Prostate-specific antigen (PSA) decline with apalutamide therapy is associated with longer survival and improved outcomes in individuals with metastatic prostate cancer: a plain language summary of the TITAN study.

WHAT IS THIS SUMMARY ABOUT?: This summary describes the results from an additional (or post hoc) analysis of the TITAN study. The TITAN study looked at whether the prostate cancer treatment apalutamide could be used to treat individuals with metastatic castration-sensitive prostate cancer (or mCSPC). A total of 1052 participants with mCSPC were included in the TITAN study. Treatment with apalutamide was compared with treatment with placebo. All participants received androgen deprivation therapy (or ADT), which is a type of hormone therapy that has been part of the main treatment for mCSPC for many years. The results showed that apalutamide plus ADT increased the length of time that participants remained alive compared with placebo plus ADT. Apalutamide plus ADT also controlled the growth of the cancer for a longer length of time compared with placebo plus ADT. Additionally, participants who received apalutamide plus ADT experienced a greater reduction in the blood levels of prostate-specific antigen (or PSA), called a deep PSA decline, compared with those who received placebo plus ADT. An additional (or post hoc) analysis was carried out to understand whether a decrease in blood PSA levels, in response to treatment, was associated with improved outcomes, including longer survival time. WHAT WERE THE RESULTS OF THE ADDITIONAL ANALYSIS?: In participants who received apalutamide plus ADT, a deep PSA decline in response to treatment was associated with longer survival time and improved outcomes. WHAT DO THESE RESULTS MEAN FOR INDIVIDUALS WITH MCSPC?: These results demonstrate that individuals with mCSPC can benefit from treatment with apalutamide plus ADT. The association seen between deep PSA decline and the longer survival time and improved outcomes highlights how PSA measurements can be used to help monitor cancer disease evolution in response to treatment. Monitoring PSA levels will assist doctors and other healthcare professionals to understand how effectively a treatment is working for a patient and to tailor their treatment approach to improve PSA decline.

Apalutamide plus androgen deprivation therapy in clinical subgroups of patients with metastatic castration-sensitive prostate cancer: A subgroup analysis of the randomised clinical TITAN study.

BACKGROUND: Whether disease burden in patients with metastatic castration-sensitive prostate cancer (mCSPC) predicts treatment outcomes is unknown. We assessed apalutamide treatment effect in TITAN patients with mCSPC by disease volume, metastasis number and timing of metastasis presentation. METHODS: These protocol-defined and post hoc analyses of the phase III randomised TITAN study evaluated clinical outcomes in patients receiving 240 mg/day apalutamide (n = 525) or placebo (n = 527) plus androgen-deprivation therapy (ADT). Subgroups were defined by volume (high: visceral and ≥1 bone metastases or ≥4 bone lesions with ≥1 beyond vertebral column/pelvis), development of metastases per conventional imaging (synchronous: at initial diagnosis; metachronous: after localised disease) and oligometastases (≤5 bone-only metastases) or polymetastases (>5 in bone ± other locations or ≤5 in bone plus other locations). Overall survival (OS), radiographic or second progression-free survival, and time to prostate-specific antigen progression or castration resistance were assessed using Cox proportional hazards models. RESULTS: Of 1052 patients, 63%, 81%, 54%, 27%, 5.7%, and 8.0% had high-volume, synchronous, synchronous/high-volume, synchronous/low-volume, metachronous/high-volume, and metachronous/low-volume disease, respectively. The OS benefit favoured apalutamide plus ADT versus ADT alone in synchronous/high-volume (hazard ratio = 0.68 [95% confidence interval: 0.53-0.87]; p = 0.002), synchronous/low-volume (0.65 [0.40-1.05]; p = 0.08), metachronous/high-volume (0.69 [0.33-1.44]; p = 0.32) and metachronous/low-volume (0.22 [0.09-0.55]; p = 0.001) subgroups. Apalutamide improved other clinical outcomes regardless of subgroup, with similar safety profiles. Most favourable outcomes were observed in oligometastatic disease. CONCLUSION: TITAN patients derived a robust benefit with apalutamide plus ADT regardless of disease volume and timing of metastasis presentation without differences in safety, supporting early apalutamide intensification in mCSPC. CLINICAL TRIAL REGISTRATION: NCT02489318.

Prostate Specific Antigen Nadir of 0.1 or Less Is a Predictor of Treatment Success in Men Undergoing Salvage Whole Prostate Gland Cryoablation.

