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PubMed1998

A randomised, placebo controlled trial of inhaled salbutamol and beclomethasone for recurrent cough.

AIMS: To test the hypothesis that inhaled salbutamol or beclomethasone will reduce the frequency of cough in children with recurrent cough. A secondary aim was to determine if the presence of airway hyperresponsiveness (AHR) can predict the response. DESIGN: Randomised, double blind, placebo controlled trial. METHODS: During a coughing phase, 43 children (age 6-17 years) with recurrent cough were randomised to receive inhaled salbutamol or placebo (phase I) for 5-7 days and then beclomethasone or placebo (phase II) for 4-5 weeks, and in a subgroup of children for 8-9 weeks. The children used an ambulatory cough meter, kept cough diaries, and performed the capsaicin cough sensitivity, hypertonic saline bronchoprovocation, and skin prick tests. RESULTS: Salbutamol or beclomethasone had no effect on cough frequency or score, irrespective of the presence of AHR. CONCLUSIONS: Most children with recurrent cough without other evidence of airway obstruction, do not have asthma and neither inhaled salbutamol nor beclomethasone is beneficial.

Administration, Inhalation↗
PubMed2006

Treatment of esophageal achalasia with Heller myotomy: retrospective evaluation of patient satisfaction and disease-specific quality of life.

BACKGROUND: Prospective randomized studies have suggested that surgery palliates esophageal achalasia more effectively than pneumatic dilatation, but for some dilatation is still the procedure of choice for initial treatment. We decided to compare achalasia symptoms before and after Heller myotomy by means of postoperative questionnaires. METHODS: The study included 22 patients who underwent Heller myotomy for achalasia at the Hotel Dieu Hospital, Queen's University, Kingston, Ont., since July 1990; 5 of them required repeat myotomy for symptom recurrence, for a total of 9 open and 18 laparoscopic procedures. Median follow-up was 43 (range 6-109) months. Preoperative and postoperative data regarding dysphagia, regurgitation, chest pain and overall patient satisfaction were gathered. Symptom scores were calculated by adding severity (0 = none, 2 = mild, 4 = moderate, 6 = severe) to frequency (0 = never, 1 = occasionally, 2 = once a month, 3 = every week, 4 = twice a week, 5 = daily). Patients having a repeat procedure were instructed to evaluate symptoms with respect to their initial myotomy. RESULTS: Seventeen (77%) patients were successfully contacted, 4 of them had subsequent repeat myotomy for symptom recurrence. Initially, overall symptom scores decreased for all but 1 patient, with mean preoperative and postoperative values of 23.1 and 7.3 respectively (p < 0.001). The patient in whom symptoms did not improve is a candidate for a repeat procedure. Repeat myotomy was performed after a median of 38 (range 23-75) months, corresponding to an overall 3-year positive outcome in 13 (76%) of the 17 patients. Fifteen (88%) patients considered their myotomies a success and 16 (94%) would choose to have this procedure again given the outcome. CONCLUSION: Heller myotomy appears to be effective in alleviating the symptoms of achalasia. Repeat myotomy is occasionally required.

Adult↗
PubMed2005

Combined linkage and association analyses of the 124-bp allele of marker D2S2944 with anxiety, depression, neuroticism and major depression.

A central issue in psychiatric genetics is whether positive findings replicate. Zubenko et al. (2002b, Mol. Psychiatry 7:460-467) reported an association of the 124-bp allele of D2S2944 with recurrent early-onset major depression for females. We tested for association of this allele to continuous measures of anxiety, depression and neuroticism in a Dutch sample of 347 males and 448 females, and to DSM-IV major depression in a subsample of 210 males and 295 females. The association of the 124-bp allele to depression in females was not replicated, but there were significant associations (not significant after correction for multiple testing) with anxiety and anxious depression in males. However, the association occurred in the absence of evidence for linkage in this region on chromosome 2.

Anxiety↗
PubMed2003

Impact of intraoperative radiation on postoperative and disease-specific outcome after pancreatoduodenectomy for adenocarcinoma: a propensity score analysis.

