Evolution of toxicity after conformal radiotherapy for prostate cancer

The limiting factor for radiation (RT) dose-escalation is normal tissue toxicity. In dose-escalation studies, it is important to determine the factors associated with toxicity and the length of follow-up period after which a particular RT dose is considered safe. We analyzed 449 prostate cancer patients treated with RT at our institution and followed for a median of 27 months. Genitourinary (GU) and gastrointerological (GI) complications were graded and analyzed using three different statistical models. Univariate and multivariate analyses were conducted for factors associated with toxicity. There was no RTOG grade 4 or 5 toxicity. Only 23 patients (5%) experienced grade 3 toxicity. After treatment, there was an initial rapid decline in the risk of toxicity following treatment, followed by an increase or stabilization of the toxicity with time of follow-up. The breakpoints between the two periods were 2 y (any toxicity) and 1 y (high toxicity) for GU and 9 months (any toxicity, high toxicity) for GI. Age, dose, fraction size, duration of treatment and hospital of treatment emerge as important factors in the probability of developing toxicity. Our study shows that delivering conventional doses using conformal techniques is associated with minimal high-grade toxicity. However, even within a narrow dose range and fraction size used, differences do emerge which should lead one to be cautious in extending the results of dose escalation study to the community practice without a sufficient follow-up.     

Salvage cryosurgery for locally recurrent prostate cancer following radiotherapy

The popularity of radiotherapy as a minimally invasive treatment for prostate cancer is increasing. Despite advancements in radiation delivery, a number of patients will fail treatment. Salvage radical prostatectomy has been the main therapeutic option for locally recurrent radiation failure prostate cancer with curative intent. The operation is technically difficult to perform and associated with significant comorbidities. Salvage cryotherapy has emerged as a minimally invasive alternative option. In this article, we review the role of cryotherapy in recurrent prostate cancer and compare its outcome with salvage radical prostatectomy.     

Salvage cryoablation for locally recurrent prostate cancer following primary radiotherapy

Context

The purpose of this paper is to review current salvage cryoablation (SCA) outcomes in patients with locally recurrent prostate cancer (PCa) following primary radiation therapy.

Objective

The objectives of this review are (1) to analyze the eligibility criteria for careful patient selection for these salvage modalities and (2) to evaluate the oncologic results and reported complication rates for these respective modalities.

Evidence acquisition

A Medline/PubMed literature search was performed of peer-reviewed scientific articles published from 1991 to 2012 regarding salvage therapy for radiorecurrent PCa. The following search terms and various permutations were used: radiorecurrent prostate cancer, local salvage treatment, salvage radical prostatectomy, salvage cryoablation, salvage brachytherapy, and salvage high-intensity focused ultrasound. Only articles written in English were included.

Evidence synthesis

SCA is a feasible and efficacious treatment modality, especially using third-generation technology, whereby the biochemical disease-free survival is estimated to be between 50% and 70% at 5-yr follow-up in properly selected patients. Severe complications such as rectourethral fistulas are significantly less common over the last decade than was reported in the past. Because there are no prospective, randomized studies and the definitions of PSA failure vary among many studies, comparisons between these different salvage modalities are limited in terms of cancer-specific outcomes. Nevertheless, in recent years, tertiary care referral centers for prostate cryotherapy have reported their treatment outcomes using rigorous treatment end points and morbidity grading systems, dramatically improving the quality of reported clinical data. Consequently, favorable predictors of treatment outcomes have been identified.

Conclusions

The inability to effectively salvage patients with locally recurrent PCa following radiation therapy has in large part resulted from the lack of sufficiently sensitive and specific diagnostic tools to detect local recurrences at an early, potentially curable stage. Consequently, a more stringent definition of biochemical failure, improved imaging techniques, and accurate PCa mapping imaging technology is greatly needed within our diagnostic armamentarium. Additional research and randomized clinical trials are required to determine which salvage modality is superior in terms of oncologic efficacy and reduced morbidity.     

