Adjuvant hormone therapy after radiation or surgery for localized or locally advanced prostate cancer

Opinion statement Prostate cancer is being diagnosed at an earlier age and earlier disease stage than previously and increasing numbers of relatively young men are receiving potentially curative radical prostatectomy or radiotherapy for early prostate cancer. Although many of these men have an excellent outcome, a significant proportion subsequently experience disease recurrence or cancer-related death. Men with unfavorable tumor characteristics at the time of radical prostatectomy or radiotherapy are particularly at high risk of experiencing disease recurrence. One strategy to improve outcome for these men is adjuvant hormone therapy (hormone therapy administered immediately after therapy of primary curative intent). Surgical castration (bilateral orchiectomy), medical castration using the luteinizing hormone-releasing hormone (LHRH) agonist goserelin, and antiandrogen monotherapy have been investigated as adjuvant hormone therapy to radical prostatectomy and radiotherapy, and each therapy has demonstrated clinical benefits because of a significant improvement in disease-free survival. Furthermore, data are available to indicate that adjuvant hormone therapy achieved by goserelin or bilateral orchiectomy improves overall survival, particularly in men at high risk of progression. Because the effects of LHRH agonists are reversible, they provide a more acceptable method of adjuvant therapy compared to bilateral orchiectomy, particularly in the adjuvant setting, and are preferred by patients. However, the adverse effects on quality of life, in particular on sexual interest and function and bone mineral density, may limit the use of LHRH agonists in some patients. However, these parameters are maintained with nonsteroidal antiandrogens. The first data from the Early Prostate Cancer program indicate that adjuvant bicalutamide 150 mg is associated with a significant improvement in progression-free survival after radical prostatectomy or radiotherapy. Gynecomastia and breast pain are the most common side effects associated with bicalutamide therapy. Medical or surgical castration in combination with an antiandrogen (combined androgen blockade) is another option for use as an adjuvant hormone therapy. However, no study has reported on the use of combined androgen blockade in this setting. Adjuvant hormone therapy provides clinicians with another treatment option for patients with early prostate cancer and unfavorable tumor characteristics.     

Survival benefit associated with adjuvant androgen deprivation therapy combined with radiotherapy for high- and low-risk patients with nonmetastatic prostate cancer

BACKGROUND: The use of adjuvant androgen deprivation therapy (ADT) combined with radiotherapy has become common in low-risk patients, although clinical trials have focused primarily on high-risk patients. This study examines the effectiveness of adjuvant ADT combined with radiotherapy for a wide range of patients treated in the 1990s. METHODS AND MATERIALS: Prostate cancer survival was examined in a population based cohort of 31,643 patients aged 65 to 85 years who were diagnosed with nonmetastatic prostate cancer and treated with external beam radiotherapy and/or brachytherapy. Instrumental variable analysis methods were used to control for selection bias. RESULTS: Patients with stage T3/T4 disease who received adjuvant ADT experienced improved 5-year and 8-year survival. No survival advantage was observed for men with T1/T2 disease during this interval. CONCLUSION: High-risk patients who receive primary radiotherapy have benefited from adjuvant ADT, whereas low-risk patients with disease confined to the prostate have not yet benefited from adjuvant therapy within the first 8 years after treatment. These findings are consistent with practice guidelines, which recommend adjuvant ADT for patients with high-risk disease.     

Hormonoradiothérapie exclusive dans la prise en charge du cancer du sein de la personne âgée : cas clinique et revue de la littérature des schémas hypofractionnés

Normofractionated radiotherapy is standard for adjuvant management of patients treated with breast conservative surgery for breast cancer. However, many elderly patients are not eligible to such strategy, either because of concurrent diseases, or because the tumor is inoperable. Several protocols of exclusive radiotherapy have been reported in the literature, frequently using hypofractionated radiotherapy and endocrine therapy. We report a case of a patient treated with exclusive endocrine and radiotherapy and address the state of the art on hypofractionated schemes for the management of elderly breast cancer patients. While hypofractionated radiotherapy does not compromise the oncologic or cosmetic outcome, there is no prospective data that assesses the place of radiotherapy for the exclusive treatment of elderly patients. This strategy should be further assessed in clinical randomized trial.     

