Marco Moschini

More Extensive Pelvic Lymph Node Dissection Improves Survival in Patients with Node-positive Prostate Cancer

BACKGROUND The role of extended pelvic lymph node dissection (ePLND) in treating prostate cancer (PCa) patients with lymph node invasion (LNI) remains controversial. OBJECTIVE The relationship between the number of removed lymph nodes (RLNs) and cancer-specific mortality (CSM) was tested in patients with LNI. DESIGN, SETTING, AND PARTICIPANTS We examined data of 315 pN1 PCa patients treated with radical prostatectomy (RP) and anatomically ePLND between 2000 and 2012 at one tertiary care centre. All patients received adjuvant hormonal therapy with or without adjuvant radiotherapy (aRT). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Univariable and multivariable Cox regression analyses tested the relationship between RLN number and CSM rate, after adjusting to all available covariates. Survival estimates were based on the multivariable model; patients were stratified according to RLN number using points of maximum separation. RESULTS AND LIMITATIONS The average number of RLNs was 20.8 (median: 19; interquartile range: 14-25). Mean and median follow-up were 63.1 and 54 mo, respectively. At 10-yr, the CSM-free survival rate was 74.7%, 85.9%, 92.4%, 96.0%, and 97.9% for patients with 8, 17, 26, 36, and 45 RLNs, respectively. By multivariable analyses, the number of RLNs independently predicted lower CSM rate (hazard ratio [HR]: 0.93; p=0.02). Other predictors of CSM were Gleason score 8-10 (HR: 3.3), number of positive nodes (HR: 1.2), and aRT treatment (HR: 0.26; all p ≤ 0.006). The study is limited by its retrospective nature. CONCLUSIONS In PCa patients with LNI, the removal of a higher number of LNs during RP was associated with improvement in cancer-specific survival rate. This implies that ePLND should be considered in all patients with a significant preoperative risk of harbouring LNI. PATIENT SUMMARY We found that removing more lymph nodes during prostate cancer surgery can significantly improve cancer-specific survival in patients with lymph node invasion.

Nerve-sparing approach during radical prostatectomy is strongly associated with the rate of postoperative urinary continence recovery

Urinary incontinence and erectile dysfunction are the most bothersome sequelae affecting health‐related quality of life in patients treated with radical prostatectomy for prostate cancer. While it has been widely reported that a nerve‐sparing approach significantly improves postoperative erectile function, the impact of neurovascular bundle preservation on urinary continence recovery is still a matter of controversy. Our study clearly demonstrates that patients treated with nerve‐sparing radical prostatectomy have higher chances of recovering full continence after surgery. The results indicate that, when technically and oncologically feasible, an attempt at a nerve‐sparing approach should be planned in order to increase the probability of achieving full continence after radical prostatectomy.

A Multi-institutional Analysis of Perioperative Outcomes in 106 Men Who Underwent Radical Prostatectomy for Distant Metastatic Prostate Cancer at Presentation

BACKGROUND Current trials are investigating radical intervention in men with metastatic prostate cancer. However, there is a lack of safety data for radical prostatectomy as therapy in this setting. OBJECTIVE To examine perioperative outcomes and short-term complications after radical prostatectomy for locally resectable, distant metastatic prostate cancer. DESIGN, SETTING, AND PARTICIPANTS A retrospective case series from 2007 to 2014 comprising 106 patients with newly diagnosed metastatic (M1) prostate cancer from the USA, Germany, Italy, and Sweden. INTERVENTION Radical prostatectomy and extended pelvic lymphadenectomy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Descriptive statistics were used to present margin status, continence, and readmission, reoperation, and overall complication rates at 90 d, as well as for 21 specific complications. Kaplan-Meier plots were used to estimate survival function. Intercenter variability and M1a/ M1b subgroups were examined. RESULTS AND LIMITATIONS Some 79.2% of patients did not suffer any complications; positive-margin (53.8%), lymphocele (8.5%), and wound infection (4.7%) rates were higher in our cohort than in a meta-analysis of open radical prostatectomy performed for standard indications. At a median follow-up of 22.8 mo, 94/106 (88.7%) men were still alive. The study is limited by its retrospective design, differing selection criteria, and short follow-up. CONCLUSIONS Radical prostatectomy for men with locally resectable, distant metastatic prostate cancer appears safe in expert hands for meticulously selected patients. Overall and specific complication rates related to the surgical extirpation are not more frequent than when radical prostatectomy is performed for standard indications, and the use of extended pelvic lymphadenectomy in all of this cohort compared to its selective use in localized/locally advanced prostate cancer accounts for any extra morbidity. PATIENT SUMMARY Men presenting with advanced prostate cancer that has spread beyond the prostate are increasingly being considered for treatments directed at the prostate itself. On the basis of results for our international series of 106 men, surgery appears reasonably safe in this setting for certain patients.