For periampullary cancer,intraoperative radiation therapy (IORT) administered to the site with the highest locoregional recurrence risk carries the rationale to improve tumor control. An IORT effect on survival remains unclear. IORT impact on postoperative outcomes after pancreatectomy for adenocarcinoma was analyzed, with a specific attempt to correct for the nonrandom IORT treatment assignment, and to account for treatment group imbalances in the interpretation of outcome differences. A propensity-score-adjusted analysis, based on variable selection by logistic regression, was used to rebalance treatments. Between 1989 and 1999, 61 patients underwent partial or total pancreatectomy for a primary periampullary adenocarcinoma at the City of Hope National Medical Center. Diagnoses included pancreatic (n = 36), duodenal (n = 11), ampullary (n = 10), and bile duct cancer (n = 4). Thirty patients received IORT to the resection area, with a median dose of 15 Gy (range: 10-20), followed by postoperative external beam radiation (n = 24). Mortality was 0%, the complication rate 61%. Of 33 patients with a documented recurrence, 6 had an isolated locoregional recurrence only (1 IORT versus 5 no IORT, = 0.05); the systemic recurrence pattern differed as well (IORT 94%, no IORT 67%; = 0.04). IORT had no significant impact on hospital stay (overall median: 17 days), disease-free survival (16 months), and overall survival (23 months) when adjusted for those most relevant variables reflecting IORT treatment group assignment propensity. After adjustment for relevant propensity factors, IORT was not linked to a significantly increased risk for complications, hospital stay, or survival hazard. The recurrence pattern may be affected in some patients, but systemic recurrences predominate. We continue to explore IORT in combination with systemic chemotherapy.

Adenocarcinoma↗
PubMed1994

Ovarian endometrial cysts: the role of gonadotropin-releasing hormone agonist and/or drainage.

OBJECTIVE: To evaluate the role of GnRH agonist (GnRH-a) and/or drainage in the management of large endometriomas. DESIGN: This prospective clinical study was conducted in a parallel and randomized design. SETTING: Department of Gynecology, Cliniques Universitaires St. Luc, Brussels, Belgium. PATIENTS: Eight infertile women with laparoscopically confirmed ovarian endometriotic cysts. After laparoscopic drainage of the ovarian cyst, patients were randomized. Patients in group I (n = 40) received no therapy. Patients in group II (n = 40) received GnRH-a therapy for 12 weeks. A second-look laparoscopy was performed after 12 weeks in each woman. RESULTS: After drainage, a quick recurrence of the endometrial cyst was observed in only group I. Indeed, the score and the cyst size were similar to the values observed before the first laparoscopy. In group II, a significant decrease in score and cyst diameter was observed. Ovarian biopsies revealed significant reduction in the stromal vascularization and a significant reduction in the mitotic activity in the group of women treated with GnRH-a. CONCLUSION: The quick recurrence of the ovarian cyst after drainage proved that drainage alone is ineffective. Drainage followed by GnRH-a was effective in the reduction of cyst size and the glandular mitotic activity.

Adult↗
PubMed2006

Laparoscopic radical prostatectomy in men older than 70 years of age with localized prostate cancer: comparison of morbidity, reconvalescence, and short-term clinical outcomes between younger and older men.

OBJECTIVES: To analyze the safety and efficacy of extraperitoneal laparoscopic radical prostatectomy (eL-RPE) in elderly versus younger men with localized prostate cancer. METHODS: Patients undergoing eL-RPE were retrospectively subdivided into group eL-RPE1 (72 men aged 71 yr and older) and group eL-RPE2 (132 men aged 59 yr and younger). Group eL-RPE1 was compared with a group of 70 contemporary, comparable patients aged 71 yr and older undergoing open retropubic radical prostatectomy (group OPEN-RPE). RESULTS: Compared with group eL-RPE2, patients of group eL-RPE1 had a higher pathologic stage (45% vs. 32% stage pT3 or greater, p<0.001) and higher Gleason score (median 7 vs. 6, p<0.001). Prostate-specific antigen recurrence was significantly worse compared with age-matched controls for younger patients with high-stage or high-grade lesions (p<0.001). Importantly operative time, analgesic requirements, hospital stay, convalescence, and complication rates were comparable. Urinary continence rate was significantly better in group eL-RPE2 at 6 mo (67% vs. 91%, respectively, p<0.001). Group eL-RPE1 and group OPEN-RPE patients had statistically similar pathologic stage and Gleason score (each p>0.05), similar operative time (p=0.12), but less blood loss (p<0.001), shorter hospital stay (p<0.001), and more rapid convalescence (p<0.001) occurred in eL-RPE1. CONCLUSIONS: eL-RPE is feasible and efficacious even in elderly patients with unfavorable, large-volume disease. eL-RPE offers the advantages of decreased blood loss, shorter hospital stay, and more rapid recovery over OPEN-RPE. However, the elderly patient must be informed preoperatively about the observed higher incontinence rate.

