Biodistribution studies on L-3-[fluorine-18]fluoro-alpha-methyl tyrosine: a potential tumor-detecting agent

OBJECTIVES: To prospectively evaluate a clinical algorithm that predicts nodal status in patients with prostate cancer and to assess the impact on the outcome. METHODS: Between September 1988 and December 1994, 192 patients with organ-confined prostate cancer and considered surgical candidates for radical perineal prostatectomy (RPP) were stratified using the algorithm: prostate-specific antigen (PSA) 20 ng/mL or less, Gleason score 7 or lower, and clinical Stage T2a or lower. Patients failing any of these criteria were placed in the high-risk group and underwent a pelvic lymphadenectomy. Patients who satisfied all the criteria were placed in the low-risk group and underwent RPP without evaluation of the pelvic lymph nodes. Another contemporaneous cohort of patients (n = 65) underwent pelvic lymphadenectomy and radical retropubic prostatectomy (RRP) without use of the algorithm and were used as a control group. Patients were monitored for at least 24 months. RESULTS: In the RPP group, 177 patients were considered low risk according to the algorithm and were not offered staging lymphadenectomy before surgery, whereas 15 patients were categorized as high risk for metastasis and underwent staging lymphadenectomy. In the RRP and lymphadenectomy group, 41 patients were considered at low risk and 24 at high risk of disease spread according to the algorithm. In the RPP group, low-risk patients (no lymphadenectomy) had a PSA recurrence rate (27%) similar to that of low-risk patients in the RRP group with negative lymph nodes (29%), P = 0.8. Similarly, high-risk patients with negative lymph nodes in both groups had a similar recurrence rate (53% for RPP and 50% for RRP). Univariate logistic regression analysis showed that PSA was the most significant predictor for disease recurrence (P = 0.0004) followed by preoperative Gleason scores (P = 0.02) and clinical stages (P = 0.03). Multivariate stepwise analysis demonstrated that Gleason score and clinical stage did not add to the prediction of recurrence over PSA alone. CONCLUSIONS: Staging lymphadenectomy can be omitted in low-risk patients without deleterious effects on the outcome as measured by PSA recurrence.     

Effectiveness of postoperative irradiation in stage IIIA non-small cell lung cancer according to regression tree analyses of recurrence risks

BACKGROUND: In the setting of grossly resected stage IIIA (N2 involvement) non-small cell lung carcinoma, the role of adjuvant postoperative thoracic radiation therapy (TRT) remains controversial. This study was initiated to subcategorize these patients into high-, intermediate-, and low-risk groups with respect to local recurrence and survival rates, and to determine whether there were certain subgroups of patients who were particularly likely or unlikely to benefit from postoperative TRT. METHODS: Two hundred twenty-four patients were studied. A regression tree analysis was used to separate patients who had undergone operation alone into groups that had a high, intermediate, or low risk of local recurrence and death. The effect of adjuvant postoperative TRT then was examined in each of these groups. RESULTS: The use of adjuvant postoperative TRT (compared with operation alone) was associated with an improvement in freedom from local recurrence and survival for patients who had an intermediate or high risk of local recurrence and death. However, the greatest level of improvement in freedom from local recurrence (p < 0.0001) and survival (p = 0.0002) associated with the use of adjuvant postoperative TRT was in the high-risk group. Similarly, but of lesser magnitude, the intermediate-risk group had improved freedom from local recurrence and survival rates with the use of adjuvant post-operative TRT (p = 0.002 and p = 0.01, respectively). For the low-risk group, the freedom from local recurrence and survival rates were not statistically different between the patients who received adjuvant postoperative TRT and those who underwent observation. CONCLUSIONS: Patients with non-small cell lung carcinoma involving ipsilateral mediastinal lymph nodes (stage IIIA) who undergo gross resection and who are at either high or intermediate risk for local recurrence and death are likely to benefit from adjuvant postoperative irradiation. The role of radiation therapy in low-risk patients is unclear. Prospective confirmation of these observations is warranted.     

