Marc Dall'Era

Active surveillance for the management of prostate cancer in a contemporary cohort

Active surveillance followed by selective treatment for men who have evidence of disease progression may be an option for select patients with early‐stage prostate cancer. In this article, the authors report their experience in a contemporary cohort of men with prostate cancer who were managed with active surveillance.

Active surveillance for early-stage prostate cancer: Review of the current literature

The natural history of prostate cancer is remarkably heterogeneous and, at this time, not completely understood. The widespread adoption and application of prostate‐specific antigen (PSA) screening has led to a dramatic shift toward the diagnosis of low‐volume, nonpalpable, early‐stage tumors. Autopsy and early observational studies have shown that approximately 1 in 3 men aged >50 years has histologic evidence of prostate cancer, with a significant portion of tumors being small and possibly clinically insignificant. Utilizing the power of improved contemporary risk stratification schema to better identify patients with a low risk of cancer progression, several centers are gaining considerable experience with active surveillance and delayed, selective, and curative therapy. A literature review was performed to evaluate the rationale behind active surveillance for prostate cancer and to describe the early experiences from surveillance protocols. It appears that a limited number of men on active surveillance have required treatment, with the majority of such men having good outcomes after delayed selective intervention for progressive disease. The best candidates for active surveillance are being defined, as are predictors of active treatment. The psychosocial ramifications of surveillance for prostate cancer can be profound and future needs and unmet goals will be discussed. Cancer 2008.

Original Articles: Prostate Cancer: The Use and Accuracy of Cross-Sectional Imaging and Fine Needle Aspiration Cytology for Detection of Pelvic Lymph Node Metastases Before Radical Prostatectomy

The role of cross-sectional pelvic imaging with computerized tomography or magnetic resonance imaging and fine needle aspiration in the assessment of pelvic lymph nodes in patients with prostate cancer is undefined. To address this issue we used formal decision analysis, comparing an imaging arm to a no imaging arm. Patient utility values were calculated, and test parameters and complication rates were extracted from the literature. Imaging was superior to no imaging only when the pretest probability of pelvic lymph node metastases was high. The most important parameter was the sensitivity of cross-sectional imaging for lymphadenopathy. When the sensitivity was 36%, which was the baseline figure derived from the literature, the probability of lymph node metastases required for imaging to be beneficial overall was 32%. We also performed a retrospective review of magnetic resonance imaging examinations at our institution in 174 patients with newly diagnosed prostate cancer and pathological confirmation of nodal status. The sensitivity for detecting nodal metastases was 25%. With this figure, the estimated probability of nodal metastases required to make imaging beneficial would be 45%, which is possible to achieve with highly selective clinical criteria. With a policy of imaging only in select patients the marginal cost is

Pathological Outcomes of Candidates for Active Surveillance of Prostate Cancer

794 per patient benefited (aborted radical prostatectomy because of nodal metastases detected with fine needle aspiration) compared to

Impact of Molecular Subtypes in Muscle-invasive Bladder Cancer on Predicting Response and Survival after Neoadjuvant Chemotherapy

50,661 per patient benefited if all patients are imaged. Thus, cross-sectional pelvic imaging before radical prostatectomy, solely for the purpose of detecting pelvic lymph node metastases, is not justified routinely. However, it is worthwhile on the basis of patient use values and cost-effectiveness in a select group of patients at high risk for nodal metastases.

Multicenter Assessment of Neoadjuvant Chemotherapy for Muscle-invasive Bladder Cancer

PURPOSE Active surveillance of prostate cancer has emerged as a viable treatment option for men with features of low risk disease. Five prospective studies have enrolled patients for active surveillance with varying inclusion criteria. We evaluated the pathological outcomes of men meeting published criteria for active surveillance who elected immediate radical prostatectomy to assess the risk of under grading and under staging in candidates for active surveillance. MATERIALS AND METHODS Data were extracted from our institutional urological oncology database for all men who underwent radical prostatectomy between 1996 and 2007. The primary outcome was pathological up staging, defined as the occurrence of extracapsular extension or seminal vesicle involvement. Pathological upgrading was identified as a secondary outcome. We determined the proportion of men who would have qualified for each published active surveillance study and the respective rates of upgrading and up staging in each group. RESULTS We identified 1,097 men who underwent radical prostatectomy with a mean age of 59 years. Overall 28% of the men experienced a Gleason upgrade, 21% had extracapsular extension and 11% had seminal vesicle involvement. In men qualifying based on published active surveillance inclusion criteria, rates of upgrading varied between 23% and 35%, the incidence of extracapsular extension ranged from 7% to 19% and seminal vesicle involvement ranged from 2% to 9%. CONCLUSIONS Varying entry criteria for active surveillance show different rates of adverse pathological features at radical prostatectomy. Predictably fewer men met the more stringent criteria but these men had a lower incidence of seminal vesicle involvement and extracapsular extension. Such data can be used to advise men of the risks of active surveillance.

