Neoadjuvant therapy followed by prostatectomy for clinically localized prostate cancer

The results of this assessment of the literature indicated that neoadjuvant therapy followed by prostatectomy may improve long-term outcomes for patients with high-risk localized disease. In addition, this approach provides a paradigm for evaluating the activity and mechanism of action of new agents as correlative studies are facilitated by the availability of tumor tissue before and after therapy. The authors determined that a multidisciplinary approach involving oncologists, urologists, and pathologists is critical to the success of this model. Recent and ongoing studies of neoadjuvant therapy followed by prostatectomy were reviewed.     

前列腺癌术前新辅助治疗的研究进展

根治性前列腺切除术是治疗局限性前列腺癌的重要方法,但前列腺癌患者术前准确临床分期较困难,常出现肿瘤切除不彻底、术后肿瘤易复发和转移.研究证实术前新辅助内分泌治疗(NHT)能缩小前列腺体积,降低PSA水平,降低手术切缘阳性率,但精囊受侵率及盆腔淋巴结转移无减少,未发现无PSA进展率及肿瘤特异性生存率方面的优势.目前的资料尚不能证实所有患者术前都必须进行新辅助内分泌治疗.     

Neoadjuvant chemotherapy followed by concurrent chemo-radiation therapy in locally advanced nasopharyngeal carcinoma

PURPOSE: To evaluate the efficacy and outcomes of neoadjuvant cisplatinum and epirubicin chemotherapy followed by concurrent cisplatinum chemotherapy with radiotherapy in patients with locally advanced nasopharyngeal carcinoma. METHODS AND MATERIALS: One hundred ten patients (80 male, 30 female) with locally advanced nasopharyngeal carcinoma, staged according to the 1997 International Union Against Cancer/American Joint Committee on Cancer classification system as IIB (n = 9), III (n = 20), IVA (n = 32), and IVB (n = 49), World Health Organization types II (n = 25) and III (n = 85), were included in this protocol between January 1998 and July 2000 at King Faisal Specialist Hospital and Research Centre. Patients underwent two cycles of induction chemotherapy with cisplatinum 100 mg/m(2) and epirubicin 70 mg/m(2) on Days 1 and 21, followed by a radical course of radiotherapy (6,600 cGy in 6.5 weeks, 200 cGy/fraction) starting on Day 42, with three cycles of concurrent cisplatinum 25 mg/m(2) for 4 days on Days 42, 63, and 84. RESULTS: Of 110 patients included in this study, intracranial extension was present in 32 (29%), and nodal stage was N3 in 49 (45%). Complete remission and partial remission were achieved in 87 patients (79%) and 23 patients (21%), respectively. At a median follow-up for surviving patients of 37 months (22-55 months), 49 of 110 patients (44%) had failed treatment: 12 with local, 9 with regional nodes, 4 locoregional, 5 locoregional plus distant areas, and 19 with distant metastases. At the time of writing, 34 patients had died; all deaths were related to the patients' cancer except for 1 patient with treatment-related toxicity. Three-year actuarial overall survival, relapse-free survival, locoregional control, and distant metastasis-free survival rates were 89%, 78%, 88%, and 89% for patients with stage IIB; 71%, 70%, 89%, and 74% for stage III; 68%, 49%, 61%, and 77% for stage IVA; and 70%, 45%, 60%, and 69% for stage IVB, respectively. One patient received only one induction cycle; all others received two cycles; however, 9 of them required 20% reduction in the second cycle dose. Ninety patients (82%) completed two or more concurrent cycles of cisplatinum. Rates of Grade 3 and 4 reactions after induction chemotherapy were as follows: anemia 1% and 0%, leukopenia 8% and 4%, nausea 27% and 0%, vomiting 25% and 0%, and infection 4% and 4%, respectively. Acute Grade 3 and 4 reactions were also observed during chemoradiotherapy: anemia 1% and 0%, leukopenia 31% and 4%, nausea 35% and 0%, vomiting 26% and 2%, infection in 4% and 2%, mucositis in 49% and 0%, and skin reaction in 39% and 0%, respectively. CONCLUSIONS: Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy is a safe and effective method of treatment for locally advanced nasopharyngeal carcinoma. Further investigations in prospective studies are required to evaluate this regimen.     

