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Recent trend of androgen deprivation therapy in newly diagnosed prostate cancer patients: Comparing between high- and middle-income Asian countries.

ABSTRACT: The number of newly diagnosed prostate cancer cases varies across Asia, with higher mortality-to-incidence ratio reported in developing nations. Androgen deprivation therapy (ADT), alone or in combination, remains the mainstay of first-line treatment for advanced prostate cancer. Key findings of extensive research and randomized controlled trials have shaped current clinical practice and influenced clinical guideline recommendations. We describe here the recent trend of ADT in newly diagnosed prostate cancer for Asia focusing on Japan (high-income country) and Malaysia (middle-income country) based on the Asian Prostate Cancer (A-CaP) Study. The combination of radiotherapy and ADT or ADT alone was common in patients with intermediate-to-high risk localized and locally advanced disease. For metastatic prostate cancer, maximum androgen blockade (gonadotrophin-releasing hormone [GnRH] agonist/antagonist plus antiandrogen) was prevalent among the Japanese patients while primary ADT alone with GnRH agonist/antagonist was widely practiced in the Malaysian cohort. Upfront combined therapy (ADT plus docetaxel or androgen receptor pathway inhibitor) has significantly improved the outcomes of patients with metastatic castration-naïve prostate cancer. Its application, however, remains low in our cohorts due to patients' financial capacity and national health insurance coverage. Early detection remains the cornerstone in prostate cancer control to improve treatment outcome and patient survival.

SUBMITTER: Lim J

PROVIDER: S-EPMC8177804 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundSeveral studies showed that androgen deprivation therapy (ADT) plus local treatment of prostate could improve metastatic prostate cancer (mPCa) patients' survival. To date there are few studies analyzed the value of prostate cryoablation in mPCa. The objective of our analysis is to evaluate the oncological results and clinical value of prostate cryoablation combined with ADT compared with ADT alone in newly diagnosed mPCa patients.MethodsNewly diagnosed mPCa patients undergoing cryoablation plus ADT (group A) between January 2011 and November 2018 were identified. Patients receiving ADT alone (group B) were selected from the same institutional prostate cancer database by propensity score matching based on clinical characteristics. Oncological results and clinical value in symptom control and primary lesion treatment were compared.ResultsFifty-four patients were included in each group. Prostate cryoablation was well tolerated. The median follow-up time was 40 (27-53) and 39 (31-54) months in group A and group B, respectively. Patients in group A had a lower median prostate-specific antigen (PSA) nadir (0.025 ng/mL vs. 0.230 ng/mL, p = 0.001), longer median failure-free survival (FFS) (39 months vs. 21 months, p = 0.005), and median metastatic castration-resistant prostate cancer (mCRPC)-free survival (39 months vs. 21 months, p = 0.007). No difference in cancer-specific survival and overall survival was found between the two groups. Multivariate Cox analysis showed combination therapy reduced the risk of FFS by 45.8% (HR = 0.542 [95% CI 0.329-0.893]; p = 0.016). Patients in group A had better clinical relief of urinary symptoms (79.1 vs. 59.1%, p = 0.044) and required less treatment of primary lesions for symptomatic relief (13.0 vs. 31.5%, p = 0.021).ConclusionsProstate cryoablation plus ADT decreases PSA nadir, prolongs FFS and mCRPC-free survival, relieves urinary symptoms and reduces the need for treating primary lesions in newly diagnosed mPCa patients compared to ADT alone.

Project description:BackgroundThis study aimed to evaluate the updated burden and temporal trends of cancer incidence and mortality in Asian countries.MethodologyThe data used in this study were retrieved from the Global Cancer Observatory, Cancer Incidence in Five Continents volumes I-XI, and the World Health Organization mortality database. These data were used to calculate the Average Annual Percentage Change (AAPC), with a 95% confidence interval (CI) by joinpoint regression analysis to determine the epidemiological trend in the past decade.ResultsIn 2020, the cancer incidence in Asia was 169.1 per 1 00 000, accounting for 49.3% of the global cancer incidence. The most common cancers included lung (13.8%), breast (10.8%) and colorectal (10.6%) cancers. Its mortality was 101.6 per 1 00 000 (58.3% of the global cancer death) with lung (19.2%), liver (10.5%) and stomach (9.9%) cancers being the most common causes of cancer death. The cancer incidence had been increasing in female population, with Korea (AAPC = 5.73, 95% CI [5.30, 6.17], P < .001), Japan (AAPC = 2.67, 95% CI [2.12, 3.23], P < .001) and Kuwait (AAPC = 2.08, 95% CI [.49, 3.69], P = .016) showing the most significant increases in the past decade. The incidence increase was also observed among population aged <40 years old, with Korea (female AAPC = 8.42, 95% CI [7.40, 9.45], P < .001; male AAPC = 5.28, 95% CI [4.23, 6.33], P <.001), China (female AAPC = 2.94, 95% CI [2.07, 3.81], P < .001; male AAPC = 1.37, 95% CI [.57, 2.18], P = .004) and Japan (female AAPC = 2.88, 95% CI [1.88, 3.88], P = .016; male AAPC = 1.59, 95% CI [.40, 2.78], P = .015) showing the most significant increases. However, there was an overall decreasing trend of cancer mortality.ConclusionsThere was a substantial burden of cancer incidence and mortality in Asia. Although there was a decreasing trend in cancer mortality, its incidence had been increasing especially among female and younger populations. Future studies could be done to further investigate the potential reasons for these epidemiologic trends.

Project description:In a phase II multicenter study, men with castration sensitive metastatic prostate cancer were treated with AT-101, a small molecule Bcl-2 inhibitor, and androgen deprivation therapy. At the end of 7 cycles of therapy in 55 patients, an undetectable PSA was achieved in 31%. However, the combination did not meet the pre-specified level of activity for further development.We conducted a phase II study in men with castration-sensitive metastatic prostate cancer to test the hypothesis that AT-101, a small molecule Bcl-2 inhibitor, has clinical activity in patients initiating androgen deprivation therapy (ADT) for metastatic prostate cancer.Patients with metastatic prostate cancer scheduled to start, or who had recently (within 6 weeks) initiated, ADT were enrolled. ADT with a luteinizing hormone-releasing hormone agonist and bicalutamide was started 6 weeks before initiation of oral AT-101, 20 mg/day for 21 days of a 28-day cycle. The primary endpoint of the study was the percentage of patients with an undetectable prostate-specific antigen (PSA) level (? 0.2 ng/mL) after 7.5 months (1.5 months of ADT alone plus 6 months of combined ADT and AT-101). To assess for an association between chromodomain helicase DNA binding protein 1 (CHD1) and drug sensitivity, fluorescence in situ hybridization with confocal microscopy was assessed in a subgroup of patients.A total of 55 patients were enrolled, with median age of 61 years and a median PSA level of 27.6 ng/dL. Of the 55 patients, 72% had a Gleason score ? 8. Three patients had visceral metastases, and the remaining patients had bone or nodal metastasis. An undetectable PSA level was achieved in 31% of the patients. Of the 31 patients, 12 experienced serious adverse events, 7 of which were considered related to study therapy. Most of the related adverse events were gastrointestinal and nervous system disorders. CHD1 assessment was feasible, with a nonsignificant association with therapeutic sensitivity in a small number of patients.The combination of ADT and AT-101 did not meet the prespecified level of activity for further development of this combination.

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Recent trend of androgen deprivation therapy in newly diagnosed prostate cancer patients: Comparing between high- and middle-income Asian countries.

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