Salivary toxicity from PSMA-targeted radiopharmaceuticals: What we have learned and where we are going.

Clinical trials of prostate-specific membrane antigen (PSMA) targeted radiopharmaceuticals have shown encouraging results. Some agents, like lutetium-177 [177Lu]Lu-PSMA-617 ([177Lu]Lu-PSMA-617), are already approved for late line treatment of metastatic castration-resistant prostate cancer (mCRPC). Projections are for continued growth of this treatment modality; [177Lu]Lu-PSMA-617 is being studied both in earlier stages of disease and in combination with other anti-cancer therapies. Further, the drug development pipeline is deep with variations of PSMA-targeting radionuclides, including higher energy alpha particles conjugated to PSMA-honing vectors. It is safe to assume that an increasing number of patients will be exposed to PSMA-targeted radiopharmaceuticals during the course of their cancer treatment. In this setting, it is important to better understand and mitigate the most commonly encountered toxicities. One particularly vexing side effect is xerostomia. In this review, we discuss the scope of the problem, inventories to better characterize and monitor this troublesome side effect, and approaches to preserve salivary function and effectively palliate symptoms. This article aims to serve as a useful reference for prescribers of PSMA-targeted radiopharmaceuticals, while also commenting on areas of missing data and opportunities for future research.

Low PSA radiographic disease progression on C11-choline PET.

Background: For men with prostate cancer, radiographic progression may occur without a concordant rise in prostate-specific antigen (PSA). Our study aimed to assess the prevalence of radiographic progression using C-11 choline positron emission tomography (PET) imaging in patients achieving ultra-low PSA values and to evaluate clinical outcomes in this patient population. Methods: In a single institution study, we reviewed the prospectively maintained Mayo Clinic C-11 Choline PET metastatic prostate cancer registry to identify patients experiencing radiographic disease progression (rDP) on C-11 choline PET scan while the PSA value was less than 0.5 ng/mL. Disease progression was confirmed by tissue biopsy or response to subsequent therapy. Clinicopathologic variables were abstracted by trained research personnel. Overall survival was estimated using the Kaplan-Meier method. Intergroup differences were assessed using the log-rank test. A univariate and multivariate Cox regression model was performed to investigate variables associated with poor survival after rDP. Results: A total of 1323 patients within the registry experienced rDP between 2011 and 2021, including 220 (16.6%) men with rDP occurring at low PSA level. A median (interquartile range [IQR]) of 54.7 (19.7-106.9) months elapsed between the time of prostate cancer diagnosis and low PSA rDP, during which 173 patients (78%) developed castration-resistant prostate cancer (CRPC). Sites of low PSA rDP included local recurrence (n = 17, 8%), lymph node (n = 90, 41%), bone (n = 94, 43%) and visceral metastases (n = 19, 9%). Biopsy at the time of rDP demonstrated small-cell or neuroendocrine features in 21% of patients with available tissue. Over a median (IQR) follow-up of 49.4 (21.3-95.1) months from the time of low PSA rDP, 46% (n = 102) of patients died. Factors associated with poorer survival outcomes include advanced age at rDP, CRPC status, bone and visceral metastasis (p value <0.05). Visceral metastases were associated with decreased overall survival (p = 0.009 by log-rank) as compared with other sites of rDP. Conclusions: Men with prostate cancer commonly experience metastatic progression at very low or even undetectable PSA levels. Periodic imaging, even at low absolute PSA values, may result in more timely identification of disease progression.

Treatment modalities and survival outcomes in prostate cancer parenchymal brain metastasis.