Impact of locoregional treatment on the early-stage breast cancer patients: a retrospective analysis

Although adequate locoregional treatment improves local and regional control in early-stage breast cancer, uncertainty still exists about the role of locoregional therapy with respect to survival. To study the impact of surgery and radiotherapy on locoregional control and survival, we combined the data of three European Organisation for Research and Treatment of Cancer (EORTC) Breast Cancer Group trials including early-stage breast cancer patients with long-term follow-up. Risk ratios (RR) were estimated for locoregional recurrence and overall survival using Cox regression models. All analyses were adjusted for tumour size, nodal status, age, adjuvant radiotherapy, adjuvant chemotherapy and trial. The combined data-set consisted of 3648 patients. The median follow-up period was 11 years. 5.9% of the patients who underwent mastectomy and 10.8% of the patients who underwent breast-conserving therapy had a locoregional recurrence (P<0.0001). The risk of death after breast-conserving therapy was similar compared with mastectomy (RR 1.07, P=0.37). Adjuvant radiotherapy after mastectomy was associated with a lower risk for locoregional recurrence (RR 0.43, P<0.001) and death (RR 0.73, P=0.001). Patients with 1-3 positive nodes benefited the most from radiotherapy after mastectomy. Breast-conserving therapy was associated with an impaired locoregional control. However, breast-conserving therapy was not associated with a worse overall survival. Adjuvant radiotherapy in mastectomised patients was associated with both a significantly superior locoregional control and overall survival. The effect of adjuvant radiotherapy was most profound in patients who had 1-3 positive nodes.     

Adjuvant Treatment Approaches after Radical Prostatectomy with Lymph Node Involvement

Objective: The aim of this study was to evaluate the adjuvant treatment preferences and effects on disease progression in patients with pathologically positive lymph node prostate cancer. Methods: Patients who underwent radical prostatectomy from the prostate cancer database of the Turkish Urooncology Association with lymph node involvement were included in the study. Database includes prostate cancer patients from many experience Urooncology centers of Turkey. Adjuvant treatment approaches and the factors that effect the PSA recurrrence was analysed. Results: Postoperative median 2 (1-3) lymph nodes were found to be positive, and the median lymph node density was reported as 0.13 (0.07-0.25). Seventy-four percent of patients received adjuvant treatment postoperatively. Seventy four of the patients (46.54%) received hormonal therapy in combination with radiotherapy; 47 of them (29.55%) received only hormonal treatment and 20(12.57%) only received radiotherapy. The number of lymph nodes removed was less in the group requiring adjuvant treatment, and this group had a higher rate of surgical margin positivity and seminal vesicle invasion. In addition, adjuvant treatment group had a statistically significant higher lymph node density. There was no significant difference in Kaplan-Meier method comparing 5-year PSA recurrence-free survival in patients with and without adjuvant therapy. When the patient clustered as non-adjuvant, only hormonal therapy and hormonal therapy with radiotherapy, a significant survival advantage was found in the hormonal therapy with radiotherapy group compared to the other two groups (p=0.043). Conclusion: No significant difference was found between two groups in terms of time until PSA recurrence during our follow-up. In subgroup analysis survival advantage was found in the hormonal therapy with radiotherapy group compared to non-adjuvant and only hormonal therapy groups.     

新型冠状病毒病疫情期间乳腺癌患者的术后辅助放疗

乳腺癌是中国女性发病率最高的恶性肿瘤,术后辅助放疗是乳腺癌综合治疗的重要组成部分。新型冠状病毒病疫情给乳腺癌的放疗带来很大的挑战。新型冠状病毒感染的患者中,院内感染占很大比重。新型冠状病毒感染的肿瘤患者比非肿瘤患者的极重症比例高。在新型冠状病毒病疫情期间,为减少患者感染的风险,需要从严掌握放疗指征,必要时可以适当延迟放疗。必须放疗时,建议采用大分割放疗模式。     

