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The gold standard treatment for high-risk NMIBC is BCG immunotherapy. Some studies suggested an immomodulatory effects for commonly used drugs (ie, ACE-I and ARBs). We aimed to determine whether these drugs impact the prognosis of patients with high-risk NMIBC treated with BCG.Retrospective analysis on 208 patients from a single academic center with primary high-risk NMIBC treated with transurethral resection followed by 6 weekly instillations of BCG and up to 12 monthly maintenance instillations. ARBs or ACE-I use at the time of treatment initiation was recorded. Inverse probability of treatment weighting (IPTW) was used to adjust for clinical and pathological covariates. IPTW-adjusted Kaplan-Meier curves and weighted Cox proportional hazards regression were used to compare 2-yr failure-free (2-yr FFS), failure-free (FFS), overall recurrence-free (RFS) and progression-free survival (PFS).A total of 68 patients were on ACE-I, and 38 on ARBs and treatment respectively. At a median follow-up of 26 months, ACE-I treatment had no significant impact on cancer-related outcomes. Conversely, patients treated with ARBs experienced significant improvements in 2-yr FFS (HR 0.3; 0.1-0.9, P = .004), FFS (HR 0.4, 0.1-0.9, P = .005), and PFS (HR 0.001;0.001-0.001, P.001). No significant impact was found for ARB use in RFS (HR 0.6; P = .09). Sensitivity analyses confirmed these results.our findings support a potential role of the angiotensin-renin system in bladder cancer development. We identified ARBs as potential beneficial drugs that seems to act in synergy with BCG-immunotherapy.

INTRODUCTION Emerging evidence supports the hypothesis that metabolic syndrome is associated with cancer pathogenesis. In particular regarding prostate cancer, observational studies from various settings report different results. This systematic review and meta-analysis aim to provide a quantitative estimate of the association between metabolic syndrome in prostate cancer, in particular Gleason Score >6, accounting for different study designs. EVIDENCE ACQUISITION A systematic research of available literature in English language until 2020 was conducted through in EMBASE, MEDLINE, Cochrane Library and NIH Registry of Clinical Trials. For each study, information regarding the study design, the population, the definition of metabolic syndrome, data relating to prostate cancer were collected. , the association between MetS and outcome of interest was determined by calculating the generic inverse variance with random effects method. EVIDENCE SYNTHESIS In the final sample 19 studies were included with total of 114329 patients, 29.4% met the criteria for metabolic syndrome. We report a significant association between metabolic syndrome and prostate cancer in cross-sectional studies (OR 1.30; 95% CI 1.13, 1.49) and for patients with clinically significant prostate cancer (OR 1.56; 95% CI 1.23, 1.99]. Association between metabolic syndrome and prostate cancer combining all studies, in cohort studies and case-control studies was not significant. CONCLUSIONS Growing evidence support the association between metabolic syndrome and prostate cancer, bias derived from observational studies might conceal further findings.

Objective: To assess the relationship between the volume of the index lesion (IL) measured at multiparametric magnetic resonance imaging (mpMRI; MRIvol) and at radical prostatectomy (RPvol), stratifying it according to Prostate Imaging-Reporting and Data System (PI-RADS) score. Patients and Methods: We identified 332 men with a positive mpMRI (single lesion with PI-RADS ≥3) who underwent systematic plus targeted biopsy and subsequent RP at two tertiary referral centres between 2013 and 2018. All mpMRIs were reviewed by experienced radiologists using PI-RADS scores. The study outcome was to assess the relationship between MRIvol (based on planimetry from MRI sequence best showing tumour) and RPvol (based on tumour involved area of each RP pathology slice). To achieve this endpoint, we performed a multivariable linear regression analysis (LRA) to predict RPvol using PI-RADS, prostate-specific antigen level, prostate volume, age, digital rectal examination, Gleason score at MRI-targeted biopsy, biopsy history and time from mpMRI to RP as covariates. Non-parametric locally estimated scatterplot smoothing (LOESS) function was used to graphically explore the relationship between MRIvol and RPvol, stratifying for PI-RADS score. Results: Overall, 24%, 49% and 27% of men had visible PI-RADS 3, 4 and 5 lesions at mpMRI. The median (interquartile range [IQR]) MRIvol and RPvol were 0.67(0.29–1.76)mL and 1.39(0.58–4.23)mL. At LRA, MRIvol was significantly correlated with a RPvol underestimation (slope: 2.4, 95% confidence interval [CI] 0.1–46.3). The non-parametric LOESS analysis showed a non-linear relationship between MRIvol and RPvol. Significant underestimation was reported across all volumes with the highest differences between MRIvol and RPvol in the low volume range (