PURPOSE: To assess factors that affect prostate biopsy results following salvage whole gland cryoablation. PATIENTS AND METHODS: One hundred seventy-four patients underwent prostate biopsy following salvage whole gland cryoablation of the prostate in the Cryo-OnLine Database registry. Wilcoxon rank-sum and χ2 tests and logistic regression analysis were used to assess predictors of positive biopsy. Prostate specific antigen (PSA) nadir was divided into a statistical tertile for comparisons between different nadir PSA cut points. RESULTS: Fifty-two of 174 (29.9%) of this highly select group of men who underwent biopsy had a posttreatment biopsy demonstrating malignant cancer. Men who had positive biopsy following salvage therapy had significantly higher median nadir PSA, shorter median time to prostate biopsy, and shorter median time to biochemical failure. Compared to the lowest tertile (PSA nadir defined as ≤0.1 ng/mL), PSA in the second tertile (0.11-0.8 ng/mL) and third tertile (>0.8 ng/mL) demonstrated increased odds ratio (OR) for positive biopsy, 4.34 (95% confidence interval [CI] 1.66, 11.4, p = 0.003) and 2.81 (95% CI 1.14, 7.00, p = 0.02), respectively, in adjusted models. In addition, men with a presalvage PSA >20 (OR 7.65; 95% CI 2.03, 28.9; p = 0.003) and Gleason score ≥8 (OR 2.26; 95% CI 0.93, 5.47; p = 0.07) had a higher OR of positive biopsy. CONCLUSIONS: Nadir PSA of 0.1 ng/mL or less following salvage cryotherapy is predictive of treatment success. Routine biopsy should be reserved for men with nadir PSA >0.1 ng/mL and patients with high risk features of prostate cancer before salvage cryoablation.

Primary Cryotherapy for High-Grade Clinically Localized Prostate Cancer: Oncologic and Functional Outcomes from the COLD Registry.

OBJECTIVE: To evaluate the oncological and functional outcomes of primary cryotherapy in men with clinically localized, high-grade prostate cancer. SUBJECTS AND METHODS: We included all men with biopsy Gleason score ≥8, localized (cT1-2) disease with a serum prostate-specific antigen (PSA) ≤50 ng/mL from the Cryo On-Line Data (COLD) registry. The primary outcome was biochemical progression free survival (BPFS) as defined by the Phoenix criteria (nadir PSA +2 ng/mL). Secondary outcomes of continence (defined as strictly no leak) and potency (able to have intercourse) were patient reported. Factors influencing BPFS were evaluated individually using Kaplan Meier and in a multivariate model using Cox regression. RESULTS: Altogether, 300 men were included for analysis. The median follow-up was 18.2 months (mean 28.4) and median BPFS was 69.8 months. Based on Kaplan-Meier analysis, the estimated 2- and 5-year BPFS rate was 77.2% and 59.1%, respectively. Neoadjuvant hormonal therapy was administered to 41% of men and this tended to occur in men with larger prostates, likely as a technical consideration for downsizing before cryosurgery. At multivariate analysis, the presence of Gleason score 9 or 10 (Hazard Ratio [HR] 1.9) and a posttreatment PSA nadir of ≥0.4 ng/mL (HR 5.7) were the only significant variables associated with biochemical progression using Cox regression. Complete continence was noted in 90.5% of men and potency in 17% of men at the 12-month follow-up. The incidence of rectourethral fistulae and urinary retention requiring intervention beyond temporary catheterization was 1.3% and 3.3%, respectively. CONCLUSION: Primary cryotherapy appears to be effective and safe in the community setting for high-grade, clinically localized prostate cancer in the short term.

Robotic-Assisted Ureteral Re-implantation: A Case Series.