ⅠB2-ⅡA期局部巨块型宫颈癌的新辅助化疗

背景与目的宫颈癌是一种严重未写妇女健康的疾病,目前手术仍是早期宫颈癌的主要治疗方法,但局部巨块型宫颈癌患者单纯手术疗效差,顺铂为基础的联合化疗用于局部晚期宫颈癌患者,可提高疗效和生存率.本研究的目的是探讨新辅助化疗对早期巨块型宫颈癌的疗效.方法对2001年9月至2002年2月收治的102例ⅠB2-ⅡA期局部巨块型宫颈癌患者分为两组,即术前化疗组和单纯手术对照组,各51例,术前化疗组术前给予PVB方案化疗1个疗程,化疗后10 d左右行广泛子宫切除和盆腔淋巴结清扫术,观察化疗后局部肿瘤体积的变化,并比较两组盆腔淋巴结转移、宫颈肌层浸润深度、脉管癌栓、宫旁及阴道切缘肿瘤浸润情况.结果术前化疗组停药后10 d进行评价,无完全缓解病例,部分缓解率为41.2%,淋巴结转移率(11/51)、脉管癌栓(5/51)及宫颈深肌层浸润率(13/51)均低于单纯手术对照组(22/51、16/51、24/51)(P＜0.05);术中出血量(116.82±45.50)ml, 明显低于未单纯手术对照组(158.93±50.69)ml(P＜0.01).3年无瘤生存率术前化疗组为80.4%,单纯手术对照组为60.8%,两组比较,差异有统计学意义(P＜0.05).结论早期巨块型宫颈癌术前化疗可缩小局部病灶以利手术,可降低淋巴结转移率,提高无瘤生存率,并不增加手术并发症.     

Neoadjuvant chemotherapy followed by extrapleural pneumonectomy in malignant pleural mesothelioma.

PURPOSE: To investigate neoadjuvant chemotherapy with cisplatin and gemcitabine followed by extrapleural pneumonectomy with or without radiation therapy in patients with potentially resectable malignant pleural mesothelioma (MPM). PATIENTS AND METHODS: Eligible patients had MPM with clinical stage T1-3, N0-2, M0 disease considered to be completely resectable and a WHO performance status of 0 to 2. Neoadjuvant chemotherapy consisted of three cycles of cisplatin 80 mg/m2 on day 1 and gemcitabine 1,000 mg/m2 on days 1, 8, and 15, given every 28 days. Surgery had to consist of a complete extrapleural pneumonectomy, including resection of pericardium and diaphragm. Postoperative radiotherapy was to be considered for all patients. RESULTS: Nineteen patients with MPM were included in this pilot study. According to the European Organization for Research and Treatment of Cancer prognostic score, two patients were in the good prognosis group, and 17 patients were in the poor prognosis group. The response rate to neoadjuvant chemotherapy was 32%. The major toxicity was thrombocytopenia. Extrapleural pneumonectomy was performed in 16 patients with no perioperative mortality. Major surgical complications occurred in six patients, and all were treated successfully. Thirteen patients received postoperative radiotherapy. The median survival time was 23 months. Two patients remain alive and free of disease 41 and 38 months after initiation of therapy. CONCLUSION: For patients with potentially operable MPM, the availability of active and well-tolerated chemotherapy regimens, the fact that extrapleural pneumonectomy can be safely performed after neoadjuvant chemotherapy in an experienced center, and the promising results regarding survival in our pilot study warrant further investigation of the role of neoadjuvant chemotherapy in a multimodality strategy.     

