Watchful waiting or watchful progression?: Prostate specific antigen doubling times and clinical behavior in patients with early untreated prostate carcinoma.
ABSTRACT Prostate specific antigen doubling time (PSAdt) is a dynamic model of prostate tumor biology. It predicts aggressive disease and subsequent clinical recurrence after radical treatment. However, as yet there is only limited evidence for its validity in the watchful waiting population.
One hundred and thirteen previously untreated patients with adenocarcinoma of the prostate who were referred to the British Columbia Cancer Agency for a management opinion subsequently were placed into a prospective watchful waiting program. The reasons for watchful waiting, previous medical history, serial PSA, and histopathologic data were recorded.
The median age of patients was 75 years (range, 49-85 years). The median follow-up from the time of the first appointment was 14 months (range, 0-58 months). The reasons for watchful waiting were correlated highly with T classification (P = 0.003) and past medical history (P = 0.002). Approximately 40% of T1 patients and 51% of T2 patients had clinical progression by 2 years, increasing to 60% at 3 years. On multivariate analysis PSAdt strongly correlated with clinical progression (P < 0.0001), stage progression (P = 0.01), and time to treatment (P = 0.0001); tumor grade and initial stage were not found to be predictive for any of the endpoints studied. Initial PSA only was significant in predicting for time to treatment (P = 0.03). Approximately 50% of patients with a PSAdt of <18 months progressed within 6 months. At last follow-up, no deaths from prostate carcinoma had been recorded. Overall survival at 2 and 5 years was 92% and 68%, respectively.
Using digital rectal examination, the findings of this study demonstrated high rates of clinical tumor progression within the watchful waiting population. PSAdt rather than standard histopathologic criteria was found to be the most powerful indicator of disease activity.
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ABSTRACT: Prostate cancer is nowadays the most common non-cutaneous cancer in men in the Western world. Since the introduction of Prostate Specific Antigen (PSA) testing in the last decade, prostate cancer incidence increased dramatically. In addition, the population is aging, and prostate cancer incidence increases with higher age. The dilemma of prostate cancer is that more men die with prostate cancer than from prostate cancer, as reflected by the observation that in 70% of men who are 80 years or older prostate cancer is diagnosed histologically on autopsy. As a consequence of this high incidence on autopsy, it may be anticipated that a large proportion of old men are diagnosed with prostate cancer when undergoing prostate biopsy and a great proportion of prostate cancers detected in screening programs may be over-diagnosed. It is as yet unclear whether PSA based screening reduces prostate cancer mortality. Due to screening with PSA most cancers are diagnosed in an early stage and therefore possibly in a curable stage. As a result, cancer is removed in an early stage, before the tumor is able to metastasize. It is conceivable that population-based early prostate cancer screening will reduce prostate cancer mortality. In order to investigate this further, randomized clinical trials have been introduced. In the USA the Prostate Lung Colorectal and Ovary cancer (PLCO) study investigates if prostate cancer screening is justified. In Europe the European Randomized Study of Screening for Prostate Cancer (ERSPC) is conducted in 8 European countries to study whether prostate cancer screening can reduce prostate cancer specific mortality at affordable costs and quality of life. The European screening centers differ with regard to the screening procedure but they share PSA testing and most other features (Table 1). At the Rotterdam section of the ERSPC the screening protocol comprises serum PSA testing followed – in case of an elevated serum PSA level- by six lateralized needle biopsies, three from each side of the prostate (systematic sextant biopsy) in men aged between 55 and 75 years. Every four years the same cohort of men is screenend. Men are excluded from screening in the 2nd round if a previous diagnosis of prostate cancer is made and those with interval carcinoma (i.e. cancers detected after the 1st round, but during the 4-year screening interval period. Unfortunately, the final outcome of the ERSPC will not be here until the end of 2008 or later. This thesis is restricted to an analysis of the data from first and second screening rounds at the Rotterdam section of the ERSPC. Awaiting the final outcome of the ERSPC, the investigations collected in this thesis are aimed to provide insight in 1) intermediate endpoints, concerning stage and grade of prostate cancer in subsequent screening rounds and the forthcoming therapy choices, 2) the efficiency of the screening protocol employed at the Rotterdam section of the ERSPC and 3) the natural biology of prostate cancer and its possible premalignant lesions.
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ABSTRACT: This retrospective review compares prostate-specific antigen (PSA) doubling time (DT) prior to the initiation of a 5-alpha-reductase inhibitor (pre-5-ARI) to after the PSA nadir (post-nadir) has been reached for patients on active surveillance for favourable-risk prostate cancer. Between 1996 and 2010, a total of 100 men with a history of 5-ARI use were captured from our active surveillance database. Twenty-nine patients had a sufficient number of PSA values to determine both pre-5-ARI and post-nadir DTs. PSADT was calculated using the general linear mixed-model method. The median follow-up was 69.5 months. The median pre-5-ARI PSADT was 55.8 (range: 6-556.8) months, while the post-nadir value was 25.2 (range: 6-231) months (p = 0.0081). Six patients were reclassified after an average of 67.7 (range: 59-95) months, due to progression in PSADT (n = 2) or Gleason score (n = 4). The median pre-5-ARI and post-nadir DTs for this group were 42.3 (range: 32.4-91.1) and 21.1 (range: 6-44.3) months, respectively. 5-ARIs significantly decreased PSADT compared to prior to their initiation. This effect may be due to preferential suppression of benign tissue following PSA nadir. The resulting PSADT would then represent a more accurate depiction of the true cancer-related DT. If validated with a larger cohort, 5-ARIs may enhance the utility of PSADT as a biomarker of disease progression in active surveillance.Canadian Urological Association journal = Journal de l'Association des urologues du Canada 11/2013; 7(11-12):450-3. DOI:10.5489/cuaj.262 · 1.92 Impact Factor
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ABSTRACT: Traditionally, clinicians have used prognostic factors such as disease stage, tumour grade, nodal status and pre-treatment prostate-specific antigen (PSA) level to stratify patients for risk of disease recurrence after primary therapy. More recently, evidence from a number of studies indicates that PSA doubling time (PSADT) subsequent to biochemical failure may also be useful in predicting clinical progression. Men with a short PSADT (<6 months) appear to be at greater risk of experiencing clinical progression than those with a longer PSADT (≥6 months). Moreover, men with a short PSADT are more likely to develop distant metastases than men with a longer PSADT, which is associated with local recurrence. Limited evidence suggests PSADT may also predict disease activity during watchful waiting: the shorter the PSADT, the greater the risk of clinical progression. While useful in predicting progression, the role of PSADT in predicting survival in early prostate cancer remains unclear. Survival results from ongoing trials promise to resolve this question. With over 8000 men enrolled, the bicalutamide (‘Casodex’)1 Early Prostate Cancer (EPC) programme is expected to provide valuable information about the natural history of prostate cancer following potentially curative therapy or during watchful waiting.European Urology Supplements 08/2002; 1(5):17–23. DOI:10.1016/S1569-9056(02)00049-0 · 3.37 Impact Factor