Adjuvant radiotherapy in endometrial carcinoma

Endometrial cancer is a common female malignancy, affecting approximately 40,000 women per year. Despite the publication of several prospective randomized trials, there continues to be controversy regarding the use of adjuvant radiation therapy in endometrial cancer management. It is clear that most women with early-stage, low-risk disease will do well without adjuvant therapy. Intermediate-risk patients are at risk for local-regional relapse, and radiotherapy has been shown to effectively reduce this risk without significantly impacting overall survival. The absence of a clear impact on survival has resulted in a lack of consensus regarding the use of radiotherapy in intermediate-risk patients. At the same time, the patterns of failure in intermediate-risk patients have resulted in differing recommendations regarding appropriate radiotherapy targets. High-risk patients are at risk for both local and distant failure, and chemotherapy has been shown to improve outcome in these patients. High-risk patients are also at risk for local failure, and targeted radiotherapy may be appropriate. In this article, we discuss the controversies surrounding the use of adjuvant radiotherapy in endometrial cancer using an evidence-based approach.     

Radiosurgery to the Postoperative Surgical Cavity: Who Needs Evidence?

There is a growing interest in adjuvant radiosurgery after resection of hematogenous brain metastases. This is exemplified by the approximately 1000 cases reported in mainly retrospective series. These cases fall into four paradigms: adjuvant radiosurgery as an alternative to whole-brain radiotherapy (WBRT), radiosurgery neoadjuvant to the surgical resection, radiosurgery as an intensification of adjuvant WBRT, and adjuvant radiosurgery for patients having failed prior WBRT. These procedures seem well tolerated, with an approximate 5% risk of radiation necrosis. Although crude local control rates for each strategy seem improved over surgery alone, multiple biases make comparisons with standard WBRT difficult without prospective data. Because evidence lags behind clinical practice, an upcoming intergroup trial will aim to clarify the value of the most common tumor bed radiosurgery strategy by randomizing oligometastatic patients between adjuvant WBRT and adjuvant radiosurgery.     

A retrospective study of the safety of BCNU wafers with concurrent temozolomide and radiotherapy and adjuvant temozolomide for newly diagnosed glioblastoma patients

Despite aggressive therapy, most patients with glioblastoma multiforme (GBM) die within 2 years of diagnosis. The efficacy and safety of carmustine (BCNU) wafers followed by radiotherapy have been demonstrated in patients with malignant glioma. However, there is a reluctance to recommend them for newly diagnosed GBM patients due to the potential toxicity of BCNU wafers combined with temozolomide (TMZ) chemotherapy and radiotherapy. The purpose of this study was to assess the safety of BCNU wafers implanted at initial surgery, followed by concurrent TMZ and radiotherapy, and then adjuvant TMZ for the treatment of newly diagnosed GBM. We conducted a retrospective analysis of clinic and hospital records of 21 newly diagnosed GBM patients who received multimodal therapy at Florida Hospital Cancer Institute from January 2003 to December 2005. Three of 21 patients had grade 3 toxicities (two with cerebritis, one with psychosis). Grade 4 toxicities were not observed. Median overall survival was 17 months, median progression-free survival was 8.5 months, and 2-year survival was 39%. Multimodal treatment with surgery, BCNU wafers, radiotherapy, and TMZ did not result in a notable increase in significant toxicities. Survival outcomes were comparable to those in other studies in which patients were treated with concurrent TMZ and radiotherapy followed by adjuvant TMZ. Thus, the implantation of BCNU wafers prior to TMZ and radiotherapy appears safe in newly diagnosed GBM patients.     

Surgical and adjuvant radiation therapy of resectable retroperitoneal soft tissue sarcomas in adults.

Primary soft tissue sarcoma of the retroperitoneum is a rare disease. A series of 11 evaluable adult patients with retroperitoneal soft tissue sarcomas is reported. These patients were treated with complete surgery and adjuvant radiation therapy (total dose from 50 to 64 Gy) using an 18 MeV linear accelerator. After a median follow-up of 48 months (range, 6-84), 4 patients had a local-regional recurrence, 3 had distant metastases, and 4 died of progressive disease. Four-year estimated disease-free survival was 54.5% and overall survival was 70%. Treatment was well tolerated by most patients: 7 patients experienced moderate gastrointestinal toxicity, mainly nausea and diarrhea, during radiotherapy; 2 cases had weight loss > 15% at the end of the therapy; and chronic ileitis was observed in 2 cases. We conclude that adjuvant radiotherapy seems to reduce the incidence of local-regional recurrences in these patients. No radiation-induced irreversible injury was observed, but one young woman had amenorrhea after radiotherapy. Controlled clinical trials are warranted to define the role and effectiveness of adjuvant radiotherapy and/or chemotherapy in retroperitoneal soft tissue sarcomas.     

