Endometrial carcinoma stage I

Standard staging and therapeutic approach to endometrial cancer involves lymph node sampling (LNS) at the time of total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO). Lymphadenectomy prolongs time of surgery and increases the risk of morbidity; where other predictors are available, it may not contribute important supplementary information. 185/247 women with stage I endometrial carcinoma underwent the standard surgery while 62 underwent TAH+BSO. Recurrence and survival were monitored for a mean of 6.5 years and retrospectively reviewed: the rates for groups with and without known lymph node status were alike [13.5% (25/185) recurrence for the former and 12.9% (8/62) for the latter, and 5-year survival rates of 75.7% (140/185) for the former and 74.2 (46/62) for the latter]. Myometrial invasion and histological grade appeared to have been highly accurate predictors without lymph node information. Because information on histological grade is available early and is highly predictive, its use could be incorporated into a revised management algorithm for stage I endometrial cancer which would depend upon ensuring lymphadenectomy for women with low grade histopathology and omitting it for those with high grades on the grounds that no further information is necessary to act appropriately.     

Clinical stage I seminoma

Stage I seminoma is highly curable. There are different treatment options for this disease: radiotherapy, surveillance and chemotherapy. In recent years, adjuvant chemotherapy in particular has been extensively evaluated. This paper offers suggestions about the advantages and disadvantages of the different strategies, which will be discussed considering prognostic factors; future perspectives will also be evaluated. Through a review of the literature and their clinical experience, the authors outline the importance of prognostic factors in the management of patients suffering from seminomas. Although no treatment modalities have demonstrated survival advantages over others, acute and late side effects, acceptability and quality of life are the main elements of comparison between them. Our findings support the hypothesis that the final decision about the treatment of these tumors depends essentially on three different aspects: risk factors, the patient's own preferences, and single-center expertise. These aspects should play a fundamental role in the final decision-making.     

Inoperable localized stage I and stage II non-small-cell lung cancer

Opinion statement Early stage, medically inoperable non-small-cell lung cancer is a treatable disease. A thorough clinical work-up is necessary to optimize management for this group of patients. Thoracic radiation therapy has been used for such patients with achievement of durable local control and prolonged survival. To improve upon the results of standard fractionation radiation therapy, novel approaches are needed. Dose escalation may further enhance local tumor control and survival rates. Efforts to minimize irradiation to normal lung parenchyma are necessary. Multiple strategies to optimize the therapeutic ratio are being investigated. Elimination of elective nodal irradiation may reduce late toxicity of treatment but may compromise locoregional control. Other strategies, such as intensity-modulated radiation therapy with dose volume histograms will help minimize lung parenchyma irradiation, which will reduce the probability of radiation pneumonitis. Chemotherapy appears to play a minimal role in the treatment of inoperable limited disease, but researchers continue to conduct investigational trials with active chemotherapeutic agents in the hopes of reducing local and distant tumor failures.     

Management of stage I testicular seminoma

Adjuvant treatment options for stage I seminoma include surveillance, radiation, and hemotherapy. Despite excellent results for both adjuvant chemotherapy and radiotherapy, many concerns have been raised in regards to the potential long-term toxicities of these treatments. To minimize the burden of treatment, there has been a shift away from adjuvant treatments for stage I testicular seminomas toward surveillance protocols for seminoma survivors. This article reviews the evidence for all adjuvant treatment options for stage I testicular seminomas with a particular focus on surveillance.     

