Ahmed, Mohamed E.

144 Background: Despite having well-recognized limitations, urologists often rely on serial PSA testing as a marker for treatment response or disease progression. To determine if PSA was indeed a reliable marker for treatment response or disease progression, we compared PSA levels against C-11 choline PET/CT in the evaluation of patients with advanced prostate cancer treated with second generation hormonal therapy (2nd-HT). Methods: We retrospectively identified 239 patients who were undergoing treatment with 2nd-HT (enzalutamide or abiraterone) for advanced prostate cancer. While on treatment, patients underwent serial PSA testing and C-11 choline PET/ CTs every 3 – 6 months. Paradoxical response was defined as increasing blood pool-corrected SUVmax of known choline-avid lesions and/or identification of new choline-avid lesions, despite stable or down-trending PSA. Results: Median (IQR) age was 70.4(64.3 – 75.7) years and median (IQR) primary Gleason Score was 8 (7 – 9). In our study, 19% of patients (n = 46/239) who were receiving 2nd-HT exhibited paradoxical response. Median (IQR) PSA and corrected SUVmax at baseline evaluation were 1.3 ng/mL (0.3 – 12.8 ng/mL) and 3.5 (1.8 – 5.8), respectively. Median (IQR) PSA and corrected SUVmax at the time of paradoxical response were 0.4 ng/mL (0.1 – 5.4 ng/mL) and 4.5 (2.8 – 6.8), respectively. The median duration of 2nd-HT treatment prior to detection of paradoxical response was 4.8 months (2.9 – 10.1 months). No significant difference was noted between patients receiving enzalutamide versus abiraterone (p = 0.35). Independent predictors of paradoxical response were prior primary systemic treatment (i.e. hormonal/chemo-hormonal therapy versus local therapy) and patient’s age at time of 2nd-HT initiation on univariate and multivariate analysis. Conclusions: Our retrospective review demonstrated prostate cancer disease progression discordant with PSA down-trending in 19% of patients receiving 2nd-HT. We conclude that in this subset of patients with advanced prostate cancer, PSA may not be a reliable marker of treatment response of disease progression, and routine radiographic evaluation in these patients is warranted.

143 Background: Systemic treatment in the management of metastatic prostate cancer is inevitable. However, there is a growing interest in metastases-directed therapy (MDT). We sought to investigate the efficacy of MDT in treating patients with solitary metastatic prostate cancer and hence, delaying initiation of systemic treatment (i.e., Androgen deprivation therapy or chemotherapy). Methods: We retrospectively identified 61 patients treated with targeted therapy in the form of surgery (n = 30), stereotactic body radiation therapy (SBRT) (n = 25), or cryotherapy (n = 7) for their solitary metastases prostate cancer. Complete response was defined by achieving a PSA value of ≤0.2 ng/ml plus resolution of the solitary metastatic lesion on C-11 choline PET choline scan, while incomplete response was defined by a residual PSA of > 0.2 ng/ml and/or radiographic evidence of disease following metastases-targeted therapy. Results: Mean (±SD) age was 68.4 (±7.8) yrs., median (IQR) primary Gleason Score was 7 (7-9) and median (IQR) pre-MDT PSA was 2 (1.3-3.8) ng/ml. Median (IQR) time from primary treatment of the prostate to MDT was 5.1 (2.7-10.1) years. None of the patients were on hormone therapy at the time of presentation with solitary metastases prostate cancer. 30 patients had bone metastases, 29 patients had lymph node metastases, 1 patient had soft tissue metastasis (pelvic metastatic mass), and another patient had visceral metastasis (to the lung). 42% of the patients (n = 26) achieved complete response to targeted therapy. Median time to initiation of 2nd line systemic treatment following MDT was 17.8 months for the complete responders versus 9.3 months for incomplete responders. 11% of the patients (n = 7) did not require 2nd line therapy after their MDT for a mean (±SD) time of 56.9 (±22.5) months. Conclusions: The use of targeted therapy in the management of patients with solitary metastatic disease or low-volume metastatic disease can provide comparable outcomes to those of systemic treatment. Further studies are warranted.

