Ulrica Wilderäng

Urinary Incontinence and Erectile Dysfunction After Robotic Versus Open Radical Prostatectomy: A Prospective, Controlled, Nonrandomised Trial

BACKGROUND Robot-assisted laparoscopic radical prostatectomy (RALP) has become widely used without high-grade evidence of superiority regarding long-term clinical outcomes compared with open retropubic radical prostatectomy (RRP), the gold standard. OBJECTIVE To compare patient-reported urinary incontinence and erectile dysfunction 12 mo after RALP or RRP. DESIGN, SETTING, AND PARTICIPANTS This was a prospective, controlled, nonrandomised trial of patients undergoing prostatectomy in 14 centres using RALP or RRP. Clinical-record forms and validated patient questionnaires at baseline and 12 mo after surgery were collected. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES Odds ratios (ORs) were calculated with logistic regression and adjusted for possible confounders. The primary end point was urinary incontinence (change of pad less than once in 24h vs one time or more per 24h) at 12 mo. Secondary end points were erectile dysfunction at 12 mo and positive surgical margins. RESULTS AND LIMITATIONS At 12 mo after RALP, 366 men (21.3%) were incontinent, as were 144 (20.2%) after RRP. The unadjusted OR was 1.08 (95% confidence interval [CI], 0.87–1.34). Erectile dysfunction was observed in 1200 men (70.4%) 12 mo after RALP and 531 (74.7%) after RRP. The unadjusted OR was 0.81 (95% CI, 0.66–0.98). CONCLUSIONS In a Swedish setting, RALP for prostate cancer was modestly beneficial in preserving erectile function compared with RRP, without a statistically significant difference regarding urinary incontinence or surgical margins. PATIENT SUMMARY We compared patient-reported urinary incontinence after prostatectomy with two types of surgical technique. There was no statistically significant improvement in the rate of urinary leakage, but there was a small improvement regarding erectile function after robot-assisted operation.

LAPPRO: A prospective multicentre comparative study of robot-assisted laparoscopic and retropubic radical prostatectomy for prostate cancer

Abstract Objective. This study describes the study design and procedures for a prospective, non-randomized trial comparing open retropubic and robot-assisted laparoscopic radical prostatectomy regarding functional and oncological outcomes. Material and methods. The aim was to achieve a detailed prospective registration of symptoms experienced by patients using validated questionnaires in addition to documentation of surgical details, clinical examinations, medical facts and resource use. Four patient questionnaires and six case-report forms were especially designed to collect data before, during and after surgery with a follow-up time of 2 years. The primary endpoint is urinary leakage 1 year after surgery. Secondary endpoints include erectile dysfunction, oncological outcome, quality of life and cost-effectiveness at 3, 12 and 24 months after surgery. Results. The study started in September 2008 with accrual continuing to October 2011. Twelve urological departments in Sweden well established in performing radical prostatectomy are participating. Personal contact with the participating departments and patients was established to ascertain a high response rate. To reach 80% statistical power to detect a difference of 5 absolute per cent in incidence of urinary leakage, 700 men in the retropubic group and 1400 in the robotic group are needed. Conclusions. The Swedish healthcare context is well suited to performing multicentre long-term prospective clinical trials. The similar care protocols and congruent specialist training are particularly favourable. The LAPPRO trial aims to compare the two surgical techniques in aspects of short- and long-term functional and oncological outcome, cost effectiveness and quality of life, supplying new knowledge to support future decisions in treatment strategies for prostate cancer.

Tobacco smoking and long-lasting symptoms from the bowel and the anal-sphincter region after radiotherapy for prostate cancer

BACKGROUND AND PURPOSE Tobacco smoking can cause vascular injury, tissue hypoxia and fibrosis as can ionizing radiation. However, we do not know if tobacco smoking increases the risk of long-term side effects after radiotherapy for prostate cancer. METHODS We identified 985 men treated with radiotherapy for prostate cancer between 1993 and 2006. In 2008, long-lasting symptoms appearing after radiotherapy for prostate cancer were assessed through a study-specific questionnaire as were smoking habits and demographic factors of all these men. In the questionnaire the prostate-cancer survivors were asked to report symptom occurrence the previous six months. RESULTS We obtained information on tobacco smoking from 836 of the 985 prostate-cancer survivors with a median time to follow-up of six years (range 2-14 years). The prevalence ratio of defecation urgency among current smokers compared to never smokers was 1.6 (95% CI 1.2-2.2). Corresponding prevalence ratio for diarrhea was 2.8 (95% CI 1.2-6.5), the sensation of bowel not completely emptied after defecation 2.1 (95% CI 1.3-3.3) and for sudden emptying of all stools into clothing without forewarning 4.7 (95% CI 2.3-9.7). CONCLUSION Tobacco smoking among prostate-cancer survivors treated with radiotherapy increases the risk of certain long-lasting symptoms from the bowel and anal-sphincter region.