Treatment options in stage I seminoma

Seminomas are most commonly diagnosed in clinical stage I (CSI). After orchiectomy, approximately 15% of patients in this stage have subclinical metastases. Adjuvant radiotherapy (ART) delivered to the retroperitoneum and ipsilateral pelvic lymph nodes has been the mainstay of treatment for many years. Although highly efficient, with long-term cancer-specific survival (CSS) rates approaching almost 100%, ART is associated with considerable long-term consequences, particularly cardiovascular toxicity and increased risk of secondary malignancies (SMN). Therefore, active surveillance (AS) and adjuvant chemotherapy (ACT) were developed as alternative treatment options. While AS prevents patient overtreatment, it is associated with strict follow-up regimens and increased radiation exposure due to repeated imaging. Due to equivalent CSS rates to ART, and lower toxicity, one course of adjuvant carboplatin presents the cornerstone of chemotherapy for CSI patients. CSS is almost 100% for patients with CSI seminoma, regardless of the chosen treatment option. Therefore, a personalized approach in treatment selection is preferred. Currently, routine radiotherapy for CSI seminoma patients is no longer recommended. Instead, it should be reserved for patients who are unfit or unwilling for AS or ACT. Identification of prognostic factors for disease relapse allowed for the development of risk-adapted treatment strategy and stratification of patients in low-risk and high-risk groups. Although risk-adapted policy needs further validation, surveillance is currently recommended in low-risk patients, while ACT is reserved for patients with a higher risk of relapse.     

Management options for stage I seminoma

Stage I seminoma is the most common clinical scenario among patients with testicular cancer. Following orchiectomy, various treatment alternatives (adjuvant radiotherapy, surveillance, chemotherapy) can be offered that yield similar efficacy results and definitive cure is the rule. However, there is no consensus on the optimal management choice and considerable debate has been raised in recent years. The pros and the cons associated with each therapy, as well as their long-term outcomes are discussed in this review. Overall burden of treatment needed, therapy-related morbidity, economic costs, quality of life issues and patient preferences should all be considered. Refinement in the knowledge of predictive factors for relapse and mounting experience with both surveillance and adjuvant chemotherapy have led to consideration of risk-adapted treatment strategies as an alternative to standard radiotherapy. Although this model needs to be improved and validated, active close surveillance for low-risk patients and adjuvant therapy for those uncompliant or at higher risk of relapse seem to be acceptable options for patients with stage I seminoma.     

The surgical management of stage I and stage II lung cancer

There have been recent advances in the treatment of non-small cell lung cancer (NSCLC). Surgical resection remains the cornerstone in the treatment of patients with stages I and II NSCLC. Anatomic lobectomy combined with hilar and mediastinal lymphadenectomy constitutes the oncologic basis of surgical resection. The surgical data favor video-assisted thoracic surgery (VATS) lobectomy over open lobectomy and have established VATS lobectomy as a gold standard in the surgical resection of early-stage NSCLC. However, the role of sublobar pulmonary resection, either anatomic segmentectomy or nonanatomic wedge resection, in patients with subcentimeter nodules may become important.     

The management strategies for stage I seminoma

About 80% of men with seminomatous testicular germ-cell cancer are diagnosed with stage I disease. For many years, the standard treatment for this patient group has been radiation to para-aortic and iliacal lymph nodes at the same side as the orchiectomy. However, iliac radiotherapy is unnecessary in patients without prior inguinal or scrotal surgery. Furthermore, in recent years, other treatment modalities for this patient group have evolved. The use of single-agent carboplatin has shown promising results, similar to the effects obtained by radiotherapy. In addition, surveillance after primary orchiectomy with no additional treatment is found to be a safe follow-up for many of these patients. On the basis of new knowledge about primary tumour risk factors, it is now possible to identify patients at a particular high risk of relapse (rete testis invasion, primary tumour size > 4 cm, or both). This will be a helpful tool to identify patients who can be safely included into a surveillance strategy, and those who could have adjuvant treatment. The final decision about treatment will depend on risk factors, capacity of the healthcare service to carry out frequent follow-up examinations and the patient's own preferences. In this paper, we will discuss advantages and disadvantages of the various treatment options in the management of stage I seminoma.     

Treatment of stage I testicular germ-cell tumors

More than a half of patients with testicular cancer are diagnosed with clinical stage I disease. In this setting, definitive cure is the rule. However, there is no consensus on the optimal treatment choice. A literature review (1990–2005) was performed in order to identify the pros and the cons associated with each therapy, as well as their long-term outcomes. Several treatment alternatives yield similar efficacy results. Thus, therapy-related morbidity, economic costs, quality-of-life issues, and patient preferences should be considered. Refinement in the knowledge of predictive factors for relapse and amounting experience with both surveillance and adjuvant chemotherapy have led to consideration of risk-adapted treatment policies as an alternative to more traditional approaches (i. e., prophylactic irradiation for seminomas and retroperitoneal lymph node dissection for non-seminomas). In conclusion, with cure rates approaching 100%, close surveillance for low-risk patients and adjuvant chemotherapy for those at high risk of relapse seems the preferred option for clinical stage I testicular cancer, in both seminoma and non-seminoma cases.     