BACKGROUND: Prostate cancer (PCa) parenchymal brain metastases are uncommon and troubling observations in the course of the disease. Our study aims to evaluate the prevalence of brain metastases among PCa patients while reporting various therapeutic modalities, clinical features, and oncological outcomes. METHODS: We retrospectively identified 34 patients with parenchymal brain metastasis out of 4575 patients using a prospectively maintained database that contains clinicopathologic characteristics of PCa patients between January 2012 and December 2021. Based on the three treatment modalities used, the patients were divided into three groups: stereotactic radiosurgery (SRS), whole brain radiotherapy (WBRT), and systemic therapy alone. The Kaplan-Meier curve was used to calculate overall survival [OS] probability and the Cox proportional hazards regression model was used to compare between groups. RESULTS: At the time of brain metastasis diagnosis, the median age was 66 years, the median (interquartile range [IQR]) prostate-specific antigen (PSA) was 2.2 (0.1-26.6) ng/ml and the median (IQR) months from initial PCa diagnosis to brain metastasis development was 70.8 (27.6-100.9). The median (IQR) primary Gleason score was 8 (7-9) and over a median (IQR) follow-up time of 2.2 (1.2-16.5) months, 76.5% (n = 26) of the patients died. Thirteen (38.2%) patients had solitary lesion, whereas 21 (61.8%) had ≥2 lesions. The lesions were supratentorial in 19 (55.9%) patients, infratentorial in six (17.6%), and both sides in nine (26.5%). Among all 34 patients, 10 (29.4%) were treated with SRS, seven (20.6%) with WBRT, and 17 (50%) with systemic therapy alone. OS varied greatly between the three treatment modalities (log-rank test, p = 0.049). Those who were treated with SRS and WBRT had better OS compared with patients who were treated with systemic therapy alone (hazard ratio: 0.37, 95% confidence interval: 0.16-0.86, p = 0.022). CONCLUSIONS: In our single-institutional study, we confirmed that PCa brain metastasis is associated with poor survival outcomes and more advanced metastatic disease. Furthermore, we found that SRS and WBRT for brain metastasis in patients with recurrent PCa appear to be associated with improved OS as compared with systemic therapy alone and are likely secondary to selection bias.

Early PSA decline after starting second-generation hormone therapy in the post-docetaxel setting predicts cancer-specific survival in metastatic castrate-resistant prostate cancer.

BACKGROUND: The objective of this study was to evaluate the prognostic value of early PSA decline following initiation of second-generation hormone therapy (2nd HT), namely abiraterone acetate or enzalutamide, in patients with taxane-refractory metastatic castrate-resistant prostate cancer (mCRPC) and evaluate utility of this metric in informing intensified surveillance/imaging protocols. METHODS: We retrospectively identified 75 mCRPC patients treated with 2nd HT following docetaxel failure (defined as PSA rise and radiographic progression). Patients were categorized patients into two cohorts based on the first PSA within 3 months after initiation of therapy: PSA reduction ≥50% (Group A) and PSA reduction <50% (Group B). The primary endpoint was cancer-specific mortality (CSM). The secondary endpoint was radiographic disease progression (rDP) on 2nd HT. In univariate and multivariate analyses, we investigated factors associated with rPD and CSM. RESULTS: We included 75 patients (52 in Group A, 23 in Group B) in the analytic cohort. Baseline clinico-demographic characteristics, including median age, primary Gleason score risk group, median pre-treatment PSA, disease burden, site of metastases, and pre-treatment ECOG score were not statistically different between the two groups. Median follow up time was 30 months and the median time to radiographic disease progression was 28.1 and 12.5 months (p = 0.002) in cohorts A and B, respectively. On univariate and multivariate analyses, both PSA reduction ≥50% and volume of metastatic disease were significantly associated with a decreased risk of radiographic disease progression (HR 0.41, 95% CI 0.21-0.80, p = 0.0113) as well as a decreased risk of cancer-specific mortality (HR 0.29, 95% CI 0.09-0.87, p = 0.0325). CONCLUSION: PSA reduction ≥50% within 3 months of starting 2nd HT was associated with significantly improved radiographic disease progression-free survival and 3-year cancer-specific mortality. This suggests using PSA 50%-decline metric in surveillance patients with on 2nd HT and identifies patients who require further evaluation with imaging.

15-year biochemical failure, metastasis, salvage therapy, and cancer-specific and overall survival rates in men treated with robotic radical prostatectomy for PSA-screen detected prostate cancer.

