Clarisse R. Mazzola

Long-term Outcomes of Patients with Lymph Node Metastasis Treated with Radical Prostatectomy Without Adjuvant Androgen-deprivation Therapy

BACKGROUND The presence of lymph node metastasis (LNM) at radical prostatectomy (RP) is associated with poor outcome, and optimal treatment remains undefined. An understanding of the natural history of node-positive prostate cancer (PCa) and identifying prognostic factors is needed. OBJECTIVE To assess outcomes for patients with LNM treated with RP and lymph node dissection (LND) alone. DESIGN, SETTING, AND PARTICIPANTS We analyzed data from a consecutive cohort of 369 men with LNM treated at a single institution from 1988 to 2010. INTERVENTION RP and extended LND. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Our primary aim was to model overall survival, PCa-specific survival, metastasis-free progression, and freedom from biochemical recurrence (BCR). We used univariate Cox proportional hazard regression models for survival outcomes. Multivariable Cox proportional hazard regression models were used for freedom from metastasis and freedom from BCR, with prostate-specific antigen, Gleason score, extraprostatic extension, seminal vesical invasion, surgical margin status, and number of positive nodes as predictors. RESULTS AND LIMITATIONS Sixty-four patients with LNM died, 37 from disease. Seventy patients developed metastasis, and 201 experienced BCR. The predicted 10-yr overall survival and cancer-specific survival were 60% (95% confidence interval [CI], 49-69) and 72% (95% CI, 61-80), respectively. The 10-yr probability of freedom from distant metastasis and freedom from BCR were 65% (95% CI, 56-73) and 28% (95% CI, 21-36), respectively. Higher pathologic Gleason score (>7 compared with ≤ 7; hazard ratio [HR]: 2.23; 95% CI, 1.64-3.04; p < 0.0001) and three or more positive lymph nodes (HR: 2.61; 95% CI, 1.81-3.76; p < 0.0001) were significantly associated with increased risk of BCR on multivariable analysis. The retrospective nature and single-center source of data are study limitations. CONCLUSIONS A considerable subset of men with LNM remained free of disease 10 yr after RP and extended LND alone. Patients with pathologic Gleason score <8 and low nodal metastatic burden represent a favorable group. Our data confirm prior findings and support a plea for risk subclassification for patients with LNM.

Impact of androgen deprivation therapy on sexual function

Many patients with prostate cancer for whom androgen deprivation therapy (ADT) is indicated are young and desire to remain sexually active. In such patients, the side effects of androgen therapy on sexual function can be a source of serious reduction in overall quality of life. Providing the appropriate treatment options in this patient population is therefore essential. Nevertheless, treating such patients is challenging and an understanding of the underlying mechanisms of sexual physiology and pathophysiology is crucial to optimal patient care. In this paper, we reviewed what was known regarding the effects of ADT on sexual function in animal models and we also provided a detailed review on the effects of ADT on sexual health in humans and its treatment.

Renal cell carcinoma (RCC) arising in native kidneys of dialyzed and transplant patients: are they different entities?

Study Type – Prognosis (case series)

Pilot study of salvage laparoscopic prostatectomy for the treatment of recurrent prostate cancer

Study Type – Therapy (case series)

Penile Rehabilitation After Prostate Cancer Treatment: Outcomes and Practical Algorithm

The number of patients diagnosed with prostate cancer was estimated to be 192,000 in 2009 according to the American Cancer Society. The prevalence of reported erectile dysfunction after radical prostatectomy has significant variance. Among the studies in which the nerve-sparing status was described, erectile function recovery adequate for sexual intercourse was achieved in 50% of patients. This article reviews the animal and human studies in this field and provides a useful penile rehabilitation algorithm.

Nodal counts during pelvic lymph node dissection for prostate cancer: an objective indicator of quality under the influence of very subjective factors

Study Type – Therapy (case series)

Androgen deprivation therapy before radical prostatectomy is associated with poorer postoperative erectile function outcomes

Study Type – Therapy (case series)

Predicting biochemical response to clomiphene citrate in men with hypogonadism.

