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

Cancers ◽  
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.

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

2020 ◽  
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 ◽  
Cancer Specific Survival ◽  
Aggressive Prostate Cancer ◽  
High Risk Prostate Cancer ◽  
Increased Risk

Abstract BackgroundThe 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 outcome. 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 an important role in the regulation of glucose metabolism, lipogenesis, lipolysis and cellular nutrient excess detoxification. We hypothesized that G3PP is involved in cancer cell growth and assessed the association of its expression with PC patient prognosis. MethodsUsing immunohistochemical staining we assessed the epithelial expression of G3PP in two different radical prostatectomy cohorts with a total of 1797 patients, for whom information on biochemical recurrence (BCR), metastasis and mortality is available. Association between biomarker expression, biochemical recurrence (BCR), bone metastasis and prostate cancer specific survival was established using log-rank and multivariable Cox regression analyses.ResultsHigh expression of G3PP prostate cancer epithelial cells is associated with an increased risk of BCR, bone metastasis and prostate cancer specific mortality. Multivariate analysis revealed high G3PP expression in tumors as an independent predictor of BCR and bone metastasis development. ConclusionsHigh G3PP expression in tumor from patients eligible for prostatectomies is a new and independent prognostic biomarker of poor prognosis and aggressive prostate cancer specifically for recurrence, bone metastasis and mortality.

Oncological outcomes of surgery in very high risk pT3b prostate cancer

2011 ◽  
Vol 18 (3) ◽  
pp. 113-119
Author(s):  
Daimantas MILONAS ◽  
Giedrė SMAILYTĖ ◽  
Darius TRUMBECKAS ◽  
Mindaugas JIEVALTAS
Keyword(s):  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Gleason Score ◽  
Cox Regression ◽  
Locally Advanced ◽  
Specific Antigen ◽  
Oncologic Outcomes ◽  
Cancer Specific Survival ◽  
Risk Of Death ◽  
Surgery Outcome

Background. The aim of the study was to present the oncologic outcomes and to determine the prognostic factors of overall (OS) and cancer-specific survival (CSS) as well as disease-progression-free survival (DPFS) after surgery for pT3b prostate cancer. Materials and methods. In 2002–2007, a pT3b stage after radical prostatectomy was detected in 56 patients. Patients were divided into groups according to the prostate-specific antigen (PSA) level (20 ng/ml), lymph nodes status (N0 vs. Nx vs. N1) and the Gleason score (6–7 vs. 8–10). The Kaplan–Meier analysis was used to calculate OS, CSS and DPFS. The Cox regression was used to identify the predictive factors of survival. Results. Five-year OS, CSS and DPFS rates were 75.1%, 79.6% and 79.3%, respectively. The survival was significantly different when comparing the Gleason 6–7 and 8–10 groups. The 5-year OS, CSS and DPFS were 91.2% vs. 48.6%, 97.1% vs. 51.1% and 93.8 vs. 51.1%, respectively. There was no difference in survival among the groups with a different PSA level. The OS and CSS but not DPFS were significantly different when comparing the N0 and N1 groups. The 5-year OS and CSS was 84.4% vs. 37.5% and 87.3% vs. 47.6%, respectively. The specimen Gleason score was a significant predictor of OS and CSS. The risk of death increased up to 4-fold when a Gleason score 8–10 was present at the final pathology. Conclusions. Radical prostatectomy may offer acceptable CSS, DPFS and OS rates in pT3b PCa. However, outcomes in patients with N1 and specimen Gleason ≥8 were significantly worse, suggesting the need of multimodality treatment in such cases. Keywords: prostate cancer, locally advanced, surgery, outcome

Role of Salvage Radical Prostatectomy for Recurrent Prostate Cancer After Radiation Therapy

2005 ◽  
Vol 23 (32) ◽  
pp. 8198-8203 ◽  
Author(s):  
Andrew J. Stephenson ◽  
James A. Eastham
Keyword(s):  
Prostate Cancer ◽  
Radiation Therapy ◽  
Radical Prostatectomy ◽  
Local Recurrence ◽  
Salvage Therapy ◽  
Biochemical Recurrence ◽  
Specific Antigen ◽  
Cancer Control ◽  
Increased Risk ◽  
Salvage Radical Prostatectomy

