Post-prostatectomy radiation therapy: Consensus guidelines of the Australian and New Zealand Radiation Oncology Genito-Urinary Group

BACKGROUND AND PURPOSE