Age Factors↗
PubMed1992

[Emergency surgery of a case of perforated gastroduodenal ulcer].

Surgical treatment of acute perforated gastric and duodenal ulcer is connected to high postoperative lethality. By emergency procedure it has to be decided between performing a simple closure or performing initially a definitive operation to control the peptic disease. The therapeutic options at our institution are based on a severity score which includes patient's age, associated pathology, grade of the peritonitis, delay between the onset of symptom and surgery, history of ulcer disease. Charts of 90 patients consecutively operated during 6 years for acute perforated ulcer were analysed. The average age was 65.5 years, the operation was performed within 6 h in 47.3% of the patients. To perform or not a definitive operation is an important therapeutic option as by simple closure 45% recurrence is observed with a lethality of 36%. Based on our scoring system, 87.9% of all the patients underwent definitive operation. The lethality rate of this series of nonselected patients (52% were older than 70 years) was low: 6.3%. The use of the severity score help to choose patients to be treated by simple closure and patients which may be submitted to definitive emergency operation with low operative risk.

Adult↗
PubMed2001

Impact of complementary oral enzyme application on the postoperative treatment results of breast cancer patients--results of an epidemiological multicentre retrolective cohort study.

PURPOSE: [corrected] To evaluate the impact of postoperative treatment with an oral enzyme (OE) preparation given complementary to an antineoplastic therapy in patients with breast cancer. METHODS: The design of this epidemiological study was a retrolective cohort analysis with parallel groups. Design and conduct of the study were performed to current standards for prospective, controlled clinical trials. A cohort of 2,339 breast cancer patients undergoing surgical intervention and radio-, chemo- or hormonal therapy were studied in 216 centres. Of the 2,339 patients, 1,283 received complementary treatment with OE and 1,056 did not receive OE. Patients with other complementary medications were excluded and the final analysis was performed with the data from 649 patients, of whom 239 (37%) were additionally treated with OE (test group) and 410 (63%) without OE (control group). The median follow-up time for the test group was 485 days and for the control group 213 days. The primary endpoint of the study was to determine whether complementary treatment with OE can reduce typical disease- or therapy-associated signs and symptoms (gastrointestinal symptoms, mental symptoms, dyspnoea, headache, tumour pain, cachexia, skin disorders, infections, and side effects associated with the antineoplastic therapy) in patients with breast cancer. Imbalances for causal effects (covariates) were adjusted for by means of the propensity score. Outcome analysis was performed by estimating the linear regression between change in symptom score and propensity score with all data and using this regression line to calculate the change in symptom score which would be expected for each patient. Tumour-associated events (recurrence, metastasis, and death) were evaluated in terms of the number of events observed and time to event. The safety of treatment with OE was analysed in terms of the number and severity of adverse events, their duration, treatment and outcome. RESULTS: For all symptoms except tumour pain, the adjusted mean improvement in symptom scores was larger in the test group than in the control group. The adjusted difference was statistically significant for all symptoms, except tumour pain and infections. The results show that the typical disease- and therapy-associated signs and symptoms in patients on complementary therapy with OE during postoperative treatment were significantly less. For 75% of the test group and 55% of the control group the physician recorded "no signs and symptoms". A clear reduction in the side effects of radiotherapy and chemotherapy was documented in 74% of the test group and 55% of the control group. Analysis of survival, recurrence, and metastasis demonstrated a reduced number of events in the test group. There was evidence of a beneficial influence of OE on time to event, although the median observation time was too short in these breast cancer patients to draw definite conclusions. The safety component was judged in 98% of the test group and 76% of the control group as "very good" or "good". In the total sample of 2,339 patients, the rate of OE-associated adverse reactions was 3.2%. All side effects were mild to moderate gastrointestinal symptoms. CONCLUSION: Complementary treatment of breast cancer patients with OE improves the quality of life by reducing signs and symptoms of the disease and the side effects of adjuvant antineoplastic therapies. This epidemiological retrolective cohort analysis provides evidence that the patients may also gain benefit by a prolongation of the time to event for cancer recurrence, metastasis and survival. OE was generally well tolerated.

