Negative impact of neoadjuvant hormonal therapy on detecting biochemical recurrence after radical prostatectomy
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ABSTRACT: Background
Routine use of neoadjuvant hormonal therapy (NHT) before radical prostatectomy (RP) is not recommended, but it is sometimes performed to reduce the prostate size and tumor volume or to prevent tumor progression during the wait times for surgery in clinical practice. On the other hand, the impact of NHT on the pattern of biochemical recurrence (BCR) is unknown. Methods
We retrospectively examined 1749 consecutive patients who underwent RP between 1996 and 2017. Among the patients who met the inclusion criteria, BCR developed in 240 of non-NHT patients and in 120 of NHT patients during the mean follow-up period of 6.9 years. We examined the impact of NHT on the PSA-doubling time (DT) following BCR at different times after RP. Results
The median PSA-DTs in non-NHT patients who experienced BCR in the first year after surgery, between 1 and 2 years, between 2 and 3 years, between 3 and 4 years, between 4 and 5 years, and at > 5 years were 5.5, 8.8, 11.3, 17.7, 18.2, and 18.4 months, respectively. On the other hand, those in NHT patients were 1.4, 4.1, 9.1, 13.4, 27.2, and 19.3 months, respectively. The differences of PSA-DTs in the first year after surgery (p < 0.001) and between 1 and 2 years (p = 0.005) were significant between non-NHT and NHT patients. Conclusion
Patients who received NHT had a higher risk of a rapid PSA increase when they experienced BCR, especially within 2 years after RP. In order to not miss the optimal timing of salvage treatment for BCR, intensive PSA follow-up is necessary. Supplementary Information
The online version contains supplementary material available at 10.1007/s10147-021-01942-8.
SUBMITTER: Matsumoto K
PROVIDER: S-EPMC8175233 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The objective of this study was to utilize a microarray platform to determine the microRNA (miRNA) expression profile in prostate cancer tissue from patients who underwent radical prostatectomy and were followed for an average of 47 months. The GeneChip® miRNA Array (Affymetrix) contains more than 46,000 probes, and more than 1,100 mature human miRNAs and transcripts. An expression level higher or lower than 1.1 with a p<0.05 were considered to be differentially expressed. When tumors with a GS<7 were compared with those with a GS≥7, five miRNAs were down-regulated and nine were up-regulated. In comparing tumors from patients with PSA <10 ng/mL vs. those with PSA ≥10 ng/mL, 21 miRNAs were down-regulated and 29 were overexpressed. There was decreased expression of 21 miRNAs and increased expression of 22 miRNAs when pT2 and pT3 tumors were compared. The comparison of the expression profiles of men with vs. without recurrent disease (PSA>0.2 ng/mL) revealed that 14 miRNAs were down-regulated and 17 were up-regulated. Considering the three prognostic factors and biochemical recurrence, miR-335 was overexpressed in pT3 tumors in patients with PSA>10 ng/mL, miR-1202 was overexpressed in recurrent tumors in which PSA >10 ng/mL, and miR-885 and miR-1226 were overexpressed in recurrent pT3 tumors. Six miRNAs (miR- 361, 378, 548, 574, 652 and 892) had decreased expression in pT3 tumors in patients with PSA >10 ng/mL. miR-16 was down-regulated in recurrent pT3 tumors. miR-92 and miR-450 exhibited decreased expression in recurrent tumors in patients with PSA > 10 ng/mL. miR-28 was down-regulated in pT3 adenocarcinomas with a GS ≥ 7. The differentially expressed miRNAs in recurrent tumors were validated using qRT-PCR in 74 additional specimens. miR-21 was overexpressed in recurrent tumors, and in the Cox model, expression levels higher than 0.64 were indicative of biochemical recurrence with a risk of 2.4. These results, which were based on clinical specimens from patients treated in a standardized way and followed for an average of 47 months, provide an initial understanding of the role of miRNAs in prostatecancer progression; the foremost representative is miR-21, which has been implicated in the progression of various human cancers.
