Shahrokh F. Shariat

Outcomes of minimally invasive simple prostatectomy for benign prostatic hyperplasia: a systematic review and meta-analysis

AbstractPurposen(1) To assess the outcomes of minimally invasive simple prostatectomy (MISP) for the treatment of symptomatic benign prostatic hyperplasia in men with large prostates and (2) to compare them with open simple prostatectomy (OSP).MethodsA systematic review of outcomes of MISP for benign prostatic hyperplasia with meta-analysis was conducted. The article selection process was conducted according to the PRISMA guidelines.ResultsTwenty-seven observational studies with 764 patients were analyzed. The mean prostate volume was 113.5xa0ml (95xa0% CI 106–121). The mean increase in Qmax was 14.3xa0ml/s (95xa0% CI 13.1–15.6), and the mean improvement in IPSS was 17.2 (95xa0% CI 15.2–19.2). Mean duration of operation was 141xa0min (95xa0% CI 124–159), and the mean intraoperative blood loss was 284xa0ml (95xa0% CI 243–325). One hundred and four patients (13.6xa0%) developed a surgical complication. In comparative studies, length of hospital stay (WMD −1.6xa0days, pxa0=xa00.02), length of catheter use (WMD −1.3xa0days, pxa0=xa00.04) and estimated blood loss (WMD −187xa0ml, pxa0=xa00.015) were significantly lower in the MISP group, while the duration of operation was longer than in OSP (WMD 37.8xa0min, pxa0<xa00.0001). There were no differences in improvements in Qmax, IPSS and perioperative complications between both procedures. The small study sizes, publication bias, lack of systematic complication reporting and short follow-up are limitations.ConclusionsMISP seems an effective and safe treatment option. It provides similar improvements in Qmax and IPSS as OSP. Despite taking longer, it results in less blood loss and shorter hospital stay. Prospective randomized studies comparing OSP, MISP and laser enucleation are needed to define the standard surgical treatment for large prostates.

Contemporary role of lymph node dissection at the time of radical nephroureterectomy for upper tract urothelial carcinoma

AbstractPurposeTo review the contemporary data on the role of lymph node dissection (LND) at the time of radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC).nMethodsA computerized bibliographic search using the following protocol (“Nephroureterectomy”) AND (“Lymphadenectomy” OR “Lymph node” OR “Lymphatic”) was performed in MEDLINE to identify all original and review articles that addressed the role of LND for UTUC.nResultsRegional lymph node (LN) boundaries of UTUC have been recently investigated in mapping studies to propose anatomic templates of LND according to the laterality and location of primary tumor. Although these anatomic templates remained poorly described, most reports supported the staging benefit of LND that allowed for risk stratification of patients with (pN+) or without (pN0) LN metastases from those who did not undergo such a procedure (pNx). In addition, the therapeutic benefit of LND at the time of RNU was supported by better oncological outcomes obtained after complete LND when compared to incomplete or no LND, especially in the group of patients with advanced disease. The number of LNs removed was also correlated with both, more accurate staging and greater cancer-specific survival after LND, whose feasibility and safety have been validated in prospective studies.ConclusionsDespite mostly based on data with level of evidence 3, our comprehensive review of the literature supports the staging and therapeutic benefits of LND at the time of RNU for UTUC, which are particularly significant for patients with muscle-invasive or locally advanced disease.

Oncologic Outcomes of Kidney Sparing Surgery versus Radical Nephroureterectomy for the Elective Treatment of Clinically Organ Confined Upper Tract Urothelial Carcinoma of the Distal Ureter

