Vito Cucchiara

Long-term Outcomes of Salvage Lymph Node Dissection for Clinically Recurrent Prostate Cancer: Results of a Single-institution Series with a Minimum Follow-up of 5 Years

BACKGROUND Prostate cancer (PCa) patients with lymph node recurrence after radical prostatectomy (RP) are usually managed with androgen-deprivation therapy. Despite the absence of prospective randomized studies, salvage lymph node dissection (LND) has been proposed as an alternative treatment option. OBJECTIVE To examine long-term outcomes of salvage LND in patients with nodal recurrent PCa documented by 11C-choline positron emission tomography/computed tomography (PET/CT) scan. DESIGN, SETTING, AND PARTICIPANTS Overall, 59 patients affected by biochemical recurrence (BCR) with 11C-choline PET/CT scan with pathologic activity treated between 2002 and 2008 were included. INTERVENTION Pelvic and/or retroperitoneal salvage LND. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES Biochemical response (BR) was defined as prostate-specific antigen (PSA) <0.2 ng/ml at 40 d after surgery. BCR for those who achieved BR was defined as a PSA >0.2 ng/ml. Clinical recurrence (CR) was defined as a positive PET/CT scan after salvage LND in the presence of a rising PSA. Kaplan-Meier curves assessed time to BCR, CR, and cancer-specific mortality (CSM). Cox regression analyses were fitted to assess predictors of CR. RESULTS AND LIMITATIONS Median follow-up after salvage LND was 81.1 mo. Overall, 35 patients (59.3%) achieved BR. The 8-yr BCR-free survival rate in patients with complete BR was 23%. Overall, the 8-yr CR- and CSM-free survival rates were 38% and 81%, respectively. In multivariable analyses evaluating preoperative variables, PSA at salvage LND represented the only predictor of CR (p=0.03). When postoperative variables were considered, BR and the presence of retroperitoneal lymph node metastases were significantly associated with the risk of CR (all p ≤ 0.04). Our study is limited by the lack of a control group. CONCLUSIONS Salvage LND may represent a therapeutic option for patients with BCR after RP and nodal pathologic uptake at 11C-choline PET/CT scan. Although most patients progressed to BCR after salvage LND, roughly 40% of them experienced CR-free survival. PATIENT SUMMARY Salvage lymph node dissection may represent a therapeutic option for selected patients with nodal recurrence after radical prostatectomy. Roughly 40% of men did not show any further clinical recurrence at long-term follow-up after surgery.

Patterns of Clinical Recurrence of Node-positive Prostate Cancer and Impact on Long-term Survival.

BACKGROUND The patterns of recurrence of patients with node-positive prostate cancer (PCa) at radical prostatectomy (RP) are still unknown. OBJECTIVE To describe recurrence patterns, to identify predictors of progression, and to test the impact of the site of clinical recurrence (CR) on cancer-specific mortality (CSM). DESIGN, SETTING, AND PARTICIPANTS We included 1003 patients with node-positive PCa treated with RP and extended pelvic lymph node dissection. Patients who experienced biochemical recurrence (BCR; n=370) and CR (n=183) were identified. CR was defined as positive imaging after BCR. Patients were stratified according to the first site of CR: local and/or nodal (recurrence in the prostatic bed and/or pelvic nodes), retroperitoneal, bony, or visceral. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Multivariable competing-risks regression analyses identified predictors of systemic recurrence (ie, retroperitoneal, bony, and/or visceral) and tested the association between the site of recurrence and CSM after accounting for the risk of other-cause mortality. RESULTS AND LIMITATIONS When considering patients experiencing BCR, pathologic Gleason score, time to BCR, and the administration of a positron emission tomography/computed tomography scan represented predictors of systemic recurrence (all p ≤ 0.002). Among patients who experienced CR, recurrence was local and/or nodal in 56 (30.5%), retroperitoneal in 25 (13.7%), skeletal in 77 (42.1%), and visceral in 25 (13.7%). Among patients experiencing local recurrence, 27 (48.2%) had positive margins, 29 (51.8%) had adjuvant radiotherapy, and 22 (39.5%) had salvage radiotherapy. Patients experiencing local and/or nodal recurrence had higher 5-yr CSM-free survival rates compared with those with retroperitoneal, skeletal, and visceral recurrence (79.3%, 76.3%, 50.8%, and 35.3%, respectively; p<0.001). The site of recurrence represented an independent predictor of CSM (p ≤ 0.04). CONCLUSIONS In approximately one-third of patients who are pN+ and experience CR, the prostatic bed and pelvic lymph nodes represent the first sites of recurrence. These patients have a more favorable prognosis compared with those with skeletal and visceral metastases. These data have important implications for the selection of the optimal postoperative management of pN+ patients who experience CR. Although patients with local and/or pelvic nodal recurrence might benefit from nonsystemic salvage therapies, men with visceral and skeletal recurrence might represent ideal candidates for systemic approaches. PATIENT SUMMARY Not all patients with pN+ prostate cancer who experience clinical recurrence harbor distant metastatic disease. Local and/or nodal recurrence occurs in one-third of these cases. These patients share a more favorable prognosis than their counterparts with systemic recurrence. These results are important for tailoring the optimal postoperative management for each node-positive patient with recurrent disease after surgery.

