Emerging minimally invasive procedures for focal treatment of organ-confined prostate cancer

Prostate cancer is the most common malignancy amongst American men. However, the majority of prostate cancer diagnoses are of low risk, organ-confined disease. Many men elect to undergo definitive treatment, but may benefit from focal therapy to maintain continence and potency. This review reports the mechanism of action and outcomes of emerging focal therapies for prostate cancer. We report the mechanism of action of focal cryotherapy, high intensity focused ultrasound, focal laser ablation, and irreversible electroporation. In addition, we reviewed the largest studies available reporting rates of urinary incontinence, erectile dysfunction, biochemical recurrence-free survival (ASTRO), and post-operative adverse events for each procedure. Each treatment modality stated has a unique mechanism in the ablation of cancerous cells. Genito-urinary symptoms following these studies report incontinence and erectile dysfunction rates ranging from 0–15% and 0–53%, respectively. Biochemical disease-free survival was reported using the ASTRO definition. Some treatment modalities lack the necessary follow-up to determine effectiveness in cancer control. No focal therapy studies reported serious adverse events. These minimally invasive procedures are feasible in a clinical setting and show promising functional and disease control results with short to medium-term follow-up. However, each treatment requires additional robust prospective studies as well as its own unique domain to determine biochemical recurrence free survival to properly determine their role in treatment of organ-confined prostate cancer.     

Radiofrequency ablation: a minimally invasive technique with multiple applications

PURPOSE: Radiofrequency ablation (RFA) of soft tissue, which has recently been approved by the United States Food and Drug Administration, destroys tumor cells by delivering an electrical current through a 15-gauge needle. This study evaluated RFA for patients with hepatic malignancies considered unresectable because of their distribution, their number, and/or the presence of liver dysfunction. PATIENTS AND METHODS: Between November 1997 and February 1999, 50 patients with 132 unresectable hepatic metastases underwent RFA of tumors from 0.5 to 9 cm in diameter. There were 41 colorectal metastases in 22 patients, 13 hepatomas in seven patients, 37 neuroendocrine metastases in six patients, and 41 noncolorectal metastases in 15 patients. Real-time ultrasonography was used to guide RFA, and lesions were ablated by applying temperatures of approximately 100 degrees C for 8 minutes. Overlapping ablations were used for larger lesions. In patients with multiple lesions, RFA was performed simultaneously with cryosurgery, resection, and/or hepatic arterial infusion. RESULTS: RFA was undertaken percutaneously on an outpatient basis in 13 patients (25 lesions). The remaining patients underwent RFA via laparoscopy (21 patients; 58 lesions) or celiotomy (16 patients; 49 lesions); mean hospital stay was 1 and 5 days, respectively. RFA was the sole therapy in 28 patients and was additional therapy in 22 patients. At a median follow-up of 6 months, 27 patients were free of disease, 17 were alive with disease, and six had died of their disease (three colon, three melanoma). Three patients whose disease recurred at a prior RFA site underwent successful percutaneous RFA. Overall, there was a significant postoperative reduction in levels of carcinoembryonic antigen, alpha-fetoprotein, serotonin, and 5-hydroxyindoleacetic acid. Intraoperative ultrasonography identified unrecognized hepatic lesions in 12 of 37 patients (32%); these lesions were successfully ablated. When performed with cryosurgery, RFA reduced the morbidity of multiple freezes. DISCUSSION: RFA is a safe and effective alternative for the ablation of unresectable hepatic malignancies and when used adjunctively can reduce the morbidity of cryosurgery. Percutaneous and laparoscopic RFA can be performed effectively with less than 24 hours of hospitalization. Intraoperative ultrasonography is essential for accurate staging.     

Percutaneous radiofrequency ablation: minimally invasive therapy for renal tumors

Currently, up to 60% of renal tumors are detected incidentally by abdominal imaging. Most of these tumors are small and localized to the kidney. Owing to the shift to lower stage at diagnosis, radical nephrectomy has fallen out of favor and has been replaced by nephron-sparing surgery. Currently, partial nephrectomy is the treatment of choice for patients with small renal tumors. As the trend towards less invasive therapy continues, laparoscopic and percutaneous ablation techniques have gained popularity for the treatment of renal tumors in patients who are high-risk surgical candidates, or have a solitary kidney, limited renal function or multifocal disease. Percutaneous radiofrequency ablation is a safe, minimally invasive treatment option for those patients.     