Adolescent↗
PubMed2005

Day-case endoscopic totally extraperitoneal inguinal hernioplasty versus open Lichtenstein hernioplasty for unilateral primary inguinal hernia in males: a randomized trial.

BACKGROUND: Endoscopic totally extraperitoneal inguinal hernioplasty (TEP) is an accepted technique for the repair of recurrent and bilateral inguinal hernia, but its role in the management of unilateral primary inguinal hernia remains controversial. The current randomized trial was undertaken to compare the postoperative and 1-year outcomes of day-case TEP and open Lichtenstein hernioplasty for unilateral primary inguinal hernia in males. METHODS: From January 2002 to January 2004, a total of 200 male patients were randomized to undergo either day-case unilateral TEP or open Lichtenstein hernioplasty under general anesthesia. The primary outcome measures included postoperative pain score, time until return to work, incidence of chronic groin pain, and recurrence rate 1 year after the operation. RESULTS: All TEP procedures were successfully performed without conversion. The mean operation time for TEP (50 +/- 13.2 min) was significantly shorter than for open Lichtenstein hernioplasty (58 +/- 17.6 min) (p < 0.001). The pain score at rest was significantly lower in the TEP group than in the open group on postoperative days 0, 1, 4, 5, and 6. On the average, the patients returned to work 8.6 days after TEP and 14 days after Lichtenstein hernioplasty (p = 0.006). Postoperative recovery and morbidity rates were otherwise comparable between the two groups. The incidence of chronic groin pain 1 year after TEP (9.9%) was significantly lower than after open surgery (21.7%) (p = 0.032). None of the patients in either group showed recurrence at the last follow-up assessment. CONCLUSIONS: Day-case TEP was superior to open Lichtenstein hernioplasty for the repair of unilateral primary inguinal hernia in males. The benefits of day-case TEP included less postoperative pain, a faster return to work, and a lower incidence of chronic groin pain.

Adult↗
PubMed2002

Breast conservation treatment in Hong Kong-early results of 203 patients: retrospective study.

OBJECTIVE: To study the clinical outcomes of patients with invasive or non-invasive breast cancer after breast conservation treatment. DESIGN: Retrospective study. SETTING: Clinical oncology department of a public hospital, Hong Kong. PATIENTS: Two hundred and three patients who received postlumpectomy radiotherapy at the Pamela Youde Nethersole Eastern Hospital between January 1994 and June 1999. INTERVENTIONS: Adjuvant radiotherapy with or without systemic adjuvant treatment. MAIN OUTCOME MEASURES: Actuarial local control rate, progression-free survival rate, disease-specific survival rate, and cosmetic score. RESULTS: The median follow-up was 3.5 years. Two of the 25 patients with carcinoma in situ only developed local recurrence; the 5-year actuarial local control rate was 91.3%. Among the 178 patients with invasive cancer, seven had a local recurrence and 12 developed distant metastases without local failure. The 5-year actuarial local control, progression-free survival, and disease-specific survival rates for patients with invasive cancer were 95.5%, 85.8%, and 95.2%, respectively. The risk of local recurrence was significantly increased for younger patients (age <40 years) and those with positive final margins. Cosmetic scores were rated good to excellent by 95.6% of patients. CONCLUSIONS: The early clinical outcomes of these patients are comparable to those in large overseas trials, which have demonstrated the equivalence of mastectomy and breast conservation treatment in terms of survival. In addition to mastectomy, with or without breast reconstruction, breast conservation treatment should be offered as an alternative to suitable Chinese women. To maximise local control, further excision or mastectomy is recommended for patients with positive final margins.

Adult↗
PubMed1997

Increasing prostate-specific antigen profile following definitive radiation therapy for localized prostate cancer: clinical observations.

