Daniel P. Nguyen

Do Patients Benefit from Routine Follow-up to Detect Recurrences After Radical Cystectomy and Ileal Orthotopic Bladder Substitution?

BACKGROUND The need for and intensity of follow-up to detect disease recurrence after radical cystectomy (RC) for transitional cell carcinoma (TCC) remains a matter for debate. OBJECTIVE To determine whether diagnosis of asymptomatic recurrence after RC by routine follow-up investigations confers a survival benefit versus symptomatic recurrence. DESIGN, SETTING, AND PARTICIPANTS Retrospective analysis of 479 patients with nonmetastatic bladder TCC receiving no neoadjuvant chemotherapy/radiation therapy and prospectively followed with a standardised protocol for a median 4.3 yr (range: 0.3-20.9) after RC at an academic tertiary referral centre. INTERVENTION RC and extended pelvic lymph node dissection with ileal orthotopic bladder substitution. MEASUREMENTS Cancer-specific survival (CSS) and overall survival (OS) probability for asymptomatic and symptomatic recurrent patients were estimated using the Kaplan-Meier method. The effects of age, nerve-sparing surgery, pathologic tumour stage, lymph node status, adjuvant chemotherapy, mode of recurrence diagnosis, and recurrence site on survival were assessed with multivariable Cox regression models. RESULTS AND LIMITATIONS Of the 174 of 479 patients (36.3%) with tumour recurrence, 87 were diagnosed by routine follow-up investigations and 87 by symptoms. Routine follow-up mostly detected lung metastases and urethral recurrences, while symptoms were predominantly the result of bone metastases and concomitant pelvic/distant recurrences. Of 24 patients with urethral recurrences, 13 had carcinoma in situ (CIS). Of these, 12 were successfully managed with urethra-sparing treatment, and 6 are still alive with no evidence of disease. Most other recurrent long-term survivors had lung and extrapelvic lymph node metastases. Cumulative 5-yr survival rates of the entire cohort were 69.8% (95% confidence interval [CI], 65.5-74.3%) for CSS and 61.9% (95% CI, 57.4-66.7%) for OS. In multivariable analysis, mode of recurrence diagnosis and site of initial recurrence were the only independent predictors of CSS and OS. Patients with recurrences detected by routine follow-up investigations and with secondary urothelial tumours as site of recurrence had a slightly but significantly higher survival probability. CONCLUSIONS Patients diagnosed with asymptomatic recurrences during our routine follow-up after RC had a slightly higher survival than patients with symptomatic recurrences. Routine follow-up appears particularly effective in early detection of urethral CIS, which can be treated conservatively. In addition, the predominance of lung and extrapelvic lymph node metastases in survivors may justify the use of routine cross-sectional imaging.

A Specific Mapping Study Using Fluorescence Sentinel Lymph Node Detection in Patients with Intermediate- and High-risk Prostate Cancer Undergoing Extended Pelvic Lymph Node Dissection

Sentinel lymph node (SLN) detection techniques have the potential to change the standard of surgical care for patients with prostate cancer. We performed a lymphatic mapping study and determined the value of fluorescence SLN detection with indocyanine green (ICG) for the detection of lymph node metastases in intermediate- and high-risk patients undergoing radical prostatectomy and extended pelvic lymph node dissection. A total of 42 patients received systematic or specific ICG injections into the prostate base, the midportion, the apex, the left lobe, or the right lobe. We found (1) that external and internal iliac regions encompass the majority of SLNs, (2) that common iliac regions contain up to 22% of all SLNs, (3) that a prostatic lobe can drain into the contralateral group of pelvic lymph nodes, and (4) that the fossa of Marcille also receives significant drainage. Among the 12 patients who received systematic ICG injections, 5 (42%) had a total of 29 lymph node metastases. Of these, 16 nodes were ICG positive, yielding 55% sensitivity. The complex drainage pattern of the prostate and the low sensitivity of ICG for the detection of lymph node metastases reported in our study highlight the difficulties related to the implementation of SNL techniques in prostate cancer. PATIENT SUMMARY There is controversy about how extensive lymph node dissection (LND) should be during prostatectomy. We investigated the lymphatic drainage of the prostate and whether sentinel node fluorescence techniques would be useful to detect node metastases. We found that the drainage pattern is complex and that the sentinel node technique is not able to replace extended pelvic LND.

Diffusion-Weighted Magnetic Resonance Imaging Detects Local Recurrence After Radical Prostatectomy: Initial Experience

Current conventional cross-sectional imaging techniques, such as contrast-enhanced computed tomography and magnetic resonance imaging (MRI), are largely inaccurate in detecting local recurrence after radical prostatectomy. We report on five patients with biochemical recurrence after radical retropubic prostatectomy and pelvic lymph node dissection for whom local recurrence could only be detected with diffusion-weighted (DW) MRI. Prior to DW-MRI, all patients had negative digital rectal examinations, negative or equivocal conventional cross-sectional imaging, and negative bone scans. All suspicious lesions on DW-MRI imaging were histologically proved to be local recurrences of prostate cancer after either transrectal ultrasound-guided or transurethral biopsy. These results should encourage other centres to test our findings.