BACKGROUND: An informed decision regarding a treatment option requires data on its long-term efficacy and side-effect profile. While the side-effects of robotic radical prostatectomy have been well-quantified, the data on its long-term efficacy are lacking. We here provide 15-year oncological outcomes of clinically-localized prostate cancer (CLPCa) patients treated with robot-assisted laparoscopic prostatectomy (RALP). METHODS: We treated 1,807 men with CLPCa with RALP between 2001 and 2005 and prospectively collected follow-up data through 2020. We examined the rates of biochemical failure (BCF), metastatic progression, secondary therapy use, PCa-specific mortality (PCSM), and overall survival (OS) using Kaplan-Meier and competing-risk cumulative incidence methods as appropriate. RESULTS: The median follow-up was 14.1 years. Six hundred eight and 312 men had D'Amico intermediate- and high-risk disease, respectively. Overall, the 15-year rates of BCF, metastasis, secondary therapy use, PCSM, and OS were 28.1%, 4.0%, 16.3%, 2.5%, and 82.1%, respectively. The rates of oncologic failure increased with increasing D'Amico (preoperative) and Diaz (postoperative) risk scores - BCF, metastasis, and PCSM rates in D'Amico low-, intermediate-, and high-risk groups at 15-years were 15.2%, 38.3%, and 44.1% [BCF], 1.1%, 4.1%, and 13.0% [metastasis], and 0.5%, 3.4%, and 6.6% [PCSM], respectively, and in Diaz risk groups 1, 2, 3, 4, and 5 were 5.5%, 20.6%, 41.8%, 66.9%, and 89.2% [BCF], 0%, 0.5%, 3.2%, 20.5%, and 60.0% [metastasis], and 0%, 0.8%, 0.6%, 13.5%, and 37.5% [PCSM], respectively. The OS rates in D'Amico low-to-high and Diaz 1-to-5 risk groups at 15-years were 85.9%, 78.6%, and 75.2%, and 89.4%, 83.2%, 80.6%, 67.2%, and 23.4%, respectively. CONCLUSIONS: Men diagnosed with clinically-localized prostate cancer in the contemporaneous PSA-screening era and treated with RALP achieve durable long-term oncological control. The data reported here (in a risk-stratified manner) represent the longest follow-up after robotic radical prostatectomy, and as such, should be of value when counseling patients regarding expected oncologic outcomes from RALP.

Metastasis-directed Therapy Without Androgen Deprivation Therapy in Solitary Oligorecurrent Prostate Cancer.

PURPOSE: As controversy remains regarding the role of metastasis-directed therapy in patients with oligometastatic prostate cancer, we sought to characterize outcomes of metastasis-directed therapy without concomitant androgen deprivation therapy in the specific subset of patients with a solitary metastatic lesion on C-11 choline positron emission tomography imaging whose primary tumor has already been treated. MATERIALS AND METHODS: We identified 124 consecutive prostate cancer patients from 2008 to 2018 with a solitary oligorecurrent metastatic lesion on positron emission tomography imaging who were treated with metastasis-directed therapy without androgen deprivation therapy from the Mayo Clinic C-11 choline registry. Metastasis-directed therapy consisted of either stereotactic body radiation therapy or surgical excision. RESULTS: Of these 124 patients, 67 were treated with surgery (median follow-up 54 months) and 57 patients were treated with stereotactic body radiation therapy (median follow-up 53 months). Of patients treated with surgery, 80.5% had >50% decline in prostate specific antigen at first follow-up, and the 3-year radiographic progression-free survival was 29%. Median time to initiation of systemic therapy in this cohort was 18.5 months (interquartile range 8.4-44.7 months). Meanwhile, for patients treated with stereotactic body radiation therapy, 40.3% had >50% decline in prostate specific antigen at first follow-up, and the 3-year radiographic progression-free survival was 17%. Similarly, median time to initiation of systemic therapy was 17.8 months (interquartile range 7.1-42.3 months). CONCLUSIONS: This study represents the first reported series of metastasis-directed therapy without androgen deprivation therapy in patients with solitary oligorecurrent metastatic prostate cancer. These results suggest that metastasis-directed therapy without androgen deprivation therapy can delay initiation of systemic therapy and highlight the need for further prospective study for select patients with solitary metastatic recurrences of prostate cancer.

Radiographic paradoxical response in metastatic castrate-resistant prostate cancer (mCRPC) managed with new generation anti-androgens: a retrospective analysis.

