Pär Lodding

Mortality results from the Göteborg randomised population-based prostate-cancer screening trial

BACKGROUND Prostate cancer is one of the leading causes of death from malignant disease among men in the developed world. One strategy to decrease the risk of death from this disease is screening with prostate-specific antigen (PSA); however, the extent of benefit and harm with such screening is under continuous debate. METHODS In December, 1994, 20,000 men born between 1930 and 1944, randomly sampled from the population register, were randomised by computer in a 1:1 ratio to either a screening group invited for PSA testing every 2 years (n=10,000) or to a control group not invited (n=10,000). Men in the screening group were invited up to the upper age limit (median 69, range 67-71 years) and only men with raised PSA concentrations were offered additional tests such as digital rectal examination and prostate biopsies. The primary endpoint was prostate-cancer specific mortality, analysed according to the intention-to-screen principle. The study is ongoing, with men who have not reached the upper age limit invited for PSA testing. This is the first planned report on cumulative prostate-cancer incidence and mortality calculated up to Dec 31, 2008. This study is registered as an International Standard Randomised Controlled Trial ISRCTN54449243. FINDINGS In each group, 48 men were excluded from the analysis because of death or emigration before the randomisation date, or prevalent prostate cancer. In men randomised to screening, 7578 (76%) of 9952 attended at least once. During a median follow-up of 14 years, 1138 men in the screening group and 718 in the control group were diagnosed with prostate cancer, resulting in a cumulative prostate-cancer incidence of 12.7% in the screening group and 8.2% in the control group (hazard ratio 1.64; 95% CI 1.50-1.80; p<0.0001). The absolute cumulative risk reduction of death from prostate cancer at 14 years was 0.40% (95% CI 0.17-0.64), from 0.90% in the control group to 0.50% in the screening group. The rate ratio for death from prostate cancer was 0.56 (95% CI 0.39-0.82; p=0.002) in the screening compared with the control group. The rate ratio of death from prostate cancer for attendees compared with the control group was 0.44 (95% CI 0.28-0.68; p=0.0002). Overall, 293 (95% CI 177-799) men needed to be invited for screening and 12 to be diagnosed to prevent one prostate cancer death. INTERPRETATION This study shows that prostate cancer mortality was reduced almost by half over 14 years. However, the risk of over-diagnosis is substantial and the number needed to treat is at least as high as in breast-cancer screening programmes. The benefit of prostate-cancer screening compares favourably to other cancer screening programs. FUNDING The Swedish Cancer Society, the Swedish Research Council, and the National Cancer Institute.

CHARACTERISTICS OF SCREENING DETECTED PROSTATE CANCER IN MEN 50 TO 66 YEARS OLD WITH 3 TO 4 NG./ML. PROSTATE SPECIFIC ANTIGEN

PURPOSE We defined the yield and nature of prostate cancer in the setting of population based, randomized prostate specific antigen (PSA) guided screening in men with PSA levels between 3 and 4 ng./ml. who were 50 to 65 years old at the time of randomization. MATERIALS AND METHODS Sextant biopsies were performed in 243 men with PSA of 3 to 4 ng./ml. Therapy decisions were based on core cancer length, histological grade and life expectancy. RESULTS Of the men 32 (13.2%) had prostate cancer constituting 23% of all of the 137 prostate cancers to data detected in the first round of our screening study. Age and PSA were similar in men with and without prostate cancer. Men with prostate cancer had significantly lower free PSA and free-to-total PSA ratio, and higher PSA density. Cancer was clinical stage T1c in 27 cases and stage T2 in 5. Hypoechoic areas were noted at transrectal ultrasound in 10 cases. Digital rectal examination and transrectal ultrasound were normal in 21 cases (66%). To date 14 patients have undergone prostatectomy. Surgical specimens showed a mean tumor volume of 1.8 cc (range 0.6 to 4.4) and significant amounts of high grade tumor were present in only 3 cases. Margins were positive in 5 cases, and pathological stage was pT2 in 8 cases and pT3 in 6. CONCLUSIONS By lowering the PSA cutoff from 4 to 3 ng./ml. an increase in cancer detection by 30% was achieved. While the addition of free-to-total ratio and PSA density may reduce the number of biopsies by about 15% with sensitivity maintained at 90%, systematic sextant biopsies were necessary in most of these mean as 66% of the tumors were negative on transrectal ultrasound and digital rectal examination. The majority of these cancers were clinically significant and suitable for curative treatment. If therapy decisions are based on the pathological findings of the biopsies, the risk of treating insignificant cancers seems low.

