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Background: The volume-outcome relationship is well-known in health care. The Experience Curve, initially developed by the Boston Consulting Group for manufacturing, offers insight on this relationship and has never before been applied to health care. Objectives: The purpose of this study was to determine the effect of experience on cost and resource utilization for the Cone procedure. Methods: We performed a retrospective review of patients who underwent Cone reconstruction for Ebstein's anomaly at Boston Children's Hospital between October 2010 and October 2021. Cardiopulmonary bypass time and aortic cross clamp time over time were evaluated using exponential regression to assess the surgeon-level learning curve. At the hospital level, length of stay and cost over time were assessed using exponential regression. Results: There were 115 patients included in the study. Median hospital length of stay was 7.9 days (IQR: 6.4-10.2 days) with a decline of 3.3% per year. Median intensive care unit [ICU] length of stay was 3.2 days (IQR: 2-5.7 days) with a decline of 10.5% per year. Adjusted direct costs indexed to 2020 prices fell by 4% per year. There was no statistically significant change in cardiopulmonary bypass or aortic cross clamp time. In mediation analysis, the reduction in cost was completely accounted for in the decline in ICU length of stay. ICU length of stay was correlated with duration of intubation. Conclusions: Increasing familiarity with Ebstein's anomaly and Cone reconstruction led to a reduction in resource utilization.
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PURPOSE: To assess if PSMA PET quantitative parameters are associated with pathologic ISUP grade group (GG) and upgrading/downgrading. METHODS: PCa patients undergoing radical prostatectomy with or without pelvic lymph node dissection staged with preoperative PSMA PET at seven referral centres worldwide were evaluated. PSMA PET parameters which included SUVmax, PSMAvolume, and total PSMA accumulation (PSMAtotal) were collected. Multivariable logistic regression evaluated the association between PSMA PET quantified parameters and surgical ISUP GG. Decision-tree analysis was performed to identify discriminative thresholds for all three parameters related to the five ISUP GGs The ROC-derived AUC was used to determine whether the inclusion of PSMA quantified parameters improved the ability of multivariable models to predict ISUP GG ≥ 4. RESULTS: A total of 605 patients were included. Overall, 2%, 37%, 37%, 10% and 13% patients had pathologic ISUP GG1, 2, 3, 4, and 5, respectively. At multivariable analyses, all three parameters SUVmax, PSMAvolume and PSMAtotal were associated with GG ≥ 4 at surgical pathology after accounting for PSA and clinical T stage based on DRE, hospital and radioligand (all p < 0.05). Addition of all three parameters significantly improved the discrimination of clinical models in predicting GG ≥ 4 from 68% (95%CI 63 - 74) to 74% (95%CI 69 - 79) for SUVmax, 72% (95%CI 67 - 76) for PSMAvolume, 74% (70 - 79) for PSMAtotal and 75% (95%CI 71 - 80) when all parameters were included (all p < 0.05). Decision-tree analysis resulted in thresholds that discriminate between GG (SUVmax 0-6.5, 6.5-15, 15-28, > 28, PSMAvol 0-2, 2-9, 9-20 and > 20 and PSMAtotal 0-12, 12-98 and > 98). PSMAvolume was significantly associated with GG upgrading (OR 1.03 95%CI 1.01 - 1.05). In patients with biopsy GG1-3, PSMAvolume ≥ 2 was significantly associated with higher odds for upgrading to ISUP GG ≥ 4, compared to PSMAvolume < 2 (OR 6.36, 95%CI 1.47 - 27.6). CONCLUSION: Quantitative PSMA PET parameters are associated with surgical ISUP GG and upgrading. We propose clinically relevant thresholds of these parameters which can improve in PCa risk stratification in daily clinical practice.
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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.
