Deep PSA response and extended time-to-nadir as robust predictors of survival in Asian patients with de novo metastatic hormone-sensitive prostate cancer receiving upfront intensified treatment.

INTRODUCTION: In de novo metastatic hormone-sensitive prostate cancer (mHSPC) treated with upfront intensification using androgen receptor signaling inhibitor or chemotherapy (Docetaxel), achieving a PSA nadir less than 0.2 ng/mL, indicative of superior survival in trials, may often be unattainable in real-world settings. We explored the predictive value of the degree of PSA decline and time to PSA nadir (TTPN) on oncological outcomes. METHODS: A prospectively maintained database of consecutive prostate cancer cases in Hong Kong was accessed. Patients diagnosed with de novo mHSPC from 2016 to 2022 and treated with upfront intensification were included in this analysis. Landmark analysis on PSA kinetics at 6-months following treatment intensification was performed. They were classified based on 1) TTPN (≥6 months vs. <6 months), and 2) a combined response (deep responders achieving both ≥95% PSA decline and TTPN ≥ 6 months vs. shallow responders). Multivariable regression analysis was employed to identify the effects of confounders. FINDINGS: A total of 131 patients were included in this analysis. Classifying patients by combined response best predicted survival outcomes. Deep responders had better progression-free survival (HR = 0.56; 95%CI = 0.34-0.91; p = 0.019), overall survival (HR = 0.50; 95%CI = 0.26-0.97; p = 0.036), and cancer-specific survival (HR = 0.43; 95%CI = 0.19-0.99; p = 0.042). Difference in overall survival remained significant after adjustment in multivariable regression analysis. CONCLUSION: Our analysis demonstrates that alternative PSA targets can predict treatment response and survival outcomes in de novo mHSPC patients in a real-world setting, providing valuable information for patient counselling and potentially guiding future trial design.

Effect of Stepwise Voltage Escalation on Treatment Outcomes following Extracorporeal Shock Wave Lithotripsy of Renal Calculi: A Prospective Randomized Study.

PURPOSE: In this study we assessed the effects of a ramping protocol in patients undergoing extracorporeal shock wave lithotripsy of renal stones. MATERIALS AND METHODS: In this prospective study patients with renal stones were randomized to receive shock wave lithotripsy delivered using a ramping protocol in group 1 (first 1,000 shocks at energy level 5 followed by 1,000 shocks at energy level 6 and 1,000 final shocks at energy level 7) and a fixed voltage protocol in group 2 (all 3,000 shocks at energy level 7). Treatment was administered using a Modulith® SLX-F2. The primary outcome was treatment success 12 weeks after a single shock wave lithotripsy session, defined as lack of a stone or a less than 4 mm stone fragment on computerized tomography. Other outcomes included the stone-free rate and the perinephric hematoma incidence. RESULTS: A total of 300 patients (150 per group) were recruited between February 2016 and June 2018. The 2 groups did not differ in baseline parameters. Group 1 received 14.8% lower energy than group 2, which was significant (p <0.001). The treatment success rate in groups 1 and 2 was 67.8% and 73.6%, respectively, which did not statistically differ (group 1 crude OR 0.753, 95% CI 0.456-1.244, p=0.268). The stone-free rate in groups 1 and 2 was 36.6% and 41.9%, respectively, which did not differ statistically between the groups. However, in groups 1 and 2 perinephric hematoma developed in 23.8% and 43.8% of patients, respectively, which was a statistically significant difference (p <0.001). CONCLUSIONS: The fixed voltage shock wave lithotripsy and ramping protocols provided similar treatment success rates for renal stones. However, the ramping protocol reduced the incidence of perinephric hematoma after shock wave lithotripsy.

Effect of Focal Zone Size on Treatment Outcomes and Renal Injury Following Extracorporeal Shockwave Lithotripsy of Renal Calculi: A Prospective Randomized Study.

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.

A cross-sectional study on gut microbiota in prostate cancer patients with prostatectomy or androgen deprivation therapy.