Percutaneous radiofrequency ablation: minimally invasive therapy for renal tumors

Currently, up to 60% of renal tumors are detected incidentally by abdominal imaging. Most of these tumors are small and localized to the kidney. Owing to the shift to lower stage at diagnosis, radical nephrectomy has fallen out of favor and has been replaced by nephron-sparing surgery. Currently, partial nephrectomy is the treatment of choice for patients with small renal tumors. As the trend towards less invasive therapy continues, laparoscopic and percutaneous ablation techniques have gained popularity for the treatment of renal tumors in patients who are high-risk surgical candidates, or have a solitary kidney, limited renal function or multifocal disease. Percutaneous radiofrequency ablation is a safe, minimally invasive treatment option for those patients.     

New advances in focal therapy for early stage prostate cancer

Introduction: Prostate focal therapy offers men the opportunity to achieve oncological control while preserving sexual and urinary function. The prerequisites for successful focal therapy are to accurately identify, localize and completely ablate the clinically significant cancer(s) within the prostate. We aim to evaluate the evidence for current and upcoming technologies that could shape the future of prostate cancer focal therapy in the next five years.

Areas covered: Current literature on advances in patient selection using imaging, biopsy and biomarkers, ablation techniques and adjuvant treatments for focal therapy are summarized. A literature search of major databases was performed using the search terms ‘focal therapy’, ‘focal ablation’, ‘partial ablation’, ‘targeted ablation’, ‘image guided therapy’ and ‘prostate cancer’.

Expert commentary: Advanced radiological tools such as multiparametric magnetic resonance imaging (mpMRI), multiparametric ultrasound (mpUS), prostate-specific-membrane-antigen positron emission tomography (PSMA-PET) represent a revolution in the ability to understand cancer function and biology. Advances in ablative technologies now provide a menu of modalities that can be rationalized based on lesion location, size and perhaps in the near future, pre-determined resistance to therapy. However, these need to be carefully studied to establish their safety and efficacy parameters. Adjuvant strategies to enhance focal ablation are under development.     

Application of minimally invasive treatment for early gastric cancer

BACKGROUND AND OBJECTIVES: Although various types of minimally invasive treatment have emerged as the best front-line therapies for early gastric cancer (EGC), there have been no established indications that these attempts are applicable. The purpose of this study was to propose indications for the application of minimally invasive therapy for EGC. METHODS: A total of 566 patients with EGC who had undergone gastrectomy with D2 or more extended lymphadenectomy, from July 1993 to December 1997 were retrospectively analyzed. The risk factors that determine lymph node metastasis were investigated by univariate and multivariate analysis. RESULTS: The rate of lymph node metastasis was 11.8% for all EGC, 3.4% for mucosal cancer, and 21.0% for submucosal cancer. Lymph node metastasis was associated with submucosal invasion, larger tumor size, undifferentiated histology, and the presence of lymphatic or blood vessel invasion (LBVI) by univariate and multivariate analyses. When LBVI was absent, there was no lymph node metastasis if the tumor was smaller than 2.5 cm with differentiated histology, and smaller than 1.5 cm with undifferentiated histology, regardless of depth of invasion. Extra-perigastric lymph node metastases were noted in patients with submucosal tumors that have LBVI while none of mucosal cancer showed extra-perigastric lymph node metastases. CONCLUSIONS: Minimally invasive treatment can be possibly applied for patients with EGC using these four independent risk factors for lymph node metastasis in EGC. For mucosal cancers, EMR is indicated for EGCs without lymph node involvement based on tumor size and histology. When we found LBVI by pathologic examination after EMR, gastrectomy with D1 lymph node dissection is mandatory. For submucosal cancers, patients with small tumors could be treated with laparoscopic wedge resection without lymph node dissection. However, patients with larger sized tumors or tumors with LBVI should be treated with extended (D2) lymph node dissection.     