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OBJECTIVES: To prospectively evaluate how the Prostate Health Index (PHI) impacts on clinical decision in a real-life setting for men with a prostate-specific antigen (PSA) level between 4 and 10 ng/mL and normal digital rectal examination. PATIENTS AND METHODS: Since 2016, the PHI has been available at no cost to eligible men in all Hong Kong public hospitals. All eligible patients who received PHI testing in all public Urology units (n = 16) in Hong Kong between May 2016 and August 2017 were prospectively included and followed up. All included men had a PHI test, with its result and implications explained; the subsequent follow-up plan was then decided via shared decision-making with urologists. Patients were followed up for 2 years, with outcomes including prostate biopsy rates and biopsy findings analysed in relation to the initial PHI measurements. RESULTS: A total of 2828 patients were followed up for 2 years. The majority (82%) had PHI results in the lower risk range (score <35). Knowing the PHI findings, 83% of the patients with elevated PSA decided not to undergo biopsy. In all, 11% and 45% opted for biopsy in the PHI score <35 and ≥35 groups, respectively. The initial detection rate of International Society of Urological Pathology (ISUP) Grade Group (GG) ≥2 cancer was higher in the PHI score ≥35 group (23%) than in the PHI score <35 group (7.9%). Amongst patients with no initial positive biopsy findings, the subsequent positive biopsy rate for ISUP GG ≥2 cancer was higher in the PHI score ≥35 group (34%) than the PHI score <35 group (13%) with a median follow-up of 2.4 years. CONCLUSION: In a real-life setting, with the PHI incorporated into the routine clinical pathway, 83% of the patients with elevated PSA level decided not to undergo prostate biopsy. The PHI pathway also improved the high-grade prostate cancer detection rate when compared to PSA-driven strategies. Higher baseline PHI predicted subsequent biopsy outcome at 2 years. The PHI can serve as a tool to individualise biopsy decisions and frequency of follow-up visits.
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There remains high morbidity and mortality with mechanical circulatory support (MCS) in failing bidirectional Glenn (BDG) physiology. We performed a retrospective analysis of children with BDG physiology supported with MCS before and after 2018. Fourteen patients met inclusion criteria (median age 1.5 years, weight 9 kg). Prior to 2018 (n = 7), with variable anticoagulation and strategies including pulsatile VAD, continuous flow VAD, and extracorporeal membrane oxygenation (ECMO), 3 (43%) of patients were transplanted with a total of 536 patient-days of support (median 59 days). Major hemocompatability-related adverse event (MHRAE) rate was 63 per 100 patient-months. After 2018 (n = 7), using a staged support strategy (ECMO to pulsatile VAD) and bivalirudin anticoagulation, 5 (71%) patients were transplanted with a total of 1260 patient-days of support (median 188 days) and MHRAE rate of 24 per 100 patient-months. Despite challenging physiology, we have observed improved survival and reduced MHRAE despite longer support duration.
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Castration-resistant prostate cancer (CRPC) is the leading cause of prostate cancer (PCa)-related death in males, which occurs after the failure of androgen deprivation therapy (ADT). PIWI-interacting RNAs (piRNAs) are crucial regulators in many human cancers, but their expression patterns and roles in CRPC remain unknown. In this study, we performed small RNA sequencing to explore CRPC-associated piRNAs using 10 benign prostate tissues, and 9 paired hormone-sensitive PCa (HSPCa) and CRPC tissues from the same patients. PiRNA-4447944 (piR-4447944) was discovered to be highly expressed in CRPC group compared with HSPCa and benign groups. Functional analyses revealed that piR-4447944 overexpression endowed PCa cells with castration resistance ability in vitro and in vivo, whereas knockdown of piR-4447944 using anti-sense RNA suppressed the proliferation, migration and invasion of CRPC cells. Additionally, enforced piR-4447944 expression promoted in vitro migration and invasion of PCa cells, and reduced cell apoptosis. Mechanistically, piR-4447944 bound to PIWIL2 to form a piR-4447944/PIWIL2 complex and inhibited tumor suppressor NEFH through direct interaction at the post-transcriptional level. Collectively, our study indicates that piR-4447944 is essential for prostate tumor-propagating cells and mediates androgen-independent growth of PCa, which extends current understanding of piRNAs in cancer biology and provides a potential approach for CRPC treatment.