Patients with isolated local recurrence of prostate cancer after radiation therapy may potentially be cured of their disease by salvage radical prostatectomy (RP). The stage-specific 5-year cancer-control rates of salvage RP resemble those of standard RP. However, the ability to effectively administer salvage treatment to patients with radiorecurrent disease is compromised by the lack of diagnostic tests with sufficient sensitivity and specificity to detect local recurrence at an early stage while it is amenable to local salvage therapy. By the time biochemical recurrence is declared using the current American Society for Therapeutic Radiology and Oncology definition, the majority of patients have advanced local disease, precluding successful local salvage therapy. When salvage RP is performed at prostate-specific antigen levels of 10 ng/mL or less, an estimated 70% of patients are free of disease at 5 years. With better patient selection and technical modifications, the morbidity associated with salvage RP has improved substantially. Rates of urinary incontinence and anastomotic stricture are acceptable, although one third of patients will experience these complications. Salvage cryotherapy is a minimally invasive alternative to salvage RP, but cancer-control rates appear to be inferior and it does not provide a clear advantage over salvage RP in terms of reduced morbidity. Patients with local recurrence after radiation therapy are at increased risk of metastatic progression and cancer-specific mortality. Currently, salvage RP represents the only curative treatment option for these patients. Salvage RP may favorably alter the natural history of biochemical recurrence after radiation therapy, but it must be instituted early in the course of recurrent disease to be effective.

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

2019 ◽  
Author(s):  
Arnas Bakavicius ◽  
Mingaile Drevinskaite ◽  
Kristina Daniunaite ◽  
Marija Barisiene ◽  
Sonata Jarmalaite ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Biochemical Recurrence ◽  
Surgical Margin ◽  
Positive Surgical Margin ◽  
Cancer Specific Survival ◽  
Increased Risk ◽  
Definitive Therapy ◽  
Treatment Naïve ◽  
The Impact ◽  
Mean Time

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.

Gleason grade grouping of prostate cancer is of prognostic value in Asian men

2017 ◽  
Vol 70 (9) ◽  
pp. 745-753 ◽  
Author(s):  
Joe Yeong ◽  
Rehena Sultana ◽  
Jonathan Teo ◽  
Hong Hong Huang ◽  
John Yuen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Biochemical Recurrence ◽  
Specific Antigen ◽  
Disease Free Survival ◽  
Gleason Grade ◽  
Kaplan Meier ◽  
Increased Risk ◽  
Asian Men ◽  
Initial Biopsy ◽  
Mixed Ethnicity

AimThe International Society of Urological Pathology made recommendations for the use of Grade Groups (GG) originally described by Epstein and colleagues over Gleason score (GS) alone in 2014, which was subsequently adopted by the WHO classification in 2016. The majority of studies validating this revision have been in Caucasian populations. We therefore asked whether the new GG system was retrospectively associated with biochemical disease-free survival in a mixed-ethnicity cohort of Asian men.MethodsA total of 680 radical prostatectomies (RPs) from 2005 to 2014 were included. GS from initial biopsy and RP were compared and used to allocate cases to GG, defined as: 1 (GS≤6); 2 (GS 3+4=7); 3 (GS 4+3=7); 4 (GS 4+4=8/5+3=8/3+5=8) and 5 (GS 9–10). Biochemical recurrence was defined as two consecutive post-RP prostate-specific antigen (PSA) levels of >0.2 ng/mL after post-RP PSA reaching the nadir of <0.1 ng/mL.ResultsOur data showed that Kaplan–Meier analysis revealed significant differences in biochemical recurrence within Gleason GG based on either biopsy or prostatectomy scoring. Multivariate analysis further confirmed that a higher GG was significantly associated with risk of biochemical recurrence. This GG system had a higher prognostic discrimination for both initial biopsy and RP than GS.ConclusionsOur study validates the use of the revised and updated GG system in a mixed-ethnicity population of Asian men. Higher GG was significantly associated with increased risk of biochemical recurrence. We therefore recommend its use to inform clinical management for patients with prostate cancer.

Risk of Prostate Cancer Recurrence in Men Treated With Radiation Alone or in Conjunction With Combined or Less Than Combined Androgen Suppression Therapy

2008 ◽  
Vol 26 (18) ◽  
pp. 2979-2983 ◽  
Author(s):  
Anthony V. D'Amico ◽  
Ming-Hui Chen ◽  
Andrew A. Renshaw ◽  
Brittany Loffredo ◽  
Philip W. Kantoff
Keyword(s):  
Prostate Cancer ◽  
Prognostic Factors ◽  
Cox Regression ◽  
Specific Antigen ◽  
Liver Function Tests ◽  
Recurrence Risk ◽  
Risk Of Recurrence ◽  
Increased Risk ◽  
Psa Recurrence ◽  
Androgen Suppression