Treatment of clinical stage I testicular cancer and a possible role for new biological prognostic parameters

Three different treatment strategies for patients with stage I non-seminomatous testicular cancer are available that will all result in long-term survival in more than 98% of the patients: a "wait and see" strategy with follow-up and chemotherapy in cases of tumour progression, retroperitoneal lymphadenectomy, with or without application of systemic chemotherapy, in cases of retroperitoneal metastases (pathological stage II disease) or primary adjuvant chemotherapy following inguinal orchiectomy. Each treatment strategy is associated with specific side-effects. In several studies histological characteristics of the primary tumour, particularly the presence of vascular invasion and of embryonal carcinoma cells, have been demonstrated to be significant prognostic factors for the risk of occult retroperitoneal metastases in patients with stage I disease. In addition, new biological prognostic factors determined by flow cytometry, cytogenetic analysis or molecular-biological DNA or RNA analysis have been investigated, among which alterations of the p53 tumour-suppressor gene may represent a promising new prognostic factor. Although alterations of p53 gene expression seem to be associated with advanced tumour stage and may predict retroperitoneal metastatic disease, the independent role of these molecular genetic alterations needs to be prospectively studied. Currently a risk-adapted treatment strategy based on the histological criteria of vascular invasion and the presence of embryonal carcinoma can be used to stratify patients into a "high-" and "low-risk" group with respect to tumour progression. While primary-nerve-sparing retroperitoneal lymphadenectomy or adjuvant chemotherapy with two cycles of platinum, etoposide and bleomycin may be appropriate for patients with a high risk (above 40%) for tumour progression, a "wait-and-see" strategy can be used for "low-risk" (less than 15% risk of progression) patients. Molecular investigations of prognostic factors may be able to improve further the stratification of patients into these different risk categories.     

Management of endometrial cancer

Preoperative assessment requires only endometrial sampling for diagnosis. Curettage is needed when endometrial sampling is unsatisfactory. Transvaginal ultrasonography may be useful in screening high-risk patients, as well as in assessing myoinvasion or cervical extension. Postsurgical pathologic prognostic factor analysis is most accurate in assigning risk for recurrence. Once the extent of disease is confirmed by the surgical staging procedure of hysterectomy, bilateral removal of the ovaries, and selective pelvic and periaortic node dissection, adjunctive therapy can be considered. Patients with low-risk stage IA and IB grade 1 disease require hysterectomy and removal of the adnexa. The poorer prognosis of patients with grade 2 or 3 histologic features in stages IB to IIB dictates considerations for adjunctive therapy. Soon randomized controlled trials will elucidate objectively what may be optimal adjunctive therapy. Ongoing prospective trials will clarify the role of operative laparoscopy. Current management guidelines are based on independent prognostic factors derived from analysis of surgicopathologic studies.     

Improving the treatment of colorectal cancer: the role of EUS

The two most important factors for determining the risk of local failure and overall prognosis in colorectal carcinoma are nodal status and the depth of tumor penetration into or through the bowel wall. These features have traditionally been determined pathologically because the clinical-staging accuracy of other imaging modalities such as computed tomography (CT) has not proven sufficiently predictive of surgical staging. However, endorectal or endoscopic ultrasonography (EUS) can be used to preoperatively evaluate nodal involvement with an accuracy of up to 86% (median: 80%) and depth of tumor penetration through the bowel wall with an accuracy of up to 97% (median: 85%) for effective clinical staging. This high staging accuracy is useful in managing colorectal cancer. Through clinical evaluation of the initial stage of colorectal cancer with EUS, a patient's risk of disease recurrence can best be determined and patients stratified for the most appropriate treatment. EUS can be used to select patients with lesions that can be treated with local excision or sphincter-sparing surgery, often combined with radiation therapy, in situations otherwise requiring an abdominoperineal resection. EUS can also be used to preoperatively identify patients with locally advanced or unresectable disease. Chemoradiation can then be given preoperatively, when it appears to be better tolerated and more effective than postoperative treatment. Unresectable tumors can often be downstaged sufficiently to allow their excision. In resectable disease, EUS can also identify patients at high risk for recurrence who would benefit from adjuvant chemoirradiation. EUS for precise staging or for earlier diagnosis of recurrence will further improve the clinical outcome of patients with colorectal tumors as significant advances both in surgical techniques and in combined chemotherapy/radiotherapy continue to be made and applied selectively in a stage-dependent manner.     

