Luc Valiquette

A Nomogram Predicting 10-Year Life Expectancy in Candidates for Radical Prostatectomy or Radiotherapy for Prostate Cancer

PURPOSE Candidates for definitive therapy for localized prostate cancer (PCa) should have life expectancy (LE) in excess of 10 years. However, LE estimation is difficult. To circumvent this problem, we developed a nomogram predicting 10-year LE for patients treated with either radical prostatectomy (RP) or external-beam radiation therapy (EBRT) and compared it with an existing tool. PATIENTS AND METHODS Between 1989 and 2000, 9,131 men were treated with either RP (n = 5,955) or EBRT (n = 3,176), without any secondary therapy and all deaths were considered unrelated to PCa. Age and Charlson comorbidity index (CCI) predicted 10-year LE in Cox regression models. We used 200 bootstrap resamples to internally validate the nomogram. RESULTS Median age was 66 years, median CCI was 1, median follow-up was 5.9 years and median actuarial survival was 13.8 years. Advanced age (P < .001), elevated CCI score (P < .001) and treatment type (EBRT v RP, P < .001) were independent predictors of poor 10 year LE. The nomogram predicting 10 year LE after either RP or EBRT was 84.3% accurate in split sample validation and was 2.9% (P = .007) more accurate than the existing tool. A cutoff of 70% or less was 84% accurate in identifying men who did not survive beyond 10 years. CONCLUSION Our nomogram can accurately identify those individuals who do not have sufficient LE to warrant definitive PCa treatment and can help optimizing therapy decision-making.

Significant upgrading affects a third of men diagnosed with prostate cancer: predictive nomogram and internal validation

To explore the rate of significant upgrading from biopsy to radical prostatectomy (RP) specimens in a contemporary cohort, and to develop a prognostic model capable of predicting the probability of significant upgrading, as previous reports indicate that up to 43% of men with low‐grade prostate cancer at biopsy will be diagnosed with high‐grade cancer at RP.

Efficacy of Botulinum Toxin A Injection for Neurogenic Detrusor Overactivity and Urinary Incontinence: A Randomized, Double-Blind Trial

PURPOSE We determined the efficacy of onabotulinumtoxinA for neurogenic detrusor overactivity secondary to spinal cord injury or multiple sclerosis. MATERIALS AND METHODS In a prospective, double-blind, multicenter study 57 patients 18 to 75 years old with neurogenic detrusor overactivity secondary to spinal cord injury or multiple sclerosis and urinary incontinence (defined as 1 or more occurrences daily) despite current antimuscarinic treatment were randomized to onabotulinumtoxinA 300 U (28) or placebo (29) via cystoscopic injection at 30 intradetrusor sites, sparing the trigone. Patients were offered open label onabotulinumtoxinA 300 U at week 36 and followed a further 6 months while 24 each in the treatment and placebo groups received open label therapy. The primary efficacy parameter was daily urinary incontinence frequency on 3-day voiding diary at week 6. Secondary parameters were changes in the International Consultation on Incontinence Questionnaire and the urinary incontinence quality of life scale at week 6. Diary and quality of life evaluations were also done after open label treatment. RESULTS The mean daily frequency of urinary incontinence episodes was significantly lower for onabotulinumtoxinA than for placebo at week 6 (1.31 vs 4.76, p <0.0001), and for weeks 24 and 36. Improved urodynamic and quality of life parameters for treatment vs placebo were evident at week 6 and persisted to weeks 24 to 36. The most common adverse event in each group was urinary tract infection. CONCLUSIONS In adults with antimuscarinic refractory neurogenic detrusor overactivity and multiple sclerosis onabotulinumtoxinA is well tolerated and provides clinically beneficial improvement for up to 9 months.

Clinicians are poor raters of life-expectancy before radical prostatectomy or definitive radiotherapy for localized prostate cancer

To test the accuracy of predicting life‐expectancy (LE) among 19 raters, as the accurate prediction of LE in candidates for definitive therapy for localized prostate cancer is crucial, and little is known of the ability of clinicians to predict LE.

