Effect of pathological high-risk features on cancer-specific mortality in non-metastatic clear cell renal cell carcinoma: a tool for optimizing patient selection for adjuvant therapy.

PURPOSE: Adjuvant therapies for non-metastatic renal cell carcinoma (nmRCC) are being tested to improve outcomes in patients with high-risk (hR) nmRCC. The objective of the current study is to test the ability of three hR features to identify patients who are at the highest risk of cancer-specific mortality (CSM) after partial or radical nephrectomy. METHODS: Within the Surveillance Epidemiology and End Results (SEER) database (1988-2013), we identified 23,632 nm "clear cell" RCC partial or radical nephrectomy patients with hR features: Fuhrman grade (FG) 3 or 4 or pathological classifications T3a or T3b or lymph node invasion (LNI), or combination of these. Kaplan-Meier analyses (KM) and multivariable Cox's regression models (CRM) evaluated the effect of hR features on CSM. RESULTS: Overall 11,568 (48.9%) patients harbored FG3-4, 5575 (23.6%) pT3a/b, 140 (0.6%) LNI, 5366 (22.7%) FG3-4 and pT3a/b, 183 (0.8%) LNI and pT3a/b, 203 (0.9%) LNI and FG3-4 and 597 (2.5%) LNI, FG3-4 and pT3a/b. Median CSM-free survival was 51, 58 and 22 months for LNI and pT3a/b, for LNI and FG3-4 and for LNI, FG3-4 and pT3a/b and was not reached for the other groups. These results remained unchanged in multivariable CRMs, where all hR features represented independent predictors. CONCLUSIONS: Individuals with combination of LNI with FG3-4 or pT3a/b and patients with all three hR features are at highest risk of CSM. In consequence, these patients may represent ideal candidates for adjuvant therapy either in clinical practice or future prospective trials.

External Beam Radiotherapy Affects Serum Testosterone in Patients With Localized Prostate Cancer.

BACKGROUND: Previous studies have examined testosterone levels after external beam radiation (EBRT) monotherapy, but since 2002 only sparse contemporary data have been reported. AIM: To examine testosterone kinetics in a large series of contemporary patients after EBRT. METHODS: The study was conducted in 425 patients who underwent definitive EBRT for localized prostate cancer from 2002 through 2014. Patients were enrolled in several phase II and III trials. Exclusion criteria were neoadjuvant or adjuvant androgen-deprivation therapy or missing data. Testosterone was recorded at baseline and then according to each study protocol (not mandatory in all protocols). Statistical analyses consisted of means and proportions, Kaplan-Meier plots, and logistic and Cox regression analyses. OUTCOMES: Testosterone kinetics after EBRT monotherapy and their influence on biochemical recurrence. RESULTS: Median follow-up of 248 assessable patients was 72 months. One hundred eighty-six patients (75.0%) showed a decrease in testosterone. Median time to first decrease was 6.4 months. Median percentage of decrease to the nadir was 30% and 112 (45.2%) developed biochemical hypogonadism (serum testosterone < 8 nmol/L). Of all patients with testosterone decrease, 117 (62.9%) recovered to at least 90% of baseline levels. Advanced age, increased body mass index, higher baseline testosterone level, and lower nadir level were associated with a lower chance of testosterone recovery. Subgroup analyses of 166 patients treated with intensity-modulated radiotherapy confirmed the results recorded for the entire cohort. In survival analyses, neither testosterone decrease nor recovery was predictive for biochemical recurrence. CLINICAL IMPLICATIONS: EBRT monotherapy influences testosterone kinetics, and although most patients will recover, approximately 45% will have biochemical hypogonadism. STRENGTHS AND LIMITATIONS: We report on the largest contemporary series of patients treated with EBRT monotherapy in whom testosterone kinetics were ascertained. Limitations are that testosterone follow-up was not uniform and the study lacked information on health-related quality-of-life data. CONCLUSION: Our findings indicate that up to 75% of patients will have a profound testosterone decrease, with up to a 40% increase in rates of biochemical hypogonadism, although the latter events will leave biochemical recurrence unaffected. Pompe RS, Karakrewicz PI, Zaffuto E, et al. External Beam Radiotherapy Affects Serum Testosterone in Patients With Localized Prostate Cancer. J Sex Med 2017;14:876-882.