BackgroundSpatial transcriptomics (ST) combines stained tissue images with spatially resolved high-throughput RNA sequencing. The spatial transcriptomic analysis includes challenging tasks like clustering, where a partition among data points (spots) is defined by means of a similarity measure. Improving clustering results is a key factor as clustering affects subsequent downstream analysis. State-of-the-art approaches group data by taking into account transcriptional similarity and some by exploiting spatial information as well. However, it is not yet clear how much the spatial information combined with transcriptomics improves the clustering result.ResultsWe propose a new clustering method, Stardust, that easily exploits the combination of space and transcriptomic information in the clustering procedure through a manual or fully automatic tuning of algorithm parameters. Moreover, a parameter-free version of the method is also provided where the spatial contribution depends dynamically on the expression distances distribution in the space. We evaluated the proposed methods results by analysing ST datasets available on the 10x Genomics website and comparing clustering performances with state-of-the-art approaches by measuring the spots stability in the clusters and their biological coherence. Stability is defined by the tendency of each point to remain clustered with the same neighbours when perturbations are applied.ConclusionsStardust is an easy-to-use methodology allowing to define how much spatial information should influence clustering on different tissues and achieving more stable results than state-of-the-art approaches.

A 62-year-old man presented with a rising serum concentration of prostate-specific antigen (PSA) to 53.3 ng/mL (to convert to μg/L, multiply by 1) and a PSA doubling time of 2.6 months. Computed tomography, fluorodeoxyglucose–positron emission tomography, and C-11 choline positron emission tomography demonstrated a parotid mass with innumerable lytic bone lesions and diffuse metastatic disease to the neck and mediastinal lymph nodes. Mediastinal lymph node biopsy revealed salivary ductal adenocarcinoma that produced PSA and demonstrated androgen receptor sensitivity. The patient had a prolonged clinical benefit to first- and second-line hormone therapy, and his PSA levels correlated with treatment response, development of hormone resistance, and progression. In summary, urologists, pathologists, and primary care providers should be aware that a rising PSA level in the setting of a head and neck mass in a patient without a history of prostate cancer does not constitute a diagnosis of metastatic prostate adenocarcinoma and that other primary tumors should be considered and a broader imaging and pathologic evaluation is indicated.

Background The clinical course in metastatic castrate-resistant prostate cancer (mCRPC) can be complicated when patients have disease progression after prior treatment with second generation hormone therapy (second HT), such as enzalutamide or abiraterone. Currently, limited data exist regarding the optimal choice of chemotherapy for mCRPC after failing second generation hormone therapy. We sought to evaluate three common chemotherapy regimens in this setting. Methods We retrospectively identified 150 mCRPC patients with disease progression on enzalutamide or abiraterone. Of these 150 patients, 92 patients were chemo-naive while 58 patients had previously received docetaxel chemotherapy before being started on second HT. After failing second HT, 90 patients were assigned for docetaxel-alone (group A), 33 patients received carboplatin plus docetaxel (group B), while 27 patients received cabazitaxel-alone (Group C). A favorable response was defined by more than or equal to 50% reduction in prostate-specific antigen from the baseline level after a complete course of chemotherapy. Survival outcomes were assessed for 30-month overall survival. Results Patients in group (B) were 2.6 times as likely to have a favorable response compared to patients in group (A) (OR = 2.625, 95%CI: 1.15-5.99) and almost three times compared to patients in group (C) (OR = 2.975, 95%CI: 1.04-8.54) (P = .0442). 30-month overall survival was 70.7%, 38.9% and 30.3% for group (B), (A), and (C), respectively (P = .008). We report a Hazard Ratio of 3.1 (95% CI, 1.31-7.35; P = .0037) between patients in group (A) versus those in group (B) and a Hazard Ratio of 4.18 (95% CI, 1.58-11.06; P = .0037) between patients in group (C) compared to those in group (B) CONCLUSION: This data demonstrates improved response and overall survival in treatment-refractory mCRPC with a chemotherapy regimen of docetaxel plus carboplatin when compared to docetaxel alone or cabazitaxel alone. Further investigations are required.

