HAROW Study Research Articles

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.

Treatment of post-prostatectomy urinary incontinence and erectile dysfunction: there is insufficient utilisation of care in German cancer survivors

PurposeTreatment of post-prostatectomy urinary incontinence (UI) and erectile dysfunction (ED) increases quality of life (QoL). Aim of our study was to evaluate the utilisation of care among patients with post-prostatectomy UI and ED in Germany.MethodsThe HAROW study documented treatment of patients with localised prostate cancer (≤ T2c) in Germany. 1260 patients underwent radical prostatectomy (RP). Patients answered validated questionnaires after a median follow-up of 6.3 years. Response rate was 76.8%.ResultsMedian age at RP was 65 (IQR 60–69) years. 14% (134/936) used more than one pad per day for UI. 25% (26/104, 30 missing) of UI patients underwent surgery to improve continence. Of patients without surgery, 41% (31/75) reported a moderate-to-severe issue concerning their incontinence with worse mental health and QoL. 81% (755/936) patients were unable to have an erection firm enough for sexual intercourse. Of all ED patients, 40% (319/793) used ED treatment regularly or tried it at least once. 49% (243/499) of patients with interest in sex never tried ED treatment. In multivariate analysis, patients not using ED treatments were older (≥ 70 years OR 4.1), and more often had preoperative ED (OR 2.3) and less interest in sex (OR 2.2). Nevertheless, 30% (73/240) of these patients had moderate-to-severe issues with their ED reporting worse mental health and QoL.ConclusionAlmost half of the patients without post-prostatectomy UI and ED treatment reported moderate-to-severe issues with a significant decrease in QoL. This indicates an insufficient utilisation of care in Germany.

Noninvasive treatment of organ-confined prostate cancer in elderly patients-results of the HAROW study

Noninvasive treatment options such as active surveillance (AS), watchful waiting (WW), and hormone deprivation therapy (HT) are particularly important in elderly patients with localized prostate cancer (PCa). We examine the use of these noninvasive treatment options in the everyday care in acohort of patients ≥70years old. In the HAROW study, the treatment of localized PCa under everyday conditions is investigated. The only inclusion criterion was newly diagnosed organ-confined PCa (≤cT2c). In AS, WW, and HT patients, we compared initial tumor and patient characteristics, follow-up examinations and changes of therapy. Of 457 patients ≥70years, 210 chose AS, 160 HT, and 87WW. Observation times were 6.3 years (AS), 7.5 years (HT), and 7.0 years (WW). AS patients (73.2 years) were younger than WW (76.0 years) and HT patients (76.9 years) and had ahigher proportion of low-risk tumors (80%) versus WW (31%) and HT (19%). Achange of therapy was observed in 47.1% of AS, 17.2% of WW and 13.1% of HT patients. Metastasis occurred in 1.0% of AS, 4.6% of WW, and 6.9% of HT patients. Overall survival was 94.3% for AS, 90.8% for WW and 81.9% for HT. Within the first 28.4months, the mean number of PSA determinations did not differ between AS and WW (6.1 vs. 5.2; p = 0.09); arebiopsy was performed in 37.6% of AS, 11.4% of WW, and 17% of HT patients. The allocation to curative and palliative strategies should be made according to patient and tumor characteristics by definition. Palliative procedures may represent concepts in older patients who initially chose acurative AS strategy.

Decision Regret after Radical Prostatectomy does Not Depend on Surgical Approach: 6-Year Followup of a Large German Cohort Undergoing Routine Care

Numerous studies have compared the outcomes of open and robot-assisted radical prostatectomy but to our knowledge only 1 study has focused on patient satisfaction and regret. We evaluated intermediate term decision regret after open and robot-assisted radical prostatectomy. The HAROW (Hormonal Therapy, Active Surveillance, Radiation, Operation, Watchful Waiting) study analyzed localized prostate cancer treatments (T2c N0 M0 or less) in Germany from 2008 to 2013. We collected intermediate term followup data on 1,260 patients after retropubic open or robot-assisted radical prostatectomy. The response rate was 76.8% (936 of 1,218 cases). A total of 404 patients underwent robot-assisted radical prostatectomy and 532 underwent open radical prostatectomy. Patients treated with the robot-assisted procedure showed more self-determined behavior. They reported an active role in surgical decision making and the surgical approach (robot-assisted radical vs open prostatectomy 39% vs 24% and 52% vs 18%, respectively, each p <0.001). Patients treated with the robot-assisted procedure more often participated actively in selecting the treating hospital (25% vs 11%), used the Internet often (87% vs 72%) and traveled an increased distance (63 vs 42 km, all p <0.001). Overall decision regret was low with a mean ± SD score of 14 ± 19 on a scale of 0-no regret to 100-high regret. Multivariate analysis showed that erectile function (OR 3.2), urinary continence (OR 1.8), freedom from recurrence (OR 1.6), an active decision making role (OR 2.2) and shorter followup (OR 0.9 per year) predicted low decision regret (score less than 15). Intermediate term functional and oncologic outcomes as well as autonomous decision making and followup time influenced decision regret after radical prostatectomy. The surgical approach was not associated with intermediate term decision regret.

