Prospective Multicenter Comparison of Open and Robotic Radical Prostatectomy: The PROST-QA/RP2 Consortium.

PURPOSE: Our goal was to evaluate the comparative effectiveness of robot-assisted laparoscopic prostatectomy (RALP) and open radical prostatectomy (ORP) in a multicenter study. MATERIALS AND METHODS: We evaluated men with localized prostate cancer at 11 high-volume academic medical centers in the United States from the PROST-QA (2003-2006) and the PROST-QA/RP2 cohorts (2010-2013) with a pre-specified goal of comparing RALP (549) and ORP (545). We measured longitudinal patient-reported health-related quality of life (HRQOL) at pre-treatment and at 2, 6, 12, and 24 months, and pathological and perioperative outcomes/complications. RESULTS: Demographics, cancer characteristics, and margin status were similar between surgical approaches. ORP subjects were more likely to undergo lymphadenectomy (89% vs 47%; p <0.01) and nerve sparing (94% vs 89%; p <0.01). RALP vs ORP subjects experienced less mean intraoperative blood loss (192 vs 805 mL; p <0.01), shorter mean hospital stay (1.6 vs 2.1 days; p <0.01), and fewer blood transfusions (1% vs 4%; p <0.01), wound infections (2% vs 4%; p=0.02), other infections (1% vs 4%; p <0.01), deep venous thromboses (0.5% vs 2%; p=0.04), and bladder neck contractures requiring dilation (1.6% vs 8.3%; p <0.01). RALP subjects reported less pain (p=0.04), less activity interference (p <0.01) and higher incision satisfaction (p <0.01). Surgical approach (RALP vs ORP) was not a significant predictor of longitudinal HRQOL change in any HRQOL domain. CONCLUSIONS: In high-volume academic centers, RALP and ORP patients may expect similar long-term HRQOL outcomes. Overall, RALP patients have less pain, shorter hospital stays, and fewer post-surgical complications such as blood transfusions, infections, deep venous thromboses, and bladder neck contractures.

Effect of Intravesical Instillation of Gemcitabine vs Saline Immediately Following Resection of Suspected Low-Grade Non-Muscle-Invasive Bladder Cancer on Tumor Recurrence: SWOG S0337 Randomized Clinical Trial.

Importance: Low-grade non-muscle-invasive urothelial cancer frequently recurs after excision by transurethral resection of bladder tumor (TURBT). Objective: To determine whether immediate post-TURBT intravesical instillation of gemcitabine reduces recurrence of suspected low-grade non-muscle-invasive urothelial cancer compared with saline. Design, Setting, and Participants: Randomized double-blind clinical trial conducted at 23 US centers. Patients with suspected low-grade non-muscle-invasive urothelial cancer based on cystoscopic appearance without any high-grade or without more than 2 low-grade urothelial cancer episodes within 18 months before index TURBT were enrolled between January 23, 2008, and August 14, 2012, and followed up every 3 months with cystoscopy and cytology for 2 years and then semiannually for 2 years. Patients were monitored for tumor recurrence, progression to muscle invasion, survival, and toxic effects. The final date of follow-up was August 14, 2016. Interventions: Participants were randomly assigned to receive intravesical instillation of gemcitabine (2 g in 100 mL of saline) (n = 201) or saline (100 mL) (n = 205) for 1 hour immediately following TURBT. Main Outcomes and Measures: The primary outcome was time to recurrence of cancer. Secondary end points were time to muscle invasion and death due to any cause. Results: Among 406 randomized eligible patients (median age, 66 years; 84.7% men), 383 completed the trial. In the intention-to-treat analysis, 67 of 201 patients (4-year estimate, 35%) in the gemcitabine group and 91 of 205 patients (4-year estimate, 47%) in the saline group had cancer recurrence within 4.0 years (hazard ratio, 0.66; 95% CI, 0.48-0.90; P<.001 by 1-sided log-rank test for time to recurrence). Among the 215 patients with low-grade non-muscle-invasive urothelial cancer who underwent TURBT and drug instillation, 34 of 102 patients (4-year estimate, 34%) in the gemcitabine group and 59 of 113 patients (4-year estimate, 54%) in the saline group had cancer recurrence (hazard ratio, 0.53; 95% CI, 0.35-0.81; P = .001 by 1-sided log-rank test for time to recurrence). Fifteen patients had tumors that progressed to muscle invasion (5 in the gemcitabine group and 10 in the saline group; P = .22 by 1-sided log-rank test) and 42 died of any cause (17 in the gemcitabine group and 25 in the saline group; P = .12 by 1-sided log-rank test). There were no grade 4 or 5 adverse events and no significant differences in adverse events of grade 3 or lower. Conclusions and Relevance: Among patients with suspected low-grade non-muscle-invasive urothelial cancer, immediate postresection intravesical instillation of gemcitabine, compared with instillation of saline, significantly reduced the risk of recurrence over a median of 4.0 years. These findings support using this therapy, but further research is needed to compare gemcitabine with other intravesical agents. Trial Registration: clinicaltrials.gov Identifier: NCT00445601.