BACKGROUND: Androgen deprivation therapy (ADT), either by medical or surgical castration, is the backbone for standard treatment of locally advanced or metastatic prostate cancer, yet it is also associated with various metabolic and cardiovascular complications. Recent evidence have shown that obesity, insulin resistance, or metabolic disturbances can be associated with changes in the gut microbiome, while animal studies also show that castration is associated with changes in the gut microbiome. This study aims to investigate whether the fecal microbiota in prostate cancer patients who had undergone prostatectomy or ADT are different, and explore changes in phylogeny and pathways that may lead to side effects from ADT. METHODS: A total of 86 prostate cancer patients (56 patients on ADT and 30 patients with prostatectomy) were recruited. The fecal microbiota was analyzed by the 16S rRNA gene for alpha- and beta-diversities by QIIME2, as well as the predicted metabolic pathways by Phylogenetic Investigation of Communities by Reconstruction of Unobserved States 2. RESULTS: The alpha-diversity was significantly lower in the ADT group. The beta-diversity was significantly different between the groups, in which Ruminococcus gnavus and Bacteroides spp were having higher relative abundance in the ADT group, whereas Lachnospira and Roseburia were reduced. The Firmicutes-to-Bacteroidetes ratio is noted to be lower in the ADT group as well. The functional pathway prediction showed that the biosynthesis of lipopolysaccharide (endotoxin) and propanoate was enriched in the ADT as well as the energy cycle pathways. This study is limited by the cross-sectional design and the clinical heterogeneity. CONCLUSIONS: There is a significant difference in gut microbiome between prostate cancer patients on ADT and prostatectomy. We theorize that this difference may contribute to the development of metabolic complications from ADT. Further longitudinal studies are awaited.

Effect of androgen deprivation therapy on cardiovascular function in Chinese patients with advanced prostate cancer: a prospective cohort study.

Androgen deprivation therapy (ADT) is the standard treatment for advanced prostate cancer, but its effect on cardiovascular and metabolic function in Asian patients is still inconclusive. We prospectively assess the effects of ADT on 36 patients with advanced prostate cancer, with reference to another 24 prostate cancer patients not requiring ADT, for 2 years. Patients' anthropometric, metabolic and vascular parameters were assessed every six-monthly. The baseline parameters of the two groups were comparable. There was a significant negative effect of the usage of ADT on the changes in BMI (p = 0.020), waist to hip ratio (p = 0.005), body fat percentage (p = 0.012), and high-density-lipoprotein (p = 0.012). ADT-patients were 4.9 times more likely to have metabolic syndrome at 24 months. (CI 0.889-27.193, p = 0.068). The Framingham risk score (p = 0.018) and pulse-wave-velocity (p = 0.024) for ADT-group were also significantly higher than controls, which signified increase in cardiovascular risk. Although there was no statistically significant difference in ischemic cardiovascular events between two groups, a trend for more events in ADT-group was observed. Therefore, Asian patients have increased cardiovascular and metabolic risks after being treated with ADT for two years. Appropriate counselling and monitoring of associated complications with ADT are essential.

Extracorporeal Shockwave Lithotripsy Could Lead to a Prolonged Increase in the Renal Fibrotic Process of Up to 2 Years.

INTRODUCTION AND OBJECTIVE: This prospective study aimed to evaluate the effect of ramping and pause protocols on renal fibrosis, blood pressure control, and renal function in patients receiving extracorporeal shockwave lithotripsy (SWL). PATIENTS AND METHODS: This study prospectively recruited 320 patients with solitary radiopaque renal stones <15 mm in size. Patients were randomized to receive one of four shockwave protocols: (1) standard protocol (no ramping or pause); (2) ramping protocol alone; (3) ramping and pause protocols; or (4) pause protocol alone. Spot urine samples were collected before and for 2 years after treatment to monitor the levels of the renal fibrosis marker procollagen III aminoterminal propeptide (PIIINP) by blinded research staffs. Blood pressure and serum creatinine levels were also monitored during follow-up. RESULTS: The four groups had comparable baseline data and treatment parameters. Significant increases (p < 0.05) in the urinary PIIINP levels from 6 weeks until 18 months after SWL were observed among all patients and in individual groups. PIIINP levels peaked at 1 year after SWL and gradually decreased to the baseline at 2 years. At the 2-year follow-up point, the overall serum creatinine levels remained significantly elevated (76.21-80.01 µmol/L, p < 0.001). Twenty (9.95%) patients developed new-onset hypertension and another 43 (36.4%) experienced worsening blood pressure control. However, no differences were observed among the four treatment groups. CONCLUSIONS: SWL led to significant increases in renal fibrosis marker levels for up to 18 months after treatment. However, no differences in changes in renal fibrosis marker and serum creatinine levels and worsening of blood pressure control were observed with respect to the use of either ramping or pause treatment protocols.