Daher C. Chade

Cancer Control and Functional Outcomes of Salvage Radical Prostatectomy for Radiation-recurrent Prostate Cancer: A Systematic Review of the Literature

CONTEXT Prostate cancer (PCa) recurrence following definitive radiation therapy (RT) remains a vexing challenge for the practicing physician. Salvage radical prostatectomy (SRP) has not been recognized yet as a valuable therapeutic option. OBJECTIVE We critically analyzed the currently available evidence on SRP as to patient selection, predictive oncologic factors, surgical technique, cancer control, surgical complications, functional outcomes, and comparison to other salvage therapies. EVIDENCE ACQUISITION A systematic review of the literature was performed in June 2011 using the Medline, Embase, and Web of Science databases, limiting the review to English-language articles published between January 1980 and June 2011. All authors reviewed the list of references and added papers relevant to the topic of the review prior to the analysis. The panel selected 40 articles according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. EVIDENCE SYNTHESIS Positive surgical margins in SRP varied from 43% to 70% in earlier publications versus 0-36% in recent publications, and pathologic organ-confined disease (OCD) was found in 22-53% versus 44-73% in earlier versus recent publications. Biochemical recurrence-free probability after SRP ranged from 47% to 82% at 5 yr and from 28% to 53% at 10 yr. Cancer-specific survival (CSS) and overall survival varied from 70% to 83% and 54% to 89% at 10 yr. Pre-SRP prostate-specific antigen value and prostate biopsy Gleason score were the strongest prognostic risk factors for progression-free survival, OCD, and CSS. Open, laparoscopic, and robotic techniques were shown to be feasible in the hands of experienced surgeons. The most frequent complications included anastomotic stricture (7-41%) followed by rectal injury (0-28%). Major complications (modified Clavien classification grade 3-5) varied from 0% to 25%. Most complications were less frequent in more recent series, except for anastomotic stricture. The majority of patients had erectile dysfunction prior to SRP (50-91%) and 80-100% after SRP. Urinary continence ranged from 21% to 90% after surgery. Limitations of this review include the absence of prospective studies and lack of comparative analyses between SRP and other therapies. CONCLUSIONS In selected patients with confirmed, localized, radiation-recurrent PCa, SRP may effectively promote durable cancer control with acceptable associated surgical morbidity and variable functional recovery.

Salvage Radical Prostatectomy for Radiation-recurrent Prostate Cancer: A Multi-institutional Collaboration

BACKGROUND Oncologic outcomes in men with radiation-recurrent prostate cancer (PCa) treated with salvage radical prostatectomy (SRP) are poorly defined. OBJECTIVE To identify predictors of biochemical recurrence (BCR), metastasis, and death following SRP to help select patients who may benefit from SRP. DESIGN, SETTING, AND PARTICIPANTS This is a retrospective, international, multi-institutional cohort analysis. There was a median follow-up of 4.4 yr following SRP performed on 404 men with radiation-recurrent PCa from 1985 to 2009 in tertiary centers. INTERVENTION Open SRP. MEASUREMENTS BCR after SRP was defined as a serum prostate-specific antigen (PSA) ≥ 0.1 or ≥ 0.2 ng/ml (depending on the institution). Secondary end points included progression to metastasis and cancer-specific death. RESULTS AND LIMITATIONS Median age at SRP was 65 yr of age, and median pre-SRP PSA was 4.5 ng/ml. Following SRP, 195 patients experienced BCR, 64 developed metastases, and 40 died from PCa. At 10 yr after SRP, BCR-free survival, metastasis-free survival, and cancer-specific survival (CSS) probabilities were 37% (95% confidence interval [CI], 31-43), 77% (95% CI, 71-82), and 83% (95% CI, 76-88), respectively. On preoperative multivariable analysis, pre-SRP PSA and Gleason score at postradiation prostate biopsy predicted BCR (p = 0.022; global p < 0.001) and metastasis (p = 0.022; global p < 0.001). On postoperative multivariable analysis, pre-SRP PSA and pathologic Gleason score at SRP predicted BCR (p = 0.014; global p < 0.001) and metastasis (p < 0.001; global p < 0.001). Lymph node involvement (LNI) also predicted metastasis (p = 0.017). The main limitations of this study are its retrospective design and the follow-up period. CONCLUSIONS In a select group of patients who underwent SRP for radiation-recurrent PCa, freedom from clinical metastasis was observed in >75% of patients 10 yr after surgery. Patients with lower pre-SRP PSA levels and lower postradiation prostate biopsy Gleason score have the highest probability of cure from SRP.