Phase III Intergroup Trial of Adjuvant Androgen Deprivation With or Without Mitoxantrone Plus Prednisone in Patients With High-Risk Prostate Cancer After Radical Prostatectomy: SWOG S9921.

Purpose Patients with high-risk prostate cancer after radical prostatectomy are at risk for death. Adjuvant androgen-deprivation therapy (ADT) may reduce this risk. We hypothesized that the addition of mitoxantrone and prednisone (MP) to adjuvant ADT could reduce mortality compared with adjuvant ADT alone. Methods Eligible patients had cT1-3N0 prostate cancer with one or more high-risk factors after radical prostatectomy (Gleason score [GS] ≥ 8; pT3b, pT4, or pN+ disease; GS 7 and positive margins; or preoperative prostate-specific antigen [PSA] > 15 ng/mL, biopsy GS score > 7, or PSA > 10 ng/mL plus biopsy GS > 6. Patients with PSA ≤ 0.2 ng/mL after radical prostatectomy were stratified by pT/N stage, GS, and adjuvant radiation plan and randomly assigned to ADT (bicalutamide and goserelin for 2 years) or ADT plus six cycles of MP. The primary end point was overall survival (OS). Median OS was projected to be 10 years in the ADT arm, requiring 680 patients per arm to detect a hazard ratio of 1.30 with 92% power and one-sided α = .05. Results Nine hundred sixty-one eligible intent-to-treat patients were randomly assigned to ADT or ADT + MP from October 1999 to January 2007, when the Data Safety Monitoring Committee recommended stopping accrual as a result of higher leukemia incidence with ADT + MP. Median follow-up was 11.2 years. The 10-year OS estimates were 87% with ADT (expected 50%) and 86% with ADT + MP (hazard ratio, 1.06; 95% CI, 0.79 to 1.43). The 10-year estimate for disease-free survival was 72% for both arms. Prostate cancer was the cause of death in 18% of patients in the ADT arm and 22% in the ADT + MP arm. More patients in the MP arm died of other cancers (36% v 18% in ADT alone arm). Conclusion MP did not improve OS and increased deaths from other malignancies. The DFS and 10-year OS in these patients treated with 2 years of ADT were encouraging compared with historical estimates, although a definitive conclusion regarding value of ADT may not be made without a nontreatment control arm.

Functional Outcomes Following Nerve Sparing Prostatectomy Augmented with Seminal Vesicle Sparing Compared to Standard Nerve Sparing Prostatectomy: Results from a Randomized Controlled Trial.

PURPOSE: Seminal vesicle sparing may reduce the risk of neurovascular bundle injury and improve functional outcomes after prostatectomy. While several observational studies have shown better functional outcomes following seminal vesicle sparing approaches, evidence from randomized trials is lacking. We performed a randomized controlled trial comparing functional and cancer control outcomes between nerve sparing prostatectomy augmented with seminal vesicle sparing and standard nerve sparing prostatectomy. MATERIALS AND METHODS: A total of 140 men with early stage prostate cancer were enrolled in a randomized phase II trial comparing nerve sparing prostatectomy augmented with seminal vesicle sparing to standard nerve sparing prostatectomy. Patient reported sexual and urinary functional scores were assessed prior to surgery, and 6 and 12 months postoperatively. Surgical margin status and prostate specific antigen recurrence were evaluated as secondary outcomes. RESULTS: There were no differences in sexual or urinary function scores after surgery between the study groups. The median urinary incontinence domain score was 92 in the nerve sparing group and 87.5 in the nerve plus seminal vesicle sparing group at 12 months (p = 0.77). Median sexual function domain scores were 73.7 in the nerve sparing group and 77.1 in the nerve sparing plus seminal vesicle sparing group at 12 months (p = 0.29). Margin status and 12-month biochemical recurrence were similar in the groups. CONCLUSIONS: Recovery of continence and sexual function was similar between the groups in this randomized controlled trial. Seminal vesicle sparing did not negatively affect margin status or 12-month biochemical (prostate specific antigen) recurrence. These results suggest limited usefulness of seminal vesicle sparing prostatectomy.