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Proteínas Argonautas , Proliferación Celular , Neoplasias de la Próstata Resistentes a la Castración , ARN Interferente Pequeño , Masculino , Humanos , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata Resistentes a la Castración/patología , ARN Interferente Pequeño/metabolismo , Proteínas Argonautas/metabolismo , Proteínas Argonautas/genética , Animales , Línea Celular Tumoral , Proliferación Celular/genética , Ratones , Apoptosis , Movimiento Celular/genética , Regulación Neoplásica de la Expresión Génica , Ratones Desnudos , ARN de Interacción con PiwiRESUMEN
INTRODUCTION: Kidney cancer is a common urological malignancy worldwide with an increasing incidence in recent years. Among all subtypes, renal cell carcinoma (RCC) represents the most predominant malignancy in kidney. Clinicians faced a major challenge to select the most effective and suitable treatment regime for patients from a wide range of modalities, despite improved understanding and diagnosis of RCC. OBJECTIVE: Recently, organoid culture gained more interest as the 3D model is shown to be highly patient specific which is hypothetically beneficial to the investigation of precision medicine. Nonetheless, the development and application of organotypic culture in RCC is still immature, therefore, the primary objective of this study was to establish an organoid model for RCC. MATERIALS AND METHODS: Patients diagnosed with renal tumor and underwent surgical intervention were recruited. RCC specimen was collected and derived into organoids. Derived organoids were validated by histological examminations, sequencing and xenograft. Drug response of organoids were compared with resistance cell line and patients' clinical outcomes. RESULTS: Our results demonstrated that organoids could be successfully derived from renal tumor and they exhibited high concordance in terms of immunoexpressional patterns. Sequencing results also depicted concordant mutations of driver genes in both organoids and parental tumor tissues. Critical and novel growth factors were discovered during the establishment of organoid model. Besides, organoids derived from renal tumor exhibited tumorigenic properties in vivo. In addition, organoids recapitulated patient's in vivo drug resistance and served as a platform to predict responsiveness of other therapeutic agents. CONCLUSION: Our RCC organoid model recaptiluated histological and genetic features observed in primary tumors. It also served as a potential platform in drug screening for RCC patients, though future studies are necessary before translating the outcomes into clinical practices.
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Carcinoma de Células Renales , Neoplasias Renales , Organoides , Humanos , Organoides/efectos de los fármacos , Organoides/patología , Neoplasias Renales/patología , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/genética , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/genética , Animales , Ratones , Femenino , Masculino , Ensayos de Selección de Medicamentos Antitumorales/métodos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Ensayos Antitumor por Modelo de Xenoinjerto , Persona de Mediana Edad , Línea Celular Tumoral , Anciano , MutaciónRESUMEN
ABSTRACT: Prostate cancer (PCa) is a significant health concern globally, necessitating effective treatment options. Typical treatment methods for early stage, particularly localized PCa, encompass radical procedures, such as radical prostatectomy (RP) and radiotherapy (RT), and nonradical focal therapy (FT). FT is a focused approach mainly used for treating small lesions limited to a specific zone of the prostate. Its objective is to achieve cancer control when minimizing damage to benign tissue. High-intensity focused ultrasound (HIFU) is one of the most used modalities in FT for the management of PCa. The progress in HIFU technology showcases continuous advancements, offering clinicians a variety of strategies to cater to diverse patient requirements. The advancements include the development of transrectal and transurethral HIFU machines that offer enhanced treatment distances, magnetic resonance imaging (MRI) fusion capabilities, real-time monitoring, and precise ablation. These improvements contribute to increased treatment effectiveness and better outcomes for patients. This narrative review aims to summarize the use of HIFU technology and its evolution, offering diverse options to clinicians, and explores the safety, effectiveness, and quality of different HIFU strategies, such as whole-gland ablation, hemigland ablation, and focal ablation. We conclude that nonwhole-gland HIFU offers similar cancer control with better short-term functional outcomes and fewer complications compared to whole-gland ablation. Combining HIFU with transurethral resection of the prostate (TURP) improves urinary function and reduces catheterization time. Focal ablation and hemigland ablation show promise in achieving cancer control when preserving continence and potency.
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OBJECTIVE: This study aims to provide an update on the clinical presentation, diagnostic workup, operative strategies, and midterm outcomes in children undergoing ventricular fibroma resection. METHODS: Single-center, retrospective cohort study of patients undergoing ventricular fibroma resection between 2000 and 2023. RESULTS: Among 52 patients, median age at surgery was 2.0 years (interquartile range, 0.8-4.6) and median tumor volume index was 69 mL/m2 (interquartile range, 49-169). Tumor distorted the atrioventricular valve/subvalvar apparatus in 30 patients (58%) and abutted major epicardial coronary arteries in 41 patients (79%). Surgery was indicated for arrythmia (n = 45, 86%), symptoms (n = 14, 27%), or hemodynamic compromise (n = 11, 21%). Tumor was debulked in 34 patients (65%), including the last 21 patients. Concomitant atrioventricular valvuloplasty was performed in 18 patients and ventricular cavity closure in 15 patients (29%). During a median follow-up of 2.4 years (interquartile range, 0.8-6.2), there was no mortality, cardiac arrests, heart transplants, or single ventricle palliation. The 15-year risk of reoperation and clinical ventricular tachycardia/fibrillation was 6.7% (95% CI, 0-14.3) and 2.4% (95% CI, 0-7.2), respectively. On latest imaging, pre- and postdebulking left ventricular ejection fraction did not significantly differ (P = .069), whereas no patients had signs of outflow tract obstruction, inflow tract obstruction, or moderate or greater atrioventricular valve regurgitation. CONCLUSIONS: Large ventricular fibromas can be resected safely with appropriate surgical planning and an emphasis on debulking. Most children maintain left ventricular function and remain free of recurrent ventricular arrhythmias at follow-up. Extended follow-up is warranted to understand whether patients remain at risk for scar-based ventricular arrhythmias in the future.