Local recurrence after retropubic radical prostatectomy for prostate cancer does not exclusively occur at the anastomotic site.

Local recurrence after radical prostatectomy (RP) for clinically organ‐confined prostate cancer is largely assumed to occur at the anastomotic site, as reflected in European and North American guidelines for adjuvant and salvage radiotherapy after RP. However, the exact site of local recurrence often remains undetermined. The present study shows that roughly one out of five patients with local recurrence after RP has histologically confirmed tumour deposits at the resection site of the vas deferens, clearly above the anastomotic site. This should be considered when offering ‘blind’ radiotherapy to the anastomotic site in patients with biochemical recurrence alone.

Repeat prostate biopsies prior to radical prostatectomy do not impact erectile function recovery and mid- to long-term continence

A growing number of men undergo repeat biopsies prior to radical prostatectomy for prostate cancer. However, the long‐term impact of repeat biopsies on functional outcomes in this patient population remains unelucidated. Thus, we compared functional outcomes between patients who underwent single biopsy versus repeat biopsies before radical prostatectomy.

More extended lymph node dissection template at radical prostatectomy detects metastases in the common iliac region and in the fossa of Marcille

To assess the effect of adding lymph nodes (LNs) located along the common iliac vessels and in the fossa of Marcille to the extended pelvic LN dissection (PLND) template at radical prostatectomy (RP).

MP20-16 A MORE EXTENDED LYMPH NODE DISSECTION TEMPLATE AT RADICAL PROSTATECTOMY DETECTS METASTASES IN THE COMMON ILIAC REGIONS AND IN THE FOSSA OF MARCILLE

OBJECTIVES To assess the effect of adding lymph nodes (LNs) located along the common iliac vessels and in the fossa of Marcille to the extended pelvic LN dissection (PLND) template at radical prostatectomy (RP). PATIENTS AND METHODS A total of 485 patients underwent RP and PLND at a referral centre between 2000 and 2008 (historical cohort: classic extended PLND template) and a total of 268 patients between 2010 and 2015 (contemporary cohort: extended PLND template including LNs located along the common iliac vessels and in the fossa of Marcille). Descriptive analyses were used to compare baseline, pathological, complication and functional data between the two cohorts. A logistic regression model was used to assess the templates effect on the probability of detecting LN metastases. RESULTS Of 80 patients in the historical cohort with pN+ disease, the sole location of metastasis was the external iliac/obturator fossa in 23 (29%), and the internal iliac in 18 (23%), while 39 patients (49%) had metastases in both locations. Of 72 patients in the contemporary cohort with pN+ disease, the sole location of metastasis was the external iliac/obturator fossa in 17 patients (24%), the internal iliac in 24 patients (33%), and the common iliac in one patient (1%), while 30 patients (42%) had metastases in >1 location (including fossa of Marcille in five patients). Among all 46 patients in the contemporary cohort with ≤2 metastases, three had one or both metastases in the common iliac region or the fossa of Marcille. The adjusted probability of detecting LN metastases was higher, but not significantly so, in the contemporary cohort. There were no differences between the two cohorts in complication rates and functional outcomes. CONCLUSION A more extended template detects LN metastases in the common iliac region and the fossa of Marcille and is not associated with a higher risk of complications; however, the overall probability of detecting LN metastases was not significantly higher.

PD15-12 THE IMPACT OF NERVE SPARING RADICAL PROSTATECTOMY ON ONCOLOGICAL AND FUNCTIONAL OUTCOMES IN PATIENTS WITH HIGH RISK PROSTATE CANCER: A RETROSPECTIVE LONG-TERM SINGLE CENTER STUDY

