Effects of Screening on Radical Prostatectomy Efficacy: The Prostate Cancer Intervention Versus Observation Trial.
The Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) trial showed that radical prostatectomy (RP) reduced prostate cancer deaths with an absolute mortality difference (AMD) between the RP and watchful waiting arms of 6.1% (95% confidence interval [CI] = 0.2% to 12.0%) after 15 years. In the United States, the Prostate Cancer Intervention Versus Observation Trial (PIVOT) produced an AMD of 3% (95% CI = -1.1% to 6.5%) after 12 years. It is not known whether a higher frequency of screen detection in PIVOT explains the lower AMD.Methods
We assumed the SPCG-4 trial represents RP efficacy and prostate cancer survival in an unscreened population. Given the fraction of screen-detected prostate cancers in PIVOT, we adjusted prostate cancer survival using published estimates of overdiagnosis and lead time to project the effect of screen detection on disease-specific deaths.ResultsOn the basis of published estimates, we assumed that 32% of screen-detected cancers were overdiagnosed and a mean lead time among non-overdiagnosed cancers of 7.7 years. When we adjusted prostate cancer survival for the 76% of case patients in PIVOT who were screen detected, we projected that the AMD after 12 years would be 2.0% (95% CI = -1.6% to 5.6%) based on variation in published estimates of overdiagnosis and mean lead time in the United States.Conclusions
If RP efficacy and prostate cancer survival in the absence of screening are similar to that in the SPCG-4 trial, then overdiagnosis and lead time largely explain the lower AMD in PIVOT. If these artifacts of screening are the correct explanation, then there is a subset of case subjects that should not be treated with RP, and identifying this subset should lead to a clearer understanding of the benefit of RP in the remaining cases.
SourceAvailable from: Shawn G Clouthier[Show abstract] [Hide abstract]
ABSTRACT: Despite extensive research effort and considerable progress, the "war on cancer" that president Nixon declared in 1971 has yet to be optimally integrated into cancer therapeutics and as such cancer remains a major medical challenge for oncologists. The dynamic and complex biology of tumor cells undergoing clonal evolution generates cells with diverse degrees of drug resistance and metastatic potential. This highlights the need to be able to access this clonal density in order to develop effective therapeutics. With this prospective, early phase single cell studies are vital for thoroughly interrogating tumor heterogeneity to uncover more about cancer cell biology and to explore new therapeutic targets leading to more successful treatments. Current evidence supports the notion that clonogenic cells within the tumor mass may potentially give rise to a population of cells with unique genomic, transcriptomic and proteomic features distinct from the rest of the tumor mass. This observation can explain drug resistance after an initial period of primary tumor response. Therefore, completely abrogating or at a minimum achieving long-term, durable control over cancer requires researchers and oncologists to employ a personalized medicine approach that includes both tumor and patient-associated variables to modify current therapeutic regimens. In this review we discuss the importance of omics and in particular single cell genomics which are increasingly promising given recently developed technology advancements to facilitate exploration of cellular heterogeneity and tumor complexity.Journal of molecular and genetic medicine: an international journal of biomedical research 10/2014; 8(3). DOI:10.4172/1747-0862.1000121
[Show abstract] [Hide abstract]
ABSTRACT: Objective To assess whether the number of cores at first prostate biopsy affect pathologic findings at radical prostatectomy (RP) in potential candidates for active surveillance (AS). Methods Two hundred seventy-five patients fulfilling Prostate Cancer Research International: Active Surveillance criteria (prostate-specific antigen level ≤10 ng/mL, prostate-specific antigen density <0.2 ng/mL/cm3, number of positive cores ≤2, T1c-T2 clinical stage, Gleason score [GS] ≤6) underwent RP between 2005 and 2013 at a single institution. Patients were stratified into 3 groups according to different biopsy schemes (≤12 vs 13-18 vs ≥19 cores). Rates of pathologically confirmed insignificant prostate cancer (pIPCa; defined as RP GS ≤6, tumor volume ≤0.5 mL, and organ-confined disease) and unfavorable disease (UD, defined as non–organ-confined disease and/or pathologic GS ≥7) at RP were stratified according to the biopsy schemes. Logistic regression analyses tested the effect of preoperative variables in predicting pIPCa and UD at RP. Results Of all, 23.3% and 33.4% patients harbored pIPCa and UD, respectively. pIPCa and UD were found in 15.7%, 32.1%, 25.3% (P = .04) and in 48.1%, 23.8%, 24.1% (P <.001) patients with ≤12, 13-18, ≥19 cores, respectively. At multivariate analyses, number of biopsy cores emerged as an independent predictor of both pIPCa (≤12 vs 13-18 cores: odds ratio [OR] = 2.34; P = .02) and UD (≤12 vs 13-18 cores: OR = 0.39; P <.01; ≤12 vs ≥19 cores: OR = 0.38; P <.01). Conclusion Among candidates for AS, number of biopsy cores emerged as an independent predictor of pIPCa and UD at RP. These findings would suggest that the extent of initial biopsy sampling should be considered when addressing patients to AS and before planning any surveillance strategies.Urology 09/2014; 84(3). DOI:10.1016/j.urology.2014.02.070 · 2.13 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Prostate cancer screening had led to the diagnosis of a large proportion of localized and low-risk disease. Many of these cancer cases are believed to be indolent and would not be clinically perceived in the absence of screening. In addition to that, the wide use of active treatment has exposed these patients to treatment-related quality-of-life impact. In this setting active surveillance as a way of deferring active treatment and reserving such treatment to cases of disease progression only has gained interest. PSA has been widely used to identify patients eligible for active surveillance and also for disease monitoring. The goal of this review was to describe the place of PSA in the monitoring of patients under active surveillance based on the existing studies and to discuss the importance of PSA in light of other existing or emerging tools to monitor prostate cancer in active surveillance.Biomarkers in Medicine 06/2014; 8(5):747-53. DOI:10.2217/bmm.14.5 · 3.22 Impact Factor