F. Montorsi

Positive Surgical Margins in Radical Prostatectomy: Outlining the Problem and Its Long-Term Consequences

CONTEXT This review focuses on positive surgical margins (PSM) in radical prostatectomy (RP). OBJECTIVE To address the etiology, incidence, and oncologic impact of PSM and discuss technical points to help surgeons minimize their positive margin rate. An evidence-based approach to assist clinicians in counseling patients with a PSM is provided. EVIDENCE ACQUISITION A literature search in English was performed using the National Library of Medicine database and the following key words: prostate cancer, surgical margins, and radical prostatectomy. Seven hundred sixty-eight references were scrutinized, and 73 were selected for rigorous review based on their pertinence, study size, and overall contribution to the field. EVIDENCE SYNTHESIS In contemporary series, PSM are reported in 11-38% of patients undergoing RP. Although variability exists in the pathologic interpretation of surgical margins, PSM are associated with an increased hazard of biochemical recurrence (BCR) and local disease recurrence as well as the need for secondary cancer treatment. A posterolateral PSM appears to confer the greatest risk of recurrence, whereas the prognostic significance of positive apical margins remains controversial. The role of preoperative imaging and intraoperative frozen section analysis are being investigated to reduce margin positivity rates. Level-1 evidence indicates that adjuvant radiotherapy (RT) in men with PSM reduces BCR rates and clinical progression and possibly improves overall survival (OS). CONCLUSIONS PSM in RP specimens are uniformly considered an adverse outcome. Regardless of approach (open or laparoscopic), attention to surgical detail is essential to minimize rates. For patients with a PSM destined to experience a cancer recurrence, RT is the only established treatment with curative potential. A randomized trial in patients with PSM comparing immediate postoperative RT to salvage RT is critically needed before definitive recommendations can be made.

Women's sexual dysfunction: a pathophysiological review

A. SALONIA, R.M. MUNARRIZ*, R. NASPRO, R.E. NAPPI†, A. BRIGANTI, R. CHIONNA‡, F. FEDERGHINI†, V. MIRONE¶, P. RIGATTI, I. GOLDSTEIN* and F. MONTORSI Departments of Urology, University Vita-Salute San Raffaele, Milan, Italy, and *Boston University School of Medicine, Boston, MA, USA, and ¶University Federico II, Naples, Italy, and Departments of Obstetrics/Gynaecology, †IRCCS S. Matteo, University of Pavia, Pavia, and ‡University VitaSalute San Raffaele, Milan, Italy

Pharmacological management of erectile dysfunction

Erectile dysfunction (ED) is a common medical condition that affects the sexual life of millions of men worldwide. Many drugs are now available for treating ED; oral pharmacotherapy represents the first‐line option for most patients with ED. Sildenafil, an inhibitor of the enzyme phosphodiesterase type 5, is currently the most widely prescribed oral agent and has a very satisfactory efficacy‐safety profile in all patient categories. Apomorphine SL is a dopamine D1‐ and D2‐receptor agonist which has recently been approved for marketing in Europe. It is best selected for treating patients with mild to moderate ED. Vardenafil and tadalafil are new phosphodiesterase type 5 inhibitors which are expected to be approved this year. Both of them have significant positive efficacy‐safety profiles. Patients who do not respond to oral pharmacotherapy or who cannot use it are good candidates for intracavernosal and intraurethral therapy. Alprostadil is the most widely used drug, both for injection therapy and for the intraurethral route. The efficacy of second‐line treatment is high but the attrition rate remains significant.

Safety of sildenafil citrate: review of 67 double-blind placebo-controlled trials and the postmarketing safety database.

Aim:  To review special safety topics associated with sildenafil and to document the tolerability of 50‐ and 100‐mg doses, overall and by age, in men with erectile dysfunction (ED).