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Widespread adoption of mpMRI has led to a decrease in the number of patients requiring prostate biopsies. 68Ga-PSMA-11 PET/CT has demonstrated added benefits in identifying csPCa. Integrating the use of these imaging techniques may hold promise for predicting the presence of csPCa without invasive biopsy. A retrospective analysis of 42 consecutive patients who underwent mpMRI, 68Ga-PSMA-11 PET/CT, prostatic biopsy, and radical prostatectomy (RP) was carried out. A lesion-based model (n = 122) using prostatectomy histopathology as reference standard was used to analyze the accuracy of 68Ga-PSMA-11 PET/CT, mpMRI alone, and both in combination to identify ISUP-grade group ≥ 2 lesions. 68Ga-PSMA-11 PET/CT demonstrated greater specificity and positive predictive value (PPV), with values of 73.3% (vs. 40.0%) and 90.1% (vs. 82.2%), while the mpMRI Prostate Imaging Reporting and Data System (PI-RADS) 4-5 had better sensitivity and negative predictive value (NPV): 90.2% (vs. 78.5%) and 57.1% (vs. 52.4%), respectively. When used in combination, the sensitivity, specificity, PPV, and NPV were 74.2%, 83.3%, 93.2%, and 51.0%, respectively. Subgroup analysis of PI-RADS 3, 4, and 5 lesions was carried out. For PI-RADS 3 lesions, 68Ga-PSMA-11 PET/CT demonstrated a NPV of 77.8%. For PI-RADS 4-5 lesions, 68Ga-PSMA-11 PET/CT achieved PPV values of 82.1% and 100%, respectively, with an NPV of 100% in PI-RADS 5 lesions. A combination of 68Ga-PSMA-11 PET/CT and mpMRI improved the radiological diagnosis of csPCa. This suggests that avoidance of prostate biopsy prior to RP may represent a valid option in a selected subgroup of high-risk patients with a high suspicion of csPCa on mpMRI and 68Ga-PSMA-11 PET/CT.
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The recurrence rate following endoscopic treatment of non-muscle-invasive bladder cancer (NMIBC) remains high. Standard treatment includes intravesical instillation of chemotoxic agents such as mitomycin C (MMC) to reduce recurrence. It is postulated that upfront administration of hyperthermic intravesical MMC (HIVEC) immediately after transurethral resection of bladder tumour (TURBT) may enhance its efficacy, but evidence from human trials is scant. This pilot study explored the safety of immediate intravesical MMC instillation following TURBT using a conductive HIVEC system (Combat BRS). Patients diagnosed with papillary bladder tumours scheduled for TURBT were recruited. Among 29 patients treated with HIVEC, there was minimal additional postoperative morbidity. The majority (79.3%) were discharged after a hospital stay of 1 d, and no patient required bladder irrigation. There were six grade I-II adverse events (20.7%) and one grade III event (3.4%). No recurrences were observed within 3 mo, and the 12-mo recurrence rate was 4.5%. The study findings demonstrate that immediate HIVEC MMC instillation following TURBT is safe. Further research is needed to assess long-term efficacy in comparison to standard cold MMC. PATIENT SUMMARY: Non-muscle-invasive bladder cancer is treated with tumour removal via a telescope inserted into the bladder through the urethra (called TURBT). We tested the safety of treating the bladder with a warm solution of a chemotherapy drug (mitomycin C) immediately after TURBT, as this may prevent tumour recurrence. The treatment was safe and well tolerated. Further trials are needed with more patients and longer follow-up to confirm the results.
