Long-term outcomes of active surveillance for clinically localized prostate cancer in a community-based setting: results from a prospective non-interventional study.

PURPOSE: To report on long-term outcomes of patients treated with active surveillance (AS) for localized prostate cancer (PCa) in the daily routine setting. METHODS: HAROW (2008-2013) was a non-interventional, health service research study about the management of localized PCa in the community setting, with 86% of the study centers being office-based urologists. A follow-up examination of all patients who opted for AS as primary treatment was carried out. Overall, cancer-specific, and metastasis-free survival, as well as discontinuation rates, were determined. RESULTS: Of 329 patients, 62.9% had very-low- and 21.3% low-risk tumours. The median follow-up was 7.7 years (IQR 4.7-9.1). Twenty-eight patients (8.5%) died unrelated to PCa, of whom 19 were under AS or watchful waiting (WW). Additionally, seven patients (2.1%) developed metastasis. The estimated 10-year overall and metastasis-free survival was 86% (95% CI 81.7-90.3) and 97% (95% CI 94.6-99.3), respectively. One hundred eighty-seven patients (56.8%) discontinued AS changing to invasive treatment: 104 radical prostatectomies (RP), 55 radiotherapies (RT), and 28 hormonal treatments (HT). Another 50 patients switched to WW. Finally, 37.4% remained alive without invasive therapy (22.2% AS and 15.2% WW). Intervention-free survival differed between the risk groups: 47.8% in the very-low-, 33.8% in the low- and 34.6% in the intermediate-/high-risk-group (p = 0.008). On multivariable analysis, PSA-density ≥ 0.2 ng/ml2 was significantly predictive for receiving invasive treatment (HR 2.55; p = 0.001). CONCLUSION: Even in routine care, AS can be considered a safe treatment option. Our results might encourage office-based urologists regarding the implementation of AS and to counteract possible concerns against this treatment option.

Active Surveillance for Incidental (cT1a/b) Prostate Cancer: Long-Term Outcomes of the Prospective Noninterventional HAROW Study.

INTRODUCTION: Optimal treatment for incidental prostate cancer (IPC) after surgical treatment for benign prostate obstruction is still debatable. We report on long-term outcomes of IPC patients managed with active surveillance (AS) in a German multicenter study. METHODS: HAROW (2008-2013) was designed as a noninterventional, prospective, health-service research study for patients with localized prostate cancer (≤cT2), including patients with IPC (cT1a/b). A follow-up examination of all patients treated with AS was carried out. Overall, cancer-specific, and metastasis-free survival and discontinuation rates were determined. RESULTS: Of 210 IPC patients, 68 opted for AS and were available for evaluation. Fifty-four patients had cT1a category and 14 cT1b category. Median follow-up was 7.7 years (IQR: 5.7-9.1). Eight patients died of which 6 were still under AS or watchful waiting (WW). No PCa-specific death could be observed. One patient developed metastasis. Twenty-three patients (33.8%) discontinued AS changing to invasive treatment: 12 chose radical prostatectomy, 7 radiotherapy, and 4 hormonal treatment. Another 19 patients switched to WW. The Kaplan-Meier estimated 10-year overall, cancer-specific, metastasis-free, and intervention-free survival was 83.8% (95% CI: 72.2-95.3), 100%, 98.4% (95% CI: 95.3-99.9), and 61.0% (95% CI: 47.7-74.3), respectively. In multivariable analysis, age (RR: 0.97; p < 0.001), PSA density ≥0.2 ng/mL2 (RR: 13.23; p < 0.001), and PSA ≥1.0 ng/mL after surgery (RR: 5.19; p = 0.016) were significantly predictive for receiving an invasive treatment. CONCLUSION: In comparison with other AS series with a general low-risk prostate cancer population, our study confirmed the promising survival outcomes for IPC patients, whereas discontinuation rates seem to be lower for IPC. Thus, IPC patients at low risk of progression may be good candidates for AS.

Utilization of Active Surveillance and Watchful Waiting for localized prostate cancer in the daily practice.

PURPOSE: To analyze the utilization of Active Surveillance (AS) and Watchful Waiting (WW) in the daily routine setting, since both are non-invasive treatment options for localized prostate cancer (PCa), which are used in a curative (AS) or palliative (WW) setting. Since differentiation of both strategies is not always clear, patients were compared with respect to the inclusion criteria, frequency of follow-up examinations (Prostate Specific Antigen = PSA tests, rebiopsies), and initiation of a deferred treatment. METHODS: HAROW is a non-interventional, health-service research study on the management of localized PCa in the community setting. Of 3169 patients, prospectively enrolled from 2008 to 2013 with a mean follow-up of 28.2 months, 468 chose AS and 126 WW. Treating urologists reported clinical variables, information on therapy and clinical course of disease. RESULTS: AS patients were significantly younger and had more low-risk tumors. No differences were seen in the number of PSA tests during follow-up: mean number of PSA tests was 6.08 for AS- and 5.18 for WW patients, more than four PSA tests were reported in 63.9% AS- and 59.5% WW patients (p = 0.136). At least one re-biopsy was performed in 39.7% AS- and 9.5% WW patients (p < 0.001). Discontinuation rates were 23.9% (n = 112) for AS and 11.9% (n = 15) for WW. Most of the AS patients opted for a curative treatment (prostatectomy = 65, radiotherapy = 30), whereas 12 WW patients received a palliative hormone therapy and three patients received radiotherapy. CONCLUSIONS: Physicians seem to distinguish clearly between AS and WW in terms of inclusion criteria and deferred therapy, whereas this differentiation tends to become indistinct in terms of follow-up examinations.