Late recurrence of stage I malignant melanoma

Although the introduction of well-established risk factors has made the clinical course and prognosis of malignant melanoma disease much more predictable, in a considerable number of patients the disease's course is still not as expected. One group to which this applies are stage I melanoma patients who develop metastatic disease after 10 years or more of a disease-free interval. In our series of 94 such patients, 6 developed late relapse of their disease. The subsequent survival of these patients did not relate to any of the primary tumors' characteristics, but to the pattern of the late recurrence. Four patients with visceral metastases were dead within 1 to 5 years following relapse, one patient with lymph node involvement is alive with metastases, and another patient with skin metastases has no signs of disease following surgery and immunotherapy. Our conclusion is that malignant melanoma patients should be placed under close follow-up for the rest of their lives.     

Intraoperative I brachytherapy for high-risk stage I non-small cell lung carcinoma

Purpose: Preliminary assessment of feasibility, efficacy, acute and chronic side effects associated with permanent intraoperative placement of ¹²⁵I vicryl mesh brachytherapy in a select group of high-risk Stage I NSCLC who have undergone video-assisted thoracoscopic resection (VATR).

Methods and Materials: From January 8, 1997 to March 16, 1998, 23 patients with Stage I NSCLC at high risk for conventional surgery due to cardiopulmonary compromise underwent combined VATR and intraoperative placement of ¹²⁵I seeds embedded in vicryl mesh. Seeds embedded in vicryl suture were attached with surgical clips to a sheet of vicryl mesh, and thoracoscopically inserted over the target area (tumor bed and staple line) with nonabsorbable suture or surgical clips. A total dose of 100–120 Gy prescribed to the periphery of the target area (defined as the staple line and tumor bed with a 1-cm margin) was delivered.

Results: The mean target area covered was 48 cm² (range 40–72) and mean total activity was 22 mCi (range 17.2–28.2). The median length of postoperative stay was 7 days. The median follow-up was 11 months (range 2–20). Postoperative CT scans of the chest revealed no dislodgement of the seeds and no local recurrence in any patient.Three patients developed distant metastasis (1 died 6 months postoperatively; the other 2 are currently alive with disease). One patient developed an ipsilateral recurrence in the right lower lobe after having had a right upper lobe resection. There were 3 postoperative deaths due to medical comorbid conditions or surgical complications (1 in the immediate postoperative period). Pulmonary function testing performed 3 months after implantation revealed no significant difference between preoperative and postoperative values: mean preoperative FVC was 2.3 L (range 1.31–3.0) and postoperative FVC was 2.2 L (range 1.1–3.9), p = 0.42; mean preoperative FEV₁ was 1.2 L (range 0.71–2.2 ), and postoperative FEV₁ was 1.5 L (range 0.8–2.9), p = 0.28.

Conclusion: Review of early data suggests that intraoperative ¹²⁵I vicryl mesh brachytherapy in high-risk Stage I NSCLC is potentially effective and well tolerated, with no significant decline in measurable pulmonary function studies and no increase in postoperative complications. Longer follow-up is needed to determine ultimate local control and survival.     

Radiotherapy in inoperable stage I lung cancer

In 38 cases of Stage I lung cancer, for which surgery was not indicated because of poor cardiopulmonary function or other reason, radical irradiation yielded excellent results. The five year survival rate was 42.1%, the 10-year survival rate 28.4% and the 15-year survival rate 17.1%. Postradiation complications which can be life-threatening, were acceptably low in incidence, and there was no radiation-related death. The results support the concept of radical irradiation being acceptable as a treatment modality for Stage I lung cancer if the patients concerned cannot have surgery because of poor cardiopulmonary function or some other reason.     

