Objective-We evaluated our experience with renal cortical tumors to determine if tumor size is associated with malignant histology and/or nuclear grade.Materials and Methods-We identified 2,675 patients treated surgically at Memorial SloanKettering for renal cell carcinoma (RCC) or a benign tumor between 1989 and 2007. Histologic subtype and tumor size were obtained from our kidney cancer database and logistic regression analyses were performed.Results-Among the 2,675 tumors, 311 (12%) were benign while 2,364 (88%) were RCC. The odds ratio for association of malignancy with tumor size was 1.16 (95% CI 1.11-1.22; p<0.001), indicating that each 1cm increase in tumor size was associated with a 16% increase in the odds of malignancy. The percentage of benign tumors decreased from 38% for those less than 1 cm to 7% for tumors 7 cm or greater. For patients with clear cell RCC, each 1 cm increase in tumor size increased the odds of a high grade (Fuhrman grade 3-4) compared with a low grade (Fuhrman grade 1-2) tumor by 25% (odds ratio 1.25, 95% CI 1.21-1.30; p<0.001). For this subset, the percentage of high grade tumors increased from 0% for tumors <1cm to 59% for tumors >7cm.Conclusions-Our results confirm previous observations suggesting that the risk of malignancy and risk of high grade tumors increases with tumor size. Patients with small renal masses have a low risk for harboring a high-grade clear cell malignancy which may be useful during initial consultation.

Study Type – Therapy (population cohort) Level of Evidence 2a What's known on the subject? and What does the study add? Clomiphene citrate (CC) has previously been documented to be efficacious in the treatment of hypogonadism. However little is known about the long term efficacy and safety of CC. Our study demonstrates that CC is efficacious after 3 years of therapy. Testosterone levels and bone mineral density measurement improved significantly and were sustained over this prolonged period. Subjective improvements were also demonstrated. No adverse events were reported. OBJECTIVE To assess the efficacy and safety of long‐term clomiphene citrate (CC) therapy in symptomatic patients with hypogonadism (HG). PATIENTS AND METHODS Serum T, oestradiol and luteinizing hormone (LH) were measured in patients who were treated with CC for over 12 months. Additionally, bone densitometry (BD) results were collected for all patients. Demographic, comorbidity, treatment and Androgen Deficiency in Aging Men (ADAM) score data were also recorded. Comparison was made between baseline and post‐treatment variables, and multivariable analysis was conducted to define predictors of successful response to CC. The main outcome measures were predictors of response and long‐term results with long‐term CC therapy in hypogonadal patients. RESULTS The 46 patients (mean age 44 years) had baseline serum testosterone (T) levels of 228 ng/dL. Follow‐up T levels were 612 ng/dL at 1 year, 562 ng/dL at 2 years, and 582 ng/dL at 3 years (P < 0.001). Mean femoral neck and lumbar spine BD scores improved significantly. ADAM scores (and responses) fell from a baseline of 7 to a nadir of 3 after 1 year. No adverse events were reported by any patients. CONCLUSIONS Clomiphene citrate is an effective long‐term therapy for HG in appropriate patients. The drug raises T levels substantially in addition to improving other manifestations of HG such as osteopenia/osteoporosis and ADAM symptoms.