Long-term Impact of Adjuvant Versus Early Salvage Radiation Therapy in pT3N0 Prostate Cancer Patients Treated with Radical Prostatectomy: Results from a Multi-institutional Series ☆

BACKGROUND Three prospective randomised trials reported discordant findings regarding the impact of adjuvant radiation therapy (aRT) versus observation for metastasis-free survival (MFS) and overall survival (OS) among patients with pT3N0 prostate cancer treated with radical prostatectomy (RP). None of these trials systematically included patients who underwent early salvage radiation therapy (esRT). OBJECTIVE To test the hypothesis that aRT was associated with better cancer control and survival compared with observation followed by esRT. DESIGN, SETTING, AND PARTICIPANTS Using a multi-institutional cohort from seven tertiary referral centres, we retrospectively identified 510 pT3pN0 patients with undetectable prostate-specific antigen (PSA) after RP between 1996 and 2009. Patients were stratified into two groups: aRT (group 1) versus observation followed by esRT in case of PSA relapse (group 2). Specifically, esRT was administered at a PSA level ≤0.5ng/ml. INTERVENTION We compared aRT versus observation followed by esRT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The evaluated outcomes were MFS and OS. Multivariable Cox regression analyses tested the association between groups (aRT vs observation followed by esRT) and oncologic outcomes. Covariates consisted of pathologic stage (pT3a vs pT3b or higher), pathologic Gleason score (≤6, 7, or ≥8), surgical margin status (negative vs positive), and year of surgery. An interaction with groups and baseline patient risk was tested for the hypothesis that the impact of aRT versus observation followed by esRT was different by pathologic characteristics. The nonparametric curve fitting method was used to explore graphically the relationship between MFS and OS at 8 yr and baseline patient risk (derived from the multivariable analysis). RESULTS AND LIMITATIONS Overall, 243 patients (48%) underwent aRT, and 267 (52%) underwent initial observation. Within the latter group, 141 patients experienced PSA relapse and received esRT. Median follow-up after RP was 94 mo (interquartile range [IQR]: 53-126) and 92 mo (IQR: 70-136), respectively (p=0.2). MFS (92% vs 91%; p=0.9) and OS (89% vs 92%; p=0.9) at 8 yr after surgery were not significantly different between the two groups. These results were confirmed in multivariable analysis, in which observation followed by esRT was not associated with a significantly higher risk of distant metastasis (hazard ratio [HR]: 1.35; p=0.4) and overall mortality (HR: 1.39; p=0.4) compared with aRT. Using the nonparametric curve fitting method, a comparable proportion of MFS and OS at 8 yr among groups was observed regardless of pathologic cancer features (p=0.9 and p=0.7, respectively). Limitations consisted of the retrospective nature of the study and the relatively small size of the patient population. CONCLUSIONS At long-term follow-up, no significant differences between aRT and esRT were observed for MFS and OS. Our study, although based on retrospective data, suggests that esRT does not compromise cancer control and potentially reduces overtreatment associated with aRT. PATIENT SUMMARY At long-term follow-up, no significant differences in terms of distant metastasis and mortality were observed between immediate postoperative adjuvant radiation therapy (aRT) and initial observation followed by early salvage radiation therapy (esRT) in case of prostate-specific antigen relapse. Our study suggests that esRT does not compromise cancer control and potentially reduces overtreatment associated with aRT.

Natural History of Clinical Recurrence Patterns of Lymph Node–Positive Prostate Cancer After Radical Prostatectomy