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BACKGROUND AND OBJECTIVE: Conventionally, standard resection (SR) is performed by resecting the bladder tumour in a piecemeal manner. En bloc resection of the bladder tumour (ERBT) has been proposed as an alternative technique in treating non-muscle-invasive bladder cancer (NMIBC). The objective of this study is to investigate whether ERBT could improve the 1-yr recurrence rate of NMIBC, as compared with SR. METHODS: A multicentre, randomised, phase 3 trial was conducted in Hong Kong. Adults with bladder tumour(s) of ≤ 3cm were enrolled from April 2017 to December 2020, and followed up until 1 yr after surgery. Patients were randomly assigned to receive either ERBT or SR in a 1:1 ratio. The primary outcome was 1-yr recurrence rate. A modified intention-to-treat analysis on patients with histologically confirmed NMIBC was performed. The main secondary outcomes included detrusor muscle sampling rate, operative time, hospital stay, 30-d complications, any residual or upstaging of disease upon second-look transurethral resection, and 1-yr progression rate. KEY FINDINGS AND LIMITATIONS: A total of 350 patients underwent randomisation, and 276 patients were histologically confirmed to have NMIBC. At 1 yr, 31 patients in the ERBT group and 46 in the SR group developed recurrence; the Kaplan-Meier estimate of 1- yr recurrence rates were 29% (95% confidence interval, 18-37) in the ERBT group and 38% (95% confidence interval, 28-46) in the SR group (p = 0.007). Upon a subgroup analysis, patients with 1-3 cm tumour, single tumour, Ta disease, or intermediate-risk NMIBC had a significant benefit from ERBT. None of the patients in the ERBT group and three patients in the SR group developed progression to muscle-invasive bladder cancer; the Kaplan-Meier estimates of 1-yr progression rates were 0% in the ERBT group and 2.6% (95% confidence interval, 0-5.5) in the SR group (p = 0.065). The median operative time was 28 min (interquartile range, 20-45) in the ERBT group and 22 min (interquartile range, 15-30) in the SR group (p < 0.001). All other secondary outcomes were similar in the two groups. CONCLUSIONS AND CLINICAL IMPLICATIONS: In patients with NMIBC of ≤ 3cm, ERBT resulted in a significant reduction in the 1-yr recurrence rate when compared with SR. The study results support ERBT as the first-line surgical treatment for patients with bladder tumours of≤ 3cm.
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Cistectomía , Recurrencia Local de Neoplasia , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/cirugía , Neoplasias de la Vejiga Urinaria/patología , Masculino , Femenino , Anciano , Cistectomía/métodos , Persona de Mediana Edad , Resultado del Tratamiento , Uretra/cirugía , Factores de TiempoRESUMEN
BACKGROUND AND OBJECTIVE: Treatment preference regarding apalutamide versus enzalutamide in prostate cancer (PCa) and the factors influencing decisions are largely unknown. Our aim was to investigate the preference for apalutamide versus enzalutamide among prostate cancer patients and their physicians and caregivers, and factors influencing their decision. METHODS: This was a prospective, open-label, randomized, crossover trial. Patients with recurrence of localized PCa or with metastatic disease not considered as high-risk or high-volume and on continued androgen deprivation therapy were recruited. All subjects received a trial of two agents, apalutamide (A) and enzalutamide (E), for 12 wk each, with a 5-wk washout period in between. The sequencing of the drugs was randomized. The primary outcome was patient preference for one the drugs, assessed at the end of the study. Other outcomes included factors influencing patient preference, a comparison of side-effect profiles, and patients' quality of life (QoL). Physician and caregiver preferences for the drugs and factors affecting their choice were also assessed. KEY FINDINGS AND LIMITATIONS: A total of 74 patients met the eligibility criteria and were randomized to the A â E or E â A arm. Of these, 66 patients (89.1%; 32 A â E, 34 E â A) completed the study. Baseline characteristics were comparable between the two groups, and â¼90% of the patients had low-volume metastatic disease. After completion of both treatments for 12 wk each, the difference in preference for A over E was 17.8%, with similar trends for preference of A over E among physicians (18.2%) and caregivers (22.4%). Fewer side effect was the most critical factor influencing the preference of patients. Among the side effects, less fatigue was the benefit of A over E most frequently reported. No notable difference in QoL was observed between the two drugs. However, the study was terminated on interim analysis and the results might not be conclusive. CONCLUSIONS: There was a trend for preference of A over E among patients with predominantly low-volume recurrent or metastatic PCa and their physicians and caregivers. Fewer side effects was the most critical factor influencing their choice. PATIENT SUMMARY: Patients with low-volume recurrent or metastatic prostate cancer tended to prefer treatment with apalutamide over enzalutamide. Side effects were the most critical factor influencing treatment preference.
