Development of diabetes mellitus following hormone therapy in prostate cancer patients is associated with early progression to castration resistance

AbstractTo identify risk factors for the prognosis of prostate cancer (PC), we retrospectively analyzed the impact of lifestyle-related disorders as well as PC characteristics at initial diagnosis on the progression to castration-resistant PC (CRPC) in PC patients undergoing hormone therapy. Of 648 PC patients, 230 who underwent hormone therapy and met inclusion criteria were enrolled in this study. CRPC developed in 48 patients (20.9%). Univariate analysis using Cox proportional hazard model indicated that newly developed diabetes mellitus (DM) following hormone therapy (postDM), but not preexisting DM, as well as PC characteristics at initial diagnosis including prostate-specific antigen (PSA) ≥ 18 were significantly associated with the progression to CRPC. A similar tendency was also observed in the relationship between newly developed hypertension following hormone therapy and CRPC progression. On the other hand, neither dyslipidemia nor hyperuricemia, regardless the onset timing, exhibited any association with CRPC progression. In multivariate analysis, postDM and PSA ≥ 18 were extracted as independent risk factors for CRPC progression (adjusted hazard ratios, 3.38 and 2.34; p values, 0.016 and 0.019, respectively). Kaplan–Meier analysis and log-rank test clearly indicated earlier progression to CRPC in PC patients who developed postDM or had relatively advanced initial PC characteristics including PSA ≥ 18. Together, the development of lifestyle-related disorders, particularly DM, following hormone therapy, as well as advanced PC characteristics at initial diagnosis is considered to predict earlier progression to CRPC and poor prognosis in PC patients undergoing hormone therapy.

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Single nucleotide polymorphisms (SNPs) as predictors of efficacy of cabazitaxel in patients with metastatic castration-resistant prostate cancer (mCRPC).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e17582 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e17582-e17582

Author(s):

Daniel Herrero Rivera ◽

Ignacio Duran ◽

Laura Marcos Kovandzic ◽

Javier Puente ◽

Begona Mellado ◽

...

Keyword(s):

Prostate Cancer ◽

Overall Survival ◽

Gleason Score ◽

Univariate Analysis ◽

Progression Free Survival ◽

Rank Test ◽

Genetic Constitution ◽

Castration Resistant Prostate Cancer ◽

Free Survival ◽

The Impact

e17582 Background: Cabazitaxel is a semi-synthetic derivative of a natural taxoid approved for the treatment of mCRPC patients (pts) after failure to docetaxel. Despite its proven efficacy, there is variability in the response, progression-free survival (PFS) and overall survival (OS) of pts. Changes in the genetic constitution of the individual such as the SNPs could explain this variability. The aim of this study was to evaluate the impact of certain SNPs in cabazitaxel activity. Methods: Clinical data from 67 mCRPC pts treated with cabazitaxel between March 2011 and October 2016 were collected. DNA was isolated from formalin fixed paraffin-embedded tumor samples. 56 SNPs in 5 genes related with metabolism and/or mechanism of action of cabazitaxel (CYP3A4, CYP3A5, ABCB1, TUBB1, CYP2C8) were chosen based on their Minor Allele Frequency, linkage disequilibrium and information from dbSNP and analyzed by TaqMan OpenArray (Lifetech). The presence/absence of mutant alleles of the selected SNPs was correlated with clinical features, progression free survival (PFS) and overall survival (OS) of prostate cancer. Chi-square test and Kaplan-Meier with log-rank test were used for statistical analyses. Results: The median age was 61 years (range 44-82). 56.7% (n = 38) had a Gleason score ≥8 and 94% had received docetaxel in first line. Type of response to cabazitaxel was associated with median OS (Partial response = 24.35 months, Stable disease = 11.16 months, Progression disease = 5.8 months; p= 0.045). Univariate analysis, showed worsed OS at 1 year for wild type status of SNP rs151352 (OR = 4, 95%CI 1.27-12.58, p= 0.029). In addition, two SNPs (rs11773597, rs1202186) were associated with radiological response to cabazitaxel ( p= 0.031 and p= 0.030 respectively). Other 7 SNPs (rs11773597, rs2235040, rs1045642, rs1419745, rs1202170, rs6949448, rs11572093) were associated ( p<0.05) with Gleason score, pain, PSA doubling time, febrile neutropenia and asthenia. Conclusions: A particular SNP profile could be predictive of efficacy and related with toxicity in mCRPC population treated with cabazitaxel after progression to docetaxel. These outcomes become particularly relevant in patient selection given the recent results of the CARD trial.

