Do Patients With Multiple Myeloma Enrolled in Clinical Trials Live Longer?

OBJECTIVES: Enrollment in clinical trials is thought to improve survival outcomes through the trial effect. In this retrospective observational cohort study, we aimed to discern differences in survival outcomes by clinical trial enrollment and race-ethnicity. MATERIALS AND METHODS: Of 1285 patients receiving care for multiple myeloma at an National Cancer Institute designated cancer center from 2012 to 2018, 1065 (83%) were nontrial and 220 (17%) were trial participants. Time to event analyses were used to adjust for baseline characteristics and account for clinical trial enrollment as a time-varying covariate. We analyzed propensity-matched cohorts of trial and nontrial patients to reduce potential bias in observational data. RESULTS: Trial patients were younger (mean age in years: 60 vs. 63; P<0.001), underwent more lines of therapy (treatment lines ≥6: 39% vs. 17%; P<0.001), and had more comorbidities than nontrial patients. After controlling for baseline characteristics and clinical trial enrollment as a time-varying covariate, no significant difference in survival was found between trial and nontrial participants (hazard ratio [HR]=1.34, 95% confidence intervals [CIs]: 0.90-1.99), or between propensity-matched trial and nontrial participants (205 patients in each cohort, HR=1.36, 95% CIs: 0.83-2.23). Subgroup analyses by lines of therapy confirmed results from overall analyses. We did not observe survival differences by race-ethnicity (Logrank P=0.09), though hazard of death was significantly increased for nontrial Black/Hispanic patients compared with trial White patients (HR=1.76, 95% CIs=1.01-3.08). CONCLUSIONS: This study did not find evidence of a significant survival benefit to trial enrollment among patients with multiple myeloma. Patients enrolled in clinical trials underwent more lines of therapy, suggesting they may have had more treatment-resistant cancers. A small survival benefit in this cohort may be obscured by the lack of difference in survival between trial and nontrial patients.

A Randomized, Controlled, 3-Arm Trial of Pharmacological Penile Rehabilitation in the Preservation of Erectile Function After Radical Prostatectomy.

BACKGROUND: Although the concept of penile rehabilitation after radical prostatectomy (RP) has been advocated for decades, there is little definitive evidence regarding its utility or the best strategy to optimize patient outcomes. AIM: The goal of this study is to analyze the ability of 3 different pharmacological strategies to preserve the ability of men to achieve spontaneous (non-medication assisted) erections after bilateral nerve-sparing RP. METHODS: This IRB- and FDA-approved study studied penile rehabilitation in a 3-arm fashion with a target enrollment of 200 patients. (i) Control arm: nightly placebo with sildenafil 100 mg on demand for sexual relations (up to 6 pills/month); (ii) nightly sildenafil arm: nightly sildenafil 50 mg and sildenafil 100 mg on demand for sexual relations (up to 6 pills/month); (iii) combination therapy arm: nightly sildenafil 50 mg (5 nights/week) plus intracavernosal injections twice/week. Inclusion criteria included bilateral nerve-sparing surgery, normal serum total testosterone, and good preoperative baseline erectile function as measured by the erectile function domain score of the IIEF (EFD) (≥24). Patients were followed with a medication use diary and the IIEF questionnaire at 6 weeks, 3 m, 6 m, 12 m, 18 m and 24 m. OUTCOMES: A difference was seen in the IIEF-EFD scores between the 3 groups at 24 months after RP. Secondary end points include the time to return of spontaneous functional erections, the time for patients to respond to oral erectogenic therapy, and the proportion of patients who have normalization of their IIEF-EFD scores. RESULTS: The study was interrupted because of failure to recruit the target study population in a reasonable timeframe. A total of 76 subjects with median age of 57 (IQR: 51, 63) years and mean IIEF-EFD of 29 (IQR: 27, 30) were initially randomized, but at 24 months, the sample sizes by group were (i) n = 4; (ii) n = 18; and (iii) n = 10, with median IIEF-EFD 24 (IQR: 18, 28), 24 (IQR: 18, 28), and 21 (IQR: 9, 26), respectively. There was no statistical difference among the groups in the final analysis. CLINICAL IMPLICATIONS: Definitive evidence for the ability of different pharmacological rehabilitation strategies to improve long-term EF outcomes might never be available. STRENGTHS & LIMITATIONS: This was a well-designed randomized and 3-arm designed trial intended to provide decisive evidence regarding the utility of penile rehabilitation. Failure to recruit the target population is the main limitation. CONCLUSION: The limited number of patients in the present trial precludes definitive interpretation. However, results indicate how challenging it is to conduct true rehabilitation studies. Miranda EP, Benfante N, Kunzel B, et al. A Randomized, Controlled, 3-Arm Trial of Pharmacological Penile Rehabilitation in the Preservation of Erectile Function After Radical Prostatectomy. J Sex Med 2021;18:423-429.