Limb-sparing treatment for soft tissue sarcomas: Influence of prognostic factors

At present, limb-sparing surgery is the most appropriate and acceptable treatment available for sarcomas of the extremities, although the right balance between conservative therapy and maximum efficacy has yet to be found. A better knowledge of prognostic factors may help in planning the appropriate strategy for each case. Eighty patients underwent limb-sparing surgery for limb sarcomas (17 had surgery alone; 19 had neo-adjuvant hyperthermic antiblastic perfusion combined or not with postoperative radiotherapy, and 44 had adjuvant radiotherapy). Univariate and multivariate analyses were made to detect statistically significant differences between subgroups and identify the more significant subset of prognostic factors. Only microscopically positive surgical margins were related to a greater risk of local recurrence, whereas overall survival was compromised by high grade and large tumor size. © 1996 Wiley-Liss, Inc.     

Adjuvant radiotherapy and health-related quality of life of patients at intermediate risk of recurrence following primary surgery for oral squamous cell carcinoma

Controversy surrounds who should receive adjuvant radiotherapy in patients with intermediate risk of recurrence of oral squamous cell carcinoma following primary surgery. The aim of this study was to compare health-related quality of life (HRQOL) outcomes of those who received adjuvant radiotherapy to those who did not in patients at intermediate-risk of recurrence. A total of 765 oral cancer patients were treated at the Regional Maxillofacial Unit, Liverpool from 1995 to 2007. After excluding 124 patients (87 primary radiotherapy, 23 died within 90 days, 14 had insufficient information for determining risk group status), 169 were low-risk, 271 intermediate-risk and 201 were high-risk. In the intermediate-risk group, 33% had adjuvant radiotherapy. Allowing for attrition, more than 70% had University of Washington quality of life data (UW-QOL). Cumulative survival was similar in those with and without adjuvant radiotherapy in a subset of patients at intermediate risk. There was little difference in overall HRQOL scores and in the socio-emotional subscale scores of the UW-QOL. However, there was a significant difference in physical subscale scores and the issue most affected was saliva. These findings support better stratification of risk in the intermediate group, and the plausibility of withholding radiotherapy without compromising survival. This can have dramatic positive benefits on patient physical outcomes, in particular saliva. Where adjuvant radiotherapy is necessary, it is appropriate to minimise adverse effects through measures such as intensity-modulated radiation therapy.     

Additional therapy for high-risk prostate cancer treated with surgery: what is the evidence?

Single-modality approaches to the treatment of high-risk prostate cancer, whether radical prostatectomy or external-beam radiotherapy, have yielded disappointing results. Treatment intensification has, thus, been the subject of considerable research activity in recent years. This review will discuss the evidence for neoadjuvant and adjuvant treatment approaches when surgery is chosen as the definitive therapy for high-risk prostate cancer. Particular emphasis will be placed on the randomized trials, both completed and in progress. Trials investigating adjuvant radiotherapy, androgen-deprivation therapy and chemotherapy will each be discussed in turn. Among these, only adjuvant radiotherapy has been shown to prolong survival after surgery, and the recently published evidence for this benefit will be discussed in detail.     

Clinical Course of Central Neurocytoma with Malignant Transformation—An Indication for Craniospinal Irradiation

Central neurocytoma is generally considered to be a benign tumor and the literature suggests that a cure may be attained by surgery ± adjuvant focal irradiation. However, there is a need for change in the therapeutic strategy for the subgroup of patients with aggressive central neurocytoma. An example case is presented and the literature on central neurocytoma cases with malignant features and dissemination via the cerebrospinal fluid is reviewed and the radiotherapeutic strategies available for central neurocytoma treatment is discussed. Nineteen cases including the present report with a malignant course and cerebrospinal fluid dissemination have been described to date, most of them involving an elevated MIB-1 labeling index. Our case exhibited atypical central neurocytoma with an initially elevated MIB-1 labeling index (25–30 %). The primary treatment included surgery and focal radiotherapy. Three years later the disease had disseminated throughout the craniospinal axis. A good tumor response and symptom relief were achieved with repeated radiation and temozolomide chemotherapy. Central neurocytoma with an initially high proliferation activity has a high tendency to spread via the cerebrospinal fluid. The chemo- and radiosensitivity of the tumor suggest a more aggressive adjuvant therapy approach. Cases with a potential for malignant transformation should be identified and treated appropriately, including irradiation of the entire neuroaxis and adjuvant chemotherapy may be considered.     