BACKGROUND: Prostatic specific antigen (PSA) has well-recognized limitations as a marker for treatment response and disease progression. Post hoc analysis of the PREVAIL trial reported 24.5% of chemotherapy naïve metastatic castration-resistant prostate cancer (mCRPC) patients on enzalutamide had radiographic progression on conventional imaging with nonrising PSA. In this study, we sought to study the discordance of imaging with PSA kinetics in mCRPC patients on second generation anti-androgens (SGA) post-chemotherapy using combined conventional imaging, and new generation imaging in the form of C-11 choline positron emission tomography/computed tomography (C[11] choline PET/CT) scan. METHODS: We retrospectively reviewed the medical records of 123 patients with mCRPC treated with SGA (Abiraterone or Enzalutamide) after docetaxel between 2016 and 2019. Patients underwent PSA testing, and C[11] choline PET/CT scan at baseline level before starting treatment with SGA, then every 3-6 months as part of their follow up evaluation. Loss of response to SGA was defined by increase in corrected maximum standardized uptake value (SUVmax) of pretreatment lesions on C-11 Choline PET/CT, and/or development of new lesions. Suspicious new lesions were confirmed by biopsy and/or conventional imaging. RESULTS: We identified 123 mCRPC patients who received SGA (Abiraterone, n = 106; Enzalutamide, n = 17) after docetaxel. Median duration of therapy was 13.9 months (interquartile range: 8.75-21.14). Approximately 43% (n = 53) of subjects in this study exhibited an increase in choline avidity while on SGA. Of this group, 60.4% of patients experienced a parallel rise in PSA (Group-A), whereas 39.6% displayed a paradoxical response (PR) (Group-B), defined as increased choline avidity combined with stable or down-trending PSA. Median PSA at time of increase in choline avidity was 3.1 ng/ml for Group-A, and 1.3 ng/ml for Group-B (p = 0.0176). Median SUVmax was similar in both groups (4.9 for Group-A, 4.6 for Group-B; p = 0.6072). The median time for increase in choline avidity was 9.5 versus 3.9 months for Group-A versus Group-B, respectively (Log-Rank = 0.0063). CONCLUSION: Nearly 40% of mCRPC patients placed on SGA post docetaxel chemotherapy will exhibit paradoxical responses to therapy, therefore, warranting close follow up with imaging. C-11 choline PET/CT imaging is a useful tool that can help in early predication of disease progression or treatment failure.

Optimizing anti-androgen treatment use among men with pathologic lymph-node positive prostate cancer treated with radical prostatectomy: the importance of postoperative PSA kinetics.

BACKGROUND: Optimal postsurgical management of prostate cancer (PCa) patients with nodal metastasis at the time of radical prostatectomy remains unclear. We sought to examine the role of postoperative PSA kinetics and pathologic tumor characteristics in guiding additional hormonal therapy use in pN1 men. METHODS: In total, 297 pN1 PCa patients treated with radical prostatectomy and ePLND between 2002 and 2018 were identified within our prospectively maintained institutional cancer data-registry. Following surgery, these patients were managed with either immediate androgen deprivation therapy (iADT) or observation with deferred ADT (dADT). The former was defined as ADT given within ≤6 months of surgery and the latter as >6 months. The primary outcome was metastasis. Regression-tree analysis was used to stratify patients into novel risk-groups based on post-prostatectomy tumor characteristics and PSA kinetics and the corresponding metastasis risk. Multivariable Cox regression analyses tested the impact of iADT versus observation ± dADT on metastasis, cancer-specific mortality, and overall mortality within each risk-group separately. RESULTS: The median follow-up was 6.1 years (IQR 3.2-9.0). Regression-tree analysis stratified patients into 3 novel risk-groups (Harrell's C-index 0.79) based on PSA-nadir and time to biochemical failure: group 1 (low-risk) included patients with time to biochemical recurrence >6 months (n = 115), while groups 2 and 3 included patients with biochemical failure within ≤6 months with a postoperative PSA-nadir <1.05 ng/mL (group 2 [intermediate-risk], n = 125) or ≥1.05 ng/mL (group 3 [high-risk], n = 57), respectively. No other patient or tumor characteristics were significant for risk stratification. Within each risk-group, the 10-year metastasis-free survival rates with iADT versus observation ± dADT use were: group 1, 100% versus 95.4% (Log-rank p = 0.738), group 2, 80.6% versus 53.5% (Log-rank p = 0.016), and group 3, 41.5% versus 0% (Log-rank p = 0.015), respectively. Adjusted Cox regression analyses confirmed the benefit of iADT utilization in reducing metastasis in group 2 (p = 0.029) and group 3 (p = 0.008) patients, with no benefit for group 1 patients (p = 0.918). Similar results were noted for cancer-specific and overall mortality. CONCLUSIONS: Following radical prostatectomy, early postoperative PSA kinetics may provide valuable information for guiding the timing of ADT initiation-this may reduce over- and undertreatment of pN1 PCa men.