Particle radiotherapy for prostate cancer

Recent advances in external beam radiotherapy have allowed us to deliver higher doses to the tumors while decreasing doses to the surrounding tissues. Dose escalation using high‐precision radiotherapy has improved the treatment outcomes of prostate cancer. Intensity‐modulated radiation therapy has been widely used throughout the world as the most advanced form of photon radiotherapy. In contrast, particle radiotherapy has also been under development, and has been used as an effective and non‐invasive radiation modality for prostate and other cancers. Among the particles used in such treatments, protons and carbon ions have the physical advantage that the dose can be focused on the tumor with only minimal exposure of the surrounding normal tissues. Furthermore, carbon ions also have radiobiological advantages that include higher killing effects on intrinsic radio‐resistant tumors, hypoxic tumor cells and tumor cells in the G0 or S phase. However, the degree of clinical benefit derived from these theoretical advantages in the treatment of prostate cancer has not been adequately determined. The present article reviews the available literature on the use of particle radiotherapy for prostate cancer as well as the literature on the physical and radiobiological properties of this treatment, and discusses the role and the relative merits of particle radiotherapy compared with current photon‐based radiotherapy, with a focus on proton beam therapy and carbon ion radiotherapy.     

Hospital burden of long-term genitourinary and gastrointestinal toxicity after radical radiotherapy for prostate cancer

Introduction

Treatment options for prostate cancer (PCa) include radical radiotherapy (RT) and radical prostatectomy, both of which have comparable oncological outcomes. The aim of this study was to investigate the hospital burden of long-term genitourinary and gastrointestinal toxicity among patients with PCa who were treated with radiotherapy at our institution.

Clinical and histopathological features of bladder cancer following radiotherapy for prostate cancer: A comparative study

IntroductionLow certainty exists on how bladder cancer (BCa) after pelvic radiotherapy (RT) differs from BCa in radiation-naive patients from a histopathological and clinical perspective. This study aims to compare histopathological features of bladder tumors between patients with previous RT for prostate cancer (PCa) and radiation-naive patients using single-institutional data and to estimate relapse-free survival (eRFS) and cystectomy-free survival (eCFS) in both groups.Materials and MethodsComparative study in adult men diagnosed with BCa in Hospital Italiano de Buenos Aires, Argentina, between January 2015 and December 2020. Included patients were categorized as previously irradiated for PCa or radiation-naive. Primary outcome: differences in prevalence of aggressiveness features of bladder tumors (variant histology; high-grade tumors; muscle-invasive disease; criteria compliance for high or very-high risk of progression) between irradiated and radiation-naive patients at diagnosis of BCa. Secondary outcomes: differences in eRFS and eCFS between groups.ResultsIn total, 34 and 291 patients were included in the Irradiated and Radiation-naive groups, respectively. Mean age at the time of diagnosis of BCa was 72.7 years (CI 95% 71.6–73.8). Median follow-up of the overall cohort was 25 months (IQR 11–45.5). Concerning primary outcomes, no statistical differences were found except for a higher prevalence of low-grade tumors between irradiated patients and high-grade tumors between radiation-naive patients (P 0.018). Regarding secondary outcomes, prior RT did not increase neither eRFS nor eCFS in both univariate and multivariate analysis.ConclusionsBCa after RT for PCa has similar histological features and cystectomy free-survival compared to BCa in a radiation-naive population. For patients with non-muscle invasive BCa arising after prostate RT, the risk of recurrences appears to be similar to non-irradiated patients.     