INTRODUCTION: Minimally invasive surgical techniques are currently used for numerous urologic disorders and generally offer decreased morbidity and equivalent outcomes compared with open surgery. There is a relative paucity of data on robot-assisted ureteral re-implantation (RAUR) in adult patients for benign stricture disease. PATIENTS AND METHODS: We retrospectively reviewed our recent experience with mid-/distal ureteral reconstruction at a single tertiary-care center. From 2010 to 2012, 13 consecutive patients presenting with benign obstruction of mid-/distal ureters were managed with RAUR. RESULTS: In all cases the operative procedure was undertaken with six-port transperitoneal access, and all procedures were completed robotically. All ureters (left, n=5; right, n=7; bilateral, n=1) were re-implanted in a standard Bricker fashion into the dome of the bladder with (n=8) or without (n=6) a psoas hitch. Catheters were removed 4-11 days postoperatively, and all cystograms were negative for leak. Stents were removed 14-48 days after surgery. All were negative for hydronephrosis. Average follow-up was 10 (range, 2-20) months. There were two grade 1, two grade 2, two grade 3, and no grade 4 or 5 complications in 3 patients. CONCLUSIONS: RAUR is a safe and effective procedure. Extensive laparoscopic lysis of adhesions represents the primary challenge to an otherwise straightforward minimally invasive surgery. At our institution, RAUR has replaced open ureteral re-implantation as the preferred treatment for benign mid-/distal ureteral stricture disease.

Using preoperative albumin levels as a surrogate marker for outcomes after radical cystectomy for bladder cancer.

OBJECTIVE: To evaluate preoperative albumin levels as a marker for comparing survival outcomes after cystectomy in patients with bladder cancer. MATERIALS AND METHODS: We performed a retrospective record review using our bladder cancer database of 238 patients from 2004 to 2011. Of these, we included 187 patients with sufficient data for analysis, aged 35 years or older, who survived to undergo cystectomy. Serum albumin levels were routinely checked the day before cystectomy. Overall survival and cancer-specific survival by albumin levels were compared using Kaplan-Meier and Cox proportional hazards regression models. Complication rates between albumin groups were compared by a 2-sample test of proportions. RESULTS: Thirty-one patients (16.5%) were in the low-albumin cohort (defined as albumin <3.5 g/dL), and 156 patients had albumin levels within normal reference ranges. Multivariable analysis showed overall survival at 3 years was 41% and 56% (adjusted hazard ratio, 1.76; P = .04) and cancer-specific survival was 57% and 72% (hazard ratio, 1.57; P = .22) in the low- and normal-albumin groups, respectively. Overall complication rates were significantly higher in the cohort with low albumin than in those with normal albumin (87% vs 65%; P = .014). CONCLUSION: Our single-institution retrospective study demonstrates that patients with low preoperative albumin levels had an increased overall mortality and cancer-specific mortality risk than those with normal albumin levels. Albumin may therefore be a reflection of disease state as well as nutritional status.

Achieving the 'bifecta' using salvage cryotherapy for locally recurrent prostate cancer: analysis of the Cryo On-Line Data (COLD) registry data.

UNLABELLED: Study Type - Outcomes (cohort). Level of Evidence 2b. What's known on the subject? and What does the study add? The cancer-specific outcomes of salvage cryotherapy for locally recurrent prostate cancer have been well established within contemporary scientific literature. However, very little is known about the outcomes of salvage cryotherapy encompassing health-related quality of life considerations such as continence after treatment. We think the present study is quite novel, as it proposes a new therapeutic endpoint to evaluate the efficacy and outcomes of salvage therapies for locally recurrent prostate cancer, which we have termed the 'bifecta'. In addition, we report that in a large multicentre data registry, such as the COLD Registry, the therapeutic 'bifecta' can be achieved in most patients. OBJECTIVES: • To evaluate the contemporary outcomes of salvage cryotherapy for locally recurrent prostate cancer using the Cryo On-Line Data (COLD) Registry. • We also evaluate the outcomes of salvage cryotherapy in achieving the therapeutic 'bifecta' consisting of: (i) achieving a post-cryotherapy nadir serum PSA level of <0.6 ng/mL and (ii) no urinary incontinence. PATIENTS AND METHODS: • A prospectively, centrally collected secure online database has been developed of patients undergoing salvage cryoablation for locally recurrent prostate cancer. Of the patients undergoing salvage cryotherapy (in the absence of neoadjuvant hormonal ablative therapy) included within the COLD Registry, complete medical records pertaining to continence status and serial PSA measurements after treatment were available in 183 patients. RESULTS: • The therapeutic 'bifecta' was achieved in 133 of these patients (72.7%). • Of the patients achieving the 'bifecta', the mean (sd) age at presentation was 71.5 (6.6) years. • Most patients (91%) had a baseline pre-salvage total serum PSA level of <10 ng/mL and a pre-treatment biopsy Gleason score of <8 (85%). • The mean duration of follow-up of patients achieving the 'bifecta' was 36.5 months. CONCLUSIONS: • The therapeutic 'bifecta', a new surrogate benchmark for salvage therapies, can be achieved in most patients undergoing salvage cryotherapy. • Therefore, salvage cryotherapy is a reasonable treatment choice for locally recurrent prostate cancer in appropriately selected patients.