Estrogen replacement to women treated for endometrial cancer

Oestrogen replacement therapy in women treated for endometrial cancer has long been considered contra-indicated. Based on a review of the literature, which shows a low risk of recurrence during oestrogen replacement therapy in women treated for low-risk endometrial cancer, we advocate that this group of patients could be offered oestrogen replacement therapy and be provided with the benefits of prevention of cardiovascular disease and osteoporosis. Further studies are needed to investigate the survival and recurrence rates of high-risk patients treated with oestrogen replacement therapy.     

Adjuvant medical therapy for colorectal cancer

In the mid-1980s, trials of adjuvant therapy for colon cancer in the United States had a "no treatment" arm, which reflected the belief that effective adjuvant chemotherapy did not exist for patients with surgically resected disease at high risk for recurrence. However, with the observation in the early 1990s that postsurgical adjuvant 5-FU plus levamisole reduced tumor recurrence and ultimately increased overall survival in stage III colon cancer, the potential of effective adjuvant chemotherapy was realized. Questions about the duration of adjuvant chemotherapy, the specifics of chemotherapy schedule/drug selection, and its use in stage II colon cancer are beginning to be clarified in large, randomized adjuvant therapy trials. In rectal carcinomas, combined modality postoperative pelvic irradiation plus chemotherapy for stage II and III disease has been shown to reduce both local and systemic recurrences and to prolong survival compared with that in patients treated with local surgery and radiation. Again, large randomized trials are attempting to clarify both the optimal chemotherapeutic agents and schedules to be used and also whether preoperative combined modality therapy can improve the resectability rate, rate of sphincter preservation, and survival. Future trials will examine new agents shown to be effective in advanced disease as well as monoclonal antibodies, such as MoAb 17-1A, that may have selective activity in minimal disease. Improvement in overall survival remains the ultimate endpoint of future adjuvant therapy trials; however, trials will also critically examine toxicity, quality of life, pharmacoeconomics, and genetic and biologic correlates that may help select more appropriate candidates for adjuvant therapies.     

Prognostic significance of tumor markers in colorectal cancer patients: DNA index, S-phase fraction, p53 expression, and Ki-67 index

Risk of colorectal cancer recurrence has traditionally been determined by use of pathologic staging. However, it is apparent that subgroups of patients exist within tumor stages whose clinical behavior differs. This study was undertaken to identify tumor-associated factors that might be predictive of outcome in patients with intermediate stages who will benefit the most from postsurgical adjuvant therapy. Seventy patients with stage II and III colorectal cancer were assessed for DNA index, S-phase fraction, p53 expression, and Ki-67 index. Tumor recurrence was analyzed by means of nonparametric tests and Cox proportional hazard models incorporating standard clinical and pathologic criteria. Of the four prognostic markers evaluated, Ki-67 index was significantly associated with disease recurrence (P = 0.02), whereas DNA index, S-phase fraction, and p53 expression were not. After stratification by tumor stage, significant associations between Ki-67 index and disease recurrence were retained in stage II tumors (P = 0.01) but not in stage III tumors (P = 0.23). Cox proportional hazard regression analysis indicated that among stage II patients, those with a Ki-67 index >45% were associated with 6.5 times greater risk for disease recurrence than those with a Ki-67 index >/=45%. It was concluded that an elevated Ki- 67 index is associated with an increased risk of tumor recurrence in stage II colorectal cancer.     

Strategies to decrease the incidence of intra-abdominal recurrence in resectable gastric cancer

Two main approaches are suggested to improve treatment results in resectable gastric cancer: extended lymphadenectomy and adjuvant antitumour therapy. Progress is to some extent stalled by the perception of gastric cancer as a pathophysiologically uniform disease; it has been demonstrated, however, that there are variants of gastric cancer associated with predominantly intra-abdominal spread or with haematogenous metastases. Recent clinicopathological studies have provided information about the mechanisms of this metastatic diversity. A review of clinical trials suggests that no single method of treatment can efficiently address all variants of gastric cancer spread, but new treatment strategies may be based on defining the pathophysiological variant of gastric cancer and selecting adjuvant therapy according to the most probable mode of tumour spread. Treatment should start with surgery which includes a 'reasonably' extended lymphadenectomy aimed at achieving an increased rate of curative resection and more accurate staging. Risk factors for peritoneal spread of tumour require the perioperative use of intraperitoneal chemotherapy. Subsequent adjuvant therapy may be indicated in patients at high risk of further cancer spread or occult metastases, as determined by pathological examination of the resected specimen.     