Management of stage I nonseminomatous germ-cell tumors

Following orchiectomy in patients with stage 1 nonseminomatous germ-cell tumors (NSGCT), there are three treatment options. Retroperitoneal lymph-node dissection (RPLND) is currently the treatment of choice in the United States and can be both diagnostic and therapeutic but is associated with surgical morbidities. Surveillance is the least invasive but carries the highest potential for relapse and can be timely and costly for both patient and physician. Primary chemotherapy avoids the morbidity of surgery while achieving similar survival rates, albeit with potentially significant side effects. The advantages and disadvantages of each treatment modality are discussed.     

Aggressive stage I grade 1 endometrial carcinoma.

BACKGROUND. Patients with Stage I Grade 1 endometrial carcinoma have an excellent prognosis and a 10-year survival rate of more than 90%. In every clinical series, however, a few patients in this group have recurrence and die of their disease. METHODS. The authors reviewed 80 patients with Stage I Grade 1 endometrial carcinoma treated at their institution from 1955-1980. Eight patients died of recurrent disease within 4 years of diagnosis. The authors studied multiple clinical and histopathologic features, estrogen receptor (ER) and progesterone receptor (PR) status, DNA flow cytometric characteristics, and the expression of c-myb, H-ras, and neu oncogenes. Results were compared with those for a control group of 11 patients who survived more than 10 years free of disease. RESULTS. The authors identified the following four statistically significant adverse prognostic factors: myometrial invasion, vascular invasion, 8 or more mitoses per 10 high-power fields, and an absence of PR. Residual tumor, aneuploidy, and high proliferative activity were associated with a more aggressive behavior, although the relationship did not reach statistical significance. CONCLUSIONS. All patients who died of disease within 4 years had tumors with two or more of the significant adverse prognostic factors.     

Intraoperative 125I brachytherapy for high-risk stage I non-small cell lung carcinoma

Purpose: Preliminary assessment of feasibility, efficacy, acute and chronic side effects associated with permanent intraoperative placement of ¹²⁵I vicryl mesh brachytherapy in a select group of high-risk Stage I NSCLC who have undergone video-assisted thoracoscopic resection (VATR).Methods and Materials: From January 8, 1997 to March 16, 1998, 23 patients with Stage I NSCLC at high risk for conventional surgery due to cardiopulmonary compromise underwent combined VATR and intraoperative placement of ¹²⁵I seeds embedded in vicryl mesh. Seeds embedded in vicryl suture were attached with surgical clips to a sheet of vicryl mesh, and thoracoscopically inserted over the target area (tumor bed and staple line) with nonabsorbable suture or surgical clips. A total dose of 100–120 Gy prescribed to the periphery of the target area (defined as the staple line and tumor bed with a 1-cm margin) was delivered.Results: The mean target area covered was 48 cm² (range 40–72) and mean total activity was 22 mCi (range 17.2–28.2). The median length of postoperative stay was 7 days. The median follow-up was 11 months (range 2–20). Postoperative CT scans of the chest revealed no dislodgement of the seeds and no local recurrence in any patient.Three patients developed distant metastasis (1 died 6 months postoperatively; the other 2 are currently alive with disease). One patient developed an ipsilateral recurrence in the right lower lobe after having had a right upper lobe resection. There were 3 postoperative deaths due to medical comorbid conditions or surgical complications (1 in the immediate postoperative period). Pulmonary function testing performed 3 months after implantation revealed no significant difference between preoperative and postoperative values: mean preoperative FVC was 2.3 L (range 1.31–3.0) and postoperative FVC was 2.2 L (range 1.1–3.9), p = 0.42; mean preoperative FEV₁ was 1.2 L (range 0.71–2.2 ), and postoperative FEV₁ was 1.5 L (range 0.8–2.9), p = 0.28.Conclusion: Review of early data suggests that intraoperative ¹²⁵I vicryl mesh brachytherapy in high-risk Stage I NSCLC is potentially effective and well tolerated, with no significant decline in measurable pulmonary function studies and no increase in postoperative complications. Longer follow-up is needed to determine ultimate local control and survival.