Exceptional pathologic complete response achieved with androgen deprivation and docetaxel therapy in Gleason 10 prostate cancer.
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ABSTRACT:
SUBMITTER: Vaishampayan U
PROVIDER: S-EPMC6357690 | biostudies-literature | 2019 Mar
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:SLCO-encoded transporters have been associated with progression to castration-resistant prostate cancer (CRPC) after initiation of androgen deprivation therapy (ADT). Although expressed at lower levels than in CRPC tissues, SLCO-encoded transporters may also play a role in response of primary prostate cancer (PCa) to ADT and biochemical recurrence. METHODS:We systematically explored expression of the 11 human SLCO genes in a large sample of untreated and ADT-treated normal prostate (NP) and primary PCa tissues, including tumors treated with neoadjuvant abiraterone. RESULTS:Transporters with the most recognized role in steroid uptake in PCa, including SLCO2B1 (DHEAS) and 1B3 (testosterone), were consistently detected in primary PCa. SLCO1B3 was nearly 5-fold higher in PCa vs NP with no difference in Gleason 3 vs 4 and no change with ADT. SLCO2B1 was detected at 3-fold lower levels in PCa than NP but was nearly 7-fold higher in Gleason 4 vs Gleason 3 and increased 3-fold following ADT (p?<?0.05 for all). CONCLUSIONS:We observed clear differences in SLCO expression in PCa vs NP samples, in Gleason 4 vs Gleason 3 tumors, and in ADT-treated vs untreated tissues. These findings are hypothesis generating due to small sample size, but suggest that baseline and ADT-induced changes in PCa OATP expression may influence steroid uptake and response to ADT, as well as uptake and response to drugs such as abiraterone and docetaxel which are also subject to OATP-mediated transport and are now being routinely combined with ADT in the metastatic castration sensitive setting.
| S-EPMC6752995 | biostudies-literature
Project description: Not available
| S-EPMC11291412 | biostudies-literature
Project description:Castration-resistant prostate cancer (CRPC) patients with liver metastases have an extremely poor prognosis. Herein, we report a rare patient who achieved a complete response by docetaxel chemotherapy for this aggressive disease. A 67-year-old Japanese male diagnosed with local prostate cancer [initial prostate specific antigen (PSA) of 10.3 ng/mL, a highest Gleason score of eight] received radical prostatectomy (RP) followed by salvage radiotherapy for PSA recurrence without distant metastases. After four years, androgen deprivation therapy was commenced for both local recurrence and elevated PSA. After a further four years, despite good control of PSA (1.2 ng/mL), other clinical findings including radiographic images revealed CRPC with multiple liver metastases. Ten cycles of docetaxel chemotherapy achieved a complete response for more than five years. In conclusion, even if a patient has CRPC with liver metastases, early diagnostic imaging irrespective of the PSA level may provide a better response to early docetaxel chemotherapy.
| S-EPMC7215045 | biostudies-literature
Project description:BackgroundPatients with biochemical disease recurrence (BCR) after definitive treatment for prostate cancer comprise a heterogeneous population for whom standard therapy options are lacking. The purpose of the current trial was to evaluate the feasibility, toxicity, and efficacy of early multimodality systemic therapy in men with BCR.MethodsEligible patients had an increasing prostate-specific antigen (PSA) level, a PSA doubling time ≤10 months, and no evidence of metastases after radical prostatectomy (RP) and/or radiotherapy (RT) for localized disease. Treatment consisted of docetaxel at a dose of 75 mg/m(2) every 3 weeks for 4 cycles, bevacizumab at a dose of 15 mg/kg every 3 weeks for 8 cycles, and androgen deprivation therapy (ADT) for 18 months. The primary endpoint was the percentage of patients who were free from PSA progression 1 year after the completion of therapy.ResultsA total of 41 patients were included in the analysis. At 1 year after the completion of ADT, 45% of patients (13 of 29 patients) and 29% of patients (5 of 17 patients) with a testosterone level ≥100 ng/dL and ≥240 ng/dL, respectively, had a PSA <0.2 ng/mL. The median follow-up was 27.5 months (interquartile range, 21.8-38.1 months). Eight patients (20%) were free from PSA progression, 19 patients (46%) did not reinitiate ADT, and 34 patients (83%) were free from metastasis. Sixteen patients (39%) experienced grade 3 and 5 patients (12%) experienced grade 4 toxicities (toxicity was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events [version 3.0]).ConclusionsMultimodality systemic therapy with docetaxel, bevacizumab, and ADT is feasible and produces PSA responses in men with BCR. Long-term follow-up is needed to determine the percentage of patients with a durable PSA response who are able to avoid having to reinitiate prostate cancer therapy.