Tumor focality in prostate cancer: implications for focal therapy

In recent years, there has been a growing interest in focal treatment for prostate cancer. Although widely used for the treatment of tumors of the breast and kidney, focal treatment for prostate cancer remains a controversial area. Criticism of focal prostate therapy has been based on the fact that prostate cancer is a multifocal disease. Until now, little attention has been paid to distinguishing between men with unifocal and those with multifocal disease because such information has little clinical relevance when treatment is aimed at the whole gland irrespective of the volume or number of cancers in the prostate. In this Review, we summarize existing knowledge and examine the issue of prostate cancer focality in the context of focal treatment.     

乳腺癌微创治疗研究进展

良好的手术效果不仅要彻底地切除肿瘤,同时也要保证患者的生活质量。因此,迫切要求外科医生改变理念,不断改进手术方式。随着现代科技的深入发展,微创治疗,即以最小的损伤达到最佳效果,已成为21世纪肿瘤学者追求的目标。今天外科手术已进入一个微创与功能保存时代,人们已不再满足乳房肿瘤的单纯医治,而且更要求在形体、功能和心理得到康复,对于临床早期的乳腺癌,常规的乳腺手术范围严重影响患者的生存质量。因此,人们正在探索各种替代常规手术的微创手术,其中包括射频消融、高强度聚焦超声、冷冻治疗、激光治疗、电化学治疗、前哨淋巴结活检代替腋窝淋巴结清除术和腋腔镜治疗等。     

乳腺癌微创治疗研究进展

良好的手术效果不仅要彻底地切除肿瘤,同时也要保证患者的生活质量.因此,迫切要求外科医生改变理念,不断改进手术方式.随着现代科技的深入发展,微创治疗,即以最小的损伤达到最佳效果,已成为21世纪肿瘤学者追求的目标.今天外科手术已进入一个微创与功能保存时代,人们已不再满足乳房肿瘤的单纯医治,而且更要求在形体、功能和心理得到康复,对于临床早期的乳腺癌,常规的乳腺手术范围严重影响患者的生存质量.因此,人们正在探索各种替代常规手术的微创手术,其中包括射频消融、高强度聚焦超声、冷冻治疗、激光治疗、电化学治疗、前哨淋巴结活检代替腋窝淋巴结清除术和腋腔镜治疗等.     

Targeted therapy in hormone refractory prostate cancer

Despite recent progress in the treatment of hormone refractory prostate cancer—with a survival advantage seen with docetaxel chemotherapy—there remains a need for further improvements in this important patient group. Novel targeted agents have promise both as single agents, and in combination with chemotherapy. However, further work is needed to identify therapeutic targets and to develop active agents with a view to introducing them into standard clinical practice.     

Minimally invasive therapy for bladder and prostate cancer

Recently, minimally invasive therapy has been a key word in the medical field. Many new therapies have been developed in the field of urology. In this area, bacillus Calmette-Guerin (BCG) instillation therapy, transurethral resection of the bladder tumor and intra-arterial infusion with irradiation therapy are noted as minimally invasive therapies for bladder cancer. Laparoscopic prostatectomy, brachytherapy, three-dimensional conformal radiotherapy (3D-CRT) and high-intensity focused ultrasound (HIFU) have also been developed as minimally invasive therapies for prostate cancer. Though the establishment of the validity of each treatment will still take time, the best treatment for each patient should be chosen case by case, including considerations of postoperative quality of life and economic efficiency.     

Patient selection for hemiablative focal therapy of prostate cancer

BACKGROUND:

The application of focal therapy for low‐risk prostate cancer (PCa) depended on appropriate patient selection. No definitive criteria existed to characterize patients who may potentially benefit from an organ‐sparing approach. We evaluated pretreatment clinical parameters that may predict unilateral PCa amenable to hemigland thermoablation.

METHODS:

In total, 538 patients with complete data from the Duke Prostate Center (DPC) Outcomes database with low‐ to low‐intermediate–risk PCa (prostate‐specific antigen<10 ng/mL, biopsy Gleason score ≤7, and clinical stage T1c‐T2b) treated with radical prostatectomy (RP) were included in the dataset. Patients underwent diagnostic prostate biopsy (PBx) at Duke or community hospitals from 1996 to 2006. Clinical and biopsy parameters were assessed as to the ability to predict PCa unilaterality verified by RP pathology.