Early Postoperative Radiotherapy is Associated with Worse Functional Outcomes in Patients with Prostate Cancer

Purpose: The effect of time between radical prostatectomy and radiation therapy on postoperative functional outcomes is still unclear in patients with surgically managed prostate cancer. We hypothesized that a shorter time between radical prostatectomy and radiotherapy might be associated with worse functional recovery rates after radical prostatectomy. Materials and Methods: We retrospectively evaluated 2,190 patients treated with radical prostatectomy and stratified according to radiotherapy schedule (adjuvant radiotherapy, salvage radiotherapy, no radiotherapy). We examined recovery rates for erectile function and urinary function according to adjuvant radiotherapy, salvage radiotherapy and no radiotherapy, and according to time from surgery to radiotherapy. Cox regression analyses were used to evaluate the impact of these predictors on functional outcomes. Results: Median followup was 48 months. The 3‐year erectile function recovery rates were 35.0%, 29.0% and 11.6% in patients who received no radiotherapy, salvage radiotherapy and adjuvant radiotherapy, respectively (p <0.001), and differed significantly according to time to radiotherapy (11.7% vs 34.7% for less than 1 year vs 1 year or more, respectively, p <0.001). The 3‐year urinary continence recovery rates were 70.7%, 59.0% and 42.2% in patients who received no radiotherapy, salvage radiotherapy and adjuvant radiotherapy, respectively (p <0.001), and differed according to time to radiotherapy (43.5% vs 62.7% for less than 1 year vs 1 year or more, respectively, p <0.001). Cox regression analyses confirmed the negative impact of early radiotherapy on recovery rates for erectile function and urinary continence. Conclusions: Time from radical prostatectomy to radiotherapy has an important role in the recovery of erectile function and urinary continence. Delayed radiotherapy is preferred to improve functional outcomes after surgery.

A Detailed Analysis of the Association Between Postoperative Phosphodiesterase Type 5 Inhibitor Use and the Risk of Biochemical Recurrence After Radical Prostatectomy

UNLABELLED A recent study reported a detrimental effect of phosphodiesterase type 5 inhibitors (PDE5-Is) on biochemical recurrence (BCR) after radical prostatectomy (RP) for prostate cancer (PCa). We tested the association between PDE5-I use, PDE5-I therapy scheme, number of PDE5-I pills taken, and BCR in 2579 patients treated with bilateral nerve-sparing RP for PCa between 2004 and 2013 at a single center. Patients were categorized according to PDE5-I use within 2 yr after surgery as on demand, rehabilitation schedule (daily PDE5-I use for at least 3 mo), and no PDE5-I use. Multivariable (MVA) Cox regression models tested the association between PDE5-I and BCR. The same analyses were repeated using the number of PDE5-I pills taken by each patient. Overall, 674 patients (26.1%) received PDE5-Is. At MVA analysis, PDE5-I use, type of administration schedule, and number of PDE5-I pills were not significantly associated with higher risk of BCR (all p ≥ 0.2) after accounting for multiple confounders including time from RP to PDE5-I use. While awaiting further studies, patients should not be denied PDE5-I treatment after RP. PATIENT SUMMARY Among patients treated with radical prostatectomy, phosphodiesterase type 5 inhibitor use was not associated with an increased risk of biochemical recurrence, regardless of the therapeutic regimen used.