Objectives The use of salvage open- radical prostatectomy (SRP) has not been studied in patients whose primary treatment, Robotic- assisted Laparoscopic prostatectomy (RALP), had failed. The aim of this study is to report our primary experience regarding technical feasibility and safety of salvage open radical prostatectomy (SRP) after robotic assisted laparoscopic prostatectomy (RALP). Methods We retrospectively reviewed the medical records of five patients (n=5) who had undergone SRP after RALP failure for clinically localized prostate cancer evidenced on imaging. Results The patients’ ages ranged from 53.1 to 65.4. They presented to us with raising PSA at their 1st post-RALP check. The median (IQR) post-RALP PSA was 1.98 (1.64 - 10) ng/ml with median (IQR) doubling time of 4 (1.8 -16.9) months. Patients underwent cross-sectional imaging (CT) and pelvic magnetic resonance imaging (MRI) that confirmed presence of residual prostatic tissue. Retropubic open salvage radical prostatectomy (SRP) was performed with no peri-operative or post-operative complications. The median follow-up duration was 7.8 years. Only one patient required addition of adjuvant salvage treatment after 9.3 yrs. for signs of cancer progression as evidenced on imaging and by raising PSA. Conclusion In this small case series, SRP was a safe and technically feasible option for management of locally recurrent prostate cancer with residual prostate left behind during primary RALP. Prolonged follow up and further studies are warranted to validate our findings.

Introduction: Adverse pathological features at radical prostatectomy such as extracapsular extension, seminal-vesicle involvement, positive surgical margins and/or lymph node invasion define a part...

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 seve...

Background Spatial transcriptomics (ST) combines stained tissue images with spatially resolved high-throughput RNA sequencing. The spatial transcriptomic analysis includes challenging tasks like clustering, where a partition among data points (spots) is defined by means of a similarity measure. Improving clustering results is a key factor as clustering affects subsequent downstream analysis. State-of-the-art approaches group data by taking into account transcriptional similarity and some by exploiting spatial information as well. However, it is not yet clear how much the spatial information combined with transcriptomics improves the clustering result. Results We propose a new clustering method, Stardust, that easily exploits the combination of space and transcriptomic information in the clustering procedure through a manual or fully automatic tuning of algorithm parameters. Moreover, a parameter-free version of the method is also provided where the spatial contribution depends dynamically on the expression distances distribution in the space. We evaluated the proposed methods results by analyzing ST data sets available on the 10x Genomics website and comparing clustering performances with state-of-the-art approaches by measuring the spots' stability in the clusters and their biological coherence. Stability is defined by the tendency of each point to remain clustered with the same neighbors when perturbations are applied. Conclusions Stardust is an easy-to-use methodology allowing to define how much spatial information should influence clustering on different tissues and achieving more stable results than state-of-the-art approaches.

The COVID-19 pandemic has resulted in immediate effects on urological practice, in particular the vast reduction in elective surgeries. These changes are likely to have long-term effects for both patients and for urologists, which will persist even after the pandemic resolves. The many facets of COVID-19’s effects on urology remain to be seen, but they might also offer opportunities to reassess and improve patient management in urology and beyond.

Introduction: Spermatic cord sarcomas represent a rare genitourinary malignancy with a challenging diagnostic and therapeutic pathway. Different histotypes have been described and prognostic factors remain poorly defined due to the paucity of data presented in literature. Methods: Retrospective chart review of 22 adult patients treated for spermatic cord sarcoma in a single institution in the last 20 years was performed. Clinicopathological characteristics of the tumors were collected with primary and subsequent treatment. Survival analysis was performed in order to identify prognostic factors of disease-specific survival. Results: The median age at diagnosis was 68 years (58–78), the most common histotype was liposarcoma (14/22), and most patients (63.6%) were found to have positive surgical margins after surgery. The 5-year cancer specific survival was 91.3%. Grading (p = 0.480), histotype (p = 0.327), and type of intervention (p = 0.732) were not associated with survival. All patients dead of disease had positive surgical margins (p = 0.172). Conclusion: We report a good prognosis at 5 years. Wide radical resection remains the first and probably the most important step; thus, according also to literature, negative surgical margins should be aimed.