RESULTS:

The strongest predictor of pathologic unilaterality was PBx unilaterality. The sensitivity and specificity for biopsy unilaterality to predict pathologic unilaterality was 88.4% and 34%, with a positive predictive value of 28% and a negative predictive value of 91%. PBx unilaterality (odds ratio [OR] = 3.88; 95% confidence interval [CI], 2.14‐7.05; P < .0005) and negative family history of PCa (OR = 1.83; 95% CI, 1.09‐3.05; P = .21) was associated with a higher probability of unilateral disease by multivariate regression.

CONCLUSIONS:

Two pretreatment clinical variables were significantly predictive of unilateral PCa: negative family history of PCa and PBx unilaterality. These variables may be used to select men with low‐ to low‐moderate–risk PCa for hemiablation. Further work is necessary to decrease the false‐negative and false‐positive rates associated with PBx to improve predictability for PCa laterality. Cancer 2009. © 2009 American Cancer Society.     

Costs of medical care after open or minimally invasive prostate cancer surgery: a population-based analysis

BACKGROUND:

Evidence suggests that minimally invasive radical prostatectomy (MRP) and open radical prostatectomy (ORP) have similar short‐term clinical and functional outcomes. MRP with robotic assistance is generally more expensive than ORP, but it is not clear whether subsequent costs of care vary by approach.

METHODS:

In the Surveillance, Epidemiology, and End Results (SEER) cancer registry linked with Medicare claims, men aged 66 years or older who received MRP or ORP in 2003 through 2006 for prostate cancer were identified. Total cost of care was estimated as the sum of Medicare payments from all claims for hospital care, outpatient care, physician services, home health and hospice care, and durable medical equipment in the first year from the date of surgical admission. The impact of surgical approach on costs was estimated, controlling for patient and disease characteristics.

RESULTS:

Of 5445 surgically treated prostate cancer patients, 4454 (82%) had ORP and 991 (18%) had MRP. Mean total first‐year costs were more than $1200 greater for MRP compared with ORP ($16,919 vs $15,692; P = .08). Controlling for patient and disease characteristics, MRP was associated with 2% greater mean total payments, but this difference was not statistically significant. First‐year costs were greater for men who were older, black, lived in the Northeast, had lymph node involvement, more advanced tumor stage, or greater comorbidity.

CONCLUSIONS:

In this population‐based cohort of older men, MRP and ORP had similar economic outcomes. From a payer's perspective, any benefits associated with MRP may not translate to net savings compared with ORP in the first year after surgery. Cancer 2012;118: 3079–86. © 2011 American Cancer Society.     

Targeted therapy for cancer

The recent approval in the US and Europe of imatinib (Gleevac?) for patients with bcr/abl-positive chronic myelogenous leukemia and the considerable public interest in new anticancer drugs that take advantage of specific genetic defects that render the malignant cells more likely to respond to specific treatment are driving a new era of integrated diagnostics and therapeutics. This review highlights the history of targeted anticancer therapies with a focus on the development of molecular diagnostics for hematologic malignancies and the emergence of trastuzumab (Herceptin?)-based therapy for advanced breast cancer. The potential of pharmacogenomic strategies and the use of high-density genomic microarrays to classify and select therapy for cancer are emphasized. This review also considers the widely held view that, in the next 5–10 years, the clinical application of molecular oncology and molecular diagnostics will further revolutionize the drug discovery and development process, customize the selection, dose and route of administration of existing and new therapeutic agents, and truly personalize medical care for cancer patients.     

Analysis of minimally invasive directional antennas for microwave tissue ablation

Abstract

Purpose: Microwave ablation (MWA) applicators capable of creating directional heating patterns offer the potential of simplifying treatment of targets in proximity to critical structures and avoiding the need for piercing the tumour volume. This work reports on improved directional MWA antennas with the objectives of minimising device diameter for percutaneous use (≤ ～13 gauge) and yielding larger ablation zones.

Methods: Two directional MWA antenna designs, with a modified monopole radiating element and spherical and parabolic reflectors are proposed. A 3D-coupled electromagnetic heat transfer with temperature-dependent material properties was implemented to characterise MWA at 40 and 77 W, for 5 and 10?min. Simulations were also used to assess antenna impedance matching within liver, kidney, lung, bone and brain tissue. The two antenna designs were fabricated and experimentally evaluated with ablations in ex vivo tissue at the two power levels and treatment durations (n?=?5 repetitions for each group).