Impact of adjuvant therapy on survival of patients with early-stage uterine papillary serous carcinoma

PURPOSE: To determine the efficacy of adjuvant therapy in patients with early-stage uterine papillary serous carcinoma. METHODS AND MATERIALS: Data were collected on all surgically staged Stage I-II uterine papillary serous carcinoma patients. Statistical analyses were performed using the Kaplan-Meier and Cox proportional hazards regression methods. RESULTS: Of 68 patients, 50 had Stage I and 18 had Stage II disease; 35 underwent adjuvant treatment, including radiotherapy in 26, chemotherapy in 7, and combined RT and chemotherapy in 2. The remaining 33 were treated expectantly. The median follow-up was 56 months (range 1-173). The 5-year overall survival rate was 69%. Of 19 patients with disease limited to the endometrium, 10 received no additional therapy, 3 of whom developed recurrence. However, all 9 women who underwent adjuvant treatment remained free of disease. Patients receiving adjuvant therapy with chemotherapy or radiotherapy had a prolonged 5-year overall and disease-free survival compared with those who were treated expectantly (85% vs. 54%, p = 0.002 for overall survival and 85% vs. 49%, p = 0.01 for disease-free survival). In multivariate analysis, adjuvant therapy (p = 0.035) and the absence of lymphovascular space invasion (p = 0.001) remained as independent prognostic factors for improved survival. CONCLUSION: Adjuvant therapy with chemotherapy or radiotherapy improves the survival of women with early-stage uterine papillary serous carcinoma.     

Postoperative radiation therapy of pT2-3N0M0 esophageal carcinoma–a review

Esophageal cancer is one of the most malignant gastrointestinal cancers worldwide. Despite advances in surgical technique, 5-year survival in pathologic stage T2-3N0M0 esophageal squamous cell carcinoma patients who are treated with surgery alone is still poor. The addition of adjuvant radiotherapy may confer a benefit for these patients. However, not all patients could get a benefit from radiotherapy and patients with esophageal squamous cell carcinoma receiving radiotherapy seem to have a disparity in treatment response. Thus, identifying effective prognostic indicator to complement current clinical staging approaches is extremely important. Those prognostic factors could give rise to a novel prognostic stratification system, which serve as criteria for selecting patients for adjuvant therapy. Consequently, it may help to define the subgroups who are more likely to benefit from postoperative radiation therapy.     

Survival benefits of adjuvant chemotherapy with oral doxifluridine (5'-DFUR) following radiotherapy in patients with unresectable pancreatic cancer.

BACKGROUND AND OBJECTIVES: The combination of 5-fluorouracil and radiotherapy is thought to be the most effective treatment for locally unresectable pancreatic carcinoma. The outcomes, however, are far from acceptable from the viewpoint of long-term survival. We assessed the survival benefits of oral adjuvant chemotherapy with doxifluridine (5'-DFUR) following radiotherapy for patients with the disease. METHODS: Thirty-five consecutive patients who underwent bypass surgery and radiotherapy for localized advanced unresectable adenocarcinoma of the pancreas head were retrospectively reviewed in regard to disease progression and survival. Ten of the 35 patients underwent adjuvant chemotherapy with 5'-DFUR after radiotherapy in an outpatient setting. RESULTS: The 1-year survival for patients treated with radiotherapy alone was 29%. The 1-, 2-, and 3-year survivals for patients treated with the adjuvant chemotherapy after radiotherapy were 50, 40, and 30%, respectively (P = 0.0069, log-rank test). The elevation of tumor markers was delayed (P = 0.0346) and local control rate was improved (P = 0.0475) in patients with chemotherapy. Multivariate analysis demonstrated that the adjuvant chemotherapy with 5'-DFUR was a significant independent prognostic factor as well as tumor size. CONCLUSIONS: The adjuvant chemotherapy with 5'-DFUR following radiotherapy led to a significant prolongation of the survival for patients with unresectable localized pancreatic cancer.     