Quality of life after open or robotic prostatectomy, cryoablation or brachytherapy for localized prostate cancer.

PURPOSE: Health related quality of life concerns factor prominently in prostate cancer management. We describe health related quality of life impact and recovery profiles of 4 commonly used operative treatments for localized prostate cancer. MATERIALS AND METHODS: Beginning in February 2000 all patients treated with open radical prostatectomy, robot assisted laparoscopic prostatectomy, brachytherapy or cryotherapy were asked to complete the UCLA-PCI questionnaire before treatment, and at 3, 6, 12, 18, 24, 30 and 36 months after treatment. Outcomes were compared across treatment types with statistical analysis using univariate and multivariate models. RESULTS: A total of 785 patients treated between February 2000 and December 2008 were included in the analysis with a mean followup of 24 months. All health related quality of life domains were adversely affected by all treatments and recovery profiles varied significantly by treatment type. Overall urinary function and bother outcomes scored significantly higher after brachytherapy and cryotherapy compared to open radical prostatectomy and robotic assisted laparoscopic radical prostatectomy. Brachytherapy and cryotherapy had a 3-fold higher rate of return to baseline urinary function compared to open radical prostatectomy and robotic assisted laparoscopic radical prostatectomy. Sexual function and bother scores were highest after brachytherapy, with a 5-fold higher rate of return to baseline function compared to cryotherapy, open radical prostatectomy and robotic assisted laparoscopic radical prostatectomy. All 4 treatments were associated with relatively transient and less pronounced impact on bowel function and bother. CONCLUSIONS: In a study of sequential health related quality of life assessments brachytherapy and cryotherapy were associated with higher urinary function and bother scores compared to open radical prostatectomy and da Vinci prostatectomy. Brachytherapy was associated with higher sexual function and bother scores compared to open radical prostatectomy, robotic assisted laparoscopic radical prostatectomy and cryotherapy.

Renal functional outcomes after cryoablation of small renal masses.

BACKGROUND AND PURPOSE: Renal function outcomes after renal cryosurgery have not been widely scrutinized. We report 2-year renal function outcomes from a single-center cohort of patients who were treated with cryoablation for small renal masses. METHODS: We performed a retrospective review of our laparoscopic and percutaneous renal cryoablation experience between January 2003 and April 2007. Global renal function was assessed using measured serum creatinine and estimated glomerular filtration rate (eGFR) (MDRD equation). Chronic kidney disease (CKD) was defined as a serum creatinine level >2.0 mg/dL or eGFR <60 mL/min/1.73 m(2). RESULTS: Sixty-two patients were included in the analysis. Mean follow-up was 30 months (range 13-63 mos). Mean tumor size was 2.33 cm (range 1-4.6 cm). Comorbid conditions were prevalent: 77% hypertension, 35% hyperlipidemia, 31% diabetes mellitus, 39% tobacco use, and 32% heart disease (coronary artery disease/congestive heart failure). Based on eGFR calculations, preoperative CKD was noted in 17 of 62 (27%) patients. De novo CKD was noted in 5 of 45 (11%) patients. Patients in whom de novo CKD developed had lower pretreatment eGFR (71.0 vs 98.4 60 mL/min/1.73 m(2), P = 0.03) and larger tumor size (2.94 vs 2.19 cm, P = 0.04) compared with patients who were maintaining normal renal function. When CKD was defined as creatinine level >2.0 mg/dL, only one and six patients were identified with preoperative and de novo CKD, respectively. CONCLUSIONS: In a cohort of renal cryosurgery patients who were characterized by highly prevalent medical comorbidities, renal function was generally well maintained, with a low rate of de novo CKD based on eGFR calculations. A serum creatinine level >2.0 mg/dL was a less sensitive measure of CKD.

Clinical collection and protein properties of expressed prostatic secretions as a source for biomarkers of prostatic disease.

