Abstract 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.
Purpose
Upper-tract urothelial carcinoma (UTUC) is a relatively uncommon disease with limited available evidence on specific topics. The purpose of this article was to review the previous literature ...to summarize the current knowledge about UTUC epidemiology, diagnosis, preoperative evaluation and prognostic assessment.
Methods
Using MEDLINE, a non-systematic review was performed including articles between January 2000 and February 2016. English language original articles, reviews and editorials were selected based on their clinical relevance.
Results
UTUC accounts for 5–10 % of all urothelial cancers, with an increasing incidence. UTUC and bladder cancer share some common risk factors, even if they are two different entities regarding practical, biological and clinical characteristics. Aristolochic acid plays an important role in UTUC pathogenesis in certain regions. It is further estimated that approximately 10 % of UTUC are part of the hereditary non-polyposis colorectal cancer spectrum disease. UTUC diagnosis remains mainly based on imaging and endoscopy, but development of new technologies is rapidly changing the diagnosis algorithm. To help the decision-making process regarding surgical treatment, extent of lymphadenectomy and selection of neoadjuvant systemic therapies, predictive tools based on preoperative patient and tumor characteristics have been developed.
Conclusions
Awareness regarding epidemiology, diagnosis, preoperative evaluation and prognostic assessment changes is essential to correctly diagnose and manage UTUC patients, thereby potentially improving their outcomes.
Abstract 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.
Study Type – Diagnostic (exploratory cohort)
Level of Evidence 2b
What’s known on the subject? and What does the study add?
Improved patient selection for conservative management, neoadjuvant ...chemotherapy, and/or extended lymphadenectomy is urgently needed. We developed a highly accurate preoperative model to predict muscle‐invasive and non‐organ‐confined upper tract urothelial carcinoma based on standard imaging and ureteroscopy features.
OBJECTIVE
• To create a preoperative multivariable model to identify patients at risk of muscle‐invasive (pT2+) upper tract urothelial carcinoma (UTUC) and/or non‐organ confined (pT3+ or N+) UTUC (NOC‐UTUC) who potentially could benefit from radical nephroureterectomy (RNU), neoadjuvant chemotherapy and/or an extended lymph node dissection.
PATIENTS AND METHODS
• We retrospectively analysed data from 324 consecutive patients treated with RNU between 1995 and 2008 at a tertiary cancer centre.
• Patients with muscle‐invasive bladder cancer were excluded, resulting in 274 patients for analysis.
• Logistic regression models were used to predict pT2+ and NOC‐UTUC. Pre‐specified predictors included local invasion (i.e. parenchymal, renal sinus fat, or periureteric) on imaging, hydronephrosis on imaging, high‐grade tumours on ureteroscopy, and tumour location on ureteroscopy.
• Predictive accuracy was measured by the area under the curve (AUC).
RESULTS
• The median follow‐up for patients without disease recurrence or death was 4.2 years.
• Overall, 49% of the patients had pT2+, and 30% had NOC‐UTUC at the time of RNU.
• In the multivariable analysis, only local invasion on imaging and ureteroscopy high grade were significantly associated with pathological stage.
• AUC to predict pT2+ and NOC‐UTUC were 0.71 and 0.70, respectively.
CONCLUSIONS
• We designed a preoperative prediction model for pT2+ and NOC‐UTUC, based on readily available imaging and ureteroscopic grade.
• Further research is needed to determine whether use of this prediction model to select patients for conservative management vs RNU, neoadjuvant chemotherapy, and/or extended lymphadenectomy will improve patient outcomes.
Abstract 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.
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.
Purpose Subclassification of nodal stage may have prognostic value in men with lymph node metastasis at radical prostatectomy. We explored the role of extranodal extension, size of the largest ...metastatic lymph node and the largest metastasis, and lymph node density as predictors of biochemical recurrence. Materials and Methods We reviewed pathological material from 261 patients with node positive prostate cancer. We examined the predictive value when adding the additional pathology findings to a base model including extraprostatic extension, seminal vesicle invasion, radical prostatectomy Gleason score, prostate specific antigen and number of positive lymph nodes using the Cox proportional hazards regression and Harrell concordance index. Results The median number of lymph nodes removed was 14 (IQR 9, 20) and the median number of positive lymph nodes was 1 (IQR 1, 2). At a median followup of 4.6 years (IQR 3.2, 6.0) 155 of 261 patients experienced biochemical recurrence. The mean 5-year biochemical recurrence-free survival rate was 39% (95% CI 33–46). Median diameter of the largest metastatic lymph node was 9 mm (IQR 5, 16). On Cox regression radical prostatectomy specimen Gleason score (greater than 7 vs 7 or less), number of positive lymph nodes (3 or greater vs 1 or 2), seminal vesicle invasion and prostate specific antigen were associated with significantly increased risks of biochemical recurrence. On subset analysis metastasis size significantly improved model discrimination (base model Harrell concordance index 0.700 vs 0.655, p = 0.032). Conclusions Our study confirms that the number of positive lymph nodes is a predictor of biochemical recurrence in men with node positive disease. The improvement in prognostic value of measuring the metastatic focus warrants further investigation.
Abstract 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.
Purpose We tested whether the combination of 4 established cell cycle regulators (p53, pRB, p21 and p27) could improve the ability to predict clinical outcomes in a large multi-institutional ...collaboration of patients with pT3-4N0 or pTany Npositive urothelial carcinoma of the bladder. We also assessed whether the combination of molecular markers is superior to any individual biomarker. Materials and Methods The study comprised 692 patients with pT3-4N0 or pTany Npositive urothelial carcinoma of the bladder treated with radical cystectomy and bilateral lymphadenectomy (median followup 5.3 years). Scoring was performed using advanced cell imaging and color detection software. The base model incorporated patient age, gender, stage, grade, lymphovascular invasion, number of lymph nodes removed, number of positive lymph nodes, concomitant carcinoma in situ and adjuvant chemotherapy. Results Individual molecular markers did not improve the predictive accuracy for disease recurrence and cancer specific mortality. Combination of all 4 molecular markers into number of altered molecular markers resulted in significantly higher predictive accuracy than any single biomarker (p <0.001). Moreover addition of number of altered molecular markers to the base model significantly improved the predictive accuracy for disease recurrence (3.9%, p <0.001) and cancer specific mortality (4.3%, p <0.001). Addition of number of altered molecular markers retained statistical significance for improving the prediction of clinical outcomes in the subgroup of patients with pT3N0 (280), pT4N0 (83) and pTany Npositive (329) disease (p <0.001). Conclusions While the status of individual molecular markers does not add sufficient value to outcome prediction in patients with advanced urothelial carcinoma of the bladder, combinations of molecular markers may improve molecular staging, prognostication and possibly prediction of response to therapy.
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