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The Impact of Pathologic Upgrading of Gleason Score 7 Prostate Cancer on the Risk of the Biochemical Recurrence after Radical Prostatectomy

BioMed Research International ◽

10.1155/2018/4510149 ◽

2018 ◽

Vol 2018 ◽

pp. 1-6 ◽

Cited By ~ 1

Author(s):

Juhyun Park ◽

Sangjun Yoo ◽

Min Chul Cho ◽

Min Hyun Cho ◽

Chang Wook Jeong ◽

...

Keyword(s):

Prostate Cancer ◽

Gleason Score ◽

Biochemical Recurrence ◽

Specific Antigen ◽

Surgical Margin ◽

Rank Test ◽

Kaplan Meier ◽

Significant Difference ◽

The Mean ◽

The Impact

Objective. To investigate the impact of pathologic upgrading of Gleason score (GS) 7 prostate cancer on the risk of the biochemical recurrence. Materials and Methods. A total of 1678 patients with postoperative GS 7 prostate cancer without lymph node metastasis were reviewed retrospectively. The patients were categorized into four groups depending on pathologic upgrading: upgraded GS 3+4, nonupgraded GS 3+4, upgraded GS 4+3, and nonupgraded GS 4+3. Kaplan-Meier multivariate model was created. Results. The mean age was significantly higher in the nonupgraded GS 4+3 group than in other groups, whereas the mean prostate-specific antigen (PSA) level was lower in the upgraded GS 3+4 group. Pathologic findings, such as extracapsular extension, seminal vesical invasion, and the surgical margin rate, were different from each other. Five-year biochemical recurrence-free survival rate was 85%, 73%, 69%, and 60% in upgraded GS 3+4, nonupgraded GS 3+4, upgraded GS 4+3, and nonupgraded GS 4+3 group, respectively. There was significant difference between the nonupgraded 4+3 and upgraded 4+3 group, as well as between upgraded 3+4 and nonupgraded 3+4 group. However, the two middle patient groups, that is, the nonupgraded GS 3+4 group and the upgraded GS 4+3 group, did not show the statistical difference (Log-rank test, p value = 0.259). Conclusion. The information on pathologic upgrading in the biopsy reports of patients could help to provide more detailed analysis for the biochemical recurrence of GS 7 prostate cancer.

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Platelet microparticles (PMP): A predictive factor of overall survival in hormone-refractory prostate cancer (HRPC) patients treated by chemotherapy

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.4639 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 4639-4639

Author(s):

A. Banu ◽

D. Helley ◽

E. Banu ◽

A. M. Fischer ◽

F. Scotte ◽

...

Keyword(s):

Overall Survival ◽

Growth Factor ◽

Predictive Factor ◽

Cancer Metastasis ◽

Cox Regression ◽

Univariate Analysis ◽

Specific Antigen ◽

Rank Test ◽

Interaction Term ◽

The Impact

4639 Background: Several studies suggest a causal relationship between platelets activation and cancer metastasis. Activated platelets release PMP, VEGF (vascular endothelial growth factor) and bFGF (basic fibroblast growth factor) which could play a role in patient outcome. Methods: Eligible chemonaive HRPC patients (pts) were required to have: ECOG performance status (PS) ≤2, progressive disease after antiandrogen withdrawal. Before chemotherapy, we quantified PMP in whole blood by flow cytometry using an anti-CD41 monoclonal antibody and plasmatic VEGF and bFGF by ELISA. As primary endpoint, we prospectively evaluated the impact of PMP on overall survival (OS) by Cox regression and log-rank test. Secondary, we studied the correlation between PMP and platelets, and their relationship with OS, incorporating an interaction term in the modelling (PMP and platelets). Results: Between July 2001 and April 2004, thirty-eight HRPC pts were treated by chemotherapy [docetaxel (92%), mitoxantrone (8%)] in our center. Median age was 69 years, with median values of hemoglobin 125 g/L, baseline prostate-specific antigen (PSA) 37.7 ng/mL, PMP 6 867 per μL, VEGF 18.1 pg/mL and bFGF 2.8 pg/mL. Significant correlations were observed between PMP and ECOG PS, hormone-sensitivity duration, Gleason and platelets. Median OS was significantly lower in pts with high PMP values (>6 788 per μL), compared to low PMP pts: 16.7 months (95% CI, 5.1–28.2) vs 25.2 months (95% CI, 20.2–30.3), P = 0.025, log-rank. Univariate analysis by Cox regression showed a significant relationship between OS and PMP level [HR = 0.41 (95% CI, 0.19–0.92), P = 0.04]. PMP kept their significance after adjusting by multivariate analysis for baseline hemoglobin, number of metastatic sites, and PSA doubling-time [HR = 0.37 (95% CI, 0.16–0.87), P = 0.02)]. An interaction term (PMP and platelets) was also predictive on OS (P = 0.01). Conclusions: PMP and their interaction with platelets were a predictive factor of OS in HRPC pts. Our analysis showed that the dynamic interaction between PMP and platelets has a major impact on outcome of HRPC pts. No significant financial relationships to disclose.