Risk-adapted treatment of clinical stage 1 non-seminoma testis cancer

250 patients with clinical stage 1 non-seminomatous germ cell tumours of the testis (NSGCT 1) were included into a prospective multicentre protocol during 1990-1994 and treated according to three risk strata: patients without tumour cell invasion of vascular structures in the testis (VASC-) and elevated serum AFP levels (AFP+) at orchiectomy were considered low risk (LR) and only observed closely. VASC- and AFP- or VASC+ and AFP+ patients were presumed intermediate risk (IR) and pathologically staged (PS) by retroperitoneal lymph node dissection (RPLND). VASC+ and AFP-patients were regarded as high risk (HR) and received adjuvant chemotherapy (PEB x 3). At a median observation time of 40 (7-68) months, all patients were alive and without evidence of active germ cell cancer. The actuarial relapse rate in the 106 LR patients was 22%, and 70% (14/20) had elevated serum tumour markers at relapse. One of 32 (3%) HR patients relapsed with a resectable retroperitoneal mature teratoma despite adjuvant chemotherapy. Only 14% of the 99 IR patients who underwent RPLND had PS2 disease, and the actuarial relapse rate in 85 PS1 patients was 18%. This multicentre study demonstrated that excellent therapeutic outcome is possible when 18 comparatively small urological and oncological centres follow a strict and formal cancer care programme. The useful prognostic effect of VASC was once again verified. Pathological staging by RPLND in NSGCT1 is, in our opinion, not necessary, with presumed low-risk patients offered surveillance and high-risk patients offered adjuvant chemotherapy.     

Atherosclerosis regression in the elderly--correlation between centrally depressed lesions and risk factors

Atherosclerotic plaque with central depression (depressed lesion) may indicate regression of atherosclerosis in the aorta. Aortic depressed lesions have a solitary elevated area of plaque with a sharply-bordered roung depression in its center and no area ulceration. This may be interpretable as a sign of regression of atherosclerosis. To clarify the pathogenesis of depressed lesion, we studied clinical risk factors such as hypercholesterolemia in patients with depressed lesions that were confirmed at autopsy. The patients were divided into 3 groups according to their total cholesterol level at autopsy: a high-risk group (> or = 220 mg/dl), a moderate-risk group (180-220 mg/dl), and a low-risk group (< or = 180 mg/dl). Depressed lesions were found in 16.4% of those in the high-risk group, in 14.6% of those in the moderate-risk group and in 69.0% of those in the low-risk group. Severe aortic atherosclerosis was found in 69.8% of the patients; 50.9% of those with severe disease were in the-low risk group. Depressed lesions were also found in those with low levels of low-density lipoprotein cholesterol (< or = 140 mg/dl), 58.8% of whom were found to have severe atherosclerosis. There was no relationship between total cholesterol level and the presence of depressed lesions. However, a clinical prevention trial may result in sufficient control of ahterosclerosis among those in the high-risk group and may also lead to regression of aortic lesions.     

Liver transplantation for small hepatocellular carcinoma: the tumor-node-metastasis classification does not have prognostic power