INTRODUCTION AND OBJECTIVE:External beam radiotherapy (EBRT) with androgen deprivation therapy (ADT), EBRT with a brachytherapy boost (EBRT+BT) with ADT, and radical prostatectomy (RP) with or with...

INTRODUCTION AND OBJECTIVE:The clinical course in metastatic castrate resistant prostate cancer (mCRPC) can be complicated when patients have disease progression after prior treatment with 2nd gene...

INTRODUCTION AND OBJECTIVE:It is well standardized to report detailed MRI characteristics of the so-called index lesion (IL) defined as the lesion with either the highest PI-RADS score or the large...

INTRODUCTION AND OBJECTIVE:Curative intent therapies such as radical prostatectomy (RP) might represent an option in prostate cancer (PCa) patients with enlarged lymph nodes at imaging (cN1), no da...

INTRODUCTION AND OBJECTIVE:Patients treated with post-prostatectomy radiation therapy (RT) are exposed to a potential risk of genitourinary (GU) and gastrointestinal (GI) toxicity. However, it is s...

INTRODUCTION AND OBJECTIVE:A rapidly changing scenario in the management of patients with PSA rising after radical prostatectomy (RP) may have determined different patterns of salvage radiation the...

INTRODUCTION AND OBJECTIVE:Salvage radiation therapy (SRT) represents a curative treatment option for patients with prostate-specific antigen (PSA) rise after radical prostatectomy (RP). However, a...

INTRODUCTION AND OBJECTIVE:The STAMPEDE trial recently demonstrated a survival benefit for patients with oligometastatic prostate cancer (PCa) treated with androgen deprivation therapy (ADT) plus p...

INTRODUCTION AND OBJECTIVE:Salvage lymph node dissection (SLND) is among possible treatment options for patients with node-recurrent prostate cancer (PCa). It is well known that preoperative imagin...

Seeding of tumor cells is a rare complication of minimally invasive surgery. We reviewed and improved current knowledge of prostate cancer seeding.A literature review was performed using MEDLINE®, Embase® and the Cochrane Library, including cases of peritoneal and port site seeding reported after minimally invasive prostatectomy. In addition, after institutionally approved chart review a descriptive summary of a single institution experience on the topic is provided.The data from 9 reported cases of port site metastases from prostate cancer in the world literature are summarized along with 3 additional cases from our experience. Similarly, 5 cases of peritoneal seeding are reviewed from the literature with the addition of 3 more cases from our institution. Good long-term outcomes are achievable with multimodality and individualized regimens, including seeding directed treatments.Although no definitive recommendation can be made for treatment strategies for these patients, there is a need for awareness and further discussion of this atypical presentation.

Patients diagnosed with clinically node-positive prostate cancer represent a population that has historically been thought to harbor systemic disease. Increasing evidence supports the role of local therapies in advanced disease, but few studies have focused on this particular population. In this review we discuss the limited role for conventional cross sectional imaging for accurate nodal staging and how molecular imaging, although early results are promising, is still far from widespread clinical utilization. To date, evidence regarding the role of radical prostatectomy and pelvic lymph node dissection in clinically node-positive disease comes from retrospective studies; overall surgery appears to be a reasonable option in selected patients, with improved oncological outcomes that could be attributed to both to its potential curative role in disease localized to the pelvis and to the improved staging to help guide subsequent multimodal treatment. The role of surgery in clinically node-positive disease needs higher-level evidence but meanwhile, radical prostatectomy with extended pelvic lymph-node dissection can be offered as a part of a multimodality approach with the patient.