The prostate gland secretes many proteins in a prostatic fluid that combines with seminal vesicle derived fluids to promote sperm activation and function. Proximal fluids of the prostate that can be collected clinically are seminal plasma and expressed-prostatic secretion (EPS) fluids. EPS represents the fluid being secreted by the prostate following a digital rectal prostate massage, which in turn can be collected in voided urine post-exam. This collection is not disruptive to a standard urological exam, and it can be repeatedly collected from men across all prostatic disease states. A direct EPS fluid can also be collected under anesthesia prior to prostatectomy. While multiple genetic assays for prostate cancer detection are being developed for the shed epithelial cell fraction of EPS urines, the remaining fluid that contains many prostate-derived proteins has been minimally characterized. Approaches to optimization and standardization of EPS collection consistent with current urological exam and surgical practices are described, and initial proteomic and glycomic evaluations of the of EPS fluid are summarized for prostate specific antigen and prostatic acid phosphatase. Continued characterization of the prostate specific protein components of EPS urine combined with optimization of clinical collection procedures should facilitate discovery of new biomarkers for prostate cancer.

Single center experience with percutaneous and laparoscopic cryoablation of small renal masses.

BACKGROUND AND PURPOSE: While partial nephrectomy remains the gold standard for the management of most small renal masses, increasing experience with renal cryoablation has suggested a viable alternative with a favorable morbidity profile and good efficacy. We report intermediate-term oncologic outcomes from a single-center experience with laparoscopic and percutaneous renal cryoablation. PATIENTS AND METHODS: We performed a retrospective review of our laparoscopic renal cryoablation (LRC) and percutaneous renal cryoablation (PRC) experience between January 2003 and April 2007. Patients with at least 12 months of follow-up were included in the analysis. Follow-up consisted of imaging and laboratory studies at regular intervals. Persistent mass enhancement or interval tumor growth was considered a treatment failure. RESULTS: Sixty-six patients (44% women/56% men; 42% African-American/58% Caucasian/other; mean body mass index, 29.7) with 72 tumors underwent either LRC (n = 52) or PRC (n = 20) with a mean follow-up of 30 months (median 25.1 mos; range 13-63 mos). Average patient age was 66.5 years (range 34-82 yrs). Mean tumor size was 2.33 cm (range 1-4.6 cm). Comorbid conditions were prevalent: 76% hypertension, 36% hyperlipidemia, 24% chronic kidney disease, 29% diabetes mellitus, 36% tobacco use, and 32% heart disease. RESULTS of pretreatment biopsy were 62% renal-cell carcinoma and 38% benign or nondiagnostic. Overall cancer-specific and cancer-free survival were 100% and 97%, respectively. There were two treatment failures (3.8%) in the LRC group and five primary failures in the PRC group (25%) (P = 0.015), four of which were salvaged with repeated PRC with no evidence of recurrence at 6 to 36 months of follow-up. There has been no significant local or metastatic progression. CONCLUSIONS: LRC and PRC achieved good oncologic control with minimal morbidity at a mean follow-up of 30 months in a patient cohort characterized by numerous comorbid conditions. PRC had a significantly higher primary treatment failure rate than LRC, but re-treatment offered salvage oncologic control with no significant complications.

Computer modeling technology to assess extracapsular tissue coverage of whole mount sections after retropubic and laparoscopic radical prostatectomy.

PURPOSE: The introduction of new surgical approaches to radical prostatectomy requires methodologies that permit valid comparison that are more expedient than long-term outcomes of biochemical local and distant failure and survival. We used a computer modeling program to assess the percent of extracapsular tissue coverage of prostate glands removed by the open retropubic and laparoscopic approaches. MATERIALS AND METHODS: Specimens were available for 15 and 17 patients who underwent open and laparoscopic radical prostatectomy, respectively. Serial whole mount sections were taken at 5 mm intervals. A genitourinary pathologist drew the contours of the prostate capsule on each tissue section. The whole mount was scanned to produce digital images. A software program was used to create a file with capsule information and a file with extraprostatic fibroadipose tissue information. Two separate point cloud files were generated to represent the capsule and extraprostatic models, and software algorithms were used to generate differences in the point clouds to quantify the extent of extracapsular tissue coverage. RESULTS: When separated into sides dissected by a nerve or nonnerve sparing technique, the overall percent of gland surface coverage by extracapsular fibroadipose tissue was statistically greater with laparoscopic dissection than with the open approach. When a segmental analysis of gland coverage was evaluated, a statistically greater percent of fibroadipose coverage was associated with laparoscopic dissection in the apical and inferolateral segments with nonnerve sparing, and in the apical segment with nerve sparing. CONCLUSIONS: This small radical prostatectomy series, analyzed by computer reconstruction as described, provides information suggesting that overall extracapsular tissue coverage is at least equal if not superior using the laparoscopic vs the open approach. This was specifically the case in areas of inferolateral and apical dissection with nonnerve sparing procedures and in areas of the apical dissection with nerve sparing procedures.

