. Kamradt ◽

M.W.W. Janssen ◽

S. Siemer ◽

...

Keyword(s):

Prostate Cancer ◽

Radical Prostatectomy ◽

Surgical Margin ◽

Nerve Sparing ◽

Positive Surgical Margin ◽

Robotic Assisted ◽

Prostate Weight ◽

Robotic Assisted Radical Prostatectomy ◽

The Impact

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Increased Cytoplasmic CD138 Expression Is Associated with Aggressive Characteristics in Prostate Cancer and Is an Independent Predictor for Biochemical Recurrence

BioMed Research International ◽

10.1155/2020/5845374 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Simon Kind ◽

Martina Kluth ◽

Claudia Hube-Magg ◽

Katharina Möller ◽

Georgia Makrypidi-Fraune ◽

...

Keyword(s):

Prostate Cancer ◽

Biochemical Recurrence ◽

Independent Predictor ◽

Surgical Margin ◽

Tumor Stage ◽

Positive Surgical Margin ◽

Gleason Grade ◽

Basal Cells ◽

Antibody Drug Conjugate ◽

Normal Prostate

Syndecan-1 (CD138) is a transmembrane proteoglycan expressed in various normal and malignant tissues. It is of interest due to a possible prognostic effect in tumors and its role as a target for the antibody-drug conjugate indatuximab ravtansine. Here, we analyzed 17,747 prostate cancers by immunohistochemistry. Membranous and cytoplasmic CD138 staining was separately recorded. In normal prostate glands, CD138 staining was limited to basal cells. In cancers, membranous CD138 positivity was seen in 19.6% and cytoplasmic CD138 staining in 11.2% of 12,851 interpretable cases. A comparison with clinico-pathological features showed that cytoplasmic CD138 staining was more linked to unfavorable tumor features than membranous staining. Cytoplasmic CD138 immunostaining was associated with high tumor stage ( p < 0.0001 ), high Gleason grade ( p < 0.0001 ), nodal metastases ( p < 0.0001 ), positive surgical margin ( p < 0.0001 ), and biochemical recurrence ( p < 0.0001 ). This also holds true for both V-ets avian erythroblastosis virus E26 oncogene homolog (ERG) fusion positive and ERG fusion negative tumors although the cytoplasmic CD138 expression was markedly more frequent in ERG positive than in ERG negative tumors ( p < 0.0001 ). Comparison with 11 previously analyzed chromosomal deletions identified a conspicuous association between cytoplasmic CD138 expression and 8p deletions ( p < 0.0001 ) suggesting a possible functional interaction of CD138 with one or several 8p genes. Multivariate analysis revealed the cytoplasmic CD138 expression as an independent prognostic parameter in all cancers and in the ERG positive subgroup. In summary, our study indicates the cytoplasmic CD138 expression as a strong and independent predictor of poor prognosis in prostate cancer. Immunohistochemical measurement of CD138 protein may thus—perhaps in combination with other parameters—become clinically useful in the future.

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