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.
The A‐ Asian Prostate Cancer Study revealed a high proportion of metastatic prostate cancer was reported in Asia, particularly in developing nations. Androgen deprivation therapy, alone or in combination, remains the mainstay of first‐line treatment for advanced prostate cancer.
Objectives:
Several therapies are available for the treatment of advanced/metastatic prostate cancer (PC). However, the systematic assessment of evidence pertaining to the use of these therapies in ...Asian patients is lacking.
Methods:
A systematic literature review (SLR) was conducted using PubMed/Medline search in May 2021 to identify the randomized/nonrandomized controlled trials (RCTs/non-RCTs) and real-world observational studies (prospective/retrospective). Only studies published as full manuscripts in English were included if reporting the efficacy, effectiveness, and/or safety of treatments in Asian patients with advanced/metastatic PC.
Results:
Of the 1,898 retrieved publications, 24 studies were included. These studies had patients with nonmetastatic castration-resistant PC (n = 2), metastatic castration-sensitive PC (n = 4), and metastatic castration-resistant PC (n = 18). Study designs included RCTs (n = 7), non-RCTs (n = 2), and real-world studies (n = 15). Treatments used in included studies were abiraterone acetate plus prednisone (AAP; n = 6), enzalutamide, lutetium-177 prostate-specific membrane antigen (177Lu-PSMA; n = 4 each), docetaxel (n = 3), apalutamide, radium-223 (n = 2 each), darolutamide, cabazitaxel, and pembrolizumab (n = 1 each). The evidence from RCTs (i.e., ARAMIS, SPARTAN, ARCHES, TITAN, LATITUDE, PREVAIL) demonstrated the clinical benefits of apalutamide, darolutamide, enzalutamide, and AAP in terms of overall, disease-free, and metastasis-free survival in Asian patients. These treatments were reported to be well tolerated, with no new safety signals identified in Asian population. The efficacy and safety profiles in Asian patients were consistent with the overall trial population. Data from real-world studies supported the effectiveness and tolerability of AAP, enzalutamide, radium-223, docetaxel, cabazitaxel, 177Lu-PSMA, and pembrolizumab in patients with advanced/metastatic PC.
Conclusions:
This SLR of the Asian data on therapies for advanced PC from the pivotal and real-world studies confirms similar efficacy and safety outcomes, consistent with the results from the pivotal clinical trials. These findings will help clinicians make better treatment decisions in clinical practice for patients with advanced/metastatic PC.
There is a paucity of information on the use of novel hormonal agents in Southeast Asian patients. We reviewed the clinical roles of novel hormonal therapy (NHT), namely abiraterone acetate (AA), ...enzalutamide, apalutamide and darolutamide, in the management of advanced prostate cancer, and data on its use in Asian patients, in order to extrapolate these findings to the Southeast Asian patient population. There are some differences in the molecular features between the NHTs, which influenced their respective permeabilities through the blood-brain barrier. The Asian sub-analyses of the landmark studies of each NHT were limited. The primary endpoints of the Asian sub-analyses generally reflect the efficacy outcomes of the respective landmark study. Hypertension, fatigue, musculoskeletal disorders, rash, and hot flushes were among the common toxicities observed in Asian patients. Real-world data on AA in the Asian setting is favourable, but data is limited for enzalutamide, apalutamide and darolutamide. Based on the sub-analyses and real-world data, the efficacy and safety of NHTs in the Asian patients showed a similar trend to the respective landmark studies. The lack of clinical trials in the Southeast Asian region hampers the ability to make a robust conclusion on any specific efficacy or safety differences that may be present; clinicians must assume that the broader Asian sub-analyses and real-world data reflects Southeast Asian patients' outcomes.