Late symptoms in long-term gynaecological cancer survivors after radiation therapy: a population-based cohort study

Background:We surveyed the occurrence of physical symptoms among long-term gynaecological cancer survivors after pelvic radiation therapy, and compared with population-based control women.Methods:We identified a cohort of 789 eligible gynaecological cancer survivors treated with pelvic radiation therapy alone or combined with surgery in Stockholm or Gothenburg, Sweden. A control group of 478 women was randomly sampled from the Swedish Population Registry. Data were collected through a study-specific validated postal questionnaire with 351 questions concerning gastrointestinal and urinary tract function, lymph oedema, pelvic bones and sexuality. Clinical characteristics and treatment details were retrieved from medical records.Results:Participation rate was 78% for gynaecological cancer survivors and 72% for control women. Median follow-up time after treatment was 74 months. Cancer survivors reported a higher occurrence of symptoms from all organs studied. The highest age-adjusted relative risk (RR) was found for emptying of all stools into clothing without forewarning (RR 12.7), defaecation urgency (RR 5.7), difficulty feeling the need to empty the bladder (RR 2.8), protracted genital pain (RR 5.0), pubic pain when walking indoors (RR 4.9) and erysipelas on abdomen or legs at least once during the past 6 months (RR 3.6). Survivors treated with radiation therapy alone showed in general higher rates of symptoms.Conclusion:Gynaecological cancer survivors previously treated with pelvic radiation report a higher occurrence of symptoms from the urinary and gastrointestinal tract as well as lymph oedema, sexual dysfunction and pelvic pain compared with non-irradiated control women. Health-care providers need to actively ask patients about specific symptoms in order to provide proper diagnostic investigations and management.

Short-term Results after Robot-assisted Laparoscopic Radical Prostatectomy Compared to Open Radical Prostatectomy

BACKGROUND Robot-assisted laparoscopic radical prostatectomy has become a widespread technique despite a lack of randomised trials showing its superiority over open radical prostatectomy. OBJECTIVE To compare in-hospital characteristics and patient-reported outcomes at 3 mo between robot-assisted laparoscopic and open retropubic radical prostatectomy. DESIGN, SETTING, AND PARTICIPANTS A prospective, controlled trial was performed of all men who underwent radical prostatectomy at 14 participating centres. Validated patient questionnaires were collected at baseline and after 3 mo by independent health-care researchers. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The difference in outcome between the two treatment groups were analysed using logistic regression analysis, with adjustment for identified confounders. RESULTS AND LIMITATIONS Questionnaires were received from 2506 (95%) patients. The robot-assisted surgery group had less perioperative bleeding (185 vs 683 ml, p<0.001) and shorter hospital stay (3.3 vs 4.1 d, p<0.001) than the open surgery group. Operating time was shorter with the open technique (103 vs 175 min, p<0.001) compared with the robot-assisted technique. Reoperation during initial hospital stay was more frequent after open surgery after adjusting for tumour characteristics and lymph node dissection (1.6% vs 0.7%, odds ratio [OR] 0.31, 95% confidence interval [CI 95%] 0.11-0.90). Men who underwent open surgery were more likely to seek healthcare (for one or more of 22 specified disorders identified prestudy) compared to men in the robot-assisted surgery group (p=0.03). It was more common to seek healthcare for cardiovascular reasons in the open surgery group than in the robot-assisted surgery group, after adjusting for nontumour and tumour-specific confounders, (7.9% vs 5.8%, OR 0.63, CI 95% 0.42-0.94). The readmittance rate was not statistically different between the groups. A limitation of the study is the lack of a standardised tool for the assessment of the adverse events. CONCLUSIONS This large prospective study confirms previous findings that robot-assisted laparoscopic radical prostatectomy is a safe procedure with some short-term advantages compared to open surgery. Whether these advantages also include long-term morbidity and are related to acceptable costs remain to be studied. PATIENT SUMMARY We compare patient-reported outcomes between two commonly used surgical techniques. Our results show that the choice of surgical technique may influence short-term outcomes.