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Prognostic role of docetaxel-induced reduction of free testosterone serum levels in metastatic prostate cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.6_suppl.144 ◽

2021 ◽

Vol 39 (6_suppl) ◽

pp. 144-144

Author(s):

Paula Kappler ◽

Stefan Brunotte ◽

Philipp Ivanyi ◽

Michael A. Morgan ◽

Christoph W. Reuter

Keyword(s):

Prostate Cancer ◽

Risk Factors ◽

Cox Regression ◽

Specific Antigen ◽

Serum Levels ◽

Prognostic Role ◽

Cycle Number ◽

Prognostic Risk Factors ◽

The Impact

144 Background: We have recently demonstrated that a salvage therapy with carboplatin plus weekly docetaxel is effective in docetaxel-refractory prostate cancer (PC) and interferes with testosterone biosynthesis (Reuter et al.; Oncol Res & Treat. 2018, 41 (suppl.1): p.10). In this study, the impact of docetaxel monotherapy on free and total testosterone serum levels (fT, TT) and the prognostic role of fT and TT were analyzed in mPC patients. Methods: 62 consecutive mPC patients were treated with at least two cycles of docetaxel (75 mg/m2 q3w; 50 mg/m2 q2w, or 35 mg/m2 q1w) until disease progression, occurrence of intolerable adverse effects or completion of the planned cycle number. Efficacy measures were done following PCWG2 recommendations. FT and TT were measured before and during chemotherapy. Results: At the current analysis (August 31, 2020), the median follow-up time was 21.2 months. Response of prostate-specific antigen (PSAR; ≥50% PSA reduction) was observed in 42/62 (67.7%) and 12/36 (33.3%) patients with measurable disease exhibited a partial remission (PR). Median progression-free survival (PFS) for all patients was 8.1 months (CI 95% 3.6, 12.5) and median overall survival (OS) was 25.7 months (CI 95% 19.4, 32.1). The most common reversible grade 3/4 toxicity was leukopenia/neutropenia (29/33.9%). Median fT and TT serum levels were reduced below the detection limit during docetaxel treatment (fT: from 0.34 pg/mL to < 0.01 pg/mL and TT: from 0.12 to < 0.05 ng/mL, respectively). Multivariate Cox regression analyses identified PSAR > 50%, fT reduction of 100% and number of organs involved as independent prognostic risk factors for PFS. Furthermore, fT reduction of 100% and FT nadir values < 0.01 pg/mL were independent prognostic risk factors for OS (p < 0.05). Conclusions: These data demonstrate that fT is an important prognostic factor for PFS and OS in mPC patients.

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The Impact of Neoadjuvant Hormone Therapy on Surgical and Oncological Outcomes for Patients With Prostate Cancer Before Radical Prostatectomy: A Systematic Review and Meta-Analysis

Frontiers in Oncology ◽

10.3389/fonc.2020.615801 ◽

2021 ◽

Vol 10 ◽

Author(s):

Lijin Zhang ◽

Hu Zhao ◽

Bin Wu ◽

Zhenlei Zha ◽

Jun Yuan ◽

...

Keyword(s):

