Is there a place for neoadjuvant hormonal therapy before radical prostatectomy or radiation therapy in the management of prostate cancer?
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Prostate Cancer and Prostatic Diseases (2000) 3, 136-144
INTRODUCTION: Antiangiogenic therapy has the potential to moderate tumour and micrometastatic growth. Its use in the perioperative period is attractive but its potential to compromise wound and anastomotic healing is a cause for concern. Tamoxifen is antiangiogenic but also favourably modifies some aspects of wound healing. We hypothesised that tamoxifen would not adversely affect skin wound and gut anastomotic healing. METHODS: A previously established model of tamoxifen, administered orally at antiangiogenic doses (20 mg/ml arachais oil/day), was used. Animals received two days pretreatment prior to laparotomy and small bowel anastomosis. Treatment was continued until completion of the study. The principal outcome measures are survival, macroscopic wound and anastomotic healing, anastomotic bursting pressure and PVA sponge granuloma hydroxyproline (OHP) content. RESULTS: Tamoxifen treated animals had fewer complications of skin wound healing than controls (4.5% vs. 19.5%; chi(2) 4.65, 1 d.f., P < 0.05). There was no significant difference in adhesion formation or macroscopic complications of anastomotic healing. Anastomotic bursting pressure was greater in tamoxifen treated animals at postoperative day 3 (39 +/- 4.4 vs. 22.5 +/- 3.5 mmHg; P < 0.01) and equal to that of controls on postoperative day 5 (144.4 +/- 9.4 vs. 127.3 +/- 10.9 mmHg; P = ns). Tamoxifen treated animals weighed significantly less than placebo controls from postoperative day 3 with no difference in mortality between groups (chi(2) = 0.06, 1 d.f., P = ns). PVA sponge granuloma OHP content on day 7 was higher in tamoxifen-treated animals (2.93 +/- 0.4 vs. 1.4 +/- 0.4 mg OHP/mg dry sponge weight; P = 0.03). CONCLUSION: Antiangiogenic therapy with tamoxifen has no demonstrable adverse effects on wound or anastomotic repair and its perioperative use is compatible with successful early surgical outcomes.
Fractures through bone tumors are often difficult to treat. We reviewed our combined experience with this problem in children, as well as the existing literature, to formulate management guidelines. For this study, prospective databases (1987 to 2002) from three referral centers were screened for pathologic fractures occurring under the age of 14 years. One hundred five patients presented with fracture through unicameral bone cyst, nonossifying fibroma, fibrous dysplasia, aneurysmal bone cyst and osteosarcoma. Seventeen patients were excluded. The most common primary locations were the proximal humerus and proximal femur. Pathologic fracture through nonossifying fibroma had the best outcome; union occurred with nonsurgical treatment in all cases. Unicameral bone cyst required surgical treatment to avoid persistence of the cyst and refracture. However fracture healing was predictable without surgical treatment. Proximal femoral lesions tended to heal in malunion if not fixed surgically. Aneurysmal bone cyst required surgical treatment for the lesion to heal and to allow the fracture to heal as well. Percutaneous sclerotherapy may be the treatment of choice for many of these lesions. Fibrous dysplasia allows fracture healing with nonoperative therapy. Progressive deformity requires followup and surgical correction. Malignant lesions presenting a pathologic fracture are best managed by initial nonoperative therapy during investigation and neoadjuvant therapy when possible, followed by definitive treatment.
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OBJECTIVES: To evaluate the effects of neo-adjuvant hormone therapy (NAHT) given prior to radiation in patients with clinically localized adenocarcinoma of the prostate. METHODS: Six hundred nine patients were treated between 1992 and 1997 with NAHT prior to radiation therapy. Clinical stage, presenting PSA and Gleason score were examined for influence on outcome. Time to post radiotherapy failure was defined from the first assessed PSA value over 4 microg/L at follow-up. Radiation therapy was confined to the prostate and seminal vesicles. Median follow-up was 2.6 years. RESULTS: PSA disease free survival (PDFS) decreased with increasing cancer risk factors (p <.0.0001). The overall duration of NAHT was significant with patients receiving >8 months having a lower failure rate than those on therapy for <3 months (p <0.0001). The PSA prior to starting radiation correlated with outcome, a PSA <=0.1 microg\L having a better PDFS than those with a PSA >=4 microg\L (P <0.0001). NAHT for >8 months gave improved PDFS in intermediate grade Gleason score 5-7, (n = 256, p <0.0001), high grade Gleason score 8-10 (n = 80, p =0.005), but not in low grade, Gleason score <=4. CONCLUSION: Neo-adjuvant hormone therapy for >8 months offers prolonged PSA disease free survival in patients with less well differentiated tumors, Gleason score >4. Clinical trials are required to confirm this.