The Effect of Tumor Location on Prognosis in Patients Treated with Radical Nephroureterectomy at Memorial Sloan-Kettering Cancer Center

BACKGROUND The prognostic impact of primary tumor location on outcomes for patients with upper-tract urothelial carcinoma (UTUC) is still contentious. OBJECTIVE To test the association between tumor location and disease recurrence and cancer-specific survival (CSS) in patients treated with radical nephroureterectomy (RNU) for UTUC. DESIGN, SETTING, AND PARTICIPANTS Prospectively collected data were retrospectively reviewed from 324 consecutive patients treated with RNU between 1995 and 2008 at a single tertiary referral center. Patients who had previous radical cystectomy, preoperative chemotherapy, previous contralateral UTUC, or metastatic disease at presentation were excluded. This left 253 patients for analysis. Tumor location was categorized as renal pelvis or ureter based on the location of the dominant tumor. Recurrences in the bladder only, in nonbladder sites, and in any site were analyzed. INTERVENTION All patients were treated with RNU. MEASUREMENTS Recurrence-free survival and CSS probabilities were estimated using Kaplan-Meier and Cox regression analyses. RESULTS AND LIMITATIONS Median follow-up for survivors was 48 mo. The 5-yr recurrence-free probability (including bladder recurrence) and CSS estimates were 32% and 78%, respectively. On multivariable analysis, pathologic stage was the only predictor for disease recurrence (p=0.01). Tumor location was not an independent predictor for recurrence (hazard ratio: 1.19; p=0.3), and there was no difference in the probability of disease recurrence between ureteral and renal pelvic tumors (p=0.18). On survival analysis, we also found no differences between ureteral and renal pelvic tumors on probability of CSS (p=0.2). On multivariate analysis, pathologic stage (p<0.0001) and nodal status (p=0.01) were associated with worse CSS. This study is limited by its retrospective nature. CONCLUSIONS Our study did not show any differences in recurrence and CSS rates between patients with ureteral and renal pelvic tumors treated with RNU.

Combining imaging and ureteroscopy variables in a preoperative multivariable model for prediction of muscle‐invasive and non‐organ confined disease in patients with upper tract urothelial carcinoma

Study Type – Diagnostic (exploratory cohort)

Comparison Between Laparoscopic and Open Radical Nephroureterectomy in a Contemporary Group of Patients: Are Recurrence and Disease-Specific Survival Associated with Surgical Technique?

BACKGROUND Open radical nephroureterectomy (ORN) is the current standard of care for upper tract urothelial carcinoma (UTUC), but laparoscopic radical nephroureterectomy (LRN) is emerging as a minimally invasive alternative. Questions remain regarding the oncologic safety of LRN and its relative equivalence to ORN. OBJECTIVE Our aim was to compare recurrence-free and disease-specific survival between ORN and LRN. DESIGN, SETTING, AND PARTICIPANTS We retrospectively analyzed data from 324 consecutive patients treated with radical nephroureterectomy (RN) between 1995 and 2008 at a major cancer center. Patients with previous invasive bladder cancer or contralateral UTUC were excluded. Descriptive data are provided for 112 patients who underwent ORN from 1995 to 2001 (pre-LRN era). Comparative analyses were restricted to patients who underwent ORN (n=109) or LRN (n=53) from 2002 to 2008. Median follow-up for patients without disease recurrence was 23 mo. INTERVENTION All patients underwent RN. MEASUREMENTS Recurrence was categorized as bladder-only recurrence or any recurrence (bladder, contralateral kidney, operative site, regional lymph nodes, or distant metastasis). Recurrence-free probabilities were estimated using Kaplan-Meier methods. A multivariable Cox model was used to evaluate the association between surgical approach and disease recurrence. The probability of disease-specific death was estimated using the cumulative incidence function. RESULTS AND LIMITATIONS Clinical and pathologic characteristics were similar for all patients. The recurrence-free probabilities were similar between ORN and LRN (2-yr estimates: 38% and 42%, respectively; p=0.9 by log-rank test). On multivariable analysis, the surgical approach was not significantly associated with disease recurrence (hazard ratio [HR]: 0.88 for LRN vs ORN; 95% confidence interval [CI], 0.57-1.38; p=0.6). There was no significant difference in bladder-only recurrence (HR: 0.78 for LRN vs ORN; 95% CI, 0.46-1.34; p=0.4) or disease-specific mortality (p=0.9). This study is limited by its retrospective nature. CONCLUSIONS Based on the results of this retrospective study, no evidence indicates that oncologic control is compromised for patients treated with LRN in comparison with ORN.