INTRODUCTION AND OBJECTIVES: Salvage radiation therapy (SRT) is a therapeutic option for men with PSA rising after radical prostatectomy (RP). While several studies have addressed potential predictors of outcome after SRT, none have investigated the role of the extent of pelvic lymph node dissection (PLND) on SRT outcomes. We hypothesised that cancer control of SRT are improved in men who underwent more extensive PLND at the time of RP. METHODS: The study included 728 patients who received SRT for either PSA rising after RP or PSA persistence after surgery that was defined as PSA level 0.1 ng/ml 1 month after RP. All patients received local radiation to the prostate and seminal vesicle bed at one of six tertiary referral centres; irradiation of the pelvic lymph node region (whole pelvic RT) was left to the discretion of the treating physician. The study outcome consisted of clinical recurrence after SRT as identified by radiologic imaging. Clinical recurrence included pelvic nodal, retroperitoneal nodal, skeletal, and visceral metastasis. Multivariable analysis tested the association between clinical recurrence and the number of lymph nodes removed, which was considered as a continuous variable. Covariates consisted of: pT stage ( pT3a vs. pT3b), pathologic Gleason score ( 7 vs. 8), surgical margin (negative vs. positive), PSA level at SRT, and radiation field (prostatic bed vs. whole pelvis). RESULTS: Median patient age was 66 years, while the median number of nodes removed at RP was 7 (IQR 0, 13). Overall, 500 (69%) patients received SRT for PSA rising after RP and 228 (31%) were irradiated for PSA persistence. Median PSA at SRT was 0.30 ng/ml. Whole pelvic SRT was delivered to 187 (27%) patients. Median follow-up was 94 months (IQR 48, 128), during which time. 27 (3.7%), 13 (2.1%), 61 (7.7%), and 11 (1.3%) patients developed pelvic, retroperitoneal, skeletal, and visceral metastasis, respectively. On multivariable analysis, the number of lymph nodes removed at RP was significantly inversely associated with the risk of clinical recurrence following SRT (hazard ratio: 0.97; 95% CI 0.95, 0.99; p1⁄40.039). CONCLUSIONS: This is the first study demonstrating a significant inverse correlation between the number of lymph nodes removed and the risk of clinical recurrence after SRT. These data suggest the need for consideration of alternative approaches to management for patients with PSA elevation after RP in whom a lower number of nodes were removed at surgery, including multimodal salvage therapy.

MP91-17 DO REPEAT PROSTATE BIOPSIES IMPACT FUNCTIONAL OUTCOMES AFTER RADICAL PROSTATECTOMY? A LONG-TERM ANALYSIS OF 1015 PATIENTS

INTRODUCTION AND OBJECTIVES: Phase 3, double-blind, multicenter Subcutaneous Testosterone Efficacy and Safety in Adult Men Diagnosed with Hypogonadism (STEADY) trial results of a novel, pre-filled auto-injector are presented. METHODS: This 1-year study enrolled 150 men with hypogonadism with 2 baseline testosterone (T) levels of <300 ng/dL. Starting doses of 75 mg of T enanthate (TE) were administered subcutaneously weekly for 6 weeks. At Week 7, blinded dose adjustments were based on Week-6 pre-dose levels. PK was obtained at Week 12. Success required 75% of patients to achieve Cavg of 300 to 1100 ng/ dL with a lower limit of a 95% 2-sided confidence interval 65%, 85% of Week 12 Cmax values of <1500 ng/dL, and 5% of Cmax values of >1800 ng/dL. Patients without Cmax determination at Week 12 were treated as 1500 ng/dL for analysis. RESULTS: 137 patients had complete Week 12 PK profiles; 98 were still receiving treatment at Week 52. At Week 12, 92.7% of patients had total T Cavg 0-168h within the range of 300 to 1100 ng/dL (100% of 50 mg; 90.4% of the 75 mg, and 95.2% of the 100 mg patients). Week 12 Cavg was 553.3 (SD 127.3) ng/dL. All Week 12 total T Cmax was <1500 ng/dL. Concentration was within range on days 1, 2, 3, 4, and 8. Daily mean total T ranged from 483.2 to 741.4 ng/dL. In Week 12, total T concentrations <300 ng/dL were observed in <3% of patients. Treatment was well tolerated. Thirty (20%) patients had treatmentemergent adverse events that led to discontinuation; most frequently reported were elevated PSA and/or hematocrit. Three (2.0%) treatmentemergent serious adverse events (SAEs) were not considered drugrelated by investigators. One SAE of death was the result of suicide. Fifteen hundred and ten of 1519 injections were reported as painless. Median compliance was 100%. CONCLUSIONS: Starting dose of 75 mg TE via the autoinjector achieved T levels within a clinically desirable, pre-defined, physiologically normal range. The TE auto-injector was safe, well tolerated, and pain-free.

Re: Oncologic Surveillance After Surgical Resection for Renal Cell Carcinoma: A Novel Risk-based Approach

Experts’ summary: Using a robust series of 2511 patients followed for a median time of 9.0 yr, Stewart-Merrill et al proposed a novel approach that enables a tailored follow-up strategy following surgical resection of clinically localized renal cell carcinoma (RCC). By means of competing risk models incorporating age, Charlson comorbidity index (CCI), pathologic tumor stage, and recurrence location (abdomen, chest, bone, other), the authors determined the points in time at which the patient’s risk of dying from a non-RCC cause exceeded that of recurrence. They found considerable variability in those time points. Among patients with pT1Nx-0 disease who had CCI <1, for example, the risk of non-RCC death began to exceed that of abdominal recurrence at 7 yr for patients aged 50–59 yr, at 2.5 yr for patients aged 60–69 yr, and at 6 mo for patients aged 80 yr. The authors concluded that their competing risks model allows for better prediction and offers an individualized surveillance strategy based on the patient’s health status and cancer characteristics. This risk-adapted approach offers the advantage of forgoing unnecessary follow-up when not needed and prolonging it when necessary but not recommended by current guidelines.