Neoadjuvant chemotherapy followed by surgery in lung cancer: Indian scenario

A vast majority of the patients with lung cancer in India present as advanced stage disease and a significant number among them have nonmetastatic locally advanced tumors which require multimodality management with curative intent. We analyzed the treatment outcome of the patients treated with of neoadjuvant chemotherapy followed by surgery approach. This was a retrospective analysis of institutional database of all non–small cell lung cancer patients who underwent neoadjuvant chemotherapy followed by curative intent surgery with/without adjuvant therapy from 2012 to 2018. Patients included were those with N2 disease; T4 or T3 disease requiring pneumonectomy or extensive adjacent structures resection. Mediastinal staging was done by PET-CT (Positron Emission Tomography - Computed Tomography) along with Endobronchial ultrasound in most cases. All the patients received platinum-based doublet chemotherapy for 3-6 cycles before surgery. Response to neoadjuvant chemotherapy and survival were analyzed. A total of 44 patients fulfilled the eligibility criteria. Majority were males (81.8%) and smokers (75%). Squamous cell carcinoma (50%) was the most common subtype. Total 43.2% patients had either T3 or T4 tumors. N2 disease (either single station or multistation) was observed in 67.2% cases. A complete pathologic response was observed in 22.7% cases. In addition, 6.8% patients had ≤10% viable tumor in the resected specimen. Residual disease in N2 nodes were found in 25% cases. Median follow-up was 35.9 months. Patients with residual N2 disease showed a trend toward inferior survival. In multivariate analysis smoking, pretreatment tumor category and final pathologic stage were significant factors for disease free but not for overall survival. This study shows that neoadjuvant chemotherapy is a feasible and effective modality for downstaging locally advanced cases of non–small cell lung cancer among the Indian patients. Patients with less than 10% residual tumor burden had a better survival. The role of surgery in those with persistently N2 needs further evaluation.     

Concurrent chemoradiotherapy followed by adjuvant chemotherapy in Asian patients with nasopharyngeal carcinoma: toxicities and preliminary results.

PURPOSE: Nasopharyngeal carcinoma (NPC) is endemic in Singapore. Nearly 60% of the patients diagnosed with NPC will present with locally advanced disease. The North American Intergroup study 0099 reported improved survival outcome in patients with locally advanced NPC who received combined chemoradiotherapy when compared to radiotherapy alone. Hence we explored the feasibility and efficacy of a similar protocol in our patients. METHODS AND MATERIALS: Between June 1996 and December 1997, 57 patients were treated with the following schedule as described. Radical radiotherapy (RT) of 66-70 Gy to the primary and neck with cisplatin (CDDP) 25 mg/m2 on days 1-4 given by infusion over 6-8 hours daily on weeks 1, 4, and 7 of the RT. This is followed by a further 3 cycles of adjuvant chemotherapy starting from week 11 from the first dose of radiation (CDDP 20 mg/m2/d and 5-fluorouracil [5-FU] 1 gm/m2/d on days 1-4 every 28 days). RESULTS: The majority of patients (68%) had Stage IV disease. About 54% of patients received all the intended treatment; 75% received all 3 cycles of CDDP during the RT phase and 63% received all three cycles of adjuvant chemotherapy. The received dose intensity of CDDP and 5-FU of greater than 0.8 was achieved in 58% and 60% of the patients respectively. Two treatment-related deaths due to reactivation of hepatitis B and neutropenic sepsis respectively, were encountered. At median follow-up of 16 months, 14 patients had relapsed, 12 systemically and 2 loco-regionally. CONCLUSION: Due to the acceptable tolerability of such a protocol in our cohort of patients, we have embarked on a Phase III study to confirm the results of the 0099 Intergroup study in the Asian context.     

Neoadjuvant chemotherapy followed by radical surgery compared to concurrent chemotherapy in stage I b2- III b cervical cancer

For the treatment of bulky cervical cancer, the most promising modality is surgery followed neoadjuvant chemotherapy( NAC-S)or concurrent chemoradiation therapy (CCRT). The purpose of this study is to compare the efficacy and complications associated with each treatment. The CCRT group included significantly more elderly and advanced patients than the NAC-S group. From 2001 to 2005, 76 consecutive previously untreated patients with bulky cervical cancer staged as I b2- III b were treated with NAC-S or CCRT. The response rate of NAC was 63% and 84% of patients received radical surgery. There was no significant difference in the intra-pelvic or extra-pelvic recurrence rate between NAC-S and CCRT group. In addition, there was no significant difference in 3-year relapse-free survival or overall survival. When we consider the bias, these results suggest that CCRT is superior to NAC-S.     

Neoadjuvant chemotherapy followed by radiotherapy in epidermoid carcinoma of anus

AIM AND BACKGROUND: The purpose of this study was to analyze the efficacy of neoadjuvant fluorouracil-cisplatin chemotherapy combined with radiotherapy for anal cancer. METHODS: Fourteen patients with epidermoid carcinoma of the anal canal were analyzed. Treatment consisted of three cycles of 5-fluorouracil (1000 mg/m2 bolus on days 1-5) and cisplatin (60 mg/m2 bolus on day 1) followed by 50.4 Gy to the pelvis and perineum over 5.5 weeks. Both inguinal lymphatics were irradiated with an identical dose schedule. The median follow-up was 78 months. RESULTS: Five-year overall survival rate and sphincter preservation rate was 85.1% and 85.7%, respectively. Response to chemoradiotherapy was the only significant factor with univariate analysis (P = 0.031). There were no complications of RTOG grade 3 or higher. CONCLUSIONS: Neoadjuvant chemotherapy with a cisplatin-based regimen rather than concurrent regimen plus radiotherapy may decrease complications without compromising survival or sphincter preservation.     