Diagnosis of local recurrence after radical prostatectomy

In the long‐term there is biochemical evidence of recurrent prostate carcinoma in ≈ 40% of patients after radical prostatectomy (RP). Detecting the site of recurrence (local vs distant) is critical for defining the optimum treatment. Pathological and clinical variables, e.g. Gleason score, involvement of seminal vesicles or lymph nodes, margin status at surgery, and especially the timing and pattern of prostate‐specific antigen (PSA) recurrence, may help to predict the site of relapse. Transrectal ultrasonography (TRUS) of the prostatic fossa in association with TRUS‐guided needle biopsy is considered more sensitive than a digital rectal examination for detecting local recurrence, especially if PSA levels are low. Although it cannot detect minimal tumour mass at very low PSA levels (<1 ng/mL) TRUS biopsy is presently the most sensitive method for detecting local recurrence. Nevertheless, the conclusive role of biopsy of the vesico‐urethral anastomosis remains unclear. However, 111In‐capromab pendetide scintigraphy and [11C]‐choline tomography (which are better than conventional imaging for detecting metastatic tumour), have low detection rates for local disease and are considered complementary to TRUS in this setting. Patients with a high PSA after RP may be managed with external beam salvage radiotherapy. An initial PSA of < 1 ng/mL, Gleason score < 8 and radiation dose of 66–70 Gy seem to be key factors in determining success. Although a positive TRUS anastomotic biopsy may predict a better outcome after radiation therapy, the need to take a biopsy in the event of PSA failure remains under investigation. The value of salvage radiation to the prostatic bed for PSA‐only progression after RP remains in question.

The use of partial nephrectomy in European tertiary care centers.

PURPOSE The objective was to define the trends of PN use over time at six tertiary care European centers. METHODS Data were retrieved from institutional databases for patients treated with either PN or radical nephrectomy (RN) for stages T(1-2)N(0)M(0) renal cell carcinoma (RCC) between 1987 and 2007. For purpose of temporal trend analyses patients were divided into five equally sized groups according to the date of surgery. Categorical and multivariable logistic regression analyses assessed predictors of PN use. RESULTS Overall 597 (31.7%) patients were treated with PN. Overall, a 4.5-fold increase of PN was recorded. The absolute increases were 41.7-86.3%, 14.9-69.3% and 8.1-35.3% for lesions < or = 2 cm, 2.1-4 cm and 4.1-7 cm (chi-square trend test p<0.001), respectively. In multivariable logistic regression models, decreasing tumor size, younger age, more contemporary date of surgery, male gender and institutional PN rate represented independent predictors of the individual probability of treatment with PN. Lack of data from community hospitals limits the generalizability of our findings. CONCLUSION Based on data from six tertiary care centers, the contemporary rate of PN ranges from 86 to 35% for renal masses < or = 2 cm to 4.1-7 cm and is indicative of excellent quality of care.

Thermo–Chemotherapy and Electromotive Drug Administration of Mitomycin C in Superficial Bladder Cancer Eradication

Objective: To assess the feasibility and safety of two novel methods for intravesical chemotherapy administration in patients suffering from superficial bladder carcinomas. To draw preliminary considerations concerning the ablative effect on marker lesion using novel approaches compared to standard intravesical chemotherapy. Methods: Eighty patients suffering from single, recurrent, low–stage, low–grade superficial bladder tumor entered a prospective nonrandomized study. Thirty–six of them were treated by means of mitomycin C instillation as a standard procedure. In 29 patients mitomycin C solution was administered in combination with local microwave–induced hyperthermia and in 15 patients the mitomycin C solution was administered according to the electromotive drug procedure. The treatment was scheduled as a short term neo–adjuvant regimen prior to transurethral resection. Feasibility and safety of the different procedures were evaluated on an outpatients basis. The local toxicity induced by different approaches was defined and compared using a subjective questionnaire. Results: Both intravesical chemotherapy administered in combination with hyperthermia and according to the electromotive drug technique appeared to be feasible and safe. Local toxicity induced by thermo–chemotherapy was more severe than that registered for electromotive drug technique and standard intravesical chemotherapy. Local toxicity was always short and self healing without early or delayed major complications. A higher complete response rate on marker lesion was observed after thermo–chemotherapy compared to other administration methods. Conclusion: The intravesical administration of mitomycin C can be safely performed in the form of both thermo–chemotherapy and electromotive drug approach with an increased ablative success rate on small superficial tumor involving only minimal local side effects.