Limb salvage surgery is a treatment of choice for sarcomas of the extremities. One of the options in skeletal reconstruction after tumour resection is by using a recycled bone autograft. The present ...accepted methods of recycling bone autografts include autoclaving, pasteurization and irradiation. At the moment there is lack of studies that compare the effectiveness of various sterilization methods used for recycling bone autografts and their effects in terms of bone incorporation. This study was performed to determine the effects of different methods of sterilization on bone autografts in rabbit by radiological, biomechanical and histopathological evaluations.
Fresh rabbit cortical bone is harvested from the tibial diaphysis and sterilized extracorporeally by pasteurization (n = 6), autoclaving (n = 6), irradiation (n = 6) and normal saline as control group (n = 6). The cortical bones were immediately reimplanted after the sterilization process. The subsequent process of graft incorporation was examined over a period of 12 weeks by serial radiographs, biomechanical and histopathological evaluations. Statistical analysis (ANOVA) was performed on these results. Significance level (α) and power (β) were set to 0.05 and 0.90, respectively.
Radiographic analysis showed that irradiation group has higher score in bony union compared to other sterilization groups (p = 0.041). ANOVA analysis of 'failure stress', 'modulus' and 'strain to failure' demonstrated no significant differences (p = 0.389) between treated and untreated specimens under mechanical loading. In macroscopic histopathological analysis, the irradiated group has the highest percentage of bony union (91.7 percent). However in microscopic analysis of union, the pasteurization group has significantly higher score (p = 0.041) in callus formation, osteocytes percentage and bone marrow cellularity at the end of the study indicating good union potential.
This experimental study shown that both irradiation and pasteurization techniques have more favourable outcome in terms of bony union based on radiographic and histopathological evaluations. Autoclaving has the worst outcome. These results indicate that extracorporeal irradiation or pasteurization of bone autografts, are viable option for recycling bone autografts. However, pasteurization has the best overall outcomes because of its osteocytes preservation and bone marrow cellularity.
Background
Multidisciplinary team meeting (MDTM) has become an increasingly important part of disease management model, particularly in cancer care. MDTM consists of a group of doctors to provide ...independent opinions on diagnostic and treatment decisions, as well as personalized therapeutic plan for patients. By selecting the most suitable treatment for patients from multiple perspectives, management by multidisciplinary team (MDT) have been shown to have advantages over traditional treatment models. The objective of this study is to determine the impact of MDTM on the management of uro-oncological cases and adherence to MDTM plans.
Methods
We retrospectively collected patients’ clinical information discussed in MDTM from 1st January 2021 to 31st December 2022 at our institution. The pre-MDTM treatment plan by the clinicians and the MDTM consensus plans were compared to assess the overall MDTM impact on patient management. Adherence to MDTM recommendations was also analyzed.
Results
Data on 432 patients discussed in MDTM from 1st January 2021 to 31st December 2022 were collected and analyzed. Prostate cancer was the most common type of cancer discussed (
n
= 212, 48.8%). MDTM had a significant impact on decision-making in 276 (63.6%) cases, with changes to patient management being observed in more than half of all cases. Adherence to MDTM outcomes was high with 383 (90.5%) of patients eventually had treatment according to the MDTM recommendation.
Conclusion
The study highlights the importance of MDTM in the management of genitourinary malignancies, particularly in cases where no original plan exists. Patient’s compliance and adherence to the MDTM consensus plan are also very encouraging.
Prostate cancer (PC) has a serious public health impact, and its incidence is rising due to the aging population. There is limited evidence and consensus to guide the management of PC in Southeast ...Asia (SEA). We present real-world data on clinical practice patterns in SEA for advanced PC care.
A paper-based survey was used to identify clinical practice patterns and obtain consensus among the panelists. The survey included the demographics of the panelists, the use of clinical guidelines, and clinical practice patterns in the management of advanced PC in SEA.