Risk stratification: a tool to predict the course of active surveillance for localized prostate cancer?

OBJECTIVE: To investigate a cohort of patients undergoing active surveillance (AS) for localized prostate cancer (PCa) with regard to possible differences in discontinuation rates, subsequent therapies, reasons for intervention and pathological findings after deferred surgery after patient stratification into very-low-risk, low-risk and intermediate-/high-risk PCa groups. PATIENTS AND METHODS: The HAROW study was a non-interventional, observational, outcomes research study on the management of localized PCa in the community setting. A total of 468 patients were prospectively enrolled in the HAROW study, with a mean follow-up of 28.5 months. Treating urologists reported clinical variables, information on therapy and clinical course of disease at 6-month intervals. RESULTS: Of 468 patients under AS, 244 were stratified into very-low-risk, 142 into low-risk and 82 into intermediate-/high-risk groups. Of these patients, 112 discontinued AS. Discontinuation rates were 25.4% in the very-low-risk, 21.1% in the low-risk and 24.4% in the intermediate-/high-risk groups (P = 0.633). The main reasons for intervention were biopsy upgrade and/or prostate-specific antigen elevation in the very-low- and low-risk groups, and patient preference in the intermediate-/high-risk group (P < 0.05). No significant differences were found regarding subsequent therapies and pathological findings after deferred surgery. CONCLUSION: Our results show no differences in the outcome of risk-stratified patients in the specified risk groups managed with AS, while switching to an invasive treatment on the patient's request was more frequent in the intermediate-/high-risk group.

Active surveillance in localized prostate cancer: comparison of incidental tumours (T1a/b) and tumours diagnosed by core needle biopsy (T1c/T2a): results from the HAROW study.

OBJECTIVE: To conduct a comparative prospective analysis of patients with incidental T1a/T1b prostate cancer (IPCa) and those with prostate cancer (PCa) diagnosed by core needle biopsy, treated by active surveillance (AS), with regard to inclusion criteria, progression and switch to deferred treatment. PATIENTS AND METHODS: The HAROW study is an observational outcomes research study on the management of localized PCa. Treating urologists reported clinical variables and information on therapy and clinical course of disease at 6-month intervals. With respect to therapy, only recommendations were made; the final decision on the therapeutic method rested with the treating physician. RESULTS: Out of 2 957 patients included in the HAROW study, 447 chose AS. The median follow-up was 28.3 months. T1a, T1b, T1c and T2a disease were diagnosed in 81, 18, 292 and 56 patients, respectively. Patients in the IPCa group had lower prostate-specific antigen (PSA) levels (4.2 vs 6.1 ng/mL) and more comorbidities than those diagnosed by core needle biospy. The IPCa group also had fewer re-biopsies (25.3 vs 43.2%) and fewer changes to invasive treatment (12.1 vs 25.9%). No significant differences were found with respect to the criteria for discontinuation, subsequent therapies and histological findings after radical prostatectomy. CONCLUSION: Urologists are highly inclined to use AS as a therapeutic option in IPCa. More patients with IPCa than those diagnosed after core needle biopsy continued on AS, which was also associated with the indication for a re-biopsy being less stringently observed.

Treatment of intermediate-risk prostate cancer with active surveillance in the routine care-Long-term outcomes of a prospective noninterventional study (HAROW).