2013-05-09 | GSE46738 | GEO
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Project description:Purpose: Available tools for prostate cancer (PC) diagnosis and prognosis are suboptimal and novel biomarkers are urgently needed. Here, we investigated the regulation and biomarker potential of the GABRE~miR-452~miR-224 genomic locus. Experimental design: GABRE/miR-452/miR-224 transcriptional expression was quantified in 80 non-malignant and 281 PC tissue samples. GABRE promoter methylation was determined by methylation-specific qPCR (MethyLight) in 35 non-malignant, 293 PC (radical prostatectomy (RP) cohort 1) and 198 PC tissue samples (RP cohort 2). Diagnostic/prognostic biomarker potential of GABRE methylation was evaluated by ROC, Kaplan-Meier, uni- and multivariate Cox regression analyses. Functional roles of miR-224 and miR-452 were investigated in PC3 and DU145 cells by viability, migration, and invasion assays and gene-set enrichment analysis (GSEA) of post-transfection transcriptional profiling data. Results: GABRE~miR-452~miR-224 was significantly downregulated in PC compared to non-malignant prostate tissue and had highly cancer-specific aberrant promoter hypermethylation (AUC=0.98). Functional studies and GSEA suggested that miR-224 and miR-452 inhibit proliferation, migration, and invasion of PC3 and DU145 cells by direct/indirect regulation of pathways related to the cell cycle and cellular motility. Finally, in uni- and multivariate analyses, high GABRE promoter methylation was significantly associated with biochemical recurrence in RP cohort 1, which was successfully validated in RP cohort 2. Conclusion: The GABRE~miR-452~miR-224 locus is downregulated and hypermethylated in PC and is a new promising epigenetic candidate biomarker for PC diagnosis and prognosis. Tumor suppressive functions of the intronic miR-224 and miR-452 were demonstrated in two PC cell lines, suggesting that epigenetic silencing of GABRE~miR-452~miR-224 may be selected for in PC.
2013-12-11 | GSE51053 | GEO
Project description:The hypersensitive prostate specific antigen (PSA) test can measure in 0.01 ng/mL units, and its efficacy for screening after radical prostatectomy (RP) has been reported. In this study, we assessed patients who underwent RP to evaluate whether the nadir value affects biochemical recurrence (BCR). From 1995 to 2014, patients classified as N0 who had negative resection margins and a nadir PSA of less than 0.2 ng/mL were evaluated. The characteristics, pathological outcomes, PSA after RP, and BCR were assessed. A total of 1483 patients were enrolled. Among them, 323 (21.78%) patients showed BCR after RP. The mean age of the BCR group was 63.86±7.31 years, and while that of the no-recurrence group was 64.06±6.82 years (P = 0.645). The mean preoperative PSA of the BCR group was 9.75±6.92 ng/mL and that of the no-recurrence group was 6.71±5.19 ng/mL (P < 0.001). The mean time to nadir (TTN) in the BCR group was 4.64±7.65 months, while that in the no-recurrence group was 7.43±12.46 months (P < 0.001). The mean PSA nadir value was 0.035±0.034 ng/mL in the BCR group and 0.014±0.009 ng/mL in the no-recurrence group (P < 0.001). In multivariable Cox regression analyses, Gleason score, positive biopsy core percentages, minimal invasive surgery, nadir PSA value, and TTN were independently associated with BCR. The mean BCR occurred at 48.23±2.01 months after RP, and there was a significant difference in BCR occurrence according to the nadir PSA value (P < 0.001). A high PSA nadir value and short TTN may predict the risk of BCR after successful RP, aiding the identification of candidates for adjuvant or salvage therapies after RP.
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Project description:ObjectivesMany previous studies have suggested that the outcome of prostate cancer (PCa) may be closely related to abnormal lipid metabolism. Therefore, in this study, we evaluated the preoperative lipid profiles of patients with clinically localized prostate cancer (PCa) who underwent radical prostatectomy (RP), with particular emphasis on the relationship between these profiles and biochemical recurrence (BCR).Patients and methodsWe evaluated 715 consecutive men with clinically localized PCa who underwent RP at our institution between January 2011 and December 2013. We defined hypertriglyceridemia as a fasting serum triglyceride (TG) level greater than 200 mg/dL. We used the Kaplan-Meier method to predict BCR-free survival and applied the log-rank test to determine the statistical significance between survival curves. Cox proportional hazard ratio (HR) models were used to identify the significant predictors of BCR according to clinicopathological variables.ResultsOf 663 patients who underwent RP for clinically localized PCa, 66 (10.0%) showed BCR during a median follow-up period of 21 months. Patients without BCR had higher levels of serum TG, and patients with hypertriglyceridemia were significantly more likely to achieve BCR-free survival in the Kaplan-Meier analysis (log-rank test, P = 0.009). In the multivariable analysis, the presence of hypertriglyceridemia (HR 0.22), pathologic Gleason score (≥ 8; HR 2.85), pathologic T stage (≥ pT3; HR 3.44), and a positive surgical margin (HR, 2.39) were still significant BCR predictors.ConclusionsWe found that preoperative hypertriglyceridemia was associated with a lower risk of BCR after RP in patients with clinically localized PCa. Our results could help to clarify the currently conflicting evidence on the relationship between serum lipid profiles, particularly the presence of hypertriglyceridemia, and the risk of BCR in PC a patients after surgery.
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