Frontiers of Radiation Therapy and Oncology最新文献

Recurrence after radiotherapy is not uncommon. Facing this situation, physicians have the choice between numerous possibilities, including simple observation, androgen ablation, salvage radical prostatectomy, cryotherapy, brachytherapy, high-intensity focused ultrasound, chemotherapy and nonconventional therapy. There is, however, no standard treatment and each case must be individually discussed.

Prostate cancer progression is commonly manifested by obstructive uropathy, regional lymphatic metastases and hematogenous metastases to the axial skeleton. Radiotherapy is a mainstay in the palliation of symptomatic metastatic prostate cancer and is most often used for the palliation of painful metastatic bone lesions, resulting in a relief of pain in about 80-90% of patients and a reduction of analgesics. In metastatic disease compromising the integrity of the spinal cord or a nerve root, radiotherapy can be used as an urgent intervention to minimize neurological dysfunction and local progression or as an adjunct to surgical decompression. Local progression is often associated with hematuria, ureteric obstruction and perineal discomfort. Symptoms of metastatic lymphadenopathy like leg edema and back discomfort caused by pelvic or paraaortic metastases are related to the immediate anatomic structures affected. Radiotherapy for localized hormone-refractory prostate cancer has an excellent local control rate; nevertheless, the prognosis is poor, the majority of patients failing with distant metastasis within few years. The role of radiotherapy in hormone-refractory and metastatic prostate cancer, considering the patient's individual situation, are presented and discussed.

Patients with advanced prostate cancer under primary androgen deprivation therapy will practically all develop progression, often associated with an asymptomatic increase in prostate-specific antigen. Recent reports are demonstrating an increased use of androgen deprivation therapy as primary or neoadjuvant treatment; however, meager clinical evidence supports the use of such treatment regimens for localized prostate cancer, except in patients with high-risk or locally advanced prostatic disease. Fortunately, the latter tumors might still be prone to some kind of secondary treatment to block androgen receptors in a primary, secondary or tertiary fashion. Secondary hormonal manipulations for affected patients include antiandrogen withdrawal, second-line antiandrogens, direct adrenal androgen inhibitors, estrogens and progestins. We discuss the emerging concept of secondary hormonal manipulation on the basis of the current literature and demonstrate prospective alternative treatment modalities.

Radical prostatectomy for treatment of prostate cancer is a technically sophisticated operation. Simpler therapies have therefore been developed in the course of decades. The decisive advantage of a radical operation is the chance of a cure with minimal collateral damage. It is the only approach that enables precise tumor staging. The 10-year progression-free survival probability is approximately 85% for a localized tumor with negative resection margins. This high cure rate is unsurpassed by competitive treatment modalities. Nowadays, experienced surgeons achieve excellent functional results (for example, recovery of continence and erectile function) with minimum morbidity. Even in the locally advanced stage, results are very good compared to those obtained with other treatment modalities. Pathological staging enables stratified adjuvant therapy based on concrete information. The overall prognosis can thus be significantly improved.

The use of hormonal therapy as an adjunct to radiotherapy has been discussed controversially for years. Results of large RTOG and EORTC trials indicate that the combination of these treatment modalities may improve survival in subsets of patients. Many questions with respect to onset, duration, type of hormonal therapy and appropriate patient selection are still under investigation. Following a short overview of the corresponding literature, evidence-based recommendations for daily clinical practice are provided.

A biochemical recurrence following prostatectomy is often diagnosed in relatively young and healthy men, and hence deemed very relevant concerning life, given the generally high life expectancy of these patients. Therefore, there is a need for a therapy that offers a long-term chance of cure. Following salvage radiotherapy in large multicenter series, about 45% of the patients treated are in biochemical complete remission 4 years after radiotherapy. The best chances of response are in those patients in whom none of the established risk factors, that will be discussed, are present. Given the established curative potential of salvage radiotherapy and the fact that there are no therapeutic alternatives with a realistic chance of cure, the rather moderate rates of side effects seem acceptable.

Research in the past 3 decades has resulted in new approaches to treat patients with hormone-refractory prostate cancer. Employing the new treatment options, we are now able to prolong survival in these patients. At present, docetaxel given on a 3-week schedule is the standard of care for patients with hormone-refractory prostate cancer. Several new treatments are under investigation in phase III trials and will further improve the treatment options for these patients within the next years.

This review outlines the different treatment options in localized prostate cancer. This information can be considered alongside other important factors, such as the individual patient's values and situation as well as the potential impact of treatment on his quality of life, in the treatment decision-making process. Taking all these factors into consideration, the data support active surveillance as an appropriate choice in patients with well or moderately differentiated, low-volume prostate cancer who have a life expectancy of less than 10 years. Men with higher-grade tumors and longer life expectancy may be at excess risk of death from prostate cancer managed with active surveillance.

Several randomized trials have demonstrated that adjuvant medical or surgical castration may improve overall survival in patients with locally advanced prostate cancer undergoing external beam radiotherapy. After radical prostatectomy, patients with positive lymph nodes seem to benefit from adjuvant hormonal treatment rather than from treatment at the time of clinical progression in terms of overall survival. In patients with locally advanced, lymph node-negative prostate cancer, adjuvant hormonal treatment after radical prostatectomy has been demonstrated to delay progression without impact on survival. The Bicalutamide Early Prostate Cancer Program, the largest ongoing prostate cancer trial in the world, investigates the effect of early treatment with 150 mg bicalutamide compared with placebo as monotherapy or adjuvant treatment after radical prostatectomy or external beam radiotherapy. It demonstrated that early treatment with bicalutamide may delay objective progression of prostate cancer irrespective of primary treatment. Considering overall survival, however, there was an advantage only in the setting of external beam radiotherapy for locally advanced prostate cancer. In patients with localized disease who initially underwent watchful waiting, there was a trend to decreased survival in the arm immediately treated with bicalutamide. Altogether, there is no indication for treatment with bicalutamide in patients with localized disease.

Although hormone therapy is widely used in the management of prostate cancer, the optimal timing of its initiation remains a matter of debate. Many studies of the last decades have reported a small but significant survival benefit and a clear delay in the development of clinical symptoms after early initiation of therapy. Patients who have localized or locally advanced prostate cancer and are not suitable for curative options like radical prostatectomy or radiotherapy can best be managed by hormone therapy alone, which has already been recognized as the optimal treatment for metastatic disease. On the other hand, long-term hormone treatment will expose the patient to the risk of substantial adverse effects, including muscle wasting, chronic fatigue and osteoporosis. Prognostic and quality-of-life factors also have an impact on the treatment decision, particularly in patients most likely to profit from an extension of the remaining life span. Based on available evidence, early hormone therapy may be recommended for men with poorly differentiated tumors or advanced disease and for those infrequently seen by their physicians. This management can prevent prostate cancer from migrating to the bones, where treatment becomes extremely difficult and cure or even longterm control of the disease is an exception.