Key Points Question Is previously occult, nonlocalized (regional or metastatic) disease detected on prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) associated with clinically significant outcomes in patients with high-risk and very high-risk prostate cancer? Findings In this cohort study of 5275 patients, a nomogram estimative of an individual’s risk of nonlocalized disease on PSMA PET/CT was significantly associated with long-term outcomes, including distant metastasis and prostate cancer–specific mortality. The nomogram performed favorably compared with other risk-stratification tools. Meaning These findings suggest that previously occult disease may be associated with outcomes in this patient population., This cohort study evaluates the prognostic significance of a nomogram that models an individual’s risk of nonlocalized upstaging on prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) and compares its performance with existing risk-stratification tools., Importance Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) can detect low-volume, nonlocalized (ie, regional or metastatic) prostate cancer that was occult on conventional imaging. However, the long-term clinical implications of PSMA PET/CT upstaging remain unclear. Objectives To evaluate the prognostic significance of a nomogram that models an individual’s risk of nonlocalized upstaging on PSMA PET/CT and to compare its performance with existing risk-stratification tools. Design, Setting, and Participants This cohort study included patients diagnosed with high-risk or very high-risk prostate cancer (ie, prostate-specific antigen [PSA] level >20 ng/mL, Gleason score 8-10, and/or clinical stage T3-T4, without evidence of nodal or metastatic disease by conventional workup) from April 1995 to August 2018. This multinational study was conducted at 15 centers. Data were analyzed from December 2020 to March 2021. Exposures Curative-intent radical prostatectomy (RP), external beam radiotherapy (EBRT), or EBRT plus brachytherapy (BT), with or without androgen deprivation therapy. Main Outcomes and Measures PSMA upstage probability was calculated from a nomogram using the biopsy Gleason score, percentage positive systematic biopsy cores, clinical T category, and PSA level. Biochemical recurrence (BCR), distant metastasis (DM), prostate cancer–specific mortality (PCSM), and overall survival (OS) were analyzed using Fine-Gray and Cox regressions. Model performance was quantified with the concordance (C) index. Results Of 5275 patients, the median (IQR) age was 66 (60-72) years; 2883 (55%) were treated with RP, 1669 (32%) with EBRT, and 723 (14%) with EBRT plus BT; median (IQR) PSA level was 10.5 (5.9-23.2) ng/mL; 3987 (76%) had Gleason grade 8 to 10 disease; and 750 (14%) had stage T3 to T4 disease. Median (IQR) follow-up was 5.1 (3.1-7.9) years; 1221 (23%) were followed up for at least 8 years. Overall, 1895 (36%) had BCR, 851 (16%) developed DM, and 242 (5%) died of prostate cancer. PSMA upstage probability was significantly prognostic of all clinical end points, with 8-year C indices of 0.63 (95% CI, 0.61-0.65) for BCR, 0.69 (95% CI, 0.66-0.71) for DM, 0.71 (95% CI, 0.67-0.75) for PCSM, and 0.60 (95% CI, 0.57-0.62) for PCSM (P

In this study published in Urologic Oncology , Waingankar and the group form Mount Sinai (1) perform an analysis on the impact of pathological complete response to neoadjuvant chemotherapy (NAC) in muscle-invasive bladder cancer (MIBC) on conditional surviving, meaning the updated probability of surviving after having survived each additional year after the treatment.

Context Neoadjuvant chemotherapy (NAC) is recommended prior to radical cystectomy in the setting of muscle-invasive bladder cancer. Despite a 5–10% survival benefit, some patients do not respond to NAC. Identification of the nonresponders could avoid side effects and delay in surgery. Objective The objective of this review is to summarize the latest evidence regarding predictors of NAC response. Evidence acquisition MEDLINE, Embase, and the Cochrane Library databases were searched for published studies including clinical, pathological, molecular, and imaging tests or factors that can be applied before or during NAC to predict its results. Evidence synthesis Patient characteristics and imaging techniques seem to have minimal utility to predict NAC response. Only advanced magnetic resonance imaging techniques seem to have a potential role. There is insufficient evidence to suggest a change in NAC paradigm for variant histology, whereas the most promising results come from molecular characterization of tumors. Conclusions No validated instrument currently exists to predict NAC response. While awaiting further evidence, no strong recommendation can be made toward a shift in paradigm. Patient summary The most effective and aggressive treatment for muscle-invasive bladder cancer is radical cystectomy preceded by effective neoadjuvant chemotherapy. In this paper, we reviewed the current literature and published evidence to identify predictors of response to neoadjuvant chemotherapy for muscle-invasive bladder cancer. To date, no instrument exists to predict which patients will respond to neoadjuvant chemotherapy.