Nomogram Predicting Prostate Cancer-specific Mortality for Men with Biochemical Recurrence After Radical Prostatectomy.

BACKGROUND: The natural history of prostate-specific antigen (PSA)-defined biochemical recurrence (BCR) of prostate cancer (PCa) after definitive local therapy is highly variable. Validated prediction models for PCa-specific mortality (PCSM) in this population are needed for treatment decision-making and clinical trial design. OBJECTIVE: To develop and validate a nomogram to predict the probability of PCSM from the time of BCR among men with rising PSA levels after radical prostatectomy. DESIGN, SETTING, AND PARTICIPANTS: Between 1987 and 2011, 2254 men treated by radical prostatectomy at one of five high-volume hospitals experienced BCR, defined as three successive PSA rises (final value >0.2 ng/ml), single PSA >0.4 ng/ml, or use of secondary therapy administered for detectable PSA >0.1 ng/ml. Clinical information and follow-up data were modeled using competing-risk regression analysis to predict PCSM from the time of BCR. INTERVENTION: Radical prostatectomy for localized prostate cancer and subsequent PCa BCR. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: PCSM. RESULTS AND LIMITATIONS: The 10-yr PCSM and mortality from competing causes was 19% (95% confidence interval [CI] 16-21%) and 17% (95% CI 14-19%), respectively. A nomogram predicting PCSM for all patients had an internally validated concordance index of 0.774. Inclusion of PSA doubling time (PSADT) in a nomogram based on standard parameters modestly improved predictive accuracy (concordance index 0.763 vs 0.754). Significant parameters in the models were preoperative PSA, pathological Gleason score, extraprostatic extension, seminal vesicle invasion, time to PCa BCR, PSA level at PCa BCR, and PSADT (all p<0.05). CONCLUSIONS: We constructed and validated a nomogram to predict the risk of PCSM at 10 yr among men with PCa BCR after radical prostatectomy. The nomogram may be used for patient counseling and the design of clinical trials for PCa. PATIENT SUMMARY: For men with biochemical recurrence of prostate cancer after radical prostatectomy, we have developed a model to predict the long-term risk of death from prostate cancer.

Prostate capsule sparing versus nerve sparing radical cystectomy for bladder cancer: results of a randomized, controlled trial.

PURPOSE: Prostate capsule sparing and nerve sparing cystectomies are alternative procedures for bladder cancer that may decrease morbidity while achieving cancer control. However, to our knowledge the comparative effectiveness of these approaches has not been established. We evaluated functional and oncologic outcomes in patients undergoing these procedures. MATERIALS AND METHODS: We performed a single institution trial in patients with bladder cancer in whom transurethral prostatic urethral biopsy and transrectal prostate biopsy were negative. Men were randomized to prostate capsule sparing or nerve sparing cystectomy with neobladder creation and stratified by Sexual Health Inventory for Men score (greater than 21 vs 21 or less). Our primary end point was 12-month overall urinary function as measured by Bladder Cancer Index. Secondary end points included sexual function, cancer control and complications. RESULTS: A total of 40 patients were enrolled in the study with 20 patients in each arm. Urinary function at 12 months decreased by 13 and 28 points in the prostate capsule and nerve sparing groups, respectively (p = 0.10). Sexual function followed a similar pattern (p = 0.06). There was no difference in recurrence-free, metastasis-free or overall survival (each p >0.05). The rate of incidentally detected prostate cancer was similar (p = 0.15). CONCLUSIONS: Our study provides a randomized comparison of prostate capsule sparing and nerve sparing cystectomy techniques. We found no difference in functional or oncologic outcomes between the 2 approaches, although our study was underpowered due to a lack of patient accrual.

Understanding the relationship between tumor size, gland size, and disease aggressiveness in men with prostate cancer.

OBJECTIVE: To determine the relationship between prostate gland and tumor volume in men undergoing radical prostatectomy (RP) for prostate cancer. We hypothesized that larger tumors within smaller prostate glands are associated with more aggressive disease characteristics. METHODS: Records of patients undergoing RP from 2000-2008 at a single institution were reviewed retrospectively. The dominant nodule was considered to be the largest focus of cancer within the prostate, and the dominant nodule-to-prostate volume ratio (DNVR) was calculated according to the ratio of the dominant nodule volume to the gland weight. Cox regression was performed to assess the relationship between DNVR and both pathologic outcomes (Cancer of the Prostate Risk Assessment post-Surgical score) and biochemical recurrence (BCR). RESULTS: At a median follow-up of 3.7 years, 174 patients (7.2%) suffered BCR. There was no linear correlation between tumor volume and gland size (R = -0.09). DNVR above the median (≥0.033 cc/gm) was closely associated with high clinicopathologic risk as measured by Cancer of the Prostate Risk Assessment post-Surgical score (hazard ratio, 35.53; 95% confidence interval, 14.42-87.55 for high- vs low-risk groups). In the univariable analysis, both tumor diameter and DNVR were associated with increased risk of BCR. However, in the multivariable model, only tumor diameter remained a significant predictor of BCR (hazard ratio, 2.02; 95% confidence interval, 1.04-3.91). CONCLUSION: Increased DNVR appears to be a characteristic of aggressive prostate tumors, although it did not predict BCR in the present study. However, these data support the association between tumor diameter and BCR after RP for prostate cancer independent of other key clinicopathologic features.