Single center experience with third-generation cryosurgery for management of organ-confined prostate cancer: critical evaluation of short-term outcomes, complications, and patient quality of life.

BACKGROUND AND PURPOSE: Technical refinements such as improved ultrasonographic localization and the routine use of urethral warmers and small-gauge needle delivery systems have renewed interest in cryosurgical treatment as a minimally invasive option for selected patients with localized prostate cancer. Only three reports of quality of life (QoL) in prostate cryoablation exist, and none report on patients treated with third-generation cryoablative technology. We critically examine our initial series of consecutive patients at a single institution undergoing primary third-generation cryosurgical treatment of localized prostate cancer with respect to treatment outcome, morbidity profile, and QoL parameters. To our knowledge, this is the first QoL report on third-generation cryoablation of the prostate. PATIENTS AND METHODS: We retrospectively review the records of 89 consecutive patients with median followup of 11 months (1-32) who have undergone third-generation cryosurgical ablation of the prostate as primary treatment for localized prostate cancer with intention to cure. Patients were risk stratified according to preprocedural parameters of prostate-specific antigen (PSA), clinical stage, and Gleason score. PSA trends were recorded and treatment effectiveness was observed using different definitions of biochemical failure. Charts were reviewed for postprocedure complications. Quality of life was measured prospectively using the University of California, Los Angeles, Prostate Cancer Index as well as American Urological Association symptom scores. We compare a percent of baseline score (%BS) for various domains between our series of patients treated with primary cryoablation with a series of patients undergoing brachytherapy for localized prostate cancer. RESULTS: Treatment success was defined by achievement of a PSA nadir of < or =0.1 ng/mL and by biochemical disease-free survival (BDFS) assessed with both a PSA threshold of < or =0.4 ng/dL over time and the American Society for Therapeutic Radiology and Oncology (ASTRO) definition of three consecutive rises in PSA. According to risk stratification, 86%, 81.5%, and 78% of low-, intermediate-, and high-risk patients, respectively, achieved a PSA nadir of < or =0.1 ng/mL. Overall, at 12 months follow-up, 94% of patients achieved BDFS using ASTRO criteria while 70% achieved BDFS using a PSA threshold of < or =0.4 ng/mL. With risk stratification, 74%, 70%, and 60% of low-, intermediate-, and high-risk patients, respectively, achieved BDFS defined by PSA threshold of < or =0.4 ng/mL. Complications were rare. The response rate for Health Related Quality of Life (HRQoL) questionnaires was 71% for cryoablation patients and 51% for brachytherapy patients. At 12 months follow-up, patients undergoing cryoablation on average achieved urinary and bowel domain scores comparable to baseline, but sexual domains remained well below baseline. When compared with a brachytherapy series with better baseline sexual function (P = 0.04) and urinary function (P = 0.03), cryotherapy patients experienced more negative impact on sexual function steadily for up to 12 months (P = 0.02). Urinary function was similar between the groups until 18 months, at which time cryoablation patients fared better (P = 0.01); this was sustained up to 24 months (P = 0.04). CONCLUSIONS: Treatment success with cryosurgery varies with definition; however, our results are comparable to other series with regard to short-term cancer control. Complication rates in this series of third-generation cryosurgical patients are low. QoL characteristics of third-generation cryoablation are similar to those described in second-generation cryoablation series. Compared with brachytherapy, cryotherapy results in less irritative and obstructive voiding symptoms in the early post-treatment period and may improve urinary function up to 24 months after treatment. In a small group of older patients with baseline erectile dysfunction undergoing cryoablation, sexual function returns to 20% of its baseline value with up to 12 months follow-up.

Robotically assisted radical laparoscopic prostatectomy in a patient with ectopic ureteral insertion into the prostate.