Most panelists (81%) voted prostate-specific antigen (PSA) as the most effective test for early PC diagnosis and risk stratification. Nearly 44% of panelists agreed that prostate-specific membrane antigen positron emission tomography-computed tomography imaging for PC diagnostic and staging information aids local and systemic therapy decisions. The majority of the panel preferred abiraterone acetate (67%) or docetaxel (44%) as first-line therapy for symptomatic mCRPC patients. Abiraterone acetate (50%) is preferred over docetaxel as a first-line treatment in metastatic castration-sensitive prostate cancer patients with high-volume disease. However, the panel did not support the use of abiraterone acetate in non-metastatic castration-resistant prostate cancer (nmCRPC) patients. Apalutamide (75%) is the preferred treatment option for patients with nmCRPC. The cost and availability of modern treatments and technologies are important factors influencing therapeutic decisions. All panelists supported the use of generic versions of approved therapies.
The survey results reflect real-world management of advanced PC in a SEA country. These findings could be used to guide local clinical practices and highlight the financial challenges of modern healthcare.
Addressing unwarranted clinical variation in oncology practices is expected to lead to improved cancer outcomes. Particularly, the application and impact of treatment guidelines on breast cancer ...outcomes are poorly studied in resource-limited settings. We measured adherence to a set of locally developed adjuvant treatment guidelines in a middle-income setting. Importantly, the impact of guidelines adherence on survival following breast cancer was determined.
Data of 3,100 Malaysian women with nonmetastatic breast cancer diagnosed between 2010 and 2017 were analyzed. Adherence to the Malaysian Clinical Practice Guidelines for Management of Breast Cancer second Edition was measured. Outcomes comprised overall survival and event-free survival.
Guideline adherence for chemotherapy, radiotherapy, hormonal therapy, and targeted therapy were 61.7%, 79.2%, 85.1%, and 26.2%, respectively. Older age was generally associated with lower adherence to guidelines. Compared with patients who were treated according to treatment guidelines, overall survival and event-free survival were substantially lower in patients who were not treated accordingly; hazard ratios for all-cause mortality were 1.69 (95% CI, 1.29 to 2.22), 2.59 (95% CI, 1.76 to 3.81), 3.08 (95% CI, 1.94 to 4.88), and 4.48 (95% CI, 1.98 to 10.13) for chemotherapy, radiotherapy, hormone therapy, and targeted therapy, respectively. Study inferences remain unchanged following sensitivity analyses.
Our study findings appear to suggest that adherence to treatment guidelines that have been adapted for resource-limited settings may still provide effective guidance in improving breast cancer outcomes.
It is of much interest to understand the efficacy of abiraterone acetate (AA) in routine clinical practice. We assessed the clinical outcome of AA in patients with metastatic castration‐resistant ...prostate cancer (mCRPC) and determined clinical factors associated with AA treatment duration in real‐world setting. This real‐world cohort consisted of 93 patients with mCRPC treated with AA in Thailand (58.1%) and Malaysia (41.9%). Primary endpoints were overall survival (OS) and biochemical progression‐free survival (bPFS). Secondary endpoints were predictors associated with AA treatment duration evaluated with Cox proportional hazards regression. Around 74% were chemotherapy‐naïve. The median AA treatment duration was 10 months (IQR 5.6‐17.1). Malaysians had a relatively lower median OS and bPFS (OS 17.8 months; 95% CI 6.4‐29.1, bPFS 10.4 months; 95% CI 8.8‐12.0) compared to Thais (OS 27.0 months; 95% CI 11.3‐42.7, bPFS 14.0 months; 95% CI 5.8‐22.2), although it did not achieve statistical significance (P > .05). Patients with longer AA treatment duration (>10 months) had lower risk of death and longer bPFS, compared to those with shorter AA treatment duration (≤10 months) (hazard ratio HR 0.10, 95% CI 0.05‐0.22 and HR 0.13, 95% CI 0.06‐0.25, respectively). Multivariable analysis showed that PSA at AA initiation, presence of PSA response and chemotherapy‐naive were independently associated with AA duration (P < .05). Abiraterone acetate is well‐tolerated in the Southeast Asian cohort with comparable survival benefits to other Asian populations in real‐world setting. Lower PSA levels at AA initiation, presence of PSA response, and chemotherapy‐naive were significant in determining AA treatment duration.