Prospective analysis of penile length changes after radical prostatectomy.

OBJECTIVES: To assess the impact of radical prostatectomy (RP) on penile dimensions. To assess the impact of phosphodiesterase-5 inhibitor (PDE5i) use on penile length changes. PATIENTS AND METHODS: Men undergoing RP were enrolled in this prospective study before surgery. Demographic, clinical and PDE5i frequency-of-use data were collected. Erectile function was measured using the erectile function domain (EFD) of the International Index of Erectile Function. A single evaluator measured stretched flaccid penile length (SFPL) before RP, and at 2 and 6 months after RP. Repeated measures analysis was used to test differences in SFPL between timepoints. Pearson correlation was used for univariate analyses and multiple regression was used for multivariable analysis. RESULTS: A total of 118 patients were evaluated at baseline, with 76 and 63 patients evaluated at 2 and 6 months, respectively. At 2 months, there was a 2.4-mm mean decrease in SFPL, while at 6 months there was no significant difference. At 6 months, those subjects who took a daily PDE5i had no SFPL loss (n = 36, 1±6.7 mm gain, P = 0.37 compared with baseline), while those subjects who did not consistently take a PDE5i had SFPL loss (n = 27, 4.4±6.6 mm loss, P < 0.002 compared with baseline). In multivariable analysis, PDE5i use at 6 months and 6-month EFD score without on-demand PDE5i were significant predictors of 6-month SFPL loss, suggesting that an increase in these variables leads to SFPL preservation. CONCLUSIONS: In this rigorously conducted prospective study of SFPL changes after RP, there was evidence of SFPL loss at 2 months, but not at 6 months after RP. PDE5i use moderated SFPL loss, with patients who regularly used PDE5i having no loss in SFPL.

Computed tomography based renal parenchyma volume measurements prior to renal tumor surgery are predictive of postoperative renal function.

INTRODUCTION: To determine whether preoperative computed tomography (CT) based renal parenchymal volume (RPV) measurements would be predictive of postoperative chronic kidney disease (CKD). MATERIALS AND METHODS: From 2005 to 2010, 189 patients with preoperative CT imaging performed at Emory University Hospital underwent renal tumor surgery. Preoperative and postoperative renal function was determined by estimating glomerular filtration rate (GFR) using standard Cockcroft-Gault (CG) and Modification of Diet in Renal Disease (MDRD) equations. Preoperative CT measured RPV was calculated to determine association of predicted preserved renal parenchyma with postoperative renal function and the development of CKD (GFR < 60 mL/min/1.73 m2). RESULTS: For the entire cohort, radical nephrectomy (RN), lower preoperative GFR, and volume of kidney without tumor were associated with the development of CKD (p = < 0.05). If the non-tumor bearing kidney constituted ≥ 50% of the total bilateral preoperative RPV, then risks of developing CKD were decreased. In patients treated with partial nephrectomy (PN) or ablation, total bilateral preoperative RPV measurements predicted postoperative renal function (CKD ≥ 3 versus CKD < 3) to a significant degree (p < 0.001). CONCLUSIONS: Preoperative CT based RPV measurements are independently associated with the development of CKD in patients undergoing renal tumor surgery. This provides urologists with another tool in the assessment of patients with renal tumors.

Prospective pilot study of smoking cessation in patients undergoing urologic surgery.

OBJECTIVE: To evaluate whether preoperative smoking cessation counseling by urologists using the Ask, Advise, and Refer approach was effective in producing abstinence in patients undergoing urologic surgery. METHODS: Smokers who were scheduled for inpatient urologic surgery were prospectively enrolled. Smoking cessation counseling consisted of an Ask, Advise, Refer approach. Validated smoking questionnaires were used to evaluate smoking cessation. The expired carbon monoxide and urine cotinine levels were measured to biochemically confirm short- and long-term smoking abstinence, respectively. RESULTS: A total of 38 patients were enrolled in the present study. A significant majority (76%) expressed a willingness to quit smoking long-term at enrollment. On the day of surgery, 9 (28%) of 32 patients reported having quit smoking. However, only 4 (13%) of 32 patients had biochemical confirmation of smoking cessation (negative carbon monoxide and urine cotinine). Similarly, at the first postoperative visit, 8 (29%) of 28 patients reported having quit smoking. However, only 4 (14%) of the 28 patients had biochemical confirmation of smoking cessation (negative carbon monoxide and urine cotinine levels). Despite these results, 89% of the patients continued to express their interest in smoking cessation. CONCLUSION: The preliminary results of the present pilot study have indicated that the short-term perioperative smoking cessation rates are modest at best. Alternative or supplemental modalities might be necessary to achieve better results and the ultimate goal of long-term smoking abstinence.