Surgical management after active surveillance for low‐risk prostate cancer: pathological outcomes compared with men undergoing immediate treatment

BACKGROUND An early report on the molecular subtyping of muscle-invasive bladder cancer (MIBC) by gene expression suggested that response to neoadjuvant chemotherapy (NAC) varies by subtype. OBJECTIVE To investigate the ability of molecular subtypes to predict pathological downstaging and survival after NAC. DESIGN, SETTING, AND PARTICIPANTS Whole transcriptome profiling was performed on pre-NAC transurethral resection specimens from 343 patients with MIBC. Samples were classified according to four published molecular subtyping methods. We developed a single-sample genomic subtyping classifier (GSC) to predict consensus subtypes (claudin-low, basal, luminal-infiltrated and luminal) with highest clinical impact in the context of NAC. Overall survival (OS) according to subtype was analyzed and compared with OS in 476 non-NAC cases (published datasets). INTERVENTION Gene expression analysis was used to assign subtypes. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Receiver-operating characteristics were used to determine the accuracy of GSC. The effect of GSC on survival was estimated by Cox proportional hazard regression models. RESULTS AND LIMITATIONS The models generated subtype calls in expected ratios with high concordance across subtyping methods. GSC was able to predict four consensus molecular subtypes with high accuracy (73%), and clinical significance of the predicted consensus subtypes could be validated in independent NAC and non-NAC datasets. Luminal tumors had the best OS with and without NAC. Claudin-low tumors were associated with poor OS irrespective of treatment regimen. Basal tumors showed the most improvement in OS with NAC compared with surgery alone. The main limitations of our study are its retrospective design and comparison across datasets. CONCLUSIONS Molecular subtyping may have an impact on patient benefit to NAC. If validated in additional studies, our results suggest that patients with basal tumors should be prioritized for NAC. We discovered the first single-sample classifier to subtype MIBC, which may be suitable for integration into routine clinical practice. PATIENT SUMMARY Different molecular subtypes can be identified in muscle-invasive bladder cancer. Although cisplatin-based neoadjuvant chemotherapy improves patient outcomes, we identified that the benefit is highest in patients with basal tumors. Our newly discovered classifier can identify these molecular subtypes in a single patient and could be integrated into routine clinical practice after further validation.

Impact of Histologic Subtype on Cancer-specific Survival in Patients with Renal Cell Carcinoma and Tumor Thrombus

BACKGROUND The efficacy of neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (BCa) was established primarily with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), with complete response rates (pT0) as high as 38%. However, because of the comparable efficacy with better tolerability of gemcitabine and cisplatin (GC) in patients with metastatic disease, GC has become the most commonly used regimen in the neoadjuvant setting. OBJECTIVE We aimed to assess real-world pathologic response rates to NAC with different regimens in a large, multicenter cohort. DESIGN, SETTING, AND PARTICIPANTS Data were collected retrospectively at 19 centers on patients with clinical cT2-4aN0M0 urothelial carcinoma of the bladder who received at least three cycles of NAC, followed by radical cystectomy (RC), between 2000 and 2013. INTERVENTION NAC and RC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The primary outcome was pathologic stage at cystectomy. Univariable and multivariable analyses were used to determine factors predictive of pT0N0 and ≤pT1N0 stages. RESULTS AND LIMITATIONS Data were collected on 935 patients who met inclusion criteria. GC was used in the majority of the patients (n=602; 64.4%), followed by MVAC (n=183; 19.6%) and other regimens (n=144; 15.4%). The rates of pT0N0 and ≤pT1N0 pathologic response were 22.7% and 40.8%, respectively. The rate of pT0N0 disease for patients receiving GC was 23.9%, compared with 24.5% for MVAC (p=0.2). There was no difference between MVAC and GC in pT0N0 on multivariable analysis (odds ratio: 0.89 [95% confidence interval, 0.61-1.34]; p=0.6). CONCLUSIONS Response rates to NAC were lower than those reported in prospective randomized trials, and we did not discern a difference between MVAC and GC. Without any evidence from randomized prospective trials, the best NAC regimen for invasive BCa remains to be determined. PATIENT SUMMARY There was no apparent difference in the response rates to the two most common presurgical chemotherapy regimens for patients with bladder cancer.

Active Surveillance for Prostate Cancer Compared With Immediate Treatment: An Economic Analysis

Study Type – Therapy (case control)
Level of Evidence 3b

The Impact of Obesity on Overall and Cancer Specific Survival in Men With Prostate Cancer

BACKGROUND Although different prognostic factors for patients with renal cell carcinoma (RCC) and vena cava tumor thrombus (TT) have been studied, the prognostic value of histologic subtype in these patients remains unclear. OBJECTIVE We analyzed the impact of histologic subtype on cancer-specific survival (CSS). DESIGN, SETTINGS, AND PARTICIPANTS We retrospectively analyzed the records of 1774 patients with RCC and TT who underwent radical nephrectomy and tumor thrombectomy from 1971 to 2012 at 22 US and European centers. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Multivariable ordered logistic and Cox regression models were used to quantify the impact of tumor histology on CSS. RESULTS AND LIMITATIONS Overall 5-yr CSS was 53.4% (confidence interval [CI], 50.5-56.2) in the entire group. TT level (according to the Mayo classification of macroscopic venous invasion in RCC) was I in 38.5% of patients, II in 30.6%, III in 17.3%, and IV in 13.5%. Histologic subtypes were clear cell renal cell carcinoma (cRCC) in 89.9% of patients, papillary renal cell carcinoma (pRCC) in 8.5%, and chromophobe RCC in 1.6%. In univariable analysis, pRCC was associated with a significantly worse CSS (p<0.001) compared with cRCC. In multivariable analysis, the presence of pRCC was independently associated with CSS (hazard ratio: 1.62; CI, 1.01-2.61; p<0.05). Higher TT level, positive lymph node status, distant metastasis, and fat invasion were also independently associated with CSS. CONCLUSIONS In our multi-institutional series, we found that patients with pRCC and vena cava TT who underwent radical nephrectomy and tumor thrombectomy had significantly worse cancer-specific outcomes when compared with patients with other histologic subtypes of RCC. We confirmed that higher TT level and fat invasion were independently associated with reduced CSS.