PURPOSEnWe compared the oncologic outcomes of radical nephroureterectomy, distal ureterectomy and endoscopic surgery for elective treatment of clinically organ confined upper tract urothelial carcinoma of the distal ureter.nnnMATERIALS AND METHODSnFrom a multi-institutional collaborative database we identified 304 patients with unifocal, clinically organ confined urothelial carcinoma of the distal ureter and bilateral functional kidneys. Rates of overall, cancer specific, local recurrence-free and intravesical recurrence-free survival according to surgery type were compared using Kaplan-Meier statistics. Univariable and multivariable Cox regression analyses were performed to assess the adjusted outcomes of radical nephroureterectomy, distal ureterectomy and endoscopic surgery.nnnRESULTSnOverall 128 (42.1%), 134 (44.1%) and 42 patients (13.8%) were treated with radical nephroureterectomy, distal ureterectomy and endoscopic surgery, respectively. Although rates of overall, cancer specific and intravesical recurrence-free survival were equivalent among the 3 surgical procedures, 5-year local recurrence-free survival was lower for endoscopic surgery (35.7%) than for nephroureterectomy (95.0%, p <0.001) or ureterectomy (85.5%, p = 0.01) with no significant difference between nephroureterectomy and distal ureterectomy. On multivariable analyses only endoscopic surgery was an independent predictor of decreased local recurrence-free survival compared to nephroureterectomy (HR 1.27, p = 0.001) or distal ureterectomy (HR 1.14, p = 0.01). Distal ureterectomy and endoscopic surgery did not significantly correlate to cancer specific or intravesical recurrence-free survival. However, when adjustment was made for ASA(®) (American Society of Anesthesiologists(®)) score, distal ureterectomy (HR 0.80, p = 0.01) and endoscopic surgery (HR 0.84, p = 0.02) were independent predictors of increased overall survival, although no significant difference was found between them.nnnCONCLUSIONSnBecause of better oncologic outcomes, distal ureterectomy could be considered the elective first line treatment of clinically organ confined urothelial carcinoma of the distal ureter.

Prognostic value of tissue and circulating levels of IMP3 in prostate cancer

Tissue levels of the oncofetal protein insulin‐like growth factor 2 (IGF2) messenger RNA‐binding protein 3 (IMP3) have been associated with poor prognosis in multiple human malignancies. However, its circulating levels have not yet been analyzed. Therefore, the aim of this study was to assess the prognostic value of both serum and tissue levels of IMP3 in prostate cancer (PC). IMP3 protein expression was analyzed in 124 PC and 13 benign prostate hyperplasia (BPH) patients using immunohistochemistry. Gene expression levels of IMP3 and its molecular target IGF2 were analyzed in 29 frozen and 26 paraffin‐embedded PC tissues using real‐time polymerase chain reaction and immunohistochemistry. Serum IMP3 levels were assessed in 94 PC and 20 BPH patients as well as in 20 controls using enzyme‐linked immunosorbent assay. IMP3 immunostaining was present in 0% (0/13) of BPHs, 15% (15/101) of clinically localized PCs and 65% (15/23) of palliatively treated metastatic PCs (pu2009<u20090.001). Accordingly, serum IMP3 concentrations were significantly higher in PC compared to BPH patients which were higher than those in controls (pu2009<u20090.001 each). The highest concentrations were detected in metastatic PC patients (pu2009=u20090.036). In patients who underwent radical prostatectomy high IMP3 serum levels were independently associated with poor cancer‐specific survival. IMP3 gene and protein expressions were not correlated with those of IGF2. In conclusion, we found enhanced IMP3 levels in tissue and serum samples of PC patients compared to non‐PC men. Moreover, IMP3 was associated with metastasis and PC‐specific survival. The tumor promoting effect of IMP3 appears to be independent from its regulatory role on IGF2 in PC.

Circulating syndecan-1 is associated with chemotherapy-resistance in castration-resistant prostate cancer