PURPOSE: To examine the natural history of patients who have received definitive radiation therapy alone for clinically localized prostate cancer and have an increasing prostate-specific antigen (PSA) profile. PATIENTS AND METHODS: One hundred fifty-one men with an increasing PSA profile after definitive radiotherapy were identified. The subsequent natural history of these men, including local recurrence, distant metastasis, and survival, was examined. In 119 men, posttreatment PSA doubling times (PSADT) were calculated using linear regression. Cox regression models were used to examine the effect of clinical and treatment variables on clinical failure and survival. RESULTS: Patients with high pretreatment PSA values, high Gleason scores, and T3 tumors were more likely to develop a PSA elevation. The median calculated post-treatment PSADT was 13 months, and 95% of patients had posttreatment PSADT of less than 3 years. PSADT was correlated with tumor stage and Gleason score. Five years after PSA elevation, the estimated rate of clinical local recurrence is 26% and the estimated rate of distant metastases is 47%. Rapid PSADT (< 12 months) and a short interval from the end of treatment to PSA elevation (< 12 months) were significant independent predictors of distant metastases. The estimated rates of overall and cause-specific survival 5 years after PSA elevation are 65% and 76%, respectively. Gleason grade is the only significant independent predictor of overall and cause-specific survival after PSA elevation. CONCLUSION: The natural history of men who have an increasing PSA profile following definitive radiotherapy is heterogeneous. In the absence of salvage therapy, at least three quarters of men will have clinical evidence of recurrent disease 5 years after a PSA elevation is detected. Men with a rapid posttreatment PSADT and a short interval from the end of treatment to an increasing PSA profile are at a very high risk of developing distant metastasis within 5 years of PSA elevation.

Actuarial Analysis↗
PubMed2002

Clinical utility of percent prostate needle biopsy tissue with cancer cutpoints to risk stratify patients before radical prostatectomy.

OBJECTIVES: The percentage of total prostate needle biopsy tissue with cancer was previously found to be a stronger predictor of biochemical failure after radical prostatectomy (RP) than either biopsy Gleason score or serum prostate-specific antigen (PSA). To improve our ability to predict preoperatively the risk of biochemical recurrence after RP, we sought to determine the cutpoints of the percentage of biopsy tissue with cancer to separate patients into low, intermediate, or high-risk groups. We then examined whether we could further stratify low, intermediate, and high-risk groups (on the basis of the PSA level and biopsy Gleason score) using the percentage of prostate needle biopsy tissue with cancer. METHODS: A single pathologist reviewed the prostate needle biopsy specimens of 217 men who underwent RP between 1991 and 2001. Biopsy specimens were examined for Gleason score and the percentage of total biopsy tissue with cancer. Cutpoints were identified to define patients with differing risk of biochemical recurrence after RP. These cutpoints were applied to low, intermediate, and high-risk patients, on the basis of PSA and biopsy Gleason score, to determine whether preoperative risk stratification could be improved. RESULTS: Using the cutpoints for the percentage of prostate needle biopsy tissue with cancer of less than 20% (low risk), 20% to less than 55% (intermediate risk), and 55% or greater (high risk), patients were separated into three groups with differing risks of biochemical failure after RP (hazard ratio 1.95, 95% confidence interval 1.37 to 2.77, P <0.001). These cutpoints further stratified patients with an intermediate (P = 0.002) or high risk (P = 0.05) of biochemical failure (on the basis of the PSA and biopsy Gleason score). However, these cutpoints provided no improvement in risk stratification for patients who were at low risk (P = 0.501) of biochemical failure (on the basis of PSA and biopsy Gleason score). CONCLUSIONS: The percentage of total prostate needle biopsy tissue with cancer can be used to stratify patients into low, intermediate, and high-risk groups preoperatively for biochemical recurrence after RP. These cutpoints could further stratify patients preoperatively who were at intermediate or high risk of biochemical failure on the basis of PSA and biopsy Gleason score.

Biopsy, Needle↗
PubMed2002

A retrospective clinical and radiographic review of 173 hydroxyapatite-coated screw cups with 5- to 10-year follow-up, showing low revision rates for fixation failure.