| S-EPMC4566852 | biostudies-literature
Project description:Purpose We evaluated the relationship between prostate-specific antigen (PSA) and overall survival in the context of a prospectively randomized clinical trial comparing androgen-deprivation therapy (ADT) plus docetaxel with ADT alone for initial metastatic hormone-sensitive prostate cancer. Methods We performed a landmark survival analysis at 7 months using the E3805 Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer (CHAARTED) database ( ClinicalTrials.gov identifier: NCT00309985). Inclusion required at least 7 months of follow-up and PSA levels at 7 months from ADT initiation. We used the prognostic classifiers identified in a previously reported trial (Southwest Oncology Group 9346) of PSA ≤ 0.2, > 0.2 to 4, and > 4 ng/mL. Results Seven hundred nineteen of 790 patients were eligible for this subanalysis; 358 were treated with ADT plus docetaxel, and 361 were treated with ADT alone. Median follow-up time was 23.1 months. On multivariable analysis, achieving a 7-month PSA ≤ 0.2 ng/mL was more likely with docetaxel, low-volume disease, prior local therapy, and lower baseline PSAs (all P ≤ .01). Across all patients, median overall survival was significantly longer if 7-month PSA reached ≤ 0.2 ng/mL compared with > 4 ng/mL (median survival, 60.4 v 22.2 months, respectively; P < .001). On multivariable analysis, 7-month PSA ≤ 0.2 and low volume disease were prognostic of longer overall survival (all P < 0.01). The addition of docetaxel increased the likelihood of achieving a PSA ≤ 0.2 ng/mL at 7 months (45.3% v 28.8% of patients on ADT alone). Patients on ADT alone who achieved a 7-month PSA ≤ 0.2 ng/mL had the best survival and were more likely to have low-volume disease (56.7%). Conclusion PSA ≤ 0.2 ng/mL at 7 months is prognostic for longer overall survival with ADT for metastatic hormone-sensitive prostate cancer irrespective of docetaxel administration. Adding docetaxel increased the likelihood of a lower PSA and improved survival.
| S-EPMC5805480 | biostudies-literature
Project description:BackgroundAndrogen-deprivation therapy (ADT) historically represented the milestone for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC). Recently, combining androgen receptor-targeted agents (ARTA) or docetaxel with ADT significantly improved clinical outcomes in this setting. The efficacy of the combined use of an ARTA with docetaxel and ADT (triplet), however, was unknown, and often conflicting data derived from subgroup analysis of randomized phase III trials. In order to better define the benefits and risks of the triplet in mHSPC, we carried out a systematic review and meta-analysis of available clinical trials.MethodsA literature search with no data restriction using Medline/PubMed, the Cochrane Library, and American Society of Clinical Oncology/European Society for Medical Oncology (ASCO/ESMO) Meeting abstracts was carried out up to April 2022. The meta-analysis was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statements. Overall survival (OS) was the primary endpoint; progression-free survival (PFS) and safety were secondary endpoints. For OS and PFS, summary hazard ratios (HRs) were calculated; for safety, risk ratio (RR) was assessed. Random- or fixed-effects models were used, depending on studies heterogeneity.ResultsFive randomized clinical trials fulfilled the prespecified inclusion criteria. The triplet significantly improved OS (fixed-effect, HR = 0.74; P < 0.00001) and PFS (fixed-effect; HR = 0.50 for clinical PFS, HR = 0.49 for radiological PFS; P < 0.0001) compared with docetaxel plus ADT. We did not show heterogeneity between treatment efficacy and the disease burden, metachronous versus synchronous presentation, concomitant versus sequential strategy. Compared with docetaxel + ADT, the triplet did not increase the risk of adverse events (AEs) (RR = 1.00, P = 0.27 for any-grade AEs; RR = 1.13, P = 0.14 for severe AEs), except for severe hypertension (RR = 1.73, P = 0.001).ConclusionsEmerging evidence supports the combination of an ARTA plus docetaxel and ADT in mHSPC patients. Given the availability of several strategies in this setting, clinical characteristics and drug safety profile may help clinicians select the appropriate treatment for mHSPC patients who are more likely to benefit from treatment intensification.
| S-EPMC9588886 | biostudies-literature
Project description:PurposeThis study aimed to compare the short-term outcomes and safety profiles of androgen-deprivation therapy (ADT)+abiraterone/prednisone with those of ADT+docetaxel in patients with de novo metastatic hormone-sensitive prostate cancer (mHSPC).Materials and methodsA web-based database system was established to collect prospective cohort data for patients with mHSPC in Korea. From May 2019 to November 2022, 928 patients with mHSPC from 15 institutions were enrolled. Among these patients, data from 122 patients who received ADT+abiraterone/prednisone or ADT+docetaxel as the primary systemic treatment for mHSPC were collected. The patients were divided into two groups: ADT+abiraterone/prednisone group (n=102) and ADT+docetaxel group (n=20). We compared the demographic characteristics, medical histories, baseline cancer status, initial laboratory tests, metastatic burden, oncological outcomes for mHSPC, progression after mHSPC treatment, adverse effects, follow-up, and survival data between the two groups.ResultsNo significant differences in the demographic characteristics, medical histories, metastatic burden, and baseline cancer status were observed between the two groups. The ADT+abiraterone/prednisone group had a lower prostate-specific antigen (PSA) progression rate (7.8% vs. 30.0%; p=0.011) and lower systemic treatment discontinuation rate (22.5% vs. 45.0%; p=0.037). No significant differences in adverse effects, oncological outcomes, and total follow-up period were observed between the two groups.ConclusionsADT+abiraterone/prednisone had lower PSA progression and systemic treatment discontinuation rates than ADT+docetaxel. In conclusion, further studies involving larger, double-blinded randomized trials with extended follow-up periods are necessary.