Oncological Outcomes After Radical Cystectomy for Bladder Cancer: Open Versus Minimally Invasive Approaches

PURPOSE The number of centers performing robotic assisted radical cystectomy has recently increased, spurring greater concerns about oncological outcomes. In this review we summarize the most comprehensive articles published on the oncological outcomes of laparoscopic assisted, robotic assisted and open radical cystectomy. MATERIALS AND METHODS A MEDLINE/PubMed literature search was conducted in March 2009 to review English language articles published from 1998 onward. Of 217 selected articles on the 3 techniques 19 studies were selected for this review. RESULTS The laparoscopic series reported recurrence-free survival rates in the range of 83% to 85% at 1 to 2 years and 60% to 77% at 2 to 3 years, while the robotic assisted studies reported recurrence-free survival rates of 86% to 91% at 1 to 2 years. Large open surgery studies showed 62% to 68% recurrence-free survival at 5 years and 50% to 60% at 10 years, with overall survival of 59% to 66% at 5 years and 37% to 43% at 10 years. Overall survival in the laparoscopic cohorts was 90% to 100% at 1 to 2 years and 50% to 87% at 2 to 3 years. Publications reporting robotic cases demonstrated a 90% to 96% overall survival in 1 to 2 years of followup. CONCLUSIONS Despite the surge of centers adopting minimally invasive approaches for radical cystectomy, the long-term effectiveness of these techniques has not yet been proven. This review of recent and landmark articles on open and minimally invasive procedures emphasizes the need for prospective controlled studies and long-term followup data to determine the proper use of laparoscopic and robotic assisted techniques in bladder cancer surgery.

Predicting biochemical recurrence-free survival for patients with positive pelvic lymph nodes at radical prostatectomy.

PURPOSE We evaluated predictors of freedom from biochemical recurrence in patients with pelvic lymph node metastasis at radical prostatectomy. MATERIALS AND METHODS Of 207 patients with lymph node metastasis treated with radical prostatectomy and bilateral pelvic lymph node dissection 45 received adjuvant androgen deprivation therapy and 162 did not. Cox proportional hazards regression models were used to investigate predictors of biochemical recurrence after radical prostatectomy. Recurrence probability was estimated using the Kaplan-Meier method. RESULTS A median of 13 lymph nodes were removed. Of the patients 122 had 1, 44 had 2 and 41 had 3 or greater positive lymph nodes. Of patients without androgen deprivation therapy 103 had 1, 35 had 2 and 24 had 3 or greater positive lymph nodes while 69 experienced biochemical recurrence. Median time to recurrence in patients with 1, 2 and 3 or greater lymph nodes was 59, 13 and 3 months, respectively. Only specimen Gleason score and the number of positive lymph nodes were independent predictors of biochemical recurrence. Recurrence-free probability 2 years after prostatectomy in men without androgen deprivation with 1 positive lymph node and a prostatectomy Gleason score of 7 or less was 79% vs 29% in those with Gleason score 8 or greater and 2 or more positive lymph nodes. CONCLUSIONS Prognosis in patients with lymph node metastasis depends on the number of positive lymph nodes and primary tumor Gleason grade. Of all patients with lymph node metastasis 80% had 1 or 2 positive nodes. A large subset of those patients had a favorable prognosis. Full bilateral pelvic lymph node dissection should be done in patients with intermediate and high risk cancer to identify those likely to benefit from metastatic node removal.

Clinical Characteristics and Outcomes of Patients With Recurrence 5 Years After Nephrectomy for Localized Renal Cell Carcinoma