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Perineo , Próstata , Neoplasias de la Próstata , Recto , Humanos , Masculino , Neoplasias de la Próstata/patología , Próstata/patología , Biopsia/métodosRESUMEN
Purpose: In the era of concurrent combination therapy in metastatic hormone sensitive prostate cancer, the impact of the testosterone level before initiating androgen deprivation therapy on treatment outcome is still uncertain. We aimed to investigate its effect on time-to-castration-resistance in a metastatic hormone sensitive prostate cancer cohort. Methods: This is a multi-center retrospective study of 5 databases from China, Japan, Austria and Spain including 258 metastatic hormone sensitive prostate cancer patients with androgen deprivation therapy initiated between 2002 and 2021. Baseline testosterone was divided into high and low groups using 12 nmol/L as cutoff level. Primary outcome was time-to-castration-resistance. Secondary outcomes were survival functions. Kaplan-Meier method was employed to evaluate the correlation between baseline testosterone and time-to-castration-resistance. Subgroup analysis was performed to elucidate the effect of upfront combination-therapy and metastatic volume. Results: Median age was 72 years. Median follow-up time was 31 months. Median pre-treatment prostate-specific-antigen level was 161 ng/mL. Majority of case were graded as International-Society-of-Urological-Pathology grade 5 (63.6%). 57.8% patients had high volume disease and 69.0% received upfront combination treatment. 44.6% of the cohort developed castration-resistance. The low testosterone group demonstrated shorter mean-time-to-castration-resistance (19.0 vs 22.4 months, p=0.031). The variance was more significant in patients without combination therapy (13.2 vs 26.3 months, p=0.015). Cancer-specific and overall survival were inferior in the low baseline testosterone level group without receiving combination therapy (p=0.001). Conclusions: Lower pre-treatment testosterone level is correlated to shorter time-to-castration resistance and worse survival in metastatic prostate cancer patients without upfront combination therapy. Those with low baseline testosterone should be encouraged to adopt combination therapy to delay progression.
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Background: The narrower focal zone (FZ) size of modern lithotripter was considered as one of the factors that resulted in suboptimal treatment result of extracorporeal shockwave lithotripsy (SWL). Therefore, we investigate the efficacy and safety of standard narrow or extended (FZ) sizes in SWL for patients with renal stones. Materials and Methods: In this prospective study conducted between April 2018 and October 2022, patients with renal stones were randomized to receive SWL with either standard or extended FZ. Treatment was delivered using a Modulith SLX-F2 lithotripter with a maximum of 3000 shocks at 1.5 Hz. The primary outcome was treatment success 12 weeks after a single SWL session, defined as the absence of a stone or stone fragment <4 mm on computed tomography. Secondary outcomes included the incidence of perinephric hematoma, stone-free rate (SFR), and changes in the urinary levels of acute renal injury markers. Results: A total of 320 patients were recruited, and 276 patients were randomized into the two groups. The two groups had similar baseline parameters. The treatment success rate was significantly better for standard FZ (74.3%) than the extended FZ group (59.3%) (p = 0.009). Standard FZ also had a significantly better SFR (Grade-A, 36.8% vs 23.0%, p = 0.013) and less pain after treatment. Both groups had similar perinephric hematoma formation rates, unplanned hospital admission rates, and changes in urinary acute renal injury markers. Conclusions: The standard narrow FZ has better treatment efficacy and similar safety compared with the extended FZ during SWL for renal stones. This clinical trial has been registered in the public domain (CCRBCTR) under trial number CUHK_CCRB00510.