We reviewed the midterm results of 173 hydroxyapatite-coated screw cups. The average follow-up was 6.5 years (range, 5-9 years). The follow-up rate was 93%. Patients were assessed using the Merle D'Aubigne-Postel clinical scoring scale and by radiographic review. Two patients had revision surgery for recurrent dislocation (1.2%), 3 patients were revised for aseptic loosening (1.7%), 1 patient underwent revision surgery because of deep prosthetic infection (0.6%), and 2 patients were revised for polyethylene wear without loosening (1.2%), which gave a total revision rate of 4.7%. The average postoperative Merle D'Aubigne-Postel scores were 5.7 for pain, 5.5 for range of motion, and 5.4 for function.

Aged↗
PubMed1999

Reboxetine, a unique selective NRI, prevents relapse and recurrence in long-term treatment of major depressive disorder.

BACKGROUND: The long-term efficacy and tolerability of the antidepressant reboxetine, a unique selective norepinephrine reuptake inhibitor (selective NRI), were assessed in an international study. METHOD: Two hundred eighty-three patients with recurrent DSM-III-R major depression who responded to 6 weeks of reboxetine treatment (> or =50% decrease in Hamilton Rating Scale for Depression [HAM-D] total score) were randomly assigned to receive reboxetine or placebo for 46 weeks in a double-blind phase. Relapse (> or =50% increase in HAM-D total score and/or a HAM-D total score > or =18) rate was the principal assessment criterion and included patients who experienced relapse or recurrence. Only patients who remained relapse-free at the end of the first 6-month treatment period were included in the relapse rate assessment at the end of the second 6-month treatment period. RESULTS: Reboxetine was associated with a markedly lower relapse rate than placebo (22% vs. 56%; p<.001) and a greater cumulative probability of a maintained response (p = .0001) during long-term treatment. Patients in remission (HAM-D total score < or =10) at the time of random assignment were less likely to relapse (16% reboxetine, 48% placebo; p<.001). The proportion of patients who were relapse-free and therefore remained in the study was significantly (p< or =.001) higher among those on reboxetine treatment than on placebo at the end of the first (61% vs. 40%) and second (88% vs. 59%) 6 months of treatment. Additional efficacy measures supported these findings. The incidence of adverse events with reboxetine was low and comparable with that for placebo. Discontinuation due to adverse events occurred infrequently. CONCLUSION: Reboxetine treatment over 1 year is more effective than placebo in the prevention of relapse in patients with recurrent depression. The low relapse rates at the end of the second 6 months of treatment further suggest that reboxetine effectively prevents recurrence of depressive symptoms following episode resolution. Reboxetine is well tolerated in long-term treatment of depression, a finding that bodes well for long-term patient compliance.

Adrenergic Uptake Inhibitors↗
PubMed1991

Value of computed tomography of the lung in the management of primary spontaneous pneumothorax.

The treatment of patients with primary spontaneous pneumothorax remains controversial, since recurrence and the ultimate need for thoracotomy [corrected] cannot be predicted. In the current study, computed tomography (CT) of the lung was performed prospectively on 26 consecutive patients with primary spontaneous pneumothorax to determine whether the size and/or the number of apical blebs would correlate with recurrence and/or need for thoracotomy [corrected]. Both the number of blebs and the bleb score (calculated by the number of blebs multiplied by a numeric value assigned a range of bleb sizes) of the affected lung was significantly greater in patients with a history of recurrent pneumothorax and/or ultimate need for thoracotomy [corrected] as treatment. CT of the lung may be useful in predicting the natural history of pneumothorax.

Adult↗
PubMed2006

Autoclaved tumor bone for reconstruction: an alternative in developing countries.

The options for reconstruction after excision of skeletal tumors include reimplanting the autoclaved tumor-bearing bone. We asked whether such bone will survive and unite with normal bone and whether the local tumor recurrence rate increases after its use. We ascertained the functional outcome (Musculoskeletal Tumor Society score) and complications in 19 patients. After wide excision, the bony segment was autoclaved at 120 degrees for 10 minutes and reimplanted at the original defect with intramedullary nails and compression plates. Twelve of our 19 patients were available for followup. The autoclaved segment united with the normal bone in 11 of the 12 patients. No patients had fracture or resorption of the autoclaved segment. Two patients had local tumor recurrence in nearby soft tissues, apparently unrelated to the autoclaved bone. The mean functional score was 70%. Complications included fatigue failure of the nail in one patient, superficial infection in three patients, and deep infection in two patients. Reconstruction with autoclaved tumor-bearing bone is a simple and effective tool in limb salvage. This technique is a cost-effective alternative for developing countries circumventing complications of prosthetic and allograft reconstruction.