前列腺癌的放射治疗进展

前列腺癌是男性最常见的恶性肿瘤之一，多见于欧美国家，美国每年新增病例约45000人，是男性肿瘤中死亡的第二大原因。我国该病在近20年来有上升的趋势。每10万男性人121发病率从60年代的0．48上升至90年代的2．4。有人估计50％以上的患者就诊时已处晚期，从而不宜手术或失去手术根治的机会。采用放射治疗则成为重要的局部治疗手段，它不     

Recurrent prostate cancer following external beam radiotherapy: follow-up strategies and management

All patients who undergo curative therapy for prostate cancer should be followed for a prolonged period of time to determine tumor control and treatment toxicity for quality assurance purposes. Follow-up duties may be reasonably shared between the oncologist and the family doctor or urologist: however, it is probable that some follow-up information specific to the irradiated patient will be lost unless the oncologist maintains regular contact with the patient, especially in the first 5 years of follow-up when late radiation effects are most likely to appear. There is no strong evidence that patients stop being at risk for recurrence at any time after treatment, and because PSA testing is an accurate, simple, and inexpensive method of determining post-RT tumor status, it is recommended that periodic PSA measurements be continued for life. In the absence of a rising PSA, all other tests and visits are unnecessary to determine post-RT tumor control. Because DRE has been shown to be of limited utility in follow-up of irradiated patients, it should be possible to effectively follow patients remotely. This could be done by asking patients to have PSA tests done, forward the results to their physicians, and report treatment toxicity when it occurs. Only abnormal results would trigger an office visit. This strategy is being evaluated in clinical trials. The alternative is to delegate the follow-up to the primary-care physician with guidelines as to when referral back is required. Follow-up frequency, and the most beneficial follow-up investigations vary from scenario to scenario, and are influenced by the likelihood of relapse, time to relapse, and planned intervention. These decisions are influenced in turn by the initial presentation--either with high or low risk factors--and by the patient's general state of health at completion of EBRT. Effective follow-up also requires active patient cooperation that only can be achieved after discussion of the goals of follow-up with the patient and with the patient's full understanding of the process. The follow-up strategy proposed in Fig. 1 is most suitable for a fit patient with low or intermediate risk factors who wishes to consider all salvage options should he relapse, or for the high-risk individual in situations in which the probability of systemic relapse is of major concern. Young patients with very adverse risk factors may benefit from even closer follow-up in the early years after EBRT and the elderly or frail may require only occasional visits to record or treat treatment toxicity and to ensure clinical non-progression.     

Erectile dysfunction following radiotherapy and brachytherapy for prostate cancer: pathophysiology, prevention and treatment

Objectives Although detrimental impact on sexual function following radiotherapy (RT) and brachytherapy decreases the quality of life of prostate cancer survivors, the etiology, pathophysiology, prophylaxis and treatment of this condition has not yet been fully clarified. We reviewed the published literature in terms of etiology, treatment and possible prevention of erectile dysfunction (ED) following RT and/or brachytherapy. Method We have reviewed the literature through a MEDLINE search. Prostate cancer, erectile dysfunction, radiotherapy, brachytherapy, treatment and quality of life were used as keywords. Conclusion Both RT and brachytherapy result in high rates of ED. Although arterial damage seems to be the main cause of ED after RT, exposure of neurovascular bundle to high levels of radiation dose has been also implicated in some studies with brachytherapy. The radiation dose received by the corpora cavernosa at the crurae of the penis may also be important in the etiology of ED. The most important predictive factor of ED following RT is the treatment modality. Intensity-modulated radiotherapy and vessel-sparing prostate radiotherapy are new techniques but those treatments may not guarantee complete preservation of the erectile function. Patients need to be correctly informed on the possible sequela of radiation-based treatments on their sexual well-being while planning their treatment. Patients should also be informed about the possible treatment modalities for ED, which may develop in due course.     