Prostate Cancer ◽

Radical Prostatectomy ◽

Hormone Therapy ◽

Meta Analysis ◽

Specific Antigen ◽

Operation Time ◽

Tumor Stage ◽

Oncological Outcomes ◽

Estimated Blood Loss ◽

The Impact

ObjectiveThis systematic study aimed to assess and compare the comprehensive evidence regarding the impact of neoadjuvant hormone therapy (NHT) on surgical and oncological outcomes of patients with prostate cancer (PCa) before radical prostatectomy (RP).MethodsLiterature searches were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Using PubMed, Web of Science, Chinese National Knowledge Infrastructure, and Wanfang databases, we identified relevant studies published before July 2020. The pooled effect sizes were calculated in terms of the odds ratios (ORs)/standard mean differences (SMDs) with 95% confidence intervals (CIs) using the fixed or random-effects model.ResultsWe identified 22 clinical trials (6 randomized and 16 cohort) including 20,199 patients with PCa. Our meta-analysis showed no significant differences in body mass index (SMD = 0.10, 95% CI: −0.08–0.29, p = 0.274) and biopsy Gleason score (GS) (OR = 1.33, 95% CI: 0.76–2.35 p = 0.321) between the two groups. However, the NHT group had a higher mean age (SMD = 0.19, 95% CI: 0.07–0.31, p = 0.001), preoperative prostate-specific antigen (OR = 0.47, 95% CI: 0.19–0.75, p = 0.001), and clinic tumor stage (OR = 2.24, 95% CI: 1.53–3.29, p < 0.001). Compared to the RP group, the NHT group had lower positive surgical margins (PSMs) rate (OR = 0.44, 95% CI: 0.29–0.67, p < 0.001) and biochemical recurrence (BCR) rate (OR = 0.47, 95% CI: 0.26–0.83, p = 0.009). Between both groups, there were no significant differences in estimated blood loss (SMD = −0.06, 95% CI: −0.24–0.13, p = 0.556), operation time (SMD = 0.20, 95% CI: −0.12–0.51, p = 0.219), pathological tumor stage (OR = 0.76, 95% CI: 0.54–1.06, p = 0.104), specimen GS (OR = 0.91, 95% CI: 0.49–1.68, p = 0.756), and lymph node involvement (OR = 0.76, 95% CI: 0.40–1.45, p = 0.404).ConclusionsNHT prior to RP appeared to reduce the tumor stage, PSMs rate, and risk of BCR in patients with PCa. According to our data, NHT may be more suitable for older patients with higher tumor stage. Besides, NHT may not increase the surgical difficulty of RP.

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Prostate Cancer

10.1093/oso/9780190676827.003.0020 ◽

2018 ◽

Author(s):

Kathryn M. Wilson ◽

Lorelei Mucci

Keyword(s):

Prostate Cancer ◽

Risk Factors ◽

Family History ◽

Prostate Specific Antigen ◽

Advanced Prostate Cancer ◽

Advanced Disease ◽

African Ancestry ◽

Specific Antigen ◽

Dietary Factors ◽

Increased Risk

Prostate cancer is among the most commonly diagnosed cancers among men, ranking second in cancer globally and first in Western countries. There are marked variations in incidence globally, and its incidence must be interpreted in the context of diagnostic intensity and screening. The uptake of prostate-specific antigen screening since the 1990s has led to dramatic increases in incidence in many countries, resulting in an increased proportion of indolent cancers that would never have come to light clinically in the absence of screening. Risk factors differ when studying prostate cancer overall versus advanced disease. Older age, African ancestry, and family history are established risk factors for prostate cancer. Obesity and smoking are not associated with risk overall, but are associated with increased risk of advanced prostate cancer. Several additional lifestyle factors, medications, and dietary factors are now emerging as risk factors for advanced disease.

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Prognostic role of docetaxel-induced suppression of free testosterone serum levels in metastatic prostate cancer patients

Scientific Reports ◽

10.1038/s41598-021-95874-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Paula Kappler ◽

Michael A. Morgan ◽

Philipp Ivanyi ◽

Stefan J. Brunotte ◽

Arnold Ganser ◽

...

Keyword(s):

Prostate Cancer ◽

Metastatic Prostate Cancer ◽

Cox Regression ◽

Specific Antigen ◽

Progression Free Survival ◽

Serum Levels ◽

Biologically Active ◽

Free Form ◽

Total Testosterone ◽

The Impact

AbstractTo date, only few data concerning the biologically active, free form of testosterone (FT) are available in metastatic prostate cancer (mPC) and the impact of FT on disease, therapy and outcome is largely unknown. We retrospectively studied the effect of docetaxel on FT and total testosterone (TT) serum levels in 67 mPC patients monitored between April 2008 and November 2020. FT and TT levels were measured before and weekly during therapy. The primary endpoint was overall survival (OS). Secondary endpoints were prostate-specific antigen response and radiographic response (PSAR, RR), progression-free survival (PFS), FT/TT levels and safety. Median FT and TT serum levels were completely suppressed to below the detection limit during docetaxel treatment (FT: from 0.32 to < 0.18 pg/mL and TT: from 0.12 to < 0.05 ng/mL, respectively). Multivariate Cox regression analyses identified requirement of non-narcotics, PSAR, complete FT suppression and FT nadir values < 0.18 pg/mL as independent parameters for PFS. Prior androgen-receptor targeted therapy (ART), soft tissue metastasis and complete FT suppression were independent prognostic factors for OS. FT was not predictive for treatment outcome in mPC patients with a history of ART.