PurposeWe determined the risk of recurrence in men enrolled on a randomized trial for prostate cancer who were treated with radiation therapy (RT) alone or in conjunction with combined or less than combined androgen suppression therapy (AST).Patients and MethodsBetween 1995 and 2001, 206 men with localized but unfavorable-risk adenocarcinoma of the prostate were randomly assigned to receive RT or RT and AST, which was defined as 6 months of both a luteinizing hormone-releasing hormone agonist and an antiandrogen. A post–random assignment hypothesis that was generated by multivariable Cox regression analyses was used to evaluate whether the risk of prostate-specific antigen (PSA) recurrence was significantly associated with months of antiandrogen use; regression analysis adjusted for known prognostic factors, comorbidity score, and medications that can elevate liver function tests sufficiently to necessitate discontinuation of the antiandrogen.ResultsAfter a median follow-up of 8.2 years (interquartile range,7.0 to 9.5 years), 81 men sustained PSA recurrence. An increasing PSA level (P < .001); Gleason score of 8, 9, or 10 (P < .001); and clinical category T2 disease (P = .005) were significantly associated with an increased risk of recurrence. However, recurrence risk was significantly decreased (adjusted hazard ratio, 0.81; 95% CI, 0.72 to 0.92; P = .001) with each additional month of antiandrogen use after analysis was adjusted for these known prognostic factors.ConclusionMen with localized but unfavorable-risk prostate cancer who were treated with RT and 6 months of planned combined AST appear to have an increased risk of recurrence when treated with less than as compared with 6 months of the antiandrogen.

scholarly journals Natural History of Untreated Prostate Specific Antigen Radiorecurrent Prostate Cancer in Men with Favorable Prognostic Indicators

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Neil E. Martin ◽  
Ming-Hui Chen ◽  
Clair J. Beard ◽  
Paul L. Nguyen ◽  
Marian J. Loffredo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Doubling Time ◽  
Cox Regression ◽  
Specific Antigen ◽  
Risk Of Death ◽  
Psa Doubling Time ◽  
Increased Risk ◽  
Psa Failure ◽  
Post Radiation

Background and Purpose. Life expectancy data could identify men with favorable post-radiation prostate-specific antigen (PSA) failure kinetics unlikely to require androgen deprivation therapy (ADT).Materials and Methods. Of 206 men with unfavorable-risk prostate cancer in a randomized trial of radiation versus radiation and ADT, 53 experienced a PSA failure and were followed without salvage ADT. Comorbidity, age and established prognostic factors were assessed for relationship to death using Cox regression analyses.Results. The median age at failure, interval to PSA failure, and PSA doubling time were 76.6 years (interquartile range [IQR]: 71.8–79.3), 49.1 months (IQR: 37.7–87.4), and 25 months (IQR: 13.1–42.8), respectively. After a median follow up of 4.0 years following PSA failure, 45% of men had died, none from prostate cancer and no one had developed metastases. Both increasing age at PSA failure (HR: 1.14; 95% CI: 1.03–1.25;P=0.008) and the presence of moderate to severe comorbidity (HR: 12.5; 95% CI: 3.81–41.0;P<0.001) were significantly associated with an increased risk of death.Conclusions. Men over the age of 76 with significant comorbidity and a PSA doubling time >2 years following post-radiation PSA failure appear to be good candidates for observation without ADT intervention.

scholarly journals Prognostic Impact of Different Gleason Patterns on Biopsy Within Grade Group 4 Prostate Cancer

2021 ◽  
Author(s):  
Keiichiro Mori ◽  
Vidit Sharma ◽  
Eva M. Comperat ◽  
Shun Sato ◽  
Ekaterina Laukhtina ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cox Regression ◽  
Multivariable Analysis ◽  
Rank Test ◽  
Prognostic Impact ◽  
Grade Group ◽  
Cancer Specific Survival ◽  
Kaplan Meier ◽  
Pathologic Features ◽  
Increased Risk

Abstract Background Grade group (GG) 4 prostate cancer (PC) is considered a single entity; however, there are questions regarding prognostic heterogeneity. This study assessed the prognostic differences among various Gleason scores (GSs) classified as GG 4 PC on biopsy before radical prostatectomy (RP). Methods We conducted a multicenter retrospective study, and a total of 1791 patients (GS 3 + 5: 190; GS 4 + 4: 1557; and GS 5 + 3: 44) with biopsy GG 4 were included for analysis. Biochemical recurrence (BCR)-free survival, cancer-specific survival, and overall survival were analyzed using the Kaplan–Meier method and the log-rank test. Logistic regression analysis was performed to identify factors associated with high-risk surgical pathologic features. Cox regression models were used to analyze time-dependent oncologic endpoints. Results Over a median follow-up of 75 months, 750 patients (41.9%) experienced BCR, 146 (8.2%) died of any causes, and 57 (3.2%) died of PC. Biopsy GS 5 + 3 was associated with significantly higher rates of GS upgrading in RP specimens than GS 3 + 5 and GS 4 + 4. On multivariable analysis adjusted for clinicopathologic features, different GSs within GG 4 were significantly associated with BCR (p = 0.03) but not PC-specific or all-cause mortality. Study limitations include the lack of central pathological specimen evaluation. Conclusions Patients with GG 4 at biopsy exhibited some limited biological and clinical heterogeneity. Specifically, GS 5 + 3 had an increased risk of GS upgrading. This can help individualize patients’ counseling and encourage further study to refine biopsy specimen-based GG classification.

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

Medicina ◽  
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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