Effect of Allogeneic Intraoperative Blood Transfusion on Survival in Patients Treated With Radical Cystectomy for Nonmetastatic Bladder Cancer: Results From a Single High-Volume Institution

BACKGROUND Previous studies have demonstrated that perioperative blood transfusion (BT) is associated with a significantly increased risk of cancer recurrence and mortality after radical cystectomy (RC). Recently, it was shown for the first time that intraoperative transfusion has a detrimental effect on cancer survival. The aim of the current study was to validate this finding in a single European institution. PATIENTS AND METHODS The study focused on 1490 consecutive nonmetastatic bladder cancer patients treated with RC at a single tertiary care referral center between January 1990 and August 2013. Kaplan-Meier analyses and Cox regression analyses were used to assess the effect of timing of BT administration (no transfusion vs. intraoperative transfusion vs. postoperative transfusion vs. intraoperative and postoperative transfusion) on cancer-specific mortality (CSM), overall mortality (OM), and disease recurrence. RESULTS Mean age at the time of RC was 67 years. Overall, 322 (21.6%) patients received intraoperative BT and 97 (6.5%) received postoperative BT. At a mean follow-up time of 125 months (median, 110 months), the 5- and 10-year CSM rate was 846 (58%) and 715 (48%), respectively. In multivariable analyses patients who received intraoperative BT had greater risk of disease recurrence (hazard ratio [HR], 1.24; P < .04), CSM (HR, 1.60; P < .02), and OM (HR, 1.45; P < .03). Conversely, this effect disappears with postoperative BT (all P > .2). CONCLUSION Our study confirms that intraoperative, but not postoperative BT, are related to a detrimental effect on survival after RC. These results should be take into account by physicians to administer BT using the correct timing.

How to optimize patient selection for robot-assisted radical prostatectomy: functional outcome analyses from a tertiary referral center.

INTRODUCTION The role of surgical approach on functional outcomes recovery in prostate cancer (PCa) patients treated with bilateral nerve-sparing radical prostatectomy (BNSRP) is still debated. In this study, we examine the association between the surgical approach and functional outcomes after BNSRP. PATIENTS AND METHODS The study included 609 patients treated with robot-assisted radical prostatectomy (RARP) or open radical prostatectomy (ORP) between June 2008 and January 2011. Erectile function recovery was defined as an International Index of Erectile Function-Erectile Function domain (IIEF-EF) score ≥22. Urinary continence recovery was defined as being completely pad-free over a 24-hour period. Patients were stratified according to their probability of postoperative erectile dysfunction and urinary incontinence, according to previously published predictive models. Multivariable logistic regression tested the association between the surgical approach and functional outcomes recovery in the overall population after stratifying patients according to their risk of erectile dysfunction and urinary incontinence. RESULTS Patients treated with RARP had higher 2-year erectile function (52.1% vs 67.8%; P<0.001) and urinary continence (72.0% vs 87.4%; P<0.001) recovery rates as compared to their ORP counterparts. After stratification according to the erectile dysfunction risk, RARP led to higher erectile function recovery rates in the low- and intermediate-risk erectile dysfunction groups (all P<0.001).This did not hold true, however, in patients at high risk of erectile dysfunction (P=0.5). Similarly, when patients were stratified according to their urinary incontinence risk, RARP was associated with a higher probability of urinary continence recovery in the very low, low, and intermediate risk groups only (all P<0.001). This did not hold true, however, in the group of men at high risk of postoperative urinary incontinence (P=0.8). CONCLUSIONS RARP leads to higher urinary continence and erectile function recovery rates compared with ORP. Not all patients benefit from this approach to the same extent, however. Accurate preoperative patient selection would result in substantial savings for the health care system.

Determinants of long-term survival of patients with locally advanced prostate cancer: the role of extensive pelvic lymph node dissection

Background:The therapeutic effect of pelvic lymph node dissection (PLND) during radical prostatectomy (RP) due to prostate cancer (PCa) is still under debate. We aimed at assessing the impact of more extensive PLND on cancer-specific mortality (CSM) in patients treated with surgery for locally advanced PCa.Methods:We examined data of 1586 pT3-T4 PCa patients treated with RP and extended PLND between 1987 and 2012 at a tertiary referral care center. Univariable and multivariable Cox regression analyses tested the relationship between the number of nodes removed and CSM rate, after adjusting for potential confounders. Survival estimates were based on the multivariable models.Results:The average number of nodes removed was 19 (median: 17; interquartile range: 11–23). Mean and median follow-up were 80 and 72 months, respectively. At multivariable analyses, Gleason score 8–10 (hazard ratio (HR): 2.5) and a higher number of positive nodes (HR: 1.06) were independently associated with higher CSM rate (all P<0.05). Conversely, higher number of removed LNs (HR: 0.94) and adjuvant radiotherapy (HR: 0.54) were independent predictors of lower CSM rates (all P⩽0.03).Conclusions:In pT3-T4 PCa patients, removal of a higher number of LNs during RP was associated with higher cancer-specific survival rates. This supports the role of more extensive PLNDs in this patient group. Further prospective studies are needed to validate our findings.