Extended pelvic lymph node dissection in prostate cancer: a 20-year audit in a single center

BACKGROUND We set to assess the impact of stage migration in prostate cancer (PCa) on the evolution of the pN1 rate and tumor characteristics in pN1 patients over the last two decades. PATIENTS AND METHODS We evaluated 5274 PCa patients treated with radical prostatectomy and anatomically extended pelvic lymph node dissection (ePLND) between 1990 and 2010. Year-per-year trends of clinical and pathological characteristics were examined. Logistic regression analyses addressed predictors of pN1. RESULTS The median number of lymph nodes (LNs) removed was 16.0. Overall, the pN1 rate was 13.8% and it decreased from 26.1% to 15.6% between 1990 and 2010 (P < 0.001). For the same period, the pN1 rate changed from 0% to 3% in the low-risk PCa, from 20% to 7% in the intermediate-risk PCa, and from 33% to 44% in the high-risk PCa (P ≤ 0.01). In pN1 patients, pre-operative cancer characteristics and the median number of positive LNs (three in 1990 versus two in 2010) did not significantly change overtime (all P ≥ 0.1). Year of surgery was not an independent predictor of pN1 (all P ≥ 0.06). CONCLUSION Based on ePLND outcomes, contemporary patients with intermediate- and high-risk PCas still harbor a significant LNI risk. In consequence, stage migration does not justify omitting or limiting the extent of PLND in these individuals.

Laparoscopic treatment of adrenal diseases: 10 years on

Since it was initially described in 1992 laparoscopic adrenalectomy (LA) has been gaining popularity amongst urologists and its range of applications has progressively widened. Ten years after the first report of LA this type of operation is presently considered to be the ‘standard of care’ for most adrenal diseases requiring surgery. We define the current role of laparoscopy in the management of surgical adrenal diseases, using a Medline search (1997–2002) to assess reports of LA, focusing on indications, approaches (transperitoneal and retroperitoneoscopic) and comparative analyses, taking particular care to evaluate operative duration, rate of conversion and transfusion, complications and hospital stay. With both approaches LA is safe and effective and, when compared with open surgery, offers the same functional results with all the advantages of minimally invasive surgery. We conclude that LA based on either approach should be considered the treatment of choice for benign adrenal lesions. Although very promising, conservative surgery and LA should still be evaluated in cases of malignancy.

The 'effectiveness' scale--therapeutic outcome of pharmacologic therapies for ED: an international consensus panel report.

Despite availability of outcome measures and scales for assessing erectile dysfunction (ED) treatment efficacy, guidelines are not available for assessing broader therapeutic outcomes or defining treatment failure in ED. An International Consensus Advisory Panel was convened to develop guidelines, definitions and a new algorithm for evaluating treatment effectiveness in ED. These new guidelines are recommended for use in both research and clinical practice. A multidisciplinary, international panel, consisting of 11 senior researchers and clinicians, was convened to address pertinent issues concerning therapeutic outcome assessment for ED. The panel utilized a modified Delphi method of consensus development and proposed a new model for outcomes assessment. This model is inherently testable, using existing instruments and current methods of assessment. Following a comprehensive literature review and discussion, the Panel recommended adoption of a new treatment effectiveness conceptual framework or theoretical model for assessing therapeutic outcomes in ED. Treatment effectiveness is presumed to be a combined function of two other factors, treatment response and treatment satisfaction. Treatment response is based on the combined assessment of efficacy and tolerability, and treatment satisfaction on the combined assessment of patient and partner satisfaction. Taken together, these two domains define an overall domain of treatment effectiveness. This therapeutic index would be derived by independently assessing treatment efficacy and satisfaction by means of event logs, questionnaires or the more typical patient interview methods. In conclusion, the Ad Hoc Advisory Consensus Panel recommends adoption of a new framework or conceptual model for conducting ED outcome trials or clinical research. The concept of ‘treatment effectiveness’ is proposed as a new ‘umbrella concept’ or distal outcome to be evaluated.