The Russian Cancer Research Center has experience in diagnosing and treating more than 800 patients with osteosarcoma who have been treated at the Clinic of General Oncology since 1952. Survival rates were no more than 10% before the 1970s when the only treatment was surgical. The use of adjuvant chemotherapy after radical surgery has increased survival up to 45-60%. In 1982 to 1986, a protocol involving intraarterial chemotherapy with adriamycin, 90 mg/m2, radiation therapy in a dose of 40 Gy, preserving surgery, and adjuvant chemotherapy was used to improve local and regional guidance. Survival was 55-60%. The high incidence of purulent complications prompted us to do away with radiation therapy. A protocol of neoadjuvant therapy that implies preoperative intraarterial monotherapy with cisplatin, 120-150 mg/m2, adriamycin, 90 mg/m2 or large-dose methotrexate (8-10 g/m2) was implemented in 1986 to 1998. The best results were achieved only in patients with complete tumor necrosis, among whom survival being over 70%. Preserving surgery following ineffective chemotherapy caused a high incidence of local relapses (30%). The second line of chemotherapy did not greatly improve prognosis when a histological response was slight. Complete tumor necrosis was noted only 10% of more than 150 patients so survival in the whole group was 40%. In 1998, a new protocol was initiated to improve immediate and late outcomes. Preoperatively, 3-4 sessions with adriamycin, 90 mg/m2 and cisplatin, 120 mg/m2, are performed. Postoperatively, 3 or 4 sessions of chemotherapy with the same drugs are made if there is a marked therapeutical pathomorphism. If a response is weak, 6 sessions with ethoposide, 100 mg/m2 and iphosphamide, 1.8 g/m2 during 1-5 days are given. This study has covered just 30 patients. The rate of a full histological responses has increased by 4 times. In every second patient, an amputable tumor could be made a resectable one. The proportion of candidates for preserving surgery has increased up to 90%. Intensified chemotherapy increased the incidence of severe adverse effects, primarily degrees 3-4 hematological toxicity reaching 40%. At the turn of centuries, osteosarcoma is a highly promising curable disease. The survivals of 65-70% and satisfactory functional results can be achieved only at highly specialized centers.
Few studies have attempted to critically identify patient- and tumor-related factors that limit sentinel node biopsy (SNB). These studies have been limited by sample size and surgeon variability. The present study attempts to enumerate these limitations in a unique group of patients. One hundred twenty-five SNBs performed by a single surgeon between May 1997 and June 2001 were reviewed. Overall SNB was successful in 96 per cent of patients with a 97 per cent correlation with the axillary node dissection. Sentinel node identification was not affected by age, tumor size, tumor location, prior segmental resection, or neoadjuvant therapy. No false negatives were noted in the neoadjuvant group. The use of blue dye alone significantly understaged patients when compared with isotope alone (P = 0.02). SNB is a highly accurate method to identify axillary metastases and its limitations are not affected by patient or tumor related factors. In the present study SNB detection by both isotope and blue dye has been shown to be superior to blue dye alone. This finding demonstrates that these limitations may be overcome with the standardization of the technique used.
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Patients with regionally extensive non-small cell lung cancer (predominantly by virtue of metastases to mediastinal lymph nodes, less commonly by direct extension into the mediastinum) were treated predominantly with chest radiation therapy alone until the early 1980s. At that time, because of the high local recurrence rate, the higher likelihood of distant metastases, and the poor 5-year survival rates, studies were begun in these patients attempting to substitute a different local treatment modality (surgery) or to use both radiation therapy and surgery to decrease local recurrence rates and to add chemotherapy as a systemic therapy to decrease distant metastases. LCSG 831 explored the use of CAP (cyclophosphamide, doxorubicin, cisplatin) chemotherapy plus radiation therapy as preoperative or neoadjuvant therapy. Thirty-nine patients entered this phase 2 trial with 33 undergoing resection. Median survival was 11 months, and 1-year survival was 43%. These results are compared with the results of other similar trials. Explanations for the poor and differing results are suggested as are possible ways to improve study design and results.
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Recently, there has been an increasing interest in the application of preoperative endocrine therapy prior to radical prostatectomy. The main purpose of this treatment modality is to enhance surgical curability and increase survival. Endocrine therapy was performed before radical prostatectomy on 40 patients between 1986 and 1993; 15 had stage B2 and 25 had stage C disease. The median duration of preoperative endocrine therapy was 3.8 months. All patients subsequently underwent radical prostatectomy, pelvic lymphadenectomy and castration. There was on average a 25.5% (0-71.8%) decrease in maximal cross-sectional area of prostate gland as determined by transrectal ultrasonography. Treatment-related histological effects, divided into three grades were as follows; excellent in 17, moderate in 11 and poor or no regression in 12. Pathological downstaging of disease status from the diagnosis made at the initial clinical examination was seen in 13 of the 40 patients (33%). At a median follow-up of 50 months (19-118 months), 36 of the 40 patients are disease-free and two died of cancer 43 and 50 months postoperatively. These findings suggest that preoperative endocrine therapy plays an important role in the management of locally advanced prostatic cancer.
OBJECTIVES: To determine the usefulness of preoperative hormone therapy in patients with organ-confined prostatic carcinoma undergoing radical prostatectomy. METHODS: 7 patients with localized prostatic carcinoma are presented. All patients were submitted to radical prostatectomy; 4 had been randomly selected for preoperative hormone therapy. RESULTS: Histological examination showed no nodal involvement in all cases. The tumor could not be identified (Po) in two of the four patients who received hormone therapy. The other two patients were staged down; the Gleason score remained unchanged in one and increased in the other. The patients who did not receive preoperative hormone therapy showed concordant clinical and pathological stages, except one in whom infiltration of the prostatic capsule was observed. No difference was found concerning the facility in performing surgery between the treated and untreated patients. CONCLUSIONS: Hormonal deprivation eliminated the tumor burden in two cases that might have been completely hormone sensitive, with no correlation in the pretreatment histological grade. Clinical downstaging is achieved by this treatment modality. However, further studies in larger series comparing the percentages of downstaging, histological downgrading, absence of tumor cells in the surgical specimen and impact on survivorship are warranted.