Outcomes following cytoreductive nephrectomy without immediate postoperative systemic therapy for patients with synchronous metastatic renal cell carcinoma.

BACKGROUND: While the recent CARMENA trial evaluated upfront cytoreductive nephrectomy (CN) among patients treated with immediate subsequent systemic therapy for metastatic renal cell carcinoma (mRCC), the role of CN in patients not immediately requiring systemic therapy remains to be determined. OBJECTIVE: To describe the oncologic outcomes of patients with de-novo synchronous mRCC who underwent CN +/- metastasis-directed therapy (MDT) and subsequent surveillance without planned immediate post-CN systemic therapy. DESIGN, SETTING, PARTICIPANTS: Adults who underwent CN for unilateral, sporadic mRCC between 1996 and 2016 without immediate postoperative systemic therapy were identified using the prospectively-maintained Mayo Clinic Nephrectomy Registry. Co-primary outcomes were survival free of systemic therapy or death and overall-survival. RESULTS: Of 156 patients who met inclusion criteria for study, 37 (24%) patients were managed after CN with surveillance alone and 119 (76%) underwent MDT. Seventy-two patients ultimately initiated systemic therapy at a median of 0.7 years (IQR 0.3-1.7). Median follow-up among survivors was 6.2 years (IQR 4.4-9.5), during which time 133 patients died. At 1, 3, and 5 years, survival free of systemic therapy or death rates were 47%, 21% and 14% and overall-survival rates were 69%, 37%, and 28%. CONCLUSION: Among carefully selected patients managed with surveillance after CN +/- MDT, approximately half may avoid systemic therapy for 1 year, with a subset achieving long-term survival free of systemic therapy or death. Having a single metastatic site and disease amenable to complete metastasectomy are features of patients who might be well served with upfront CN +/- MDT.

Prognostic role of 11C-choline PET/CT scan in patients with metastatic castrate resistant prostate cancer undergoing primary docetaxel chemotherapy.

BACKGROUND: We sought to assess the prognostic utility of 11C-choline positron emission tomography/computed tomography (PET/CT) in patients with metastatic castrate resistant prostate cancer (mCRPC) undergoing primary docetaxel chemotherapy. METHODS: We performed a single institution retrospective analysis of 77 mCRPC patients who were treated with 6 cycles of docetaxel chemotherapy, and who also underwent 11C-choline PET/CT scans at baseline (before chemotherapy), mid-course (after 3 cycles), and posttherapy (after 6 cycles). We evaluated treatment response based on percent change in blood pool-corrected maximum standardized uptake value (SUVmax) of the target lesion on PET/CT, as well as percent change in serum prostate specific antigen (PSA). Logistic regression analysis was used to identify factors associated with complete treatment response. Progression free survival (PFS) analysis was performed using log-rank test and shown on Kaplan-Meier plot. RESULTS: Percent change in blood pool-corrected SUVmax on mid-course scan was a significant predictor of complete response (odds ratio [OR]: 0.98, 95% confidence interval [CI]: 0.96-0.99, p = .0003), whereas percent change in PSA was not (OR: 0.99, 95% CI: 0.99-1.01, p = .6025). 57 of 77 patients (74%) achieved ≥20% reduction in blood pool-corrected SUVmax on mid-course; these patients were 3.6 times more likely to achieve complete response after full 6 cycles of docetaxel chemotherapy, compared to patients with <20% reduction in blood pool-corrected SUVmax (OR: 3.56, 95% CI: 1.04-16.52, p = .0420). Median PFS in the complete response group was 35.1 months (95% CI: 26.0-52.7 months), compared to 9.4 months (95% CI: 6.9-13.0 months) in the incomplete response group (p = .0005). CONCLUSIONS: Our study showed that mid-course and posttherapy 11C-choline PET/CT evaluation for mCRPC patients undergoing primary docetaxel chemotherapy can predict full course treatment response and PFS, respectively. 11C-choline PET/CT imaging may provide valuable prognostic information to guide treatment choices for patients with mCRPC.