Tumoral recurrence rate and survival of patients with hepatocellular carcinoma (HCC) treated by orthotopic liver transplantation (OLT) depend on tumor stage. Thereby, from the beginning of our program, we selected only patients with solitary tumors < or = 5 cm without vascular invasion, thus avoiding the use of the tumor-node-metastasis (TNM) staging system as a selection tool. The present study reports the results obtained in 58 consecutive patients (52 +/- 8 years, 47 males) with HCC (7 incidentals) transplanted between 1989 and 1995. Transplantation was indicated because of tumor diagnosis in 40 cases and advanced liver failure in 18. Mean tumor size at staging was 28.2 +/- 12.1 mm. No adjuvant treatment was applied during the waiting period (58.9 +/- 45.1 days). The pathological tumor-node-metastasis (pTNM) classification allocated 15 patients to stage I, 19 to stage II, 11 to stage IIIA, and 13 to stage IVA showing preoperative understaging in 43% of the cases with known tumor. After a median follow up of 31 months, only two patients have shown tumor recurrence and fifteen have died, the 1-, 3-, and 5-year survival being 84%, 74%, and 74%. All HCV+ patients remain infected and 94% showed significant liver disease (6 cirrhosis). Six patients have had a second transplant. In conclusion, the application of restrictive criteria not following the TNM staging system prompts excellent results for liver transplantation in patients with HCC, both in terms of survival and disease recurrence, even without applying adjuvant treatment; however, the survival data should be tempered by the appearance of complications that may worsen the long-term prognosis.     

NM23-H1 immunostaining is inversely associated with tumour staging but not overall survival or disease recurrence in colorectal carcinomas

The NM23-H1 gene product has been recently identified as a potential metastasis suppressor. Studies on breast carcinomas have shown an inverse correlation between NM23-H1 status and stage of carcinogenesis and overall survival. However, in colorectal cancer, conflicting data have been reported. This study aimed to investigate whether NM23-H1 immunostaining is correlated with tumour stage, overall survival, disease recurrence, tumour differentiation, age and sex in colorectal carcinomas for the Singapore population using chi-square analysis. The staining was performed on 141 paraffin-embedded surgical specimens collected between 1991 and 1992 using a monoclonal anti-NM23-H1 antibody. Follow-up of patients was until time of death or for 5 years. There was a very significant inverse association between tumour staging and NM23-H1 status (P = 0.0004). However, NM23-H1 expression was not significantly correlated to overall 5-year survival, disease recurrence, tumour differentiation, age or sex. Thus, although NM23-H1 may be involved in suppressing metastasis, NM23-H1 immunohistochemistry has no prognostic value in colorectal cancer. This is the first report of a significant inverse association of NM23-H1 status with tumour staging in colorectal cancer which showed no correlation with overall survival or disease recurrence. Our result thus cautions against the practice of equating an inverse relation of genetic markers with tumour staging to survival or disease recurrence.     

Lesion-induced plasticity as a potential mechanism for recovery and rehabilitative training

OBJECTIVES: To compare the potential years of life saved (YOLS) associated with risk factor modification in the primary and secondary prevention of cardiovascular disease (CVD). METHODS: The CVD life expectancy model estimates the risk of death due to coronary disease, stroke, and other causes based on the levels of independent risk factors (such as age, blood pressure, and blood lipid levels) found in the cohort of the Lipid Research Clinics. The model was validated by comparing its predictions with the observed fatal outcomes of 9 randomized clinical trials. We then estimated the YOLS associated with treating hyperlipidemia or hypertension among hypothetical patient groups with and without CVD at baseline. We defined high-risk patients as those with 3 risk factors (hyperlipidemia, cigarette smoking, and hypertension) and low-risk patients as those with isolated hypertension or hyperlipidemia. RESULTS: The fatal events predicted by the model were consistent with the clinical trial results. Among men and women with hyperlipidemia without CVD, the forecasted benefits of lipid therapy were substantially greater among high-risk groups vs low-risk groups (4.74-0.78 YOLS vs 2.50-0.25 YOLS, respectively). Among those with CVD, the forecasted benefits of treatment were similar for both high-risk and low-risk groups (4.65-0.65 YOLS vs 3.84-0.58 YOLS, respectively). The results for hypertension therapy also demonstrated greater benefits for high-risk vs low-risk patients undergoing primary prevention therapy (1.34-0.29 YOLS vs 0.85-0.13 YOLS, respectively), and the forecasted benefits in secondary prevention were similar (1.26-0.23 YOLS vs 1.00-0.23 YOLS, respectively). CONCLUSIONS: The clinical approach to risk factor modification in primary prevention should be different from that in secondary prevention. The forecasted benefits of therapy among patients without CVD are greatest in the presence of other risk factors. Among those with CVD, the benefits of therapy are equivalent, thereby obviating the need to target high-risk patients.     