Adolescent↗
PubMed2002

Radical radiation for localized prostate cancer: local persistence of disease results in a late wave of metastases.

PURPOSE: To assess whether failure to maintain local control (LC) of prostate cancer after radiation therapy results in a higher incidence of distant metastasis (DM). PATIENTS AND METHODS: From 1972 to 1999, 1,469 patients with clinically localized prostate cancer were treated with radical radiation therapy. Disease outcome was retrospectively reviewed for all patients with more than 2 years of follow-up. RESULTS: The actuarial 10-year LC rate was 79%. Gleason score > or = 7, prostate-specific antigen (PSA) more than 15, and T3 to T4 tumors predicted a higher incidence of local failure (LF) (palpable recurrence or positive rebiopsy). The 10-year distant metastasis-free survival (DMFS) was 74%. Gleason score > or = 7, PSA more than 15, and T3 to T4 tumors predicted a higher incidence of distant failure. LF was the strongest predictor for DM in a multivariate model. The 10-year DMFS for LC and LF patients was 77% and 61%, respectively. Median time to distant failure was prolonged in patients with LF compared with patients with locally controlled disease (54 v 34 months). Hazard rate analysis of the time to DM revealed that patients who maintain LC have a lower rate of DM, which remains constant over time. Patients who ultimately develop LF have a higher initial rate of DM, which increases with time. CONCLUSION: Patients with locally persistent prostate cancer are at greater risk of DM. The higher initial hazard of DM is consistent either with an increased likelihood of subclinical micrometastases before treatment or with posttreatment tumor embolization. The prolonged time to appearance of DM in locally failing patients and the increasing hazard of DM over time is most consistent with a late wave of metastases from a locally persistent tumor.

Aged↗
PubMed2001

Adjuvant and salvage radiation therapy after radical prostatectomy for adenocarcinoma of the prostate.

PURPOSE: To evaluate the outcome of adjuvant and salvage radiotherapy (RT) after radical prostatectomy (RP) for clinically localized prostate cancer using conventional clinical end-points, and the biochemical relapse-free rate (bRFR). METHODS: Between 1987 and 1994, 113 node negative, hormonally naïve men received RT 1 month to 12 years after RP. Adjuvant RT was given for positive resection margins and/or pT3 disease. Salvage RT was given for a persistently elevated prostatic specific antigen (PSA), a rising PSA, or palpable recurrence post RP. Clinical and biochemical endpoints determined outcome. Log-rank testing and the Cox proportional hazards model identified factors predictive for biochemical relapse free rate. RESULTS: Median follow-up after RT was 3.7 years (range 0.2-9 years). Five-year clinical local control was 95% for patients with no palpable evidence of disease and 59% for those with palpable recurrence (P < 0.0001). 5-year bRFR was 81% for adjuvant RT, 19% for salvage of biochemical recurrence, 0% for patients with palpable disease (P < 0.0001). Improved bRFR for adjuvant and salvage RT was predicted by a Gleason score < 7 vs. 7 vs. > 7 (hazard ratio 1.53; 95% CI 0.99-2.35) and an undetectable pre-RT PSA vs. PSA < 2.0 ng/ml vs. PSA > 2.0 ng/ml (hazard ratio 3.81; 95% CI 2.47-5.87). Seminal vesicle involvement was not a statistically significant independent predictor of bRFR. CONCLUSIONS: The most favourable bRFR was observed for adjuvant therapy. Salvage was most successful with a pre-RT PSA < 2.0 ng/ml, or Gleason score < 7. Few patients with a pre-RT PSA > 2.0 ng/ml were salvaged, and none with palpable recurrence. These patients require investigation of alternative salvage strategies.

Adenocarcinoma↗