Robotic Puboprostatic Fistula Repair with Holmium Laser Pubic Debridement.

INTRODUCTION AND OBJECTIVE: Urosymphyseal fistula (UF) with osteomyelitis most commonly occurs as a result of prostate cancer and benign prostate hyperplasia therapy. UF presentation typically includes debilitating pelvic pain exacerbated with ambulation. Traditional management required open surgical genitourinary (GU) reconstruction with pubectomy leading to significant morbidity. However, progressive utilization of robotic approaches and advances in holmium laser technology has led to a less invasive alternative. Herein, we present our series of robotic-assisted holmium laser debridement of pubic osteomyelitis in the setting of UF. METHODS: After physical exam, all patients presenting with concerns for GU fistula and osteomyelitis are evaluated with BMP, CBC, serum albumin, urine culture, and cystoscopy. Patients often present with previously obtained CT abdomen/pelvis. However, all patients presenting with concerns of pubic osteomyelitis should undergo a MRI of the pelvis to characterize the pubis. Specific indications for holmium laser debridement of the pubic bone include: 1) history of sacral insufficiency fractures which eliminate management with partial pubectomy due to risk of pelvic ring instability and 2) mild osteomyelitis which can be managed with debridement. The patient is placed in dorsal lithotomy position. After the robot is docked, the space of retzius is developed and the fistula is resected down to the pubic bone. The symphysis is debrided using the Cobra grasper followed by holmium laser debridement at 2J and 50Hz settings. Appropriate GU reconstruction versus urinary diversion is then performed per clinical judgement. Antibiotic beads are then placed in the symphyseal defect. If available, an interposition flap may be advanced between the urethra/bladder and symphysis. RESULTS: In our series of four patients, all patients underwent successful robotic pubic symphyseal debridement and were discharged without experiencing a major complication. At follow up (7-16 months) there have been no fistula recurrence or recurrent episodes of osteomyelitis. CONCLUSION: Robotic assisted pubic symphyseal debridement with a holmium laser is feasible, safe, and efficacious in this small series with short follow up. This approach represents a minimally invasive alternative to open pubectomy while minimizing incisions and overall morbidity. Additional long-term data is necessary before wide spread adoption of this approach.

Incidence of Venous Thromboembolism and Safety of Perioperative Subcutaneous Heparin During Inflatable Penile Prosthesis Surgery.

OBJECTIVE: To identify the incidence of venous thromboembolism (VTE) risk factors, postoperative VTE, and to assess the morbidity of perioperative pharmacologic VTE prophylaxis in men undergoing inflatable penile prosthesis (IPP) surgery. METHODS: We retrospectively reviewed 215 patients undergoing IPP surgery between July 2017 and June 2019. Univariate and multivariate statistical analyzes were performed to assess pre-operative Caprini risk score and compare post-operative day 0 scrotal drain output, scrotal hematoma formation, and VTE in men who received subcutaneous heparin (SqH) vs those who did not receive SqH. RESULTS: Of 215 IPP patients, 84% were classified as high or highest risk for VTE utilizing the Caprini risk score. A total of 119 (55%) received perioperative SqH with or without additional anti-thrombotics. Post-operative day 0 scrotal drain output was higher in those who received SqH compared to those who did not receive SqH, 99.9 mL vs 75.6 mL, respectively (P = .001). Minor scrotal hematomas occurred in similar rates in patients who received perioperative SqH vs those who did not, 3.8% vs 6.3%, respectively (P = .38). Similar results were found on subgroup analysis when eliminating patients who received SqH concurrently with other anti-thrombotics. The overall rate of postoperative VTE was 0.9%. No post-operative infections occurred. CONCLUSION: Patients undergoing IPP surgery are at elevated risk for VTE. To our knowledge, this is the first study showing SqH use in the perioperative IPP surgery setting is safe when used in conjunction with a scrotal drain. Preoperative VTE risk stratification may be performed and can be used to guide clinical decision making regarding pharmacologic prophylaxis.