胰腺癌新辅助与辅助放疗进展

新辅助和辅助放疗在胰腺癌中的作用还不明确.对于可切除的胰腺癌首选手术,新辅助放疗只是手术存在困难时的补充;对于交界可切除及局部晚期的胰腺癌,基于化疗基础上联合放疗的新辅助治疗方案,可提高R0切除率并提高局控率;由于现有的临床试验的结果不一致,胰腺癌术后辅助放疗存在争议,但对于非R0切除及pN1的患者,建议在辅助化疗的基...     

A Systematic Overview of Radiation Therapy Effects in Ovarian Cancer

A systematic review of radiation therapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on radiation therapy for ovarian cancer is based on data from six randomized trials. Moreover, data from one prospective study and three retrospective studies were used. In total, 10 scientific articles are included, involving 1 282 patients. The results were compared with those of a similar overview from 1996 including 15 042 patients. The conclusions reached can be summarized in the following points: There is no scientific documentation supporting adjuvant radiotherapy for early-stage, low-risk patients.No studies have been reported where adjuvant radiotherapy has been compared with no adjuvant therapy in early-stage, high-risk patients.Adjuvant radiotherapy, either whole abdominal irradiation or intraperitoneal p³², has been compared with adjuvant chemotherapy in early-stage, high-risk patients. There is no scientific evidence to show that there is a difference in efficacy.There is some evidence to suggest that adjuvant radiotherapy after radical surgery leads to an increase in disease-free survival rate for patients with advanced-stage ovarian cancer.There is little documentation on long-term side effects (second malignancy) after adjuvant radiotherapy and no conclusions can be drawn.     

Paclitaxel and carboplatin adjuvant therapy alone or with radiotherapy for resected nonsmall cell lung carcinoma: a feasibility study of the Minnie Pearl Cancer Research Network

BACKGROUND: The objective of this study was to determine the feasibility and toxicity of paclitaxel and carboplatin given in the adjuvant setting alone for patients with resected Stage IB disease and combined with radiotherapy for patients with resected Stages II and IIIA disease and selected patients with Stage IIIB and IV disease (Revised International System for Staging of Lung Cancer). METHODS: One hundred two patients with resected nonsmall cell lung carcinoma were treated in the postoperative period with 3 courses of paclitaxel 200 mg/m(2) intravenously (i.v.) over 1 hour and carboplatin area under the curve of 6 i.v. every 3 weeks for 3 courses. Patients with Stage IB received no further therapy, and those with higher stages also subsequently received radiotherapy plus concurrent weekly paclitaxel and carboplatin over 6 weeks. The median age was 61 years, with 56 men and 46 women, and the predominant histologic type was adenocarcinoma. Twenty pneumonectomies, 80 lobectomies, and 2 other procedures were performed. Ninety percent of the patients (92 of 102) received all 3 courses of adjuvant paclitaxel and carboplatin (84% received full doses). Seventy-three percent received full doses of radiotherapy and concurrent weekly chemotherapy (49 of 67 patients), and 14 others received greater than 75% of the radiotherapy and concurrent chemotherapy. RESULTS: Toxicity of the chemotherapy was mild with only three hospitalizations for neutropenia and fever and no treatment-related deaths. Severe hypersensitivity occurred in six patients (6%). Concurrent radiation therapy and weekly chemotherapy also was well tolerated with the exception of Grade 3-4 esophagitis observed in 27% (17 of 67 patients). Follow-up was short with a median of 10 months, and 65% of all patients remained progression free. CONCLUSIONS: Three courses of paclitaxel and carboplatin is tolerable, feasible, and can be delivered in most patients in the adjuvant setting. Subsequently, in higher stage patients, concurrent postoperative radiation therapy and weekly paclitaxel and carboplatin is well tolerated and delivered in most patients. Definitive prospective randomized Phase III adjuvant trials are warranted.