Quality control of radical prostatectomy: a feasibility study

The aim of this study was to assess whether the quality of the surgical act could be an important prognostic factor for patients undergoing radical prostatectomy. This study also aims to investigate whether the surgical quality can be assessed by any means. Questionnaires were collected from 23 different institutes including 232 radical prostatectomies (RPr) performed for T1T2 prostate cancer. Blood loss, duration of surgery, margin status, postoperative prostate specific antigen (PSA) and urinary incontinence were analysed and correlated with the yearly number of RPr performed. The mean values obtained for each parameter were very different in the various centres. The outcome in terms of tumour control and incontinence could not be related to a higher or lower number of RPr performed. Quality control of RPr is feasible on the basis of an analysis of a few parameters, such as surgical margins, postoperative PSA and incontinence, that might recognise urologists that perform better or poorer than a proposed average.     

Neoadjuvant intra-arterial infusion chemotherapy combined with hormonal therapy for locally advanced breast cancer

To determine the efficacy of combined neoadjuvant intra-arterial infusion chemotherapy and hormonal therapy for treating locally advanced breast cancer, we compared the outcomes of patients with or without this therapy, and also assessed histologic response. Ninety-four patients with locally advanced breast cancer (stage IIIa, 56; stage IIIb, 38). Nineteen stage IIIa and 17 stage IIIb patients received intra-arterial plus hormonal therapy while 37 stage IIIa and 21 stage IIIb patients with similar ages and follow-up durations did not. Treated patients received intra-arterial epirubicin plus oral medroxy-progesterone. Five-year disease-free survival rates were 77.5% for intra-arterially treated and 33.0% for other patients in stage IIIa, and 70.5% for intra-arterially treated and 38.1% for other patients in stage IIIb. Five-year overall survival rates were 94.4% for intra-arterially treated and 61.7% for other patients in stage IIIa, and 90.9% for intra-arterially treated and 56.3% for other patients in stage IIIb. Ten-year overall survival rates in stage IIIb were 90.9% for treated and 22.5% for other group patents. All differences were statistically significant (p<0.05). Good histologic response to intra-arterial therapy was seen in 75% of the primary tumors and 71% of involved lymph nodes. Neoadjuvant intra-arterial therapy with hormonal therapy yielded better survival rates than no intra-arterial therapy or our previous intra-arterial regimen.     

Negative impact of neoadjuvant hormonal therapy on detecting biochemical recurrence after radical prostatectomy

International Journal of Clinical Oncology - Routine use of neoadjuvant hormonal therapy (NHT) before radical prostatectomy (RP) is not recommended, but it is sometimes performed to reduce the...     

Radical prostatectomy: surgical techniques and preliminary results

Prostatic cancer (PC) is a frequent finding in aged men. In fact, 3% of males have the chance to die of PC. Radical prostatectomy by the retropubic approach with pelvic lymphadenectomy was made in 97 males. The treatment was performed in the urological department of the MSMSU urological chair from 1995 to 2001. 69 patients followed up for 3-64 months after the operation were eligible for analysis of the outcomes. The patients had the following PC stages: T1--11 patients, T2--44 patients, T3--14 patients. Prostate-specific antibodies ranged within 2.9-67.8 ng/ml (the mean level 16.7 ng/ml). The results of the treatment were satisfactory in 65 (94.2%) of 69 patients. The operation did not take more than 2.5 hours, mean blood loss was under 870 ml. Adequate urination after the catheter was removed resumed in 41 (59.4%) of 69 patients. Active urinary incontinence was observed within one year after the operation in 25 (36.2%) patients, total incontinence--in 3 (4.3%) patients. 51% patients retained the erectile function after nerve-sparing operation. Most of the patients had an unevenful postoperative period. During the follow-up 3 patients died of acute myocardial infarction (n = 1), intestinal cancer (n = 1) and distant PC metastases (n = 1). A postoperative fall in the PSA level under 0.3 ng/ml occurred in 49 (71%) patients, under 2 ng/ml in 7 patients (10%). In 19% of patients with pT2-3 the PCA rose over 2.0 ng/ml. Radical prostatectomy is indicated for patients with local prostatic cancer (stage T1 or T2) and probable survival from 10 to 15 years and longer. A nerve-sparing, sphincter-sparing and ablastic variant of this operation is widely used world-wide and is a method of choice for therapy of patients with retropubic prostatic cancer.     