Do margins matter? The influence of positive surgical margins on prostate cancer-specific mortality.

BACKGROUND: Positive surgical margins (PSMs) in radical prostatectomy (RP) specimens are a frequent indication for adjuvant radiotherapy and are used as a measure of surgical quality. However, the association between PSMs and prostate cancer-specific mortality (CSM) is poorly defined. OBJECTIVE: Analyze the association of PSMs with CSM, adjusting for fixed and time-dependent parameters. DESIGN, SETTING, AND PARTICIPANTS: Fine and Gray competing risk regression analysis was used to model the clinical data and follow-up information of 11,521 patients treated by RP between 1987 and 2005. Two extended models were used that adjusted for the use of postoperative radiotherapy, which was handled as a time-dependent covariate. Postoperative radiotherapy was modeled as a single parameter and also as early and late therapy, based on the prostate-specific antigen level at the start of treatment (≤0.5 vs >0.5 ng/ml). INTERVENTION: RP for clinically localized prostate cancer and selective use of secondary local and/or systemic therapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The outcome measure was prostate cancer-specific mortality. RESULTS AND LIMITATIONS: The 15-yr CSM rates for patients with PSMs and negative surgical margins were 10% and 6%, respectively (p<0.001). No significant association between PSM and CSM was observed in the conventional model with fixed covariates (hazard ratio [HR]: 1.04; 95% confidence interval [CI], 0.7-1.5; p=0.8) or in the two extended models that adjusted for postoperative radiotherapy (HR: 0.96; 95% CI, 0.7-1.4; p=0.9), or early and late postoperative radiotherapy (HR: 1.01; 95% CI, 0.7-1.4; p=0.9). CONCLUSIONS: PSMs alone are not associated with a significantly increased risk of CSM within 15 yr of RP. However, urologists should continue to strive to avoid PSMs, as they increase a man's risk of biochemical recurrence and need for secondary therapy and may be a source of considerable patient anxiety.

Open surgical partial nephrectomy for upper tract urothelial carcinoma.

We aimed to determine the ability of partial nephrectomy to prevent end-stage renal disease and tumor recurrence or progression in patients with upper tract urothelial carcinoma. Retrospectively, eight patients undergoing partial nephrectomy for upper tract urothelial carcinoma were identified and their medical records reviewed. All patients had imperative indications for nephron sparing, and diagnosis of upper tract urothelial carcinoma not adequately amenable to endoscopic management. Although three patients suffered acute tubular necrosis, only one required postoperative hemodialysis. During the follow-up period 25% (2/8) developed end-stage renal disease, including the one patient who had received postoperative hemodialysis. Recurrences occurred in five of seven patients with adequate oncological surveillance. Recurrences were successfully treated endoscopically in 80% (4/5) patients, and one patient had metastases. Of the eight patients, four have died. Death occurred 4 months, 1 year, 1.2 years and 3.5 years after partial nephrectomy. Of these patients, one succumbed to metastatic disease; the exact cause of death is unknown in the other three, but there was no documentation of metastatic cancer. The mean duration of follow up in the remaining four patients, all without evidence of metastatic urothelial cancer, is 71 months (range 22-108 months). In summary, partial nephrectomy for upper tract urothelial carcinoma in patients with imperative indications averts end-stage renal disease in most patients, and appears to be associated with acceptable disease-specific survival. Partial nephrectomy is a sparingly used option in patients with upper tract urothelial carcinoma refractory to endoscopic management who have imperative indications for nephron sparing.

A one-day couple group intervention to enhance sexual recovery for surgically treated men with prostate cancer and their partners: a pilot study.

Researchers evaluated the acceptance and effectiveness of a group intervention that provided education about post-prostatectomy sexual recovery and peer support for couples. Couples valued the intervention and retained the information. Partners became accepting of erectile dysfunction and communicated more openly about upsetting topics.