Pubectomy and urinary reconstruction provides definitive treatment of urosymphyseal fistula following prostate cancer treatment.

OBJECTIVE: To describe the natural history, reconstructive solutions, and functional outcomes of those men undergoing pubectomy and urinary reconstruction after prostate cancer treatment. PATIENTS AND METHODS: This study retrospectively identified 25 patients with a diagnosis of urosymphyseal fistula (UF) following prostate cancer therapy who were treated with urinary reconstruction with pubectomy. This study describes the natural history, reconstructive solutions, and functional outcomes of this cohort. RESULTS: All 25 patients had a history of pelvic radiotherapy for prostate cancer. The median (interquartile range [IQR]) time from prostate cancer treatment to diagnosis of UF was 11 (6, 16.5) years. The vast majority of men (24/25; 96%) presented with debilitating groin pain during ambulation. Posterior urethral stenosis was common (20/25; 80%), with 60% having repetitive endoscopic treatments. Culture of pubic bone specimens demonstrated active infection in 80%. Discordance between preoperative urine and intraoperative bone cultures was common, 21/22 (95.5%). After surgery, major 90-day complications (Clavien-Dindo Grade III and IV) occurred in eight (32%) patients. Pain was significantly improved, with resolution of pain (24/25; 96%) and restoration of function, the median (IQR) preoperative Eastern Cooperative Oncology Group Performance Status (ECOG PS) was 3 (2, 3) vs median postoperative ECOG PS score of 0 (0, 1). CONCLUSION: Endoscopic urethral manipulation after radiation for prostate cancer is a risk factor for UF. Conservative management will not provide symptom resolution. Fistula decompression, bone resection, and urinary reconstruction effectively treats chronic infection, improves pain and ECOG PS scores.

A Rare Case of Prostate-Specific Antigen-Producing Metastatic Parotid Adenocarcinoma Developing Androgen Receptor Resistance.

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.

Adding carboplatin to chemotherapy regimens for metastatic castrate-resistant prostate cancer in postsecond generation hormone therapy setting: Impact on treatment response and survival outcomes.

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-naïve 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.

Treatment Outcomes in Patients With Symptomatic Lymphoceles Following Radical Prostatectomy Depend Upon Size and Presence of Infection.

OBJECTIVE: To guide treatment decisions for symptomatic lymphoceles after radical prostatectomy. We examined our experience to create a treatment algorithm. MATERIALS AND METHODS: We evaluated all patients that underwent radical prostatectomy at our institution from 2003 to 2012. Presenting signs, management and treatment outcomes were evaluated. RESULTS: Of the 8081 patients who underwent radical prostatectomy from 2003 to 2012, we identified 123 (1.5%) patients who developed a symptomatic lymphocele, 70 sterile and 53 infected. Percutaneous aspiration was performed in 26 of 123 (21%) patients, of those, 100% recurred. A drain was placed in 86 of 123 (70%) patients for a median of 13 vs 33 days for the infected and sterile lymphocele groups, respectively (P <.001). The median duration of drainage for sterile lymphoceles was 15 vs 58 days for lymphoceles <10 cm vs ≥10 cm (P <.001). Percutaneous drainage was successful in 93% and 86% of patients with infected and sterile lymphoceles, respectively. Laparoscopic unroofing was performed in 18 sterile lymphocele patients (15%) with a success rate of 94%. CONCLUSION: Aspiration of symptomatic lymphoceles should be reserved for diagnostic purposes due to a high risk of recurrence. Infected lymphoceles are optimally treated with drain placement and antibiotics, and have excellent resolution rates. While sterile lymphoceles <10 cm can be successfully managed with drain placement, if drainage and sclerotherapy fail, laparoscopic unroofing should be considered. For patients with sterile lymphoceles ≥10 cm there should be a shared decision-making process to weigh the risk of a protracted course if a drain is utilized vs upfront laparoscopic unroofing.