Results: The computed specific absorption rate (SAR) patterns for both antennas were similar, although simulations indicated slightly greater forward penetration for the parabolic antenna. Based on simulations for antennas inserted within different tissues, the proposed antenna design appears to offer good impedance matching for a variety of tissue types. Experiments in ex vivo tissue showed radial ablation depths of 19?±?0.9?mm in the forward direction for the applicator with spherical reflector and 18.7?±?0.7?mm for the applicator with parabolic reflector.

Conclusion: These results suggest the applicator may be suitable for creating localised directional ablation zones for treating small and medium-sized targets with a percutaneous approach.     

微创手术治疗前列腺癌的疗效研究

目的：探讨经腹腔入路腹腔镜微创手术治疗前列腺癌患者的临床效果。方法选取经腹腔入路腹腔镜微创手术治疗的53例患者作为微创组,及采用开放经耻骨前列腺癌根治术治疗的47例患者作为对照组,比较两组患者手术相关指标及并发症的发生率。结果两组患者术后淋巴结阳性率、精囊阳性率、切缘阳性率差异均无统计学意义（P﹥0.05）;微创组患者的手术时间长于对照组患者,差异有统计学意义（P﹤0.05）;微创组患者术中出血量、导尿管留置时间、胃肠道功能恢复时间、术后下床时间、住院时间均低于对照组患者,差异有统计学意义（P﹤0.05）;术后3个月、6个月,两组患者尿控率、生化复发率差异均无统计学意义（P﹥0.05）。结论经腹腔入路腹腔镜微创手术治疗前列腺癌与传统开腹手术效果相当,但是具有手术创伤小、恢复快的优势。     

Interstitial devices for minimally invasive thermal ablation by high-intensity ultrasound

Interstitial ultrasound applicators have been proposed for treating deep-seated tumours that cannot be reached with extra-corporeal high-intensity focused ultrasound. In addition, interstitial ultrasound offers several advantages compared with conventional ablation technology (radiofrequency, microwaves, cryotherapy) in terms of penetration, speed of coagulation, ability to direct and control the thermal lesion and compatibility with image monitoring. The ultrasound source is brought as close as possible to the target in order to minimize the effects of attenuation and phase aberration along the ultrasound pathway. The present paper is a review of the interstitial applicators that were described during the last decade in the literature. It is presented in three sections. The technical aspects common to all applicators are first described. For example, most-described applicators are sideview applicators whose active element is water-cooled and operates at rather high frequency (above 3?MHz) in order to promote heating. Then the different potential techniques for monitoring treatment administered by the interstitial route are presented and illustrated through a review of image-guided interstitial thermal ablation. Three major techniques of imaging are used for guiding interstitial treatment: MRI, ultrasound and fluoroscopy. The third section goes in to further detail on diverse described medical applications.     

Experience with conformal proton therapy for early prostate cancer

A study was conducted to evaluate the use of proton beam therapy for the treatment of organ-confined prostate cancer. This is a preliminary assessment of treatment-related morbidity and tumor response. Sixteen patients with T1-T2b prostate cancer underwent proton beam therapy. Acute and late toxicity was scored according to the National Cancer Institute Common Toxicity Criteria Grading System (version 2.0, April 1999) and to the Radiation Therapy Oncology Group grading system, respectively. Local control was assessed using magnetic resonance imaging (MRI) and prostate-specific antigen (PSA) values. Although skin toxicity and bladder irritability were commonly observed, none of the patients developed grade III or IV toxicity. Of 9 patients in whom the primary lesion was detected by MRI, partial response and no change (NC) was observed in 6 (66.7%) and 3 (33.3%) patients, respectively. Four patients presented normal PSA value before treatment due to the previous endocrine therapy. However, the other 12 patients with elevated PSA value before treatment showed complete response. No patients showed PSA failure within the median follow-up period of 11.9 months. Although longer follow-up is necessary, minimum toxicity and good short-term clinical responses were observed following proton beam therapy in T1-T2 prostate cancer patients.