Search Results (6)

Background: The efficacy of intermittent androgen deprivation therapy (ADT) for biochemical recurrence (BCR) after robot-assisted radical prostatectomy (RARP) is unknown, and its usefulness in Japanese practice needs to be investigated. Methods: We conducted a retrospective analysis of 85 patients who underwent RARP and were selected for intermittent ADT for postoperative recurrence at Kanazawa University Hospital between 2009 and 2019. Intermittent ADT was administered for 2 years. If prostate-specific antigen levels increased post-treatment, intermittent ADT was reinitiated. The median follow-up period was 47 months. Results: The 73 patients had completed the initial course of ADT, and 12 were under initial ADT. The 5-year castration-resistant prostate-cancer-free survival rates, cancer-specific survival, and overall survival were 92.7%, 98.3%, and 94.7%, respectively. A subgroup analysis of 69 patients who completed intermittent ADT was conducted to evaluate the BCR rate following initial ADT. The 5-year BCR-free survival rate was 53.2%. Multivariate analysis identified testosterone ≤ 0.03 ng/mL during ADT as the sole predictor of BCR after ADT. Conclusions: Salvage intermittent ADT may be an effective treatment option for BCR after RARP. In addition, it would be useful to confirm strong testosterone suppression as a criterion for transition to intermittent therapy. Full article

Debate has surrounded whether the participation of trans women in female sporting categories is fair, specifically the retained male physiological advantage due to increased testosterone compared to cisgender females. Recently, individual sporting organisations have been investigating and assessing policies regarding trans women athlete participation in female categories, resulting in several banning participation. This review aims to discuss the scientific evidence and provide appropriate guidance for the inclusion of trans women in elite competitive female fencing categories. Fencing is an intermittent sport, where competitions can span 1 to 3 days. The lunge is the most common movement used to attack opponents, where a successful hit relies on the speed of the action. Male puberty induced increased circulating testosterone promotes a greater stature, cardiovascular function, muscle mass, and strength compared to cisgender females, culminating in a ~12–40% sport performance advantage. Elite cisgender male fencers perform significantly higher, ~17–30%, jump heights and leg power measures compared to elite cisgender female fencers, resulting in faster lunges. Trans women receiving androgen-suppression therapy for 12 months showed significant reductions in strength, lean body mass, and muscle surface area, but even after 36 months, the measurements of these three indices remained above those for cisgender females. Previous male muscle mass and strength can be retained through continuation of resistance training. The literature reviewed shows that there is a retained physiological advantage for trans women who have undergone male puberty when participating in the elite competitive female fencing category. A proposed solution of an open or third gender category for elite fencing competition promotes fair competition, while allowing trans women to compete in their chosen sport. Full article

Previous studies on prostate cancer modeling under hormonal therapy successfully fit clinical serum androgen data, under the assumption that the levels of intracellular and serum androgen are similar. However, such an assumption may not hold throughout the course of treatment. In this paper, we propose a model that directly accounts for serum androgen and its interaction with intracellular androgen. We establish biological links between the model and clinical data, and discuss in detail parameter ranges and the initialization of model variables. We further investigate parameter sensitivity over time, which gauges the maximum effect of varying each parameter and allows us to fix some parameters, to increase the robustness of the parameter fitting process. By relying on the characteristics of intermittent androgen suppression therapy (IAS), we employ a two-part weighted error function for fitting. We also carry out mathematical analyses to study the dynamic aspects of the system with different androgen thresholds. We find that the proposed model shows superior forecasting ability, compared to its predecessor. Furthermore, we demonstrate the impact of androgen on the dynamics of the androgen-dependent and -independent cancer cells, which suggests the discrete description of androgen dependency may not give a realistic characterization of the cancer population. We show that IAS has certain characteristics that need to be considered for parameter estimation. Our results demonstrate that the model and the fitting scheme are viable for similar applications of prostate cancer modeling under hormonal therapy. Full article

Predicting the timing of a castrate resistant prostate cancer is critical to lowering medical costs and improving the quality of life of advanced prostate cancer patients. We formulate, compare and analyze two mathematical models that aim to forecast future levels of prostate-specific antigen (PSA). We accomplish these tasks by employing clinical data of locally advanced prostate cancer patients undergoing androgen deprivation therapy (ADT). While these models are simplifications of a previously published model, they fit data with similar accuracy and improve forecasting results. Both models describe the progression of androgen resistance. Although Model 1 is simpler than the more realistic Model 2, it can fit clinical data to a greater precision. However, we found that Model 2 can forecast future PSA levels more accurately. These findings suggest that including more realistic mechanisms of androgen dynamics in a two population model may help androgen resistance timing prediction. Full article

Intermittent androgen suppression (IAS) therapy for prostate cancer patients attempts to maintain the hormone dependence of the tumor cells by cycles alternating between androgen suppression (AS) and treatment cessation till a certain prostate-specific antigen (PSA) threshold is reached. Side effects are expected to be reduced, compared to standard continuous androgen suppression (CAS) therapy. The present study examined the effect of IAS on bone metabolism by determinations of serum procollagen I N-terminal peptide (PINP), a biochemical marker of collagen synthesis. A total of 105 treatment cycles of 58 patients with prostate cancer stages ≥pT2 was studied assessing testosterone, PSA and PINP levels at monthly intervals. During phases of AS lasting for up to nine months PSA levels were reversibly reduced, indicating apoptotic regression of the prostatic tumors. Within the first cycle PINP increased at the end of the AS period and peaked in the treatment cessation phase. During the following two cycles a similar pattern was observed for PINP, except a break in collagen synthesis as indicated by low PINP levels in the first months off treatment. Therefore, measurements of the serum PINP concentration indicated increased bone matrix synthesis in response to >6 months of AS, which uninterruptedly continued into the first treatment cessation phase, with a break into each of the following two pauses. In summary, synthesis of bone matrix collagen increases while degradation decreases during off-treatment phases in patients undergoing IAS. Although a direct relationship between bone matrix turnover and risk of fractures is difficult to establish, IAS for treatment of biochemical progression of prostate tumors is expected to reduce osteoporosis in elderly men often at high risk for bone fractures representing a highly suitable patient population for this kind of therapy. Full article

Androgen deprivation therapy (ADT) has been a cornerstone in the management of advanced prostate cancer for more than 50 years, but several aspects of the therapy remain controversial. Research since the mid-1980s has looked at the use of intermittent androgen suppression (IAS) as a way to reduce the side effects and costs of continuous androgen suppression. During that same time, testing for prostate-specific antigen resulted in forward stage migration both at diagnosis and at the time of treatment initiation. Earlier treatment has led to prolonged periods of ADT and increasing recognition of the resultant metabolic complications. With preclinical evidence suggesting a potential benefit for IAS in terms of time to androgen independence, with phase II and III studies producing optimistic results, and with the potential for reductions in cost and complications, IAS has become a popular modality of therapy around the globe. Large prospective randomized studies, currently ongoing, will ultimately determine the legitimate place of IAS in the treatment of prostate cancer. Full article