Role of Magnetic Resonance Imaging in Prostate Cancer Screening: A Pilot Study Within the Göteborg Randomised Screening Trial

BACKGROUND Magnetic resonance imaging (MRI) and targeted biopsies (TB) have shown potential to more accurately detect significant prostate cancer compared with prostate-specific antigen (PSA) and systematic biopsies (SB). OBJECTIVE To compare sequential screening (PSA+MRI) with conventional PSA screening. DESIGN, SETTING, AND PARTICIPANTS Of 384 attendees in the 10th screening round of the Göteborg randomised screening trial, 124 men, median age 69.5 yr, had a PSA of ≥ 1.8 ng/ml and underwent a prebiopsy MRI. Men with suspicious lesions on MRI and/or PSA ≥ 3.0ng/ml were referred for biopsy. SB was performed blinded to MRI results and TB was performed in men with tumour-suspicious findings on MRI. Three screening strategies were compared (PSA ≥ 3.0+SB; PSA ≥ 3.0+MRI+TB and PSA ≥ 1.8+MRI+TB). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Cancer detection rates, sensitivity, and specificity were calculated per screening strategy and compared using McNemars test. RESULTS AND LIMITATIONS In total, 28 cases of prostate cancer were detected, of which 20 were diagnosed in biopsy-naïve men. Both PSA ≥ 3.0+MRI and PSA ≥ 1.8+MRI significantly increased specificity compared with PSA ≥ 3.0+SB (0.92 and 0.79 vs 0.52; p<0.002 for both), while sensitivity was significantly higher for PSA ≥ 1.8+MRI compared with PSA ≥ 3.0+MRI (0.73 vs 0.46, p=0.008). The detection rate of significant cancer was higher with PSA ≥ 1.8+MRI compared with PSA ≥ 3.0+SB (5.9% vs 4.0%), while the detection rate of insignificant cancer was lowered by PSA ≥ 3.0+MRI (0.3% vs 1.2%). The primary limitation of this study is the small sample of men. CONCLUSION A screening strategy with a lowered PSA cut-off followed by TB in MRI-positive men seems to increase the detection of significant cancers while improving specificity. If replicated, these results may contribute to a paradigm shift in future screening. PATIENT SUMMARY Major concerns in prostate-specific antigen screening are overdiagnosis and underdiagnosis. We evaluated whether prostate magnetic resonance imaging could improve the balance of benefits to harm in prostate cancer screening screening, and we found a promising potential of using magnetic resonance imaging in addition to prostate-specific antigen.

Long-term symptoms after radiotherapy of supraclavicular lymph nodes in breast cancer patients

BACKGROUND AND PURPOSE Irradiation of the supraclavicular lymph nodes has historically increased the risk of brachial plexopathy. We report long-term symptoms after modern radiotherapy (based on 3D dose planning) in breast cancer patients with or without irradiation of the supraclavicular lymph nodes. MATERIAL AND METHODS We collected information from 814 women consecutively treated with adjuvant radiotherapy for breast cancer. The women had breast surgery with axillary dissection (AD) or sentinel node biopsy (SNB). The breast area was treated to 50 Gy in 2.0 Gy fractions. Women with >three lymph node metastases had regional radiotherapy (RRT) to the supraclavicular lymph nodes. Three to eight years after radiotherapy, they received a questionnaire asking about paraesthesia, oedema, pain, and strength in the upper limb. RESULTS Paraesthesia was reported by 38/192 (20%) after AD with RRT compared to 68/505 (13%) after AD without RRT (relative risk [RR] 1.47; 95% confidence interval [CI] 1.02-2.11) and by 9/112 (8%) after SNB without RRT (RR 2.46; 95% CI 1.24-4.90). Corresponding risks adjusted for oedema (RR 1.28; 95% CI 0.93-1.76) and (RR 1.75; 95% CI 0.90-3.39). In women ≤ 49years with AD and RRT, 27% reported paraesthesia. No significant pain or decreased strength was reported after RRT. CONCLUSION Radiotherapy to the supraclavicular lymph nodes after axillary dissection increases the occurrence of paraesthesia, mainly among younger women. When adjusted for oedema the contribution from radiotherapy is no longer formally statistically significant indicating that there is also an indirect effect mediated by the oedema.