Iatrogenic ureteral injury after gynecological surgery.

Iatrogenic ureteral injury can occur in many different settings, however, the majority occur in the context of gynecological procedures. We present a case of a ureteral injury during vaginal hysterectomy for severe pelvic organ prolapse. We provide a discussion on the diagnosis and management of ureteral injury after gynecological surgery. In addition, we compare and contrast the American Urologic Association and European Association of Urology guidelines and offer a short, concise algorithm on the management of all type of ureteral injuries.

Adjuvant Therapies in Nonmetastatic Renal-Cell Carcinoma: A Review of the Literature.

To conduct a review of literature on adjuvant therapy in nonmetastatic renal-cell carcinoma (nmRCC) treated with nephrectomy and to describe the efficacy of adjuvant agents on cancer control outcomes. A review of the literature was performed in January 2018 to identify all studies evaluating adjuvant therapy in patients with nmRCC treated with nephrectomy using PubMed, Embase, Medline, and Cochrane Library databases. The following keywords were used: adjuvant therapy, renal-cell carcinoma, nonmetastatic, targeted molecular therapy, kidney cancer. The ClinicalTrials.gov website was queried to identify ongoing trials. Traditional adjuvant therapy agents consisted of interferon α, interleukin 2, autologous tumor cell vaccines, and monoclonal antibodies. None provided survival benefit. Three contemporary studies (S-TRAC, ASSURE, and PROTECT) using targeted therapy compared sunitinib to placebo (S-TRAC), sunitinib or sorafenib to placebo (ASSURE), and pazopanib to placebo (PROTECT), with controversial results. In contrast to ASSURE and PROTECT, S-TRAC demonstrated improved disease-free survival. Several trials that use checkpoint immunotherapy agents or vascular endothelial growth factor receptor tyrosine kinase inhibitors are ongoing. Many traditional therapies have shown no success as adjuvant therapy for nmRCC after nephrectomy. Targeted adjuvant therapy for nmRCC after nephrectomy showed controversial results, and its routine use is not currently endorsed.

Tumor characteristics, treatments, and oncological outcomes of prostate cancer in men aged ≤50 years: a population-based study.

BACKGROUND: To examine clinical characteristics, treatment modalities and oncological outcomes of prostate cancer (PCa) according to young (≤50) vs. old age. METHODS: Of 407,599 men with primary adenocarcinoma of the prostate within the Surveillance, Epidemiology and End Results (SEER)-database (2004 to 2013), 18,387 were aged ≤50 years (4.5%). Time trends, cumulative incidence, and competing risks regression (CRR) analyses tested for differences between young and old patients. Multi-variable analyses were adjusted for year of diagnosis, race, marital status, Gleason Score, clinical tumor stage, and lymph node status. RESULTS: Younger men had more favorable tumor characteristics: lower Gleason Score, lower median PSA, and lower rates of metastases at diagnosis compared to their older counterparts. Over time, no local treatment (NLT) rates increased, radical prostatectomy (RP), and brachytherapy (BT) rates decreased and external beam radiation (EBRT) rates remained unchanged. Moreover, the rate of de novo metastatic prostate cancer increased in young patients from 2% (2004) to 3.2% (2013) (p = 0.004). CRR models showed no difference in prostate cancer-specific mortality (PCSM) between young and old, across all local treatment types. CONCLUSIONS: Young PCa patients have more favorable disease characteristics at presentation, are less frequently treated with RP or BT and more frequently benefit of NLT. PCSM did not differ between young and old patients. However, it is worrisome that recently more young PCa patients are diagnosed at a metastatic stage.