Biopsy Core Number Represents One of Foremost Predictors of Clinically Significant Gleason Sum Upgrading in Patients With Low-risk Prostate Cancer

OBJECTIVES To examine the effect the number of biopsy cores taken has on the rate of clinically significant Gleason sum upgrading (GSU) in patients with low-risk prostate cancer. METHODS We analyzed the data from 301 patients with low-risk prostate cancer (clinical Stage T1c-T2a, prostate-specific antigen <or=10 ng/mL, and biopsy Gleason sum <or=6) who underwent an extended (>or=10-core) prostate biopsy. Prostate-specific antigen level, clinical stage, biopsy Gleason sum, prostate volume, year of diagnosis, number of biopsy cores taken, and number of positive cores were used as predictors in logistic regression models addressing the rate of clinically significant GSU (defined as upgrading from biopsy Gleason sum 5-6 to radical prostatectomy Gleason sum of >or=7). Regression coefficients were used to estimate the predictive accuracy of individual variables, as well as their combined effect in the prediction of GSU. RESULTS The median number of biopsy cores taken was 18. Upgrading was recorded in 96 (31.9%). In men assessed with 10-12 cores, the rate of GSU was 47.9% compared with 23.5% if >18 cores were taken (P < .001). In multivariate analyses, the consideration of the variable defining the number of cores added 9.0% (P < .001) to the ability to predict GSU. CONCLUSIONS Patients with low-risk prostate cancer assessed with fewer biopsy cores are at a substantially greater risk of GSU. The number of biopsy cores taken represents one of the foremost predictors of GSU and should be taken into consideration during clinical decision-making in patients who are candidates for watchful waiting, active surveillance, or brachytherapy.

A population based assessment of perioperative mortality after cystectomy for bladder cancer.

PURPOSE Large variability exists in the rates of perioperative mortality after cystectomy. Contemporary estimates range from 0.7% to 5.6%. We tested several predictors of perioperative mortality and devised a model for individual perioperative mortality prediction. MATERIALS AND METHODS We relied on life tables to quantify 30, 60 and 90-day mortality rates according to age, gender, stage (localized vs regional), grade, type of surgery (partial vs radical cystectomy), year of cystectomy and histological bladder cancer subtype. We fitted univariable and multivariable logistic regression models using 5,510 patients diagnosed with bladder cancer and treated with partial or radical cystectomy within 4 SEER (Surveillance, Epidemiology, and End Results) registries between 1984 and 2004. We then externally validated the model on 5,471 similar patients from 5 other SEER registries. RESULTS At 30, 60 and 90 days the perioperative mortality rates were 1.1%, 2.4% and 3.9%, respectively. Age, stage and histological subtype represented statistically significant and independent predictors of 90-day mortality. The combined use of these 3 variables and of tumor grade resulted in the most accurate model (70.1%) for prediction of individual probability of 90-day mortality after cystectomy. CONCLUSIONS The accuracy of our model could potentially be improved with the consideration of additional parameters such as surgical and hospital volume or comorbidity. While better models are being developed and tested we suggest the use of the current model in individual decision making and in informed consent considerations because it provides accurate predictions in 7 of 10 patients.

LONG-TERM FOLLOWUP OF INITIAL Ta GRADE 1 TRANSITIONAL CELL CARCINOMA OF THE BLADDER

PURPOSE We evaluate the long-term outcome of initial Ta grade 1 transitional cell carcinoma. MATERIALS AND METHODS A total of 152 patients with initial Ta grade 1 bladder tumor were followed for a mean of 76 months (range 6 to 241). Recurrence was defined as positive findings on cystoscopy or biopsy. Progression was defined as an increase in tumor grade or stage. RESULTS Tumor recurrence in 83 of 152 patients (55%) was noted within 12 months of followup in 38 patients (46%), between 12 and 24 in 11 (13%), and between 24 and 60 in 22 (27%). A significant number of recurrences (12, 14%) were diagnosed more than 60 months after the first tumor. Of 83 patients with recurrence 31 (37%) had progression, including 21 to grade 2 and 2 to grade 3 disease. Carcinoma in situ was diagnosed in 3 patients and 5 had muscle invasive disease. Progression occurred more than 24 months after initial diagnosis in 20 patients and more than 60 months after first tumor event (2 had carcinoma in situ and 2 had muscle invasive disease) in 12. CONCLUSIONS Ta grade 1 bladder transitional cell carcinomas have a high recurrence rate and progression is not uncommon. These findings warrant close long-term followup, even when in some settings the trend is to discontinue followup after 5 years without any abnormal findings.