Value of postoperative radiotherapy for thyroid cancer

A series of 405 patients with thyroid cancer treated by surgery with or without postoperative radiotherapy from February 1958 through 1979 is reported. The immediate evaluation of the operation was that it was either incomplete or complete. Incomplete surgery implied that there was (1) possible residual tumor in the operative field, the result of difficult dissection of the tumor off the neighboring organs or tissues, as assessed by the surgeon; (2) multiple (more than five) lymph nodes involved; (3) positive border of the removed lesions; or (4) microscopic evidence of tumor in the operative field. Complete surgery implied through extirpation of cancer grossly and microscopically. In 297 patients who had complete surgery, 238 patients treated by surgery alone had a 5-year survival rate of 92% (218/238), while 59 patients who received postoperative radiotherapy had a 5-year survival rate of 78% (46/59). The optimum dose of postoperative radiotherapy was 50-70 Gy in 5 to 8 weeks, with the spinal dose kept under 40 Gy. Our experience shows that postoperative radiotherapy did not improve the survival of patients who had had complete surgery. Yet, in 108 patients who had incomplete surgery, surgery alone yielded a 5-year survival rate of 33% (19/57), while surgery plus radiotherapy yielded a 5-year survival of 71% (36/51). Our observation shows a remarkable benefit with postoperative radiotherapy in patients who have had incomplete surgery (P less than 0.05). According to pathologic criteria, postoperative radiotherapy was more effective in well-differentiated cancers than in poorly differentiated ones. It was equally effective in untreated as well as recurrent lesions. The prognosis for younger patients was better, but the sex of the patients did not affect prognosis.     

Radiation for prostate cancer: use of biochemical failure as an endpoint following radiotherapy

The introduction of prostate-specific antigen (PSA) as a reliable tumor marker for prostate cancer brought significant changes in endpoints after therapy and in outcome reporting. Over the last 15 years we have collected follow-up information in this new era and struggled with failure definitions using this new tool. Parameters for failure after radiation were especially controversial due to the fact that, unlike surgery, a variable amount of normal prostate function and PSA production remained. In 1996, the ASTRO Consensus Conference established a PSA failure definition based on the available information at the time. It was commonly used for outcome reporting subsequently although criticisms have been voiced and alternate definitions proposed. A recently assembled multi-institutional database was used both for long-term outcome reporting with external beam radiation and to test various other failure definitions. A summary of these results and the associated issues are presented here.     

Androgen deprivation therapy in men with node-positive prostate cancer treated with postoperative radiotherapy

BackgroundIn men with node-positive prostate cancer after radical prostatectomy there are limited data on the value of adding androgen deprivation therapy (ADT) to postoperative radiotherapy.ObjectiveTo determine whether there is a clear oncologic benefit to ADT in the setting of node-positive prostate cancer treated with postoperative radiotherapy.MethodsWe analyzed data for 372 prostate cancer patients treated at San Raffaele Hospital with postoperative radiotherapy for node-positive disease after radical prostatectomy, 272 received both ADT and radiotherapy. Eighty-six men were followed without an event for more than 10 years.ResultsPatients who received postoperative radiotherapy + ADT had more aggressive disease, with higher preoperative PSA level, higher rate of ISUP grade 5, pT3b-T4 tumors and ≥3 positive nodes. At multivariable Cox regression, the comparison between men treated by postoperative radiotherapy + ADT vs. radiotherapy alone did not show a significant difference for overall (hazards ratio: 0.91; 95% confidence interval: 0.45, 1.84; P = 0.8) and cancer-specific survival (hazards ratio: 5.39; 95% confidence intervalI: 0.70, 41.39; P = 0.11). These results remained consistent in a number of sensitivity analyses, including propensity score matching. Consideration of 95% CIs suggests that a clinically significant benefit of ADT in node-positive patients receiving radiotherapy after surgery is unlikely.ConclusionsWe can exclude the sort of large survival benefit that would be required to justify the risks and toxicities of ADT in men with node-positive disease receiving postoperative radiotherapy. Awaiting larger and more powered studies on this topic, men with pN+ prostate cancer treated with postoperative radiotherapy should not receive ADT outside well-controlled clinical trials.     

External beam radiotherapy for localized prostate cancer

Radiotherapy (XRT) is a curative treatment option for prostate cancer (PCa). Recent XRT technologies allow higher dose therapy that lead to increased local control with less adjacent tissue damage. Additionally, receiving neo-adjuvant or adjuvant hormonotherapy (HT) during radiation therapy increases the curative effect. The aim of this paper is to review the current literature and guidelines on external beam radiation therapy for PCa. However, brachytherapy and radiosurgery, a recently evolving relatively new technology for the radiotherapeutic management of localized PCa, are beyond the scope of this paper.