Lack of effect of Miller Fisher sera/plasmas on transmitter release from PC12 cells

Endometrial cancer staging is obtained by the analysis of the surgical-pathological parameters. Therefore, surgery represents the first approach to this neoplasia. Surgical-pathological data analysis informs us of the main prognostic factors and the spread of the disease. On the basis of these findings, the risk of recurrence can be estimated and adjuvant treatments can be planned. A protocol for staging and treatment of endometrial carcinoma has been designed by the authors. After surgery, adjuvant therapy (chemotherapy or radiotherapy or the two modalities combined) is suggested by analysis of the prognostic factors. The aim of the protocol is to increase the relapse-free survival and to improve the quality of life of endometrial cancer patients.     

Management of malignant tumors of the salivary glands

Results of treatment for patients with salivary gland carcinoma have improved in recent years, most likely due to earlier diagnosis and the use of more effective locoregional therapy. Salivary gland tumors are treated surgically, often in conjunction with postoperative radiation therapy when the tumor is malignant. Good results rest strongly on the performance of an adequate, en bloc initial resection. Radical neck dissection in indicated in patients with obvious cervical metastasis, and limited neck dissection may be appropriate in patients with clinically negative nodes in whom occult nodal involvement is likely. Postoperative radiation therapy should be administered when the tumor is high stage or high grade, the adequacy of the resection is in question, or the tumor has ominous pathologic features. Neutron beam therapy shows promise in controlling locoregional disease but requires further study. No single chemotherapeutic agent or combination regimen has produced consistent results. At present, chemotherapy is clearly indicated only for palliation in symptomatic patients with recurrent and/or unresectable cancers. Patients with salivary gland carcinomas must be followed for long periods, as recurrence may occur a decade or more following therapy. Distant metastasis appears to occur in approximately 20% of patients.     

The use of selective lymphadenectomy in squamous cell carcinoma of the wrist: a case report

Squamous cell carcinoma is the second most common skin cancer in humans and has a rate of metastasis of 0.5%-5.9%. Regional lymphadenectomy is generally not recommended for patients with advanced lesions and clinically node-negative disease. Selective lymphadenectomy using preoperative lymphoscintigraphy and intraoperative radiolymphoscintigraphy and vital dye injections to identify the sentinel lymph node may help in staging patients with upper-extremity squamous cell carcinoma while avoiding the complications of a complete axillary node dissection. The case of a patient with a large squamous cell carcinoma of the wrist with clinically negative findings on axillary examination who was found to have a sentinel lymph node containing metastatic tumor is presented. Although this treatment method is still considered investigational, it holds great promise for nodal staging by being able to detect occult metastatic nodal disease in otherwise clinically node-negative patients.     

The role of isochorismate hydroxymutase genes entC and menF in enterobactin and menaquinone biosynthesis in Escherichia coli

PURPOSE: At a time both when late complications and second malignancies have become a growing concern and when staging laparotomy has been largely abandoned and comparative studies for staging Hodgkin's disease by state of the art computed tomography (CT) vs. lymphangiography have revealed minimal differences in results for these procedures, our purpose for undertaking this study was twofold. Our initial reason was to determine and compare probabilities for negative abdominal findings for patients with Stage I presentations with those for patients with Stage II as determined by lymphangiography and subsequently by laparotomy for those patients who had negative lymphangiograms. Our second reason, being an extension of the first, was to create a resource that can be used in conjunction with other information for arriving at appropriate treatment decisions including giving either more or particularly less than standard institutional therapy and especially with respect to the abdomen. METHODS AND MATERIALS: Data on 714 patients with prelymphangiogram Stage I-II upper torso presentations of Hodgkin's disease were entered prospectively in our database between 1968 and 1987. Twenty-eight with lymphocyte predominant disease, who had both negative lymphangiogram and negative laparotomy findings and 17 with questionable diagnoses of lymphocyte-depleted or unclassified disease were excluded from subsequent analyses of 669 patients with nodular sclerosis (NS) and mixed cellularity (MC) diagnoses. RESULTS: Stage I: in final logistic models, negative lymphangiogram findings were associated strongly with a combination of no constitutional symptoms and nodular sclerosis histology, whereas negative laparotomy findings correlated strongly with a combination of no constitutional symptoms and female sex. Predicted probabilities depended on the ratios of favorable to unfavorable characteristics. Stage II: in final logistic models, negative lymphangiogram findings were associated strongly with a combination of no constitutional symptoms, nodular sclerosis histology, age <40 years, and <4 involved sites, whereas negative laparotomy findings correlated strongly with a combination of <4 involved sites and mediastinal disease. Predicted probabilities again depended on the ratios of favorable to unfavorable characteristics. CONCLUSION: This study demonstrated that probabilities for negative abdominal findings for patients with supradiaphragmatic presentations of NS and MC Hodgkin's disease depended on: 1) whether the disease presented as Stage I or as Stage II; 2) whether staging was limited to a lymphangiogram or whether it included a laparotomy; and 3) or whether the clinical features associated with the presenting stage and methods of staging were favorable or unfavorable.     