5577 Background: Prostate specific antigen (PSA) has well-recognized limitations as a marker for treatment response and disease progression. A post hoc analysis of the PREVAIL trial reported 24.5% of chemotherapy naïve mCRPC patients on enzalutamide had radiographic progression on conventional imaging with non-rising PSA. In this study, we sought to retrospectively compare PSA levels with C-11 choline positron emission tomography/ computed tomography (PET/CT) images in patients with m-CRPC on 2nd-HT with prior use of chemotherapy. Methods: We identified 123 patients with mCRPC on 2nd-HT following prior use of docetaxel chemotherapy (Abiraterone, n = 106; Enzalutamide, n = 17). Patients underwent serial PSA testing and C-11 choline PET/ CTs every 3–6 months. Disease progression was defined by the increase in blood pool corrected maximum standardized uptake value (SUVmax) of the index lesion on C-11 choline PET/CT scan. Suspicious lesions were confirmed by biopsy and/or conventional imaging. Results: Approximately 43% (n = 53) of patients had radiographic disease progression while on 2nd-HT. At time of radiographic progression, 60.4% of patients showed a parallel rise in PSA (Group-A), while 39.6% showed a paradoxical response; defined as radiographic progression with stable or down-trending PSA (Group-B). Median PSA at time of progression was 3.1 ng/ml for Group-A, and 1.3 ng/ml for Group-B (p-value = 0.0176). Median SUVmax was the same (4.9 Group-A, 4.6 Group-B; p-value = 0.6072). Bone-predominance progression was more significant in Group-B (90%) versus Group-A (65%) (p-value = 0.0309). The median time for radiographic progression was 9.5 months versus 3.9 months for Group-A and Group-B, respectively (Log-Rank = 0.0063). Conclusions: Metabolic imaging is a useful tool that should complement PSA in the evaluation of treatment response and disease progression in mCRPC patients on 2nd-HT, especially considering the paradoxical response observed in our data.

e17540 Background: The clinical course in metastatic castrate-resistant prostate cancer (mCRPC) can be complicated when patients have disease progression after treatment with 2nd generation hormone therapy (2nd-HT), such as enzalutamide or abiraterone. Currently, limited data exist regarding the optimal choice of chemotherapy for mCRPC after failing 2nd-HT. We sought to evaluate three common chemotherapy regimens in this setting. Methods: We retrospectively identified 150 patients with mCRPC with disease progression on enzalutamide or abiraterone. 92 patients were chemo-naïve, while 58 patients had previously received docetaxel chemotherapy prior to 2nd-HT. After failing 2nd-HT, 90 patients received docetaxel-alone (group A), 33 patients received carboplatin plus docetaxel (group B), while 27 patients received cabazitaxel-alone (Group C). Favorable response was defined by ≥50% reduction in PSA level from baseline after a complete course of chemotherapy. Survival outcome was assessed for 30-month overall survival. Results: Mean (SD) age was 71.2 (8.28), 69.5(8.38) and 67.2 (8.36) for group (A), (B) and (C), respectively. Mean (SD) pre-chemotherapy PSA was 63.8 (138.18), 58.5 (118.15) and 53.7 (88.15) for group (A), (B) and (C), respectively. Mean (SD) Gleason score was 7.9 (1.1), 8.4 (0.88) and 8.1 (1.06) for group (A), (B) and (C), respectively. Patients in group (B) were 2.6 times more likely to have a favorable response compared to group (A) (OR = 2.625, 95%CI: 1.15 - 5.99) and almost 3 times compared to patients in group (C) (OR = 2.975, 95%CI: 1.04 – 8.54) (p-value = 0.0442). We report a Hazard Ratio (HR) of 3.1 (95% CI 1.31-7.35; p = 0.0037) between patients in group (A) versus group (B), and a HR of 4.18 (95% CI 1.58-11.06; p = 0.0037) between patients in group (C) versus group (B). Thirty-month overall survival was 70.7%, 38.9%, and 30.3% for group (B), (A), and (C) respectively (p-value = 0.008). Conclusions: Our data demonstrate improved response and cancer-specific survival in patients with treatment-refractory mCRPC on docetaxel plus carboplatin compared to docetaxel or cabazitaxel alone. Selection bias is inherent in any retrospective study; however, our finding suggests that clinicians may consider docetaxel plus carboplatin in mCRPC patients who fail 2nd-HT. Further prospective studies are warranted.

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.