Active surveillance and watchful waiting for localized prostate cancer in elderly patients &gt;70 years in a community-based setting: Results from the HAROW study.

e16577 Background: Since more than half of patients with prostate cancer (PCa) are older than 70 years, this age group remains underrepresented in clinical trials. Possible non-invasive treatment options for these patients include Active Surveillance (AS) and Watchful Waiting (WW). In this prospective, non-interventional, health services research study, the use of different treatment options for localized PCa are observed under everyday conditions. The subgroups of patients ≥ 70 years, receiving AS- or WW are presented in terms of inclusion criteria, follow-up examinations and changes in treatment strategy. Methods: The study was conducted from July 2008 to July 2013 at 259 study centers in Germany, mainly office based urologists. The mean follow-up was 27.6 months. Clinical data (tumor category, digital rectal examination, PSA level, Gleason score, Charlson Comorbidity Index = CCI) and information about therapy and disease progression were collected at the time of study inclusion and subsequently at six-month intervals. According to the non-interventional study design, only recommendations were made for enrollment, course and discontinuation of AS and WW. The final therapeutic decision rested with treating physicians. Results: Overall, 2957 patients were enrolled, of whom 1165 were ≥ 70 years. 210 patients received AS and 87 patients received WW. AS patients were younger (73.9 vs. 76.8 years, p ≤ 0.001). The rate of low, intermediate and high risk tumors was 81.6%, 14.6% and 3.9% in the AS- and 39.1%, 43.5% and 17.4% in the WW-group (p ≤ 0.001). No differences were seen in the average number of PSA testing during the course of follow-up (AS = 3.97 vs WW = 3.79, p = 0.95). 37.6% of the AS patients and 12.4% of the WW patients received at least one follow-up biopsy. Conclusions: The results of HAROW indicate a clear distinction between AS and WW in terms of inclusion criteria. Interestingly, no clear distinction was seen in terms of follow-up examinations, since both groups were monitored frequently with PSA tests and even re-biopsies were performed in WW patients, neither of which is usually provided in WW programs.

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

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. 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. 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. 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.

The Treatment of Localized Prostate Cancer in Everyday Practice in Germany.

Prostate cancer is now often diagnosed in the localized, welldifferentiated stage. In the HAROW study, we investigated the care situation with respect to the various treatment options for localized prostate cancer in everyday clinical practice in Germany. Study physicians for this prospective, multicenter observational study were recruited through the Federation of German Urologists. At six-month intervals, clinical variables were recorded (T category, prostate-specific antigen [PSA], Gleason score, d'Amico risk profile, Charlson Comorbidity Index [CCI]) and patients filled out questionnaires (QLQ-C30) regarding their indicationrelated quality of life (QoL). Covariance analysis was used to adjust for the variable distribution of patient features among the treatment groups. Data from 2957 patients were available for analysis. The mean followup time was 28.4 months overall, and 47.6 months in the active surveillance (AS) group. Younger patients and patients with a CCI of 0 or 1 predominated in the AS and surgery groups; older patients and patients with a CCI of 2 or above predominated in the groups in which palliative treatment strategies such as hormone therapy (HT) and watchful waiting were applied. The HT group had the highest percentage of patients with a Gleason score of 8 or above (21.2%), while the AS group had the highest percentage of patients with a Gleason score of 6 or below (92.5%), as well as the lowest mean PSA value (5.8 ± 3.4 ng/mL) and the highest percentage of patients with a low-risk profile (82.5%). Of 468 patients in the AS group, 170 (36.3%) underwent a change of treatment strategy. After adjustment for the severity of disease, no significant difference with respect to the global quality of life was found between AS and the curative treatment options over the long term. The study physicians drew a clear distinction between curative and palliative treatment strategies, and the inclusion criteria for AS were largely respected. The observed preference for surgery in low-risk patients indicates overtreatment in this patient 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

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. 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. 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. 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 Incidental Prostate Cancer by Active Surveillance: Results of the HAROW Study

Objective: To report on a cohort of patients with incidental prostate cancer (IPC) that was treated by an active surveillance (AS) protocol in the HAROW study. Materials and Methods: The HAROW study is an observational study on the management of localized prostate cancer in Germany. Treating urologists were reporting clinical parameters, information on therapy and clinical course of disease at 6-month intervals. Results: In total, 3,169 patients were enrolled. In 224 patients were found an IPC and 104 (46%) of them were put on an AS protocol. The mean follow-up was 26.5 months. Tumor progression was noted in 16 patients. In 11 patients, AS was replaced by a definite intervention. In univariate and multivariate analyses, only PSA density correlated with progression. Conclusion: This is the first prospective description of an IPC patient cohort on AS as part of an outcomes research study. AS was selected as a therapeutic strategy in nearly half of the patients (46%). Only a minor proportion (16%) displayed progression. Of the clinical parameters, only PSA density correlated with progression.

PCN171 - Quality of Life (QOL) During Treatment of Newly Diagnosed Locally Confined Low-Risk Prostate Cancer (LCLRPC) in Germany: Results of the Harow Study

PCN171 - Quality of Life (QOL) During Treatment of Newly Diagnosed Locally Confined Low-Risk Prostate Cancer (LCLRPC) in Germany: Results of the Harow Study

PCN129 - Cost-Minimization Analysis (CMA) of Different Strategies to Treat Newly Diagnosed Locally Confined Low-Risk Prostate Cancer (LCLRPC) in Germany: Results of the Harow Study

PCN129 - Cost-Minimization Analysis (CMA) of Different Strategies to Treat Newly Diagnosed Locally Confined Low-Risk Prostate Cancer (LCLRPC) in Germany: Results of the Harow Study

PCN136 - Cost-Utility Analysis (CUA) of Different Strategies to Treat Newly Diagnosed Locally Confined Low-Risk Prostate Cancer (LCLRPC) in Germany: Results of the Harow Study

PCN136 - Cost-Utility Analysis (CUA) of Different Strategies to Treat Newly Diagnosed Locally Confined Low-Risk Prostate Cancer (LCLRPC) in Germany: Results of the Harow Study

272 The HAROW study – an observational health service study, capturing current low-risk-prostate cancer treatment practice patterns in Germany

272 The HAROW study – an observational health service study, capturing current low-risk-prostate cancer treatment practice patterns in Germany