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Hypogonadism is a prevalent problem, increasing in frequency as men age. It is most commonly treated by testosterone supplementation therapy but in younger patients this can lead to testicular atrophy with subsequent exogenous testosterone dependency and may impair spermatogenesis. Clomiphene citrate (CC) may be used as an alternative treatment in these patients with hypogonadism when maintenance of fertility is desired. This study shows that CC is a safe and efficacious drug to use as an alternative to exogenous testosterone. Not only have we validated previous findings of other papers but have proven our findings over a much longer period (mean duration of treatment 19 months). This prospective study is the largest to date assessing both the objective hormone response to CC therapy as well as the subjective response based on a validated questionnaire. OBJECTIVE To prospectively assess the andrological outcomes of long‐term clomiphene citrate (CC) treatment in hypogonadal men. PATIENTS AND METHODS We prospectively evaluated 86 men with hypogonadism (HG) as confirmed by two consecutive early morning testosterone measurements <300 ng/dL. The cohort included all men with HG presenting to our clinic between 2002 and 2006 who, after an informed discussion, elected to have CC therapy. CC was commenced at 25 mg every other day and titrated to 50 mg every other day. The target testosterone level was 550 ± 50 ng/dL. Testosterone (free and total), sex hormone binding globulin, oestradiol, luteinizing hormone and follicle stimulating hormone were measured at baseline and during treatment on all patients. Once the desired testosterone level was achieved, testosterone/gonadotropin levels were measured twice per year. To assess subjective response to treatment, the androgen deficiency in aging males (ADAM) questionnaire was administered before treatment and during follow‐up. RESULTS Patients' mean (standard deviation [sd]; range) age was 29 (3; 22–37) years. Infertility was the most common reason (64%) for seeking treatment. The mean (sd) duration of CC treatment was 19 (14) months. At the last evaluation, 70% of men were using 25 mg CC every other day, and the remainder were using 50 mg every other day. All mean testosterone and gonadotropin measurements significantly increased during treatment. Subjectively, there was an improvement in all questions (except loss of height) on the ADAM questionnaire. More than half the patients had an improvement in at least three symptoms. There were no major side effects recorded and the presence of a varicocele did not have an impact on the response to CC. CONCLUSION Long‐term follow‐up of CC treatment for HG shows that it appears to be an effective and safe alternative to testosterone supplementation in men wishing to preserve their fertility.

With the increasing number of patients surviving cancer, there is increasing interest in long-term quality of life, especially with respect to cancer-related infertility. Although infertility most commonly occurs as the result of treatment with gonadotoxic agents, it can also manifest before treatment has commenced. Current fertility preservation strategies for the postpubertal male patient with cancer focus on sperm cryopreservation before therapy. Sperm acquisition techniques should be discussed with the patient as early as possible, by either an oncologist or a specialist in male reproduction. For patients rendered infertile by cancer treatment who did not cryopreserve sperm beforehand, there are no techniques currently available to restore fertility. For the prepubertal male patient, cryopreservation of sperm is impossible. However, emerging research--primarily in animal models--into promising fertility preservation and restoration strategies might provide a clinical solution in the future. Advances in the protection and cryopreservation of spermatogonial stem cells (SSCs) might translate into clinical options for fertility preservation before treatment. Restoring fertility after treatment might also be possible via SSC autotransplantation or in vitro maturation of SSCs. Before any of these techniques become clinically viable, a number of scientific, logistical and ethical issues will need to be resolved.

Objective We analyzed the oncological outcome after laparoscopic radical prostatectomy (LRP) in a consecutive series of patients with prostate cancer. Material and Methods from 1998 to 2007, 1564 consecutive patients (median age 61 years, IQ range 56, 66) with clinically localized prostate cancer (cT1c-cT3a) were treated with LRP by two surgeons either at IMM (Paris, France) or MSKCC (New York, USA). Progression of disease was defined as a PSA of 0.1 ng/ml or greater with confirmatory rise, or initiation of secondary therapy and the information was available for 1422 patients. Patients were stratified as low, intermediate or high risk based on the pretreatment prostate cancer nomogram progression free probability of >90%, 89% to 71% and < 70% respectively. Results The overall 5-year and 8-year probability of freedom from progression was 78% (95% CI 74%–82%) and 71% (95% CI 63%, 78%) respectively. For low, intermediate and high risk cancer, the 5-year progression free probability was 91% (95% CI 85%–95%), 77% (95% CI 71%–82%) and 53% (95% CI 40%–65%) respectively. Surgical margins were positive in 13% of cases. The 5-year progression free probability was 49% (95%C.I. 35%– 61%) when the surgical margins were positive vs. 83% (95%C.I. 79%– 86%) in negative surgical margins cases. Nodal metastases were detected in 3% of the patients after limited pelvic lymph node dissection and in 10% after a standard pelvic lymph node dissection (p<0.001). The 3 year probability of freedom from progression for node positive patients was 49%. There were 22 overall deaths and 2 deaths from prostate cancer. Conclusion Laparoscopic radical prostatectomy provided 5 and 8-year cancer control in 78 and 71% of patients with clinically localized prostate cancer and 53% of those with high risk cancers at 5 years. A pelvic lymph node dissection limited to the external iliac nodal group is inadequate for detecting nodal metastases.