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Cálculos Renales , Litotricia , Humanos , Cálculos Renales/terapia , Litotricia/efectos adversos , Litotricia/métodos , Masculino , Femenino , Estudios Prospectivos , Persona de Mediana Edad , Resultado del Tratamiento , Adulto , Riñón , Anciano , Lesión Renal Aguda/etiología , Lesión Renal Aguda/terapiaRESUMEN
PURPOSE: The study aimed at investigating prostate cancer patients' choice of androgen deprivation treatment (ADT) and possible factors that would affect their preferences of ADT. METHODS: This was a single-centre cross-sectional study investigating the usage and preferences of ADT. Consecutives prostate cancer patients who were receiving injectable luteinizing hormone-releasing hormone (LHRH) agonist or antagonist were recruited from the prostate cancer clinic in a tertiary academic hospital. Patients who received bilateral orchidectomy or those who could not consent to the study were excluded. Disease characteristics, treatment information and patient background were documented. The survey collected information related to their change in ADT regimen, preferences on drug usage (routes and frequency of administration) and their reasons. A hypothetical set of three drug formularies was designed. Questions regarding patient preference and the contributing reasons raised in the format of questionnaire. RESULTS: 100 patients completed the survey. Most patients started with more frequent injections (3-monthly, 54%; 1-monthly, 38%) and switched to 6-monthly injections (89%) at the time of the survey. Primary reasons for the change were healthcare opinion (72%) and less frequent treatment (51%). Three options of ADT (oral daily, 1-monthly and 6-monthly injection) with the same efficacies and side effect profile were offered: 61% preferred 6-monthly injection, 1% preferred 1-monthly injection and 38% preferred oral regimen. When patients were informed of lower cardiovascular side effects in 1-monthly injection or daily oral drug, patients' preference was 56% (6-monthly), 6% (1-monthly), and 39% (oral). Patients with polypharmacy (more than 5 regular medications) were more inclined to choose injections (p = 0.025). Patient age, educational background, employment status, marriage status and disease status were not found to be statistically significant contributing factors to patient preference. CONCLUSION: 6-monthly ADT injection was the preferred ADT despite greater cardiovascular risks. Among 1-monthly or daily oral LHRH antagonist, more patients prefer oral option. Convenience factor was highly valued.
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Antagonistas de Andrógenos , Hormona Liberadora de Gonadotropina , Prioridad del Paciente , Neoplasias de la Próstata , Humanos , Masculino , Estudios Transversales , Neoplasias de la Próstata/tratamiento farmacológico , Anciano , Antagonistas de Andrógenos/administración & dosificación , Antagonistas de Andrógenos/uso terapéutico , Persona de Mediana Edad , Administración Oral , Hormona Liberadora de Gonadotropina/agonistas , Inyecciones , Esquema de Medicación , Pueblo Asiatico , Encuestas y Cuestionarios , Anciano de 80 o más AñosRESUMEN
BACKGROUND AND PURPOSE: This prospective study aimed to investigate adaptive magnetic resonance (MR)-guided stereotactic body radiation therapy (MRgSBRT) with rectal spacer for localized prostate cancer (PC) and report 1-year clinical outcomes. MATERIALS AND METHODS: Thirty-four consecutive patients with low- to high-risk localized PC that underwent 5-fraction adaptive MRgSBRT with rectal spacer were enrolled. The dosimetric comparison was performed on a risk- and age-matched cohort treated with MRgSBRT but without a spacer at a similar timepoint. Clinician-reported outcomes were based on Common Terminology Criteria for Adverse Events. Patient-reported outcomes were based on the Expanded Prostate Cancer Index Composite (EPIC) questionnaire at baseline, acute (1-3 months), subacute (4-12 months), and late (> 12 months) phases. RESULTS: The median follow-up was 390 days (range 28-823) and the median age was 70 years (range 58-82). One patient experienced rectal bleeding soon after spacer insertion that subsided before MRgSBRT. The median distance between the midline of the prostate midgland and the rectum after spacer insertion measured 7.8 mm (range 2.6-15.3), and the median length of the spacer was 45.9 mm (range 16.8-62.9) based on T2-weighted MR imaging. The use of spacer resulted in significant improvements in target coverage (V100% > 95% = 98.6% [range 93.4-99.8] for spacer vs. 97.8% [range 69.6-99.7] for non-spacer) and rectal sparing (V95% < 3 cc = 0.7 cc [range 0-4.6] for spacer vs. 4.9 cc [range 0-12.5] for non-spacer). Nine patients (26.5%) experienced grade 1 gastrointestinal toxicities, and no grade ≥ 2 toxicities were observed. During the 1-year follow-up period, EPIC scores for the bowel domain remained stable and were the highest among all other domains. CONCLUSIONS: MRgSBRT with rectal spacer for localized PC showed exceptional tolerability with minimal gastrointestinal toxicities and satisfactory patient-reported outcomes. Improvements in dosimetry, rectal sparing, and target coverage were achieved with a rectal spacer. Randomized trials are warranted for further validation.