OBJECTIVESnDocetaxel chemotherapy is a standard treatment for castration-resistant prostate cancer (CRPC). Rapidly expanding treatment options for CRPC provide reasonable alternatives for those who are resistant to docetaxel. Therefore, prediction of docetaxel resistance has become of great clinical importance. Syndecan-1 (SDC1) has been currently shown to be involved in chemotherapy resistance in various malignancies including prostate cancer. The predicting value of serum SDC1 level has not been evaluated yet.nnnPATIENTS AND METHODSnWe assessed the baseline levels of SDC1 in serum samples of 75 patients with CRPC who received docetaxel therapy until the appearance of therapy resistance. In one patient who was treated with three treatment series, we assessed also 6 additional serum samples collected during a 1-year treatment period. Serum SDC1 levels were correlated with clinical outcomes as well as with serum levels of MMP7.nnnRESULTSnPretreatment SDC1 serum levels were not associated with patients age, the presence of bone or visceral metastases. In univariable analyses, patients performance status, the presence of bone or visceral metastases, high pretreatment prostate specific antigen and SDC1 levels were significantly associated with cancer-specific survival. In multivariable analysis patients performance status (P = 0.005), presence of bone or visceral metastases (P = 0.013) and high SDC1 level (P = 0.045) remained independent predictors of patients survival. In the patient with available follow-up samples serum SDC1 level increased from 50 to 300ng/ml at radiographic progression. Serum concentrations of SDC1 were correlated with those of MMP7 (r = 0.420, P = 0.006).nnnCONCLUSIONSnOur present results together with currently published data suggest a role for SDC1 shedding in chemotherapy resistance. Determination of serum SDC1 may contribute to the prediction of docetaxel resistance and therefore may help to facilitate clinical decision-making regarding the type and timing of therapy for patients with CRPC.

Matrix metalloproteinase 7, soluble Fas and Fas ligand serum levels for predicting docetaxel resistance and survival in castration-resistant prostate cancer

To assess the predictive value of pre‐chemotherapy matrix metalloproteinase 7 (MMP‐7), soluble Fas (sFas) and Fas ligand (FasL) serum levels, as well as their changes during therapy.

Re: Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer

Experts’ comments Bone strength is the sum of numerous factors including bone quantity, mineral density, and tissue material properties. Preventing loss of bone mass after androgen deprivation therapy (ADT) is an integral part of treatment for prostate cancer in contemporary urologic oncology. However, urologists may not sufficiently be aware of the impact of individual contributing factors in bone health. Osteoporosis, which affects many elderly populations, is a skeletal disorder characterized by compromised bone strength which reflects the integration of two main features: bone density and bone quality [1]. Bone density, usually expressed as bone mineral density, accounts for approximately 70% of total bone strength, whereas bone quality, including architecture, turnover, damage accumulation, and mineralization, accounts for the remaining 30%. All these factors are influenced by collagen cross-linking [2]. Reductions in bone quality occur with aging, as evidenced by a loss of total collagen content at six skeletal sites and changes in serum and urine bone-quality–related markers observed in 40 healthy male subjects [2]. Senescence-related factors including oxidative stress, a manifestation of metabolic syndrome, may be responsible. Such processes may be further accelerated by ADT. The prime focus of the urologic community has been to sustain BMD, not to improve bone quality, to prevent SREs after ADT. Bisphosphonate and denosumab are often used for this purpose because they suppress bone resorption. These strategies alone may not be sufficient for SRE prevention in all elderly males with prostate cancer [3]. The development of new strategies for bone health is currently under investigation. The use of denosumab and teriparatide, a recombinant parathyroid hormone analog, in combination improves bone quality more than either drug alone for postmenopausal osteoporosis [4]. Knowledge and understanding of the pathophysiology of bone fragility after ADT are essential to improve the quality of care for patients with prostate cancer.

Re: nadir testosterone within first year of androgen-deprivation therapy (ADT) predicts for time to castration-resistant progression: a secondary analysis of the PR-7 trial of intermittent versus continuous ADT.

Task Force recommendation statement. Ann Intern Med 2012;157: 120–34. [3] Hamoen EHJ, de Rooij M, Witjes JA, Barentsz JO, Rovers MM. Use of the Prostate Imaging Reporting and Data System (PI-RADS) for prostate cancer detection with multiparametric magnetic resonance imaging: a diagnostic meta-analysis. Eur Urol 2015;67: 1112–21. [4] Fütterer JJ, Briganti A, De Visschere P, et al. Can clinically significant prostate cancer be detected with multiparametric magnetic resonance imaging? A systematic review of the literature. Eur Urol. In press. http://dx.doi.org/10.1016/j.eururo.2015.01.013 [5] Schoots IG, Petrides N, Giganti F, et al. Magnetic resonance imaging in active surveillance of prostate cancer: a systematic review. Eur Urol 2015;67:627–36.