Results of a randomized, population-based study of biennial screening using serum prostate-specific antigen measurement to detect prostate carcinoma.

The purpose of the current study was to evaluate the effectiveness of a prostate carcinoma screening program in which serum prostate‐specific antigen (PSA) levels were measured.

INGUINAL HERNIA AFTER RADICAL RETROPUBIC PROSTATECTOMY FOR PROSTATE CANCER: A STUDY OF INCIDENCE AND RISK FACTORS IN COMPARISON TO NO OPERATION AND LYMPHADENECTOMY

PURPOSE The incidence, mechanisms and risk factors of inguinal hernia after radical retropubic prostatectomy are sparsely elucidated in the literature. We determined the rate of inguinal hernia after radical retropubic prostatectomy and compared it to the incidence in patients with prostate cancer who did not undergo operation or underwent only pelvic lymph node dissection. MATERIALS AND METHODS We followed 375, 184 and 65 men who underwent radical retropubic prostatectomy plus pelvic lymph node dissection, pelvic lymph node dissection only and no surgery with respect to inguinal hernia for a mean of 39, 47 and 45 months, respectively. The prostatectomy group was also evaluated in regard to the potential risk factors of previous hernia surgery and post-prostatectomy anastomotic stricture. RESULTS The incidence of hernia was 13.6%, 7.6% and 3.1% in the prostatectomy, lymph node dissection and unoperated group, respectively. The difference was statistically significant in the prostatectomy and unoperated groups according to the Mantel-Cox log rank test and Cox proportional hazards rate. Previous hernial surgery and post-prostatectomy anastomotic stricture were more common in patients with an inguinal hernia after prostatectomy. CONCLUSIONS The incidence of inguinal hernia is clearly increased in men who have undergone radical retropubic prostatectomy plus pelvic lymph node dissection compared with those who undergo no surgery for prostate cancer. Inguinal hernia appears to develop more often in men with prostate cancer who undergo radical retropubic prostatectomy and pelvic lymph node dissection than in those who undergo pelvic lymph node dissection only. While surgical factors trigger hernial development, previous hernial surgery and post-prostatectomy anastomotic stricture may be important risk factors. In fact, the latter may largely explain the difference in the incidence of inguinal hernia in our lymph node dissection and prostatectomy groups. Prophylactic surgical procedures must be evaluated to address this problem.

Would prostate cancer detected by screening with prostate-specific antigen develop into clinical cancer if left undiagnosed? A comparison of two population-based studies in Sweden.

Objective To assess the risk of over‐diagnosing and over‐treating prostate cancer if population‐based screening with serum prostate‐specific antigen (PSA) is instituted.

Population-based screening for prostate cancer by measuring free and total serum prostate-specific antigen in Sweden

To report the initial results from Sweden of a large population‐based randomized study of screening using prostate‐specific antigen (PSA) to detect prostate cancer, as the efficacy of such screening to decrease prostate cancer mortality has not yet been proven.

Bicalutamide 150 mg in addition to standard care for patients with early non-metastatic prostate cancer Updated results from the Scandinavian Prostate Cancer Period Group-6 Study after a median follow-up period of 7.1 years

Objective. The Early Prostate Cancer (EPC) programme is evaluating the efficacy and tolerability of bicalutamide following standard care (radiotherapy, radical prostatectomy or watchful waiting) in patients with localized (T1–2, N0/N×) or locally advanced (T3–4, any N; or any T, N + ) non-metastatic prostate cancer. Herein we report the latest findings after a median follow-up period of 7.1 years from the Scandinavian Prostate Cancer Group (SPCG)-6 study, one of three trials in the EPC programme. Material and methods. A total of 1218 patients were randomized on a 1:1 basis to either bicalutamide 150 mg/day (n=607) or placebo (n=611) following standard care; 81.4% were followed conservatively (watchful waiting). The primary endpoints were objective progression-free survival (PFS) and overall survival (OS). Results. In patients with localized disease there was no significant difference in PFS [hazard ratio (HR) 0.85; 95% CI 0.69–1.06; p=0.15] and a trend towards decreased OS with bicalutamide plus standard care compared with standard care alone (HR 1.23; 95% CI 0.96–1.58; p=0.11). In patients with locally advanced disease, bicalutamide significantly improved PFS, reducing the risk of progression by 53% compared with standard care alone (HR 0.47; 95% CI 0.37–0.59; p<0.001). The median time to progression was 8.8 years for bicalutamide plus standard care and 7.1 years for standard care alone. There was a significant improvement in OS with bicalutamide plus standard care, with a reduction in the risk of death of 35% versus standard care alone (HR 0.65; 95% CI 0.50–0.85; p=0.001). Conclusion. This analysis of the SPCG-6 study showed that bicalutamide plus standard care offers significant PFS and OS benefits for patients with locally advanced disease, but not for those with localized disease.