Return to Continence After Radical Retropubic Prostatectomy: A Randomized Trial of Verbal and Written Instructions Versus Therapist-Directed Pelvic Floor Muscle Therapy

OBJECTIVES To test the effectiveness of weekly postoperative pelvic floor muscle training (PFMT) versus supportive telephone contact by a urology nurse for men at 4 weeks after radical prostatectomy. METHODS This was a randomized controlled trial in three Canadian centers. At 4 weeks after surgery, standardized verbal and written instruction about PFMT was provided to all subjects. Randomization occurred after initial instruction. Continence was defined as 8 g or less of urine loss on a 24-hour pad test. Primary outcome was grams of urine loss on pad test; secondary outcomes were International Prostate Symptom Score (IPSS), Incontinence Impact Questionnaire (IIQ-7) score, cost, and perception of urine loss as a problem. Data were obtained at baseline (preoperatively) and at weeks 4, 8, 12, 16, and 28 and 1 year after surgery. RESULTS A total of 216 men were enrolled; 11 were dry or withdrew at 4 weeks. Ninety-nine were randomized to the control group and 106 to the treatment group. There were no group differences at baseline for prostate-specific antigen level (mean [standard deviation] 8.4 [10.4] ng/mL; 7.6 [4.6] ng/mL), Gleason score (6.3 [0.86]), IPSS, IIQ-7 score, pad test, or voiding diary. At 8 weeks 23% of the control group and 20% of the treatment group were continent; at 12 weeks, 28% and 32%; 16 weeks, 40% and 44%; 28 weeks, 50% and 47%; and at 52 weeks, 64% and 60%, respectively. There were no significant differences between groups at any time point for the outcome variables. CONCLUSIONS Verbal instruction and written information with telephone support seemed to be as effective as intensive PFMT. Less-intense therapy may be more cost-effective.

The Rate of Secondary Malignancies After Radical Prostatectomy Versus External Beam Radiation Therapy for Localized Prostate Cancer: A Population-Based Study on 17,845 Patients

PURPOSE External-beam radiation therapy (EBRT) may predispose to secondary malignancies that include bladder cancer (BCa), rectal cancer (RCa), and lung cancer (LCa). We tested this hypothesis in a large French Canadian population-based cohort of prostate cancer patients. METHODS AND MATERIALS Overall, 8,455 radical prostatectomy (RP) and 9,390 EBRT patients treated between 1983 and 2003 were assessed with Kaplan-Meier and Cox regression analyses. Three endpoints were examined: (1) diagnosis of secondary BCa, (2) LCa, or (3) RCa. Covariates included age, Charlson comorbidity index, and year of treatment. RESULTS In multivariable analyses that relied on incident cases diagnosed 60 months or later after RP or EBRT, the rates of BCa (hazard ratio [HR], 1.4; p = 0.02), LCa (HR, 2.0; p = 0.004), and RCa (HR 2.1; p <0.001) were significantly higher in the EBRT group. When incident cases diagnosed 120 months or later after RP or EBRT were considered, only the rates of RCa (hazard ratio 2.2; p = 0.003) were significantly higher in the EBRT group. In both analyses, the absolute differences in incident rates ranged from 0.7 to 5.2% and the number needed to harm (where harm equaled secondary malignancies) ranged from 111 to 19, if EBRT was used instead of RP. CONCLUSIONS EBRT may predispose to clinically meaningfully higher rates of secondary BCa, LCa and RCa. These rates should be included in informed consent consideration.

Impact of chronic prostatitis‐like symptoms on the quality of life in a large group of men

To assess the prevalence of chronic prostatitis (CP) and chronic pelvic pain syndrome (CPPS) symptoms in a large group of men, using the National Institute of Health‐Chronic Prostatitis Symptom Index (NIH‐CPSI), and to evaluate which of the NIH‐CPSI symptoms had the most detrimental effect on quality of life (QoL).