AbstractBackgroundOptimal sequencing of systemic therapy in the management for metastatic castration resistant prostate cancer (mCRPC) remains poorly elucidated. The CHAARTED and STAMPEDE studies have proven that early chemotherapy in the hormone‐sensitive setting yields a greater net survival advantage than docetaxel for mCRPC. In a retrospective study, we attempt to investigate the two most common treatment sequences for mCRPC and investigate whether earlier chemotherapy for mCRPC is consequential to survival outcomes.MethodsWe identified 112 patients with mCRPC treated at the Mayo Clinic between 2011 and 2017. We identified two cohorts, 80 patients (group A) received full course docetaxel chemotherapy followed by second generation hormone therapy (2nd gen androgen deprivation therapy [ADT]; Abiraterone or Enzalutamide) and 32 patients (group B) treated with 2nd gen ADT followed by docetaxel. The primary endpoint evaluated was 3‐year cancer‐specific survival.ResultsMean prostate specific antigen at initiation of first treatment was 32.0 in group A and 21.7 in group B (P = .4). Bone metastases were more prevalent in group B (87% vs 58%, P = .01). All other clinicopathologic variables were statistically similar between group A and group B. Three‐year cancer‐specific survival was 87.4% vs 64.1% for group A and group B, respectively (P = .016). We report a univariate hazard ratio of 3.61 (95% CI, 1.74‐9.5, 0 P = .01). Three‐year overall survival was 82.4% and 60.8% for group A and group B, P = .01. These results held true when excluding patients with lymph node only metastasi.ConclusionOur data indicates that sequence of systemic therapy may influence outcomes for mCRPC and that docetaxel should be considered before 2nd generation ADT. Our results support the importance of earlier chemotherapy in the castration resistant state.

Purpose: Pelvic lymph node dissection is an important step during robotic radical prostatectomy. The collection of lymphatic fluid (lymphocele) is the most common complication with potentially severe impact; therefore, different strategies have been proposed to reduce its incidence. Materials and Methods: In this systematic review, EMBASE, MEDLINE, Cochrane Library, and NIH Registry of Clinical Trials were searched for articles including the following interventions: transperitoneal vs extraperitoneal approach, any reconfiguration of the peritoneum, the use of pelvic drains, and the use of different sealing techniques and sealing agents. The outcome evaluated was the incidence of symptomatic lymphocele. Randomized, nonrandomized, and/or retrospective studies were included. Results: Twelve studies were included (including one ongoing randomized clinical trial). Because of heterogeneity of included studies, no meta-analysis was performed. No significant impact was reported by different sealing techniques and agents or by surgical approach. Three retrospective, nonrandomized studies showed a potential benefit of peritoneal reconfiguration to maximize the peritoneal surface of reabsorption. Conclusion: Lymphocele formation is a multistep and multifactorial event; high-quality literature analyzing risk factors and preventive measures is rather scarce. Peritoneal reconfiguration could represent a reasonable option that deserves further evaluation; no other preventive measure is supported by current evidence.

ABSTRACT Kidney stone disease involves the aggregation of stone-forming salts consequent to solute supersaturation in urine. The development of novel therapeutic agents for this predominantly metabolic and biochemical disorder have been hampered by the lack of a practical pre-clinical model amenable to drug screening. Here, Drosophila melanogaster, an emerging model for kidney stone disease research, was adapted as a high-throughput functional drug screening platform independent of the multifactorial nature of mammalian nephrolithiasis. Through functional screening, the therapeutic potential of a novel compound commonly known as arbutin that specifically binds to oxalate, a key component of kidney calculi, was identified. Through isothermal titration calorimetry, high-performance liquid chromatography and atomic force microscopy, arbutin was determined to interact with calcium and oxalate in both free and bound states, disrupting crystal lattice structure, growth and crystallization. When used to treat patient urine samples, arbutin significantly abrogated calculus formation in vivo and outperformed potassium citrate in low pH urine conditions, owing to its oxalate-centric mode of action. The discovery of this novel antilithogenic compound via D. melanogaster, independent of a mammalian model, brings greater recognition to this platform, for which metabolic features are primary outcomes, underscoring the power of D. melanogaster as a high-throughput drug screening platform in similar disorders. This is the first description of the use of D. melanogaster as the model system for a high-throughput chemical library screen. This article has an associated First Person interview with the first authors of the paper.