| S-EPMC11216961 | biostudies-literature
Project description:Purpose: The combination of docetaxel chemotherapy and androgen deprivation therapy (ADT) has become a standard treatment for patients with metastatic prostate cancer. The recently accrued phase III CALGB 90203 trial was designed to investigate the clinical effectiveness of this treatment approach earlier in the disease. Specimens from this trial offer a unique opportunity to interrogate the acute molecular response to docetaxel and ADT and identify potential biomarkers.Experimental Design: We evaluated baseline clinical data, needle biopsies, and radical prostatectomy (RP) specimens from 52 (of 788) patients enrolled on CALGB 90203 at one high volume center. Pathology review, tumor and germline-targeted DNA sequencing (n = 72 genes), and expression profiling using NanoString platform (n = 163 genes) were performed to explore changes in critical prostate cancer pathways linked to aggression and resistance.Results: Three of 52 patients had only microfocal residual cancer at prostatectomy. The most common alterations included TMPRSS2-ERG fusion (n = 32), TP53 mutation or deletion (n = 11), PTEN deletion (n = 6), FOXA1 (n = 6), and SPOP (n = 4) mutation, with no significant enrichment in posttreated specimens. We did not observe AR amplification or mutations. The degree of AR signaling suppression varied among treated tumors and there was upregulation of both AR and AR-V7 expression as well as a subset of neuroendocrine and plasticity genes.Conclusions: These data support the feasibility of targeted and temporal genomic and transcriptome profiling of neoadjuvant-treated prostate cancer with limited formalin-fixed paraffin embedded tissue requirement. Characterization of the heterogeneity of treatment response and molecular outliers that arise posttreatment provides new insight into potential early markers of resistance. Clin Cancer Res; 23(22); 6802-11. ©2017 AACR.
| S-EPMC5690882 | biostudies-literature
Project description:Androgen deprivation (AD) is commonly used in neoadjuvant and adjuvant setting with prostate cancer (PC) radiotherapy. This prospective study assessed whether cognitive functioning is impaired during 12 months of AD therapy. Longitudinal testing of 25 patients treated with AD and curative radiotherapy was undertaken at baseline, and at 6 and 12 months. CogniSpeed software was used for measuring attentional performances. Other cognitive performances were evaluated using verbal, visuomotor and memory tests. The Beck depression inventory was employed to evaluate depressive mood and EORTC QLQ-C30 for quality of life (QoL). During longitudinal testing of the AD group, no impairment in cognitive performances was found. Instead, improvement was observed in object recall (immediate, P=0.035; delayed, P<0.001), and in semantic memory (P=0.037). In QoL, impairment in physical function was observed. Androgen deprivation of 12 months appears to be associated with preserved cognitive functioning, although physical impairment occurs. These results have implications for counseling and psychosocial support of patients in the context of treatment options in PC.
| S-EPMC2376935 | biostudies-other
Project description:BackgroundCastration resistance occurs in most patients with metastatic hormone-sensitive prostate cancer who are receiving androgen-deprivation therapy. Replacing androgens before progression of the disease is hypothesized to prolong androgen dependence.MethodsMen with newly diagnosed, metastatic, hormone-sensitive prostate cancer, a performance status of 0 to 2, and a prostate-specific antigen (PSA) level of 5 ng per milliliter or higher received a luteinizing hormone-releasing hormone analogue and an antiandrogen agent for 7 months. We then randomly assigned patients in whom the PSA level fell to 4 ng per milliliter or lower to continuous or intermittent androgen deprivation, with patients stratified according to prior or no prior hormonal therapy, performance status, and extent of disease (minimal or extensive). The coprimary objectives were to assess whether intermittent therapy was noninferior to continuous therapy with respect to survival, with a one-sided test with an upper boundary of the hazard ratio of 1.20, and whether quality of life differed between the groups 3 months after randomization.ResultsA total of 3040 patients were enrolled, of whom 1535 were included in the analysis: 765 randomly assigned to continuous androgen deprivation and 770 assigned to intermittent androgen deprivation. The median follow-up period was 9.8 years. Median survival was 5.8 years in the continuous-therapy group and 5.1 years in the intermittent-therapy group (hazard ratio for death with intermittent therapy, 1.10; 90% confidence interval, 0.99 to 1.23). Intermittent therapy was associated with better erectile function and mental health (P<0.001 and P=0.003, respectively) at month 3 but not thereafter. There were no significant differences between the groups in the number of treatment-related high-grade adverse events.ConclusionsOur findings were statistically inconclusive. In patients with metastatic hormone-sensitive prostate cancer, the confidence interval for survival exceeded the upper boundary for noninferiority, suggesting that we cannot rule out a 20% greater risk of death with intermittent therapy than with continuous therapy, but too few events occurred to rule out significant inferiority of intermittent therapy. Intermittent therapy resulted in small improvements in quality of life. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00002651.).
| S-EPMC3682658 | biostudies-literature