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Major post-prostate biopsy complications under antibiotic augmentation prophylaxis protocol

Journal of Clinical Urology ◽

10.1177/2051415820984037 ◽

2021 ◽

pp. 205141582098403

Author(s):

Antônio Antunes Rodrigues ◽

Valdair Muglia ◽

Emanuel Veras de Albuquerque ◽

Rafael Ribeiro Mori ◽

Rafael Neuppmann Feres ◽

...

Keyword(s):

Risk Factors ◽

Body Mass Index ◽

Antibiotic Prophylaxis ◽

Body Mass ◽

Bacterial Resistance ◽

Univariate Analysis ◽

Specific Antigen ◽

Outlet Obstruction ◽

Psa Density ◽

Biopsy Complications

Objective: To identify risk factors for major post-biopsy complications under augmented prophylaxis protocol. The risk factors already described mainly comprise outdated antibiotic prophylaxis protocols. Material and methods: This retrospective cohort study included patients that underwent transrectal ultrasound-guided biopsies, from 2011 to 2016. All patients had received antibiotic prophylaxis with ciprofloxacin and gentamicin. Patients were grouped according to the presence or absence of post-biopsy complications. Demographic variables and possible risk factors based on routine clinical assessment were registered. Correlation tests, univariate and multivariate analyses were used to identify risk factors for post-biopsy complications. Results: Of the 404 patients that were included, 25 (6.2%) presented 27 post-biopsy complications, distributed as follows: acute urinary retention ( n = 14, 3.5%), infections ( n = 11, 2.7%) and hemorrhage ( n = 2, 0.5%). On univariate analysis, patients who presented complications showed higher body mass index and post-voiding residual volumes. Multivariate analysis identified ethnicity and prostate-specific antigen (PSA) density as possible risk factors for biopsy complications. The presence of bacterial resistance identified by rectal swabs did not correlate with the incidence of complications and infections. Conclusions: Non-infectious post-biopsy complications were more frequent than infectious ones in this cohort. Higher post-voiding residual volumes and PSA density, that indicates prostate enlargement, were identified as risk factors and interpreted as secondary to bladder outlet obstruction. The higher body mass index and ethnicity were also identified as risk factors and attributed to the heterogeneity of the patients included. Level of evidence: Not applicable for this multicentre audit.

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Risk Factor Analysis for Infection after Medial Open Wedge High Tibial Osteotomy

Journal of Clinical Medicine ◽

10.3390/jcm10081727 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1727

Author(s):

Ta-Wei Liu ◽

Chih-Hao Chiu ◽

Alvin Chao-Yu Chen ◽

Shih-Sheng Chang ◽

Yi-Sheng Chan

Keyword(s):

Diabetes Mellitus ◽

Risk Factors ◽

Multivariate Analysis ◽

High Tibial Osteotomy ◽

Univariate Analysis ◽

Arthroscopic Surgery ◽

Underlying Disease ◽

Tibial Osteotomy ◽

Open Wedge ◽

Wedge High Tibial Osteotomy

Background: Medial open wedge high tibial osteotomy (MOWHTO) is a well-established treatment for osteoarthritis of the medial tibiofemoral compartment. Surgical site infection (SSI) after MOWHTO is a devastating complication that may require further surgery. In this study, we aimed to identify the risk factors for infection after MOWHTO over 1 to 4 years of follow-up. Methods: Fifty-nine patients who underwent MOWHTO combined with knee arthroscopic surgery were included in this prospective study. Artificial bone grafts were used in all cases. Possible risk factors, including sex, age, body mass index (BMI), underlying disease, hospitalization length, correction angle, and surgery time, were recorded. Both univariate and multivariate analysis were used. Results: A total of 59 patients who underwent 61 operations were included. Eleven patients (18.0%) were reported to have SSI. Univariate analysis showed that smoking and diabetes mellitus were positively associated with SSI. Multivariate analysis showed that smoking and age were positively associated with SSI. Three patients (4.9%) were reported to suffer from deep SSI, requiring surgical debridement, all of whom were male smokers. Conclusion: Smoking, diabetes mellitus, and old age were identified to be possible risk factors of SSI after MOWHTO. These findings are common risk factors of SSI after orthopedic surgery according to the literature. Patient selection should be performed cautiously, and postoperative prognosis for MOWHTO should be carefully explained to patients who smoke.

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