Background: We report here the long-term outcomes of patients with intermediate-risk prostate cancer (PCa) treated with active surveillance (AS) in a daily routine setting. Material and methods: HAROW (2008-2013) was a noninterventional, health service research study investigating the management of localized PCa in a community setting. A substantial proportion of the study centers were office-based urologists. A follow-up examination of all intermediate-risk patients with AS was conducted. Overall, cancer-specific, metastasis-free, and treatment-free survival rates, as well as reasons for discontinuation, were determined and discussed. Results: Of the 2957 patients enrolled, 52 with intermediate-risk PCa were managed with AS and were available for evaluation. The median follow-up was 6.8 years (interquartile range, 3.4-8.6 years). Seven patients (13.5%) died of causes unrelated to PCa, of whom 4 were under AS or under watchful waiting. Two patients (3.8%) developed metastasis. The estimated 8-year overall, cancer-specific, metastasis-free, and treatment-free survival rates were 85% (95% confidence interval [CI], 72%-96%), 100%, 93% (95% CI, 82%-100%), and 31% (95% CI, 17%-45%), respectively. On multivariable analysis, prostate-specific antigen density of ≥0.2 ng/mL2 was significantly predictive of receiving invasive treatment (hazard ratio, 3.29; p = 0.006). Reasons for discontinuation were more often due to patient's or physician's concerns (36%) than due to observed clinical progression. Conclusions: Although survival outcome data for intermediate-risk patients managed with AS in real-life health care conditions were promising, rates of discontinuation were high, and discontinuation was often a patient's decision, even when the signs of disease progression were absent. This might be an indication of higher levels of mental burden and anxiety in this specific subgroup of patients, which should be considered when making treatment decisions. From a psychological perspective, not all intermediate-risk patients are optimal candidates for AS.

Predictive value of the UICC and AJCC 8th edition tumor-nodes-metastasis (TNM) classification for patients treated with radical prostatectomy.

BACKGROUND: According to the 8th-edition of the tumor-nodes-metastasis-classification localized prostate cancer (PCa) can be divided into two categories (cT1,cT2), two stages (SI,SII), and, by incorporating prostate-specific-antigen (PSA) and WHO-grade (Gleason-Score), into prognostic stage groups (PSG I,IIA,IIB,IIC,III). We examined the predictive value of these systems for an organ-confined disease (pT≤2), favorable WHO-grade ≤2 (Gleason-score ≤7a), and biochemical-free-survival (BFS) after radical prostatectomy (RP). METHODS: Data were collected in a prospective, non-interventional, multicenter health-service-research study for the treatment of localized PCa (HAROW) with 687 patients receiving RP. Mean Follow-up was 31.7 months. RESULTS: Organ-confined disease was present in 76.5% and 63.6% of cT1 and cT2 patients, 75.7% and 59.6% of SI and SII, and 84.6%, 81.6%, 72.8% and 42.5% of PSG I, IIA, IIB and ≥ IIC (p = 0.001). Favorable WHO-grade (Gleason-Score) was present in 75.4% and 60.7% of cT1 and cT2 patients, 74.3% and 56.5% of SI and SII patients, and 86.1%,85.6%,73.3% and 29.5% of PSG I, IIA, IIB and ≥ IIC (p = 0.001). Probability of BFS was 92.0% and 91.5% for cT1 and cT2 (p = 0.990), 91.1% and 94.2% for SI and S II (p = 0.286) and 96.6%,95.1%,91.4% and 78.8% for PSG I,IIA,IIB and ≥ IIC (p = 0.001). CONCLUSIONS: CT 1/cT2 and S I/II subgrouping is feasible to predict a different pT-category and a favorable WHO-grade (Gleason-Score) after RP, but failed to predict a different BFS. With the additional information of WHO-grade (Gleason-Score) and PSA, the PSG represents an approach for the prediction of all examined endpoints which is a useful tool to help clinicians to advise their patients.

[TNM-Classification of localized prostate cancer : The clinical T-category does not correspond to the required demands]. / TNM-Klassifikation des lokalisierten Prostatakarzinoms : Die cT-Kategorie entspricht nicht ihren klinischen Erfordernissen.

BACKGROUND: The TNM staging system for localized prostate cancer (PCa) divides tumors based on clinical parameters into a clinical (c)T category and, after radical prostatectomy (RP), a pathological (p)T category. OBJECTIVES: This study examines the extent to which the cT and the pT category correspond to each other and whether the two categories differ in their prediction for organ-confined disease. PATIENTS AND METHODS: Data of 687 RP patients were collected in a prospective, noninterventional, multicenter health service research study for the treatment of localized PCa (HAROW). Group comparisons were performed by analysis of variance and student t­test as well as the chi-squared test or the Fisher exact test. RESULTS: Clinical cT1 category (62.9%) and pathological pT2c category (56.6%) were diagnosed most frequently. The correspondence of cT and pT category was 15% for cT2a , 10.5% for cT2b, and 55% for cT2c. An extraprostatic extension (≥pT3) was observed for the categories cT1 and cT2 in 23.5% and 36.4% (p < 0.001), differences in the subcategories cT2a-c were not significant: cT2a = 28.8%, cT2b = 42.1%, and cT2c = 38.8% (p = 0.194). Tumors with a pathologically extraprostatic extension were not recognized clinically in >50%. CONCLUSIONS: For localized PCa there is low agreement between clinical and pathologic T category, thus, often leading to understaging. An adaptation of the T classification of the TNM system with division into "not palpable" and "palpable" appears sufficient for a prognostic prediction.