Radiotherapy vs. hormonal therapy for the management of locally recurrent prostate cancer following radical prostatectomy

Forty patients out of 273 who had undergone radical surgery for adenocarcinoma of the prostate at Duke University Medical Center between 1970 and 1983 developed palpable, biopsy-proven local recurrence without evidence of distant metastases. Of these 40 patients, 16 were treated with irradiation alone (Group I) and 16 patients were treated with hormonal therapy only (Group II). The remaining eight patients received either no therapy (4 patients) or both radiotherapy and hormonal therapy (4 patients) and are not further analyzed. Local control, as determined by palpation, was achieved in 14/16 patients in Group I versus only 7/16 patients in Group II (p less than 0.05). Subsequently, six patients in each group have relapsed, all with distant metastases. Thus, 8/16 patients in Group I remain alive without disease versus only 1/16 patients in Group II (p less than 0.05). There was no difference in survival between Groups I and II. No patient in either group has died free of disease. In Group I, 4/16 patients have died with cancer. Six of 16 in Group II have died with cancer. Severe complications occurred more frequently following irradiation compared to hormonal therapy. Irradiation appears to be superior to hormonal therapy in achieving local control and prolonging disease-free survival. Neither therapy conveys an advantage over the other in terms of survival. Thus, even if local control is achieved, distant failure may be an inevitable consequence of locally recurrent prostate cancer. Therefore, prevention of local recurrence after radical prostatectomy is of paramount importance. These findings support the use of adjuvant post-operative irradiation in patients at high risk for local recurrence.     

Induction chemotherapy followed by radical local therapy for locally advanced non-small cell lung cancer

Many patients who receive a diagnosis of non-small cell lung cancer (NSCLC) have locally advanced disease at initial presentation. Historically, these patients were treated with primary thoracic radiation therapy and had poor long-term survival rates, secondary to both progression of local disease and development of distant metastases. With the goal of improving clinical outcomes, multiple concepts of combined-modality therapy for locally advanced NSCLC have been investigated. The rationale for using chemotherapy in the induction regimen is to eliminate subclinical metastatic disease while improving local control. The optimal treatment of locally advanced NSCLC continues to evolve, but combined-modality therapy has led to improved survival rates compared to treatment with radiation alone and has become the new standard of care. This report reviews the major trials that have investigated various combinations of surgery, radiation therapy, and chemotherapy in the treatment of locally advanced NSCLC.     

Neoadjuvant chemotherapy followed by surgical cytoreduction in advanced epithelial ovarian cancer

AIMS: To study the role of neoadjuvant chemotherapy (NACT) followed by surgical cytoreduction in the management of advanced epithelial ovarian cancers. MATERIALS AND METHODS: A retrospective analysis of 82 patients with advanced epithelial ovarian cancers (stage IIIC and IV) who were treated with NACT followed by surgical cytoreduction between 1995 and 2004 was performed. Response to NACT, optimal cytoreduction rate, disease-free survival and overall survival were analyzed. RESULTS: There were 59 patients (72%) with stage IIIC disease and 23 (28%) with stage IV disease. Diagnosis was established by imaging, ascitic fluid cytology and CA-125 estimations in 75% and by laparotomy in 25% of the patients. After NACT, complete response occurred in 17 patients (20.7%), 50 (61.0%) had partial response and no response was documented in 15 (18.3%) patients. Optimal surgical cytoreduction could be achieved in 72% of the patients. At the median follow-up of 34 months (range 6-102 months), 5-year disease-free and overall survivals were 31 and 32% respectively. The median disease free interval was 25.4 months. On multivariate analysis, degree of optimal cytoreduction was the only factor (P < 0.05) affecting survival. CONCLUSIONS: NACT followed by surgical cytoreduction is a promising treatment strategy for the management of advanced epithelial ovarian cancers. A significant number of patients exhibit response to NACT. Downstaging following NACT leads to higher optimal cytoreduction rates and improved survival in comparison to historical controls.