Association of abiraterone acetate duration with (a) overall survival and (b) biochemical progress free survival in metastatic castration‐resistant prostate cancer.
Treatment intensification with androgen deprivation therapy (ADT) and androgen receptor pathway inhibitors (ARPi) have led to improved survival in advanced prostate cancer. However, ADT is linked to ...significant cardiovascular toxicity, and ARPi also negatively impacts cardiovascular health. Together with a higher prevalence of baseline cardiovascular risk factors reported among prostate cancer survivors at diagnosis, there is a pressing need to prioritise and optimise cardiovascular health in this population. Firstly, While no dedicated cardiovascular toxicity risk calculators are available, other tools such as SCORE2 can be used for baseline cardiovascular risk assessment. Next, selected patients on combination therapy may benefit from de-escalation of ADT to minimise its toxicities while maintaining cancer control. These patients can be characterised by an exceptional PSA response to hormonal treatment, favourable disease characteristics and competing comorbidities that warrant a less aggressive treatment regime. In addition, emerging molecular and genomic biomarkers hold the potential to identify patients who are suited for a de-escalated treatment approach either with ADT or with ARPi. One such biomarker is AR-V7 splice variant that predicts resistance to ARPi. Lastly, optimization of modifiable cardiovascular risk factors for patients through a coherent framework (ABCDE) and exercise therapy is equally important. This article aims to comprehensively review the cardiovascular impact of hormonal manipulation in metastatic hormone-sensitive prostate cancer, propose overarching strategies to mitigate cardiovascular toxicity associated with hormonal treatment, and, most importantly, raise awareness about the detrimental cardiovascular effects inherent in our current management strategies involving hormonal agents.
Sterilization and re-usage of tumour bone for reconstruction after tumour resection is now gaining popularity in the East. This recycle tumour bone needs to be sterilized in order to eradicate the ...tumour cells before re-implantation for limb salvage procedures. The effect of some of these treatments on the integrity and sterility of the bone after treatment has been published but there has yet been a direct comparison between the various methods of sterilization to determine the one method that gives the best tumour kill without compromising the bone's structural integrity.
This study was performed to evaluate the effect of several sterilization methods on the mechanical behavior of human cortical bone graft and histopathology evaluation of tumour bone samples after being processed with 4 different methods of sterilization. Fresh human cortical tumour bone is harvested from the diaphyseal region of the tumour bone were sterilized by autoclave (n =10); boiling (n =10); pasteurization (n =10); and irradiation (n =10). There were also 10 control specimens that did not receive any form of sterilization treatment. The biomechanical test conducted were stress to failure, modulus and strain to failure, which were determined from axial compression testing. Statistical analysis (ANOVA) was performed on these results. Significance level (α) and power (β) were set to 0.05 and 0.90, respectively.
ANOVA analysis of 'failure stress', 'modulus' and 'strain to failure' demonstrated significant differences (p < 0.05) between treated cortical bone and untreated specimens under mechanical loading.'Stress to failure' was significantly reduced in boiled, autoclaved and irradiated cortical bone samples (p < 0.05). 'Modulus' detected significant differences in the boiled, autoclaved and pasteurization specimens compared to controls (p < 0.05). 'Strain to failure' was reduced by irradiation (p < 0.05) but not by the other three methods of treatments.Histopathology study revealed no viable tumour cell in any of four types of treatment group compared to the untreated control group.
Sterilization of cortical bone sample by pasteurization and to a lesser extent, irradiation does not significantly alter the mechanical properties when compared with untreated samples. Mechanical properties degrade with the use of high temperature for sterilization (boiling). All methods of sterilization gave rise to 100 percent tumour kill.
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