Robotically assisted laparoscopic radical prostatectomy (RaLRP) has become an alternative surgical treatment option for patients with localized prostate cancer. Rare anatomic variations result in modification of established techniques. We describe the first successful completion of RaLRP for localized prostate cancer in a patient with coexisting complete left ureteral duplication and ectopic insertion of the upper pole moiety ureter into the prostatic urethra. After standard radical prostate excision and vesicourethral anastomosis, the unique anatomy in this case required additional reconstructive maneuvers including construction of a Y-type conjoined ureteral anastomosis and ureteroneocystotomy. The procedure was safely completed without open conversion. Operative time was 420 min and EBL was 200 mL. Ureteral stents were removed in six weeks and IVP showed no evidence of obstruction. When faced with a ureteral anomaly, RaLRP can be safely completed. Robotic technology is helpful in performing additional delicate reconstructive maneuvers.

Prospective longitudinal comparative study of early health-related quality-of-life outcomes in patients undergoing surgical treatment for localized prostate cancer: a short-term evaluation of five approaches from a single institution.

BACKGROUND AND PURPOSE: Quality of life (QoL) issues are a vital concern for the majority of patients seeking therapeutic intervention once they are found to have prostate cancer. A prospective longitudinal comparison using validated QoL instruments is a valuable technique to evaluate outcome differences. We evaluated the short-term QoL changes from baseline of five surgical approaches for localized prostate carcinoma delivered at a single institution. PATIENTS AND METHODS: A prospective longitudinal survey of 719 patients with newly diagnosed prostate cancer was initiated in 2001. The surgical procedures performed during this time period were open radical prostatectomy (ORP), laparoscopic radical prostatectomy (LRP), da Vinci robotic prostatectomy (dVP), (103)Pd brachytherapy ((103)Pd), and prostate cryoablation (PCryo). An Institutional Review Board-approved questionnaire comprised of validated QoL instruments (UCLA Prostate Cancer Index and American Urological Association Symptom Index [SI]) was mailed to enrolled patients prior to their selected surgery and again at 1, 3, 6, 9, 12, 18, 24, and 36 months after therapy. A percent of baseline score calculation including data from all five treatment cohorts for follow-up months 1, 3, and 6 was compared within groups. Group I consisted of patients undergoing ORP, LRP, or dVP. Group II consisted of patients undergoing (103)Pd or PCryo. RESULTS: Between January 2000 and April 2005, 498 patients (69%) were enrolled who completed the baseline questionnaire and at least one follow-up survey at 1, 3, or 6 months. The mean patient age at ORP, LRP, dVP, (103)Pd, and PCryo was 59, 61, 60, 67, and 72 years, respectively. Within Group I, early recovery of sexual function (at 3 months) appeared to occur sooner after dVP (35% return to baseline [RTB]) than ORP (24% RTB) and LRP (21% RTB) (P = 0.03). No other significant differences were noted, and trends toward improvement were seen in all groups. Within Group II, PCryo (18% RTB) had a more negative impact on sexual function at 3 months than did 103Pd (63% RTB) (P = 0.007), although a significant difference in baseline sexual function was also noted (P = 0.001). Early urinary function (at 1 month) was better after (103)Pd (82% RTB) than PCryo (72%) (P = 0.05), but this difference was lost at 6 months. In addition, the irritative and obstructive symptoms evaluated by the AUA SI were significantly worse (P = 0.003) at 3 months after (103)Pd than after PCryo. CONCLUSIONS: Different surgical approaches for the treatment of localized prostate cancer affect the shortterm QoL results in different ways. Urinary, sexual, and bowel function and bother are affected to a similar degree by ORP, LRP, and dVP. In an older population, the tissue destruction resulting from PCryo appears to relieve obstructive and irritative urinary symptoms but at the sacrifice of sexual function compared with (103)Pd.

Open-label trial evaluating the safety and efficacy of zoledronic acid in preventing bone loss in patients with hormone-sensitive prostate cancer and bone metastases.

