Feasibility Study: Watchful Waiting For Localized Low To Intermediate Grade Prostate Carcinoma With Selective Delayed Intervention Based On Prostate Specific Antigen, Histological And/Or Clinical Progression

Active surveillance provides a unique opportunity to study biomarkers of prostate cancer behaviour, although only small volumes of tumor tissue are typically available. We have evaluated a technique for constructing tissue microarrays (TMAs) from needle biopsies for assessing immunohistochemical markers in localized prostate cancer managed by active surveillance. TMAs were constructed from diagnostic prostate biopsies for 60 patients with localized prostatic adenocarcinoma in a prospective cohort study of active surveillance. Radical treatment was recommended for a prostate-specific antigen (PSA) velocity greater than 1 ng ml À1 per year or adverse histology in repeat biopsies, defined as Gleason score X4 þ 3 or 450% of cores involved. Sections from the TMAs were stained with H&E, P63/AMACR and Ki-67. Time to radical treatment was analysed with respect to clinical characteristics and Ki-67 LI. At a median follow up of 36 months, 25/60 (42%) patients had received radical treatment. On univariate analysis, PSA density (P ¼ 0.001), Gleason score (P ¼ 0.001), clinical T stage (P ¼ 0.01), Ki-67 LI (P ¼ 0.02) and initial PSA (P ¼ 0.04) were associated with time to radical treatment. On multivariate analysis, PSA density (P ¼ 0.01), Ki-67 LI (P ¼ 0.03) and Gleason score (P ¼ 0.04) were independent determinants of progression to radical treatment. TMAs constructed from prostate needle biopsies can be used to assess immunohistochemical markers in localized prostate cancer managed by active surveillance. Ki-67 LI merits further study as a possible biomarker of early prostate cancer behaviour.

Section: Introductionmentioning

confidence: 99%

Biopsy tissue microarray study of Ki-67 expression in untreated, localized prostate cancer managed by active surveillance

Jhavar

Bartlett

Kovács

et al. 2008

“…Indications for treatment were PSA progression, defined as a PSADT o2 y; histologic progression, defined as upgrading to Gleason score Z8 on rebiopsy; or clinical progression. By the time of the latest update, 15 206 men had entered the study. They ranged in age from 49 to 84 y with a median of 70 y.…”

Section: Initial Results Of Active Surveillancementioning

confidence: 99%

“…There is no consensus on the selection criteria used to identify patients for surveillance. [15][16][17] My own policy is to offer active surveillance as an option to men who have clinical stage T1/2 disease, a primary Gleason grade of r3, with r50% of biopsy cores involved and a PSA level of o15 ng/ml. Initial analyses have shown that the variation in the findings between initial and repeat biopsies, at least within the first few years of surveillance, reflect the limitations of sampling, rather than tumour evolution.…”

Section: Initial Results Of Active Surveillancementioning

confidence: 99%

Active surveillance of early prostate cancer: rationale, initial results and future developments

Parker

2004

Active surveillance is a new strategy that aims to individualise therapy by selecting only those men with significant cancers for curative therapy based on early evidence of disease progression. Active surveillance must be distinguished from watchful waiting, which for decades has described a policy of observation with the use of palliative treatment for symptomatic progression. The rationale for active surveillance is discussed, based on our knowledge of the natural history of PSA-detected early prostate cancer. The initial results of active surveillance have demonstrated its feasibility. Ongoing studies seek to optimise the active surveillance protocol, and to determine the long-term outcomes. Looking ahead, dietary intervention in men on active surveillance could become an important new paradigm for prostate cancer management.

“…Some guidelines have been developed to evaluate men on watchful waiting protocols. 10 A recent study provides evidence that in clinically localized prostate cancer, radical prostatectomy may reduce the cancer-specific but not the overall mortality compared to watchful waiting. 2 At first glance, the debate regarding treatment seems easier in locally advanced disease, as it is known that patients with node positive disease, receiving no therapy will die due to prostate cancer within a short period of time.…”

Section: Discussionmentioning

confidence: 99%

Comparison of external radiation therapy vs radical prostatectomy in lymph node positive prostate cancer patients

Kuefer

Volkmer

Loeffler

et al. 2004

Introduction: Treatment options for lymph node positive prostate cancer are limited. We retrospectively compared patients who underwent external radiotherapy (ERT) to patients treated by radical prostatectomy (RPX). Materials and Methods: A total of 102 lymph node positive patients from the RPX series at Ulm University were evaluated. In all, 76 patients received adjuvant androgen withdrawal as part of their primary treatment. In the ERT group, 44 patients were treated at the University of Michigan using a fractionated regimen. Of these, 21 patients received early adjuvant hormonal therapy. Patients with neoadjuvant therapy before RPX or ERT were excluded. Results: In the RPX group, PSA nadir (nadirp0.2 vs 40.2 ng/ml) showed a strong association with outcome. In the ERT group, pretreatment PSA was an independent predictor of outcome (P ¼ 0.04) and patients with adjuvant hormonal therapy had a significant longer recurrence-free interval compared to patients without adjuvant therapy (P ¼ 0.004). Comparing only patients with adjuvant hormonal treatment after cancer-specific therapy, the ERT-treated patients had a borderline longer PSA recurrence-free survival time compared to the RPX-treated patients (P ¼ 0.05). Conclusions: In case of positive lymph nodes, RPX and ERT might be considered and need to be explained to the patient. For future treatment decisions, the presented findings and a potential survival benefit need to be evaluated in a larger prospective setting.