Stage I corpus cancer: is teletherapy necessary?

OBJECTIVE: Our aim was to evaluate the perioperative morbidity after hysterectomy and lymphadenectomy as primary treatment of endometrial cancer and to analyze the recurrence and survival of patients classified as having surgical stage I disease who did not receive adjunctive teletherapy. STUDY DESIGN: Over a 10-year interval 444 patients underwent extensive surgical staging for corpus cancer. Perioperative events were recorded prospectively. Outcome events were updated after the last year of study. RESULTS: After patients with high-risk histologic types of cancer were excluded, 396 patients were evaluable. The risk of extrauterine disease, detected in 21.8% of patients, increased with increasing lack of tumor differentiation. The associated surgical morbidity, including blood loss (mean 336 ml), surgical site infection (3.5%), thromboembolic events (1.5%), and urinary injury (0.6%), and deaths (0.6%) did not differ from those in reports of women undergoing lesser operative procedures. Late complications, including lymphocyst (1.2%), leg edema (1.8%), and hernia (2.9%), were infrequent. Recurrence and survival analysis indicated a calculated 5-year survival of 97% of all patients with surgical stage I disease. There was a significant survival difference related to grade and stage for women in whom disease was confined to the uterus. Overall survival in patients with stage IA (100%) was significantly different (p < 0.0001) from that of patients with stage IB (97%) and stage IC (93%). All recurrences included a distal component. CONCLUSION: Extensive surgical staging including lymphadenectomy can be performed safely. Our results suggest that the risk of pelvic recurrence is not increased and the risk of survival is not compromised in those women not receiving adjunctive teletherapy.     

Calculated prostate cancer volume greater than 4.0 cm3 identifies patients with localized prostate cancer who have a poor prognosis following radical prostatectomy or external-beam radiation therapy

PURPOSE: Patients with palpable extraprostatic disease (T3) have a poor prostate-specific antigen (PSA) failure-free (bNED) survival rate after radical prostatectomy (RP) or external-beam radiation therapy (RT). This study was performed to validate or refute the prognostic value of the previously defined calculated prostate cancer volume (cV(Ca)). PATIENTS AND METHODS: For patients with clinically localized disease (T1c,2), a Cox regression multivariable analysis was used to assess the ability of the cV(Ca) value to predict time to posttherapy PSA failure following RP or RT. RESULTS: The cV(Ca) value was a significant predictor (P < or = .0005) of time to posttherapy PSA failure in both an RP and RT data set independent of the one used to derive the cV(Ca)-based clinical staging system. In both RP- and RT-managed patients, estimates of 3-year bNED survival were not statistically different for patients with either T1c,2 disease and a cV(Ca) greater than 4.0 cm3 (RP, 27%; RT, 18%) or T3 disease (RP, 37%; RT, 34%). Despite pathologic T2 disease, the 3-year estimate of bNED survival was at most 51% in RP-managed patients with T1c,2 disease and cV(Ca) greater than 4.0 cm3. CONCLUSION: A cV(Ca) greater than 4.0 cm3 identified patients with T1c.2 disease whose bNED survival was poor after RT or RP despite pathologic T2 disease that suggests the presence of occult micrometastatic disease in many of these patients. Prospective randomized trials to evaluate the impact on survival of adjuvant systemic therapy in these high-risk patients are justified.