PURPOSE We analyzed characteristics in patients with recurrent renal cell carcinoma 5 years or later after nephrectomy and determined predictors of survival after recurrence. MATERIALS AND METHODS From July 1989 to October 2008 at total of 2,368 nephrectomies were done for clinically localized, unilateral renal cell carcinoma at our institution. Of 256 patients with disease recurrence 44 had recurrence 5 years or more after nephrectomy. We compared clinicopathological characteristics in patients with disease recurrence before vs after 5 years. Survival from time of recurrence was assessed based on Memorial Sloan-Kettering Cancer Center risk score, symptoms at recurrence, metastasectomy, tumor diameter, and recurrence stage and site. RESULTS Patients with late recurrence tended to have fewer symptoms at presentation, smaller tumors (median 8.5 vs 7 cm) and less aggressive disease (pT1 in 18% vs 39%). Median overall survival was 6.1 years from time of recurrence. Five-year actuarial survival was 85% in 28 patients at favorable risk and 14% in 10 at intermediate risk (log rank p <0.001). The 5-year estimated overall survival rate was 72% in 31 patients with incidentally detected recurrence and 39% in 11 with symptoms at recurrence (log rank p = 0.01). CONCLUSIONS Data suggest that patients with cancer recurrence 5 years after nephrectomy are at favorable risk and have long-term median survival. A favorable Memorial Sloan-Kettering Cancer Center risk score and absent symptoms related to metastasis are associated with longer survival in these patients.

Clinical Outcomes of Primary Bladder Carcinoma In Situ in a Contemporary Series

PURPOSE The natural history of primary bladder carcinoma in situ has not been well described. We describe patterns of disease recurrence and progression, and identify clinical outcome predictors of primary carcinoma in situ after bacillus Calmette-Guerin therapy. MATERIALS AND METHODS We performed a retrospective analysis of 155 patients diagnosed with isolated primary high grade carcinoma in situ at a tertiary center from 1990 to 2008 who underwent transurethral resection followed by intravesical bacillus Calmette-Guerin therapy. The end points included time to disease recurrence, time to progression to invasive disease (cT1 or higher) or to muscle invasive disease (cT2 or higher), or early radical cystectomy. Predictors included gender, age, race, smoking history, presenting symptoms, carcinoma in situ pattern (focal, multiple or diffuse) and response to bacillus Calmette-Guerin. RESULTS A total of 155 patients received bacillus Calmette-Guerin therapy within 6 months. The 5-year cumulative incidence of progression to cT1 or higher was 45% (95% CI 37-55) and to cT2 or higher was 17% (95% CI 12-25) adjusting for the competing risk of radical cystectomy. Of 130 patients evaluated for response to bacillus Calmette-Guerin 81 (62%) were considered responders. Response to bacillus Calmette-Guerin was significantly associated with progression to cT1 or higher/radical cystectomy (HR 0.59, 95% CI 0.36-0.95, p = 0.029) and to cT2 or higher/radical cystectomy (HR 0.53, 95% CI 0.32-0.88, p = 0.015). This association was largely driven by the higher rate of early radical cystectomy among nonresponders. CONCLUSIONS Despite bacillus Calmette-Guerin therapy and early radical cystectomy, patients with primary carcinoma in situ had a high rate of disease progression. Response to bacillus Calmette-Guerin was significantly associated with a lower rate of disease progression or early radical cystectomy.

Clinical Outcome of Primary Versus Secondary Bladder Carcinoma In Situ

PURPOSE Differences in clinical outcome are still unclear between primary and secondary bladder carcinoma in situ. We compared the clinical outcomes of primary and secondary carcinoma in situ, and identified predictive factors. MATERIALS AND METHODS We retrospectively analyzed the records of 476 patients with high grade cTis, including 221 with primary and 255 with secondary carcinoma in situ, from 1990 to 2008 at a high volume cancer center after transurethral resection and intravesical bacillus Calmette-Guerin therapy. End points were time to progression to invasive disease (cT1 or higher) or radical cystectomy before progression, and progression to muscle invasive disease (cT2 or higher) or radical cystectomy before progression. We used Cox proportional hazards regression models. RESULTS Patients with primary carcinoma in situ responded significantly more within 6 months of bacillus Calmette-Guerin than those with secondary carcinoma in situ (65% vs 39%, p <0.001). In the primary vs secondary groups the 5-year cumulative incidence of progression to cT1 or higher was 43% (95% CI 36-51) vs 32% (95% CI 27-39) and for progression to cT2 or higher it was 17% (95% CI 12-23) vs 8% (95% CI 5-13). On multivariate analysis primary carcinoma in situ was significantly more likely to progress to cT1 or higher (HR 1.38, 95% CI 1.05-1.81, p = 0.020) and to cT2 or higher, or radical cystectomy (HR 1.72, 95% CI 1.27-2.33, p = 0.001). We found no significance for age, gender or response to bacillus Calmette-Guerin as outcome predictors. Median followup was 5.1 years. CONCLUSIONS Patients presenting with primary carcinoma in situ have a worse outcome than those with secondary carcinoma in situ, suggesting a need to differentiate these 2 entities in the treatment decision process.