OBJECTIVES: To evaluate the efficacy and safety of zoledronic acid in preventing bone loss in patients with hormone-sensitive prostate cancer and bone metastases who were receiving androgen deprivation therapy. METHODS: Patients received zoledronic acid 4 mg as a 15-minute infusion every 3 weeks for 1 year. Bone mineral density of the lumbar spine (L2 to L4) and total hip was measured by dual-energy x-ray absorptiometry at baseline and 12 months. Biochemical markers of bone turnover (N-telopeptide and bone alkaline phosphatase) and serum creatinine levels were evaluated at baseline and during the study. Skeletal-related events were assessed at each study visit. RESULTS: Of the 221 enrolled patients, 202 and 221 patients were included in the efficacy and safety analyses, respectively. The mean increase in bone mineral density of the lumbar spine and total hip was 7.7% (P <0.001) and 3.6% (P <0.001), respectively. Decreases in N-telopeptide and bone alkaline phosphatase levels were significant and sustained. The median time to the first skeletal-related event was not reached; 11.9% of patients had a skeletal-related event. Arthralgia (20.4%), nausea (14%), fatigue (14%), and back pain (12.2%) were the most common adverse events. Adverse events due to renal function deterioration were infrequent. The mean maximal change in serum creatinine level from baseline was 0.3 mg/dL. CONCLUSIONS: Zoledronic acid administration for 1 year to patients with hormone-sensitive prostate cancer and bone metastases who were receiving androgen deprivation therapy was safe and prevented bone loss, as demonstrated by significant increases in bone mineral density and sustained suppression of biochemical markers of bone turnover.

Modified running vesicourethral anastomosis after robotically assisted laparoscopic radical prostatectomy: use of solitary Lapra-Ty to secure posterior approximation.

OBJECTIVES: We describe a novel method of ensuring posterior approximation and preventing urinary leak during the running anastomosis of robotically assisted laparoscopic prostatectomy. METHODS: Two 3-0 Monocryl RB-1 sutures are tied end-to-end. The undyed suture is placed first at the 5-o'clock position on the bladder side outside-in and then through the urethra at the same location inside-out. Proceeding clockwise, the suture is placed twice more through both the bladder and the urethra. With gentle manipulation, the suture is cinched down to provide secure posterior approximation; however, if tension is released from the suture coming from the urethra, the approximation may loosen and could result in a potential "gap" and site for anastomotic leakage. To prevent potential loosening, tension is maintained on the stitch as a single Lapra-Ty is placed at the base of the suture as it leaves the urethra. When the tension is released, the posterior approximation is tightly maintained and the remaining anastomosis is completed. RESULTS: We have performed 110 robotically assisted laparoscopic prostatectomies. Six urinary leaks requiring prolonged catheterization were identified in our first 90 patients (6.7%). We have not experienced any urinary leakage or short-term complications in the subsequent 20 patients using this technique. CONCLUSIONS: We describe a novel technique to ensure secure posterior approximation during the vesicourethral anastomosis after robotically assisted laparoscopic prostatectomy. A single Lapra-Ty clip placed early during the anastomosis prevents potential "gaps" in the approximation that may be the source of troublesome leakage.

Prospective longitudinal comparative study of health-related quality of life in patients undergoing invasive treatments for localized prostate cancer.

BACKGROUND AND PURPOSE: Health-related quality of life (QoL) concerns are important for patients selecting treatment options for clinically localized prostate cancer and are critical in evaluating outcomes. We report pretreatment and post-treatment general and disease-specific QoL for the following invasive interventions: open radical prostatectomy (ORP), laparoscopic radical prostatectomy (LRP), and palladium-103 ((103)Pd) brachytherapy. PATIENTS AND METHODS: We performed a prospective longitudinal survey of 452 patients with newly diagnosed prostate cancer treated at a single medical center between 2001 and 2003. An Institutional Review Board-approved questionnaire comprised of validated QoL instruments was sent to patients scheduled to undergo ORP (N = 186), LRP (N = 116), or brachytherapy (N = 150). The same questionnaire was sent out 1, 3, 6, 9, and 12 months after therapy. Comparisons were made between the groups to determine if the choice of therapy resulted in differences in QoL. RESULTS: General QoL scores were minimally affected by the choices; however, the disease-specific domains of bowel, urinary, and sexual function were adversely affected by all modalities. The ORP and LRP groups were similar among disease-specific domains and received lower post-treatment urinary and sexual scores than the (103)Pd patients. At 12 months, 38% of ORP and 46% of LRP patients had returned to baseline urinary function compared with 75% of (103)Pd patients. At 12 months, 63% of (103)Pd patients had returned to baseline sexual function compared with 19% of both the LRP and ORP patients. CONCLUSIONS: Invasive treatments for localized prostate cancer have little impact on general QoL but significantly affect disease-specific domains. Both ORP and LRP have a greater initial negative impact on urinary and sexual function than (103)Pd. The differences among the treatments with regard to QoL provide information to patients faced with choosing a treatment.