Outcome of Laterally Directed Sextant Biopsies of the Prostate in Screened Males Aged 50–66 Years

Objective: Prostate cancer has its most frequent location in the posterior–lateral part of the gland. The aim of this study was to evaluate the cancer detection rate of six systemic prostate biopsies with mid lobar biopsies taken far laterally in the prostate. Patients and Methods: A total of 692 patients (aged 50–66 years) enrolled in a screening study underwent prostate biopsies because of an elevated serum prostate–specific antigen (PSA; ≧3ng/ml) level. The outcome of the biopsies was related to findings at digital rectal examination (DRE) and transrectal ultrasound (TRUS) and to the location within the prostate. Results: Prostate cancer was detected in 164 patients. DRE and TRUS were suspicious of malignancy in 66 cases (40%) and 84 cases (51%), respectively. The two biopsies taken far laterally midlobar in the prostate detected as many as 83% of the cancers and when combined with two apical biopsies, 96% of all cancers were detected. Conclusion: At PSA screening in this age–group, only 57% of the prostate cancers detectable by sextant biopsies were palpable or visible at TRUS. Most of the cancers (96%) were detectable by only four systematic, carefully directed biopsies. In men with normal DRE, the two lateral midlobar biopsies should be taken first during the biopsy procedure.

Hyperbaric Oxygen Treatment in Radiation-Induced Cystitis and Proctitis: A Prospective Cohort Study on Patient-Perceived Quality of Recovery

PURPOSE In this prospective cohort study, the effects of hyperbaric oxygen treatment (HBOT) were evaluated concerning patient-perceived symptoms of late radiation-induced cystitis and proctitis secondary to radiation therapy for pelvic cancer. METHODS AND MATERIALS Thirty-nine patients, 35 men and 4 women with a mean age of 71 (range, 35-84) years were included after informed consent and institutional ethics approval. They had all been treated with radiation therapy for prostate (n=34), cervix (n=2), or rectal (n=3) cancer using external beam radiation at a dose of 25 to 75 Gy. Patients with hematuria requiring blood transfusion were excluded. The HBOT was delivered with 100% oxygen for 90 minutes at 2.0 to 2.4 atmospheres (ATA). Mean number of treatments was 36 (28-40). Symptoms were prospectively assessed using the Expanded Prostate Index Composite score before, during, and 6 to 12 months after HBOT. RESULTS The HBOT was successfully conducted, and symptoms were alleviated in 76% for patients with radiation cystitis, 89% for patients with radiation proctitis, and 88% of patients with combined cystitis and proctitis. Symptom reduction was demonstrated by an increased Expanded Prostate Index Composite score in the urinary domain from 50±16 to 66±20 after treatment (P<.001) and in the bowel domain from 48±18 to 68±18 after treatment (P<.001). For 31% of the patients with cystitis and 22% with proctitis, there were only trivial symptoms after HBOT. The improvement was sustained at follow-up in both domains 6 to 12 months after HBOT. No severe side effects were observed related to HBOT, and treatment compliance was high. CONCLUSIONS HBOT can be an effective and safe treatment modality for late radiation therapy-induced soft tissue injuries in the pelvic region.

Primary Carcinoid Tumour with Ossification Masquerading as Calyx Stone in a Horseshoe Kidney

A case of renal carcinoid tumour arising within a teratoma in a horseshoe kidney in a 23-year-old male is reported. The presenting symptom was abdominal pain, and bone tissue within the tumour was initially misinterpreted as a calyx stone, leading to unsuccessful attempts at extracorporeal shock-wave lithotripsia and percutaneous lithotripsia. This unusual tumour is over-represented in patients with horseshoe kidney and other congenital developmental renal defects.