Thromboembolic Complications in 3,544 Patients Undergoing Radical Prostatectomy with or without Lymph Node Dissection

PURPOSE Lymph node dissection in patients with prostate cancer may increase complications. An association of lymph node dissection with thromboembolic events was suggested. We compared the incidence and investigated predictors of deep venous thrombosis and pulmonary embolism among other complications in patients who did or did not undergo lymph node dissection during open and robot-assisted laparoscopic radical prostatectomy. MATERIALS AND METHODS Included in study were 3,544 patients between 2008 and 2011. The cohort was derived from LAPPRO, a multicenter, prospective, controlled trial. Data on adverse events were extracted from patient completed questionnaires. Our primary study outcome was the prevalence of deep venous thrombosis and/or pulmonary embolism. Secondary outcomes were other types of 90-day adverse events and causes of hospital readmission. RESULTS Lymph node dissection was performed in 547 patients (15.4%). It was associated with eightfold and sixfold greater risk of deep venous thrombosis and pulmonary embolism events compared to that in patients without lymph node dissection (RR 7.80, 95% CI 3.51-17.32 and 6.29, 95% CI 2.11-18.73, respectively). Factors predictive of thromboembolic events included a history of thrombosis, pT4 stage and Gleason score 8 or greater. Open radical prostatectomy and lymph node dissection carried a higher risk of deep venous thrombosis and/or pulmonary embolism than robot-assisted laparoscopic radical prostatectomy (RR 12.67, 95% CI 5.05-31.77 vs 7.52, 95% CI 2.84-19.88). In patients without lymph node dissection open radical prostatectomy increased the thromboembolic risk 3.8-fold (95% CI 1.42-9.99) compared to robot-assisted laparoscopic radical prostatectomy. Lymph node dissection induced more wound, respiratory, cardiovascular and neuromusculoskeletal events. It also caused more readmissions than no lymph node dissection (14.6% vs 6.3%). CONCLUSIONS Among other adverse events we found that lymph node dissection during radical prostatectomy increased the incidence of deep venous thrombosis and pulmonary embolism. Open surgery increased the risks more than robot-assisted surgery. This was most prominent in patients who were not treated with lymph node dissection.

Feelings of loss and uneasiness or shame after removal of a testicle by orchidectomy: a population-based long-term follow-up of testicular cancer survivors

Few data illustrate the mans reaction to orchidectomy. We investigated long-lasting feelings of loss and uneasiness or shame about the body after removal of a testicle by orchidectomy. We identified 1173 eligible men diagnosed with non-seminomatous testicular cancer treated according to the national cancer-care programmes Swedish-Norwegian Testicular Cancer Group I-IV between 1981 and 2004. We asked the survivors about feelings of loss and uneasiness or shame after having had a testicle removed by orchidectomy. We obtained information from 960 (82%) testicular cancer survivors. We found that 32% of these men miss or previously missed their removed testicle(s) and that 26% have or previously had feelings of uneasiness or shame about their body because of the removed testicle(s). Men who had never been offered a prosthesis reported feelings of loss [relative risk (RR): 2.0; 95% confidence interval (CI): 1.3-3.0] and uneasiness or shame (RR: 2.0; 95% CI: 1.3-3.2) to a higher extent than those who had been offered, but rejected a prosthesis. An orchidectomy may result in long-lasting feelings of loss and uneasiness or shame in some men; offering a testicular prosthesis may hinder this experience.

Pain and Mean Absorbed Dose to the Pubic Bone After Radiotherapy Among Gynecological Cancer Survivors

PURPOSE To analyze the relationship between mean absorbed dose to the pubic bone after pelvic radiotherapy for gynecological cancer and occurrence of pubic bone pain among long-term survivors. METHODS AND MATERIALS In an unselected, population-based study, we identified 823 long-term gynecological cancer survivors treated with pelvic radiotherapy during 1991-2003. For comparison, we used a non-radiation-treated control population of 478 matched women from the Swedish Population Register. Pain, intensity of pain, and functional impairment due to pain in the pubic bone were assessed with a study-specific postal questionnaire. RESULTS We analyzed data from 650 survivors (participation rate 79%) with median follow-up of 6.3 years (range, 2.3-15.0 years) along with 344 control women (participation rate, 72 %). Ten percent of the survivors were treated with radiotherapy; ninety percent with surgery plus radiotherapy. Brachytherapy was added in 81%. Complete treatment records were recovered for 538/650 survivors, with dose distribution data including dose-volume histograms over the pubic bone. Pubic bone pain was reported by 73 survivors (11%); 59/517 (11%) had been exposed to mean absorbed external beam doses <52.5 Gy to the pubic bone and 5/12 (42%) to mean absorbed external beam doses ≥ 52.5 Gy. Thirty-three survivors reported pain affecting sleep, a 13-fold increased prevalence compared with control women. Forty-nine survivors reported functional impairment measured as pain walking indoors, a 10-fold increased prevalence. CONCLUSIONS Mean absorbed external beam dose above 52.5 Gy to the pubic bone increases the occurrence of pain in the pubic bone and may affect daily life of long-term survivors treated with radiotherapy for gynecological cancer.