BACKGROUND Patients with lymph node (LN)-positive prostate cancer (PCa) at radical prostatectomy (RP) face a high risk of cancer recurrence. Nevertheless, recurrence patterns of LN-positive PCa and their prognostic significance remain understudied in the literature. OBJECTIVE To analyze a large single-institution series with long-term follow-up to elucidate the various clinical recurrence patterns of LN-positive PCa and their association with oncologic outcomes. DESIGN, SETTING, AND PARTICIPANTS Years 1987-2012 of a prospectively maintained institutional RP registry were queried for men with LN-positive PCa at RP. Clinical recurrences were categorized as local, nodal, skeletal, or visceral. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS In addition to descriptive statistics and Kaplan-Meier analysis, univariable and multivariable Cox proportional hazards models were constructed to predict recurrence and to quantify the impact of recurrence patterns on cancer-specific mortality (CSM). RESULTS AND LIMITATIONS Data from 1011 men with LN-positive PCa at RP were analyzed with 17.6 yr of median follow-up. The 15-yr clinical recurrence rate was 33% (95% confidence interval [CI], 31-35%) for all patients and 52.2% (95% CI, 47.3-57.1%) for patients with biochemical recurrence. The solitary locations were skeletal (n=94, 55%), nodal (n=59, 34%), local soft tissue (n=29, 17%), and visceral (n=8, 5%). Significant multivariable predictors of recurrence were Gleason score 8-10, number of positive nodes, pathologic Gleason score, and more recent year of surgery. The 15-yr CSM after clinical recurrence was 80%, with a mean overall survival of 30 mo after recurrence. On multivariable analysis, recurrences after 5 yr from RP (hazard ratio [HR]: 0.05), multiple recurrences (HR: 1.97), skeletal (HR: 3.13), and visceral metastases (HR: 7.43) were independently associated with CSM (all p<0.05). CONCLUSIONS Recurrences after RP for LN-positive PCa are heterogeneous in terms of time from RP, location, and number of concomitant lesions. PATIENT SUMMARY We found that impact of recurrence patterns on cancer-specific mortality varies significantly and allows these patients to be stratified for purposes of prognostication, follow-up, and therapy.

Incorporation of tissue-based genomic biomarkers into localized prostate cancer clinics

Localized prostate cancer (PCa) is a clinically heterogeneous disease, which presents with variability in patient outcomes within the same risk stratification (low, intermediate or high) and even within the same Gleason scores. Genomic tools have been developed with the purpose of stratifying patients affected by this disease to help physicians personalize therapies and follow-up schemes. This review focuses on these tissue-based tools. At present, four genomic tools are commercially available: Decipher™, Oncotype DX®, Prolaris® and ProMark®. Decipher™ is a tool based on 22 genes and evaluates the risk of adverse outcomes (metastasis) after radical prostatectomy (RP). Oncotype DX® is based on 17 genes and focuses on the ability to predict outcomes (adverse pathology) in very low-low and low-intermediate PCa patients, while Prolaris® is built on a panel of 46 genes and is validated to evaluate outcomes for patients at low risk as well as patients who are affected by high risk PCa and post-RP. Finally, ProMark® is based on a multiplexed proteomics assay and predicts PCa aggressiveness in patients found with similar features to Oncotype DX®. These biomarkers can be helpful for post-biopsy decision-making in low risk patients and post-radical prostatectomy in selected risk groups. Further studies are needed to investigate the clinical benefit of these new technologies, the financial ramifications and how they should be utilized in clinics.

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.

Evaluation of positive surgical margins in patients undergoing robot-assisted and open radical prostatectomy according to preoperative risk groups

OBJECTIVES Recent studies showed that robot-assisted radical prostatectomy (RARP) represents an oncologically safe procedure in patients with prostate cancer (PCa), where the rate of positive surgical margins (PSMs) might be lower in patients treated with RARP as compared with that of those undergoing the open approach (open RP [ORP]). The aim of this study is to analyze the rate of PSMs according to preoperative risk groups in a large cohort of patients treated with RARP and ORP in a single institution with standardized surgical technique and pathological examination. MATERIALS AND METHODS We evaluated 6,194 consecutive patients with PCa undergoing either ORP (71.1%) or RARP (28.9%) between 1992 and 2014. Logistic regression analyses were used to test the association between type of surgery and PSMs in each preoperative risk group (low vs. intermediate vs. high) after adjusting for confounders. RESULTS Overall, 21.6% patients had PSMs. RARP was associated with a lower rate of PSMs in low-risk (11.5 vs. 15.4%, P = 0.01), intermediate-risk (18.9 vs. 23.5%, P = 0.008), and high-risk patients (19.7 vs. 30.1%, P<0.001). In multivariable analyses, after stratification according to risk group categories, no difference in PSMs between RARP and ORP was observed for low-risk (odds ratio [OR] = 0.87, P = 0.46) and intermediate-risk patients (OR = 0.84, P = 0.19). Conversely, RARP was associated with lower odds of PSMs in high-risk patients (OR = 0.69, P = 0.04). Similar results were observed when our analyses were repeated after accounting for pathological characteristics, in patients treated between 2006 and 2014 and in a cohort of men treated by high-volume surgeons (all P≤ 0.03). CONCLUSIONS The introduction of RARP at our institution led to a significant reduction in the risk of PSMs in patients with PCa with high-risk disease.

Extent of lymph node dissection at nephrectomy affects cancer-specific survival and metastatic progression in specific sub-categories of patients with renal cell carcinoma (RCC)

To test whether the number of lymph nodes removed affects cancer‐specific survival (CSS) or metastatic progression‐free survival (MPFS) in different renal cell carcinoma (RCC) scenarios.

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.