INTRODUCTION Clomiphene citrate (CC) is as an effective treatment for men with hypogonadism (HG). Identifying the ideal candidate for this strategy has to date largely relied upon a patients interest in preservation of testicular volume and spermatogenesis. AIM This analysis was undertaken to define if predictors existed of robust elevation in serum testosterone (T) levels in response to CC. METHODS Seventy-six men with a diagnosis of HG (two separate early morning total T levels <300 ng/dL) opting for CC therapy constituted the study population. Demographic, comorbidity data, and physical and laboratory characteristics were recorded. Laboratory tests were conducted 4 weeks after commencement and every 6 months thereafter. Multivariable analysis was conducted to define if predictors of biochemical response could be identified. Parameters included in the model were patient age, mean testicular volume, varicocele presence, and baseline total T, free T, and luteinizing hormone (LH) levels. MAIN OUTCOME MEASURE Successful biochemical response to CC, defined as an increase of ≥200 ng/dL in total T level at ≥6 months after commencing CC, was the main outcome measure. RESULTS Mean age was 46 ± 22 years. Mean pretreatment testicular volume was 16 ± 8 mL. Mean baseline T and LH levels were 179 ± 72 ng/dL and 7.2 ± 5.6 IU/mL, respectively. Mean total T on CC was 467 ± 190 ng/dL. Forty-seven patients (62%) met the responder definition, with a mean increase in total T levels of 302 ± 76 (204-464) ng/dL. In CC responders, the mean LH rise was 5.6 ± 3.1 IU/mL. On multivariable analysis, factors predictive of CC response included: mean testicular volume (adjusted [adj.] r = 0.32, P < 0.01), mean testicular volume ≥14 mL (hazard ratio [HR] 2.2, P < 0.01), LH level (adj. r = 0.48, P < 0.001), and LH level ≤6 IU/mL (HR 3.5, P < 0.001). CONCLUSION These data indicate that two thirds of men with HG meet a robust responder definition and that pretreatment testicular volume and LH levels (in continuous and dichotomized fashions) are predictors of response.

Targeting the VEGF pathway in metastatic bladder cancer

Introduction: Bladder cancer represents 7% of all new cancers diagnosed in the USA in 2015. Furthermore, the mortality of metastatic bladder cancer has not decreased substantially in the last four decades. Angiogenesis is known to play a major role in the pathogenesis of bladder cancer. Areas covered: The following article provides an overview of the first results of agents targeting the VEGF pathway in the treatment of metastatic bladder cancer. Expert opinion: Despite a few clinical trials providing preliminary encouraging results, the overall outcomes of the first published trials have been rather disappointing. In some instances, especially the case of trials which have investigated the use of new targeted agents as a single agent, no significant improvement in outcomes was seen, or was not sustained. In other cases, such as with combination trials, intolerable adverse effects have compromised the trials, due to overlapping toxicity between the targeted agent and chemotherapeutic agent(s). Further trials are warranted possibly combining different targeted agents or the use of sequential therapy. A better selection of the patient population may also be a key factor to improve patient outcomes, as many predictive factors of response seem to have already been identified.

NADiA ProsVue prostate-specific antigen slope is an independent prognostic marker for identifying men at reduced risk of clinical recurrence of prostate cancer after radical prostatectomy.

OBJECTIVE To validate the hypothesis that men displaying serum prostate-specific antigen (PSA) slopes ≤ 2.0 pg/mL/mo after prostatectomy, measured using a new immuno-polymerase chain reaction diagnostic test (NADiA ProsVue), have a reduced risk of clinical recurrence as determined by positive biopsy, imaging findings, or death from prostate cancer. MATERIALS AND METHODS From 4 clinical sites, we selected a cohort of 304 men who had been followed up for 17.6 years after prostatectomy for clinical recurrence. We assessed the prognostic value of a PSA slope cutpoint of 2.0 pg/mL/mo against established risk factors to identify men at low risk of clinical recurrence using uni- and multivariate Cox proportional hazards regression and Kaplan-Meier analyses. RESULTS The univariate hazard ratio of a PSA slope >2.0 pg/mL/mo was 18.3 (95% confidence interval 10.6-31.8) compared with a slope ≤ 2.0 pg/mL/mo (P <.0001). The median disease-free survival interval was 4.8 years vs >10 years in the 2 groups (P <.0001). The multivariate hazard ratio for PSA slope with the covariates of preprostatectomy PSA, pathologic stage, and Gleason score was 9.8 (95% confidence interval 5.4-17.8), an 89.8% risk reduction for men with PSA slopes ≤ 2.0 pg/mL/mo (P <.0001). The Gleason score (<7 vs ≥ 7) was the only other significant predictor (hazard ratio 5.4, 95% confidence interval 2.1-13.8, P = .0004). CONCLUSION Clinical recurrence after radical prostatectomy is difficult to predict using established risk factors. We have demonstrated that a NADiA ProsVue PSA slope of ≤ 2.0 pg/mL/mo after prostatectomy is prognostic for a reduced risk of prostate cancer recurrence and adds predictive power to the established risk factors.