Comparing long‐term outcomes of primary and progressive carcinoma invading bladder muscle after radical cystectomy

To assess the impact of primary or progressive status on recurrence‐free survival (RFS), cancer‐specific mortality (CSM) and overall mortality (OM) after radical cystectomy (RC) for muscle‐ invasive bladder cancer (MIBC).

The Impact of Perioperative Blood Transfusion on Survival of Bladder Cancer Patients Submitted to Radical Cystectomy: Role of Anemia Status

BACKGROUND The prognostic role of perioperative blood transfusion (PBT) in patients who underwent radical cystectomy (RC) for bladder cancer (BCa), although supported by clinical evidence, still remains to be assessed definitively. OBJECTIVE To investigate the impact of PBT on RC patients for overall survival and after stratifying according to preoperative anemia status and to define whether the oncologic impact may be assumed to be a primary effect of PBT or attributed to the reduced preoperative hemoglobin (Hb) level. DESIGN, SETTING, AND PARTICIPANTS A total of 1490 consecutive patients with nonmetastatic BCa who underwent RC and pelvic lymph node dissection between January 1990 and August 2013 at a single referral center entered the study. PBT and preoperative Hb levels were statistically correlated with postoperative oncologic outcomes. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Kaplan-Meier analyses were used to evaluate the impact of PBT on overall mortality (OM) and cancer-specific mortality (CSM). Multivariable Cox regression analyses tested the relationship between PBT and the risk of OM and CSM in the overall population and after stratifying patients according to the severity of their anemia. RESULTS AND LIMITATIONS A total of 580 patients (38.9%) received PBT. Mean postoperative follow-up was 125.13 mo (median: 110 mo). Overall 5- and 10-yr CSM survival rates were 58.3% and 47.6%, respectively. At multivariable Cox regression analyses, PBT could not be associated with an increased risk of either CSM or OM (all p > 0.3). Conversely, preoperative Hb levels were significantly associated with OM (hazard ratio [HR]: 0.88; confidence interval [CI], 0.83-0.95) and CSM (HR: 0.84; 95% CI, 0.77-0.95) (all p<0.001). A significant detrimental effect of PBT on OM (HR: 1.65; 95% CI, 1.08-2.52) and CSM (HR: 1.68; 95% CI, 1.04-2.70) (all p<0.03) was found in patients without preoperative anemia status. CONCLUSIONS In nonanemic BCa patients proposed for RC, PBT is associated with a significant detrimental effect on CSM and OM. This effect seems to be attributable to the direct impact of PBT, regardless of the preoperative Hb value. PATIENT SUMMARY In nonanemic patients proposed for radical cystectomy, a negative prognostic impact of perioperative blood transfusion should be taken into account.

Penile rehabilitation after radical prostatectomy: does it work?

Context Erectile dysfunction (ED) represents one of the most common long-term side effects in patients with clinically localized prostate cancer (PCa) undergoing nerve-sparing radical prostatectomy (RP). Objective To analyze the role of penile rehabilitation in the recovery of erectile function (EF) after nerve-sparing RP. Evidence synthesis Penile rehabilitation is defined as the use of any intervention or combination with the goal not only to achieve erections sufficient for satisfactory sexual intercourses, but also to return EF to preoperative levels. The concept of rehabilitation is based on the implementation of protocols aimed at improving oxygenation, preserving endothelial structure, and preventing smooth muscle structural alterations. Nowadays, the most commonly adopted approaches for penile rehabilitation after nerve-sparing RP are represented by the administration of phosphodiesterase type-5 inhibitors (PDE5-Is), intracorporeal injection therapy, vacuum erection devices (VED), and the combination of these therapies. Several basic science studies support the rational for the adoption of penile rehabilitation protocols. Particularly, rehabilitation, set as early as possible, seems to be better than leaving the erectile tissues unassisted. On the other hand, results from solid prospective randomized trials finally assessing the long-term beneficial effects of PDE5-Is, intracavernosal injections, or VED on EF recovery after surgery are still lacking. Conclusions Although preclinical evidences support the rationale for penile rehabilitation after nerve-sparing RP, clinical studies reported conflicting results regarding its efficacy on long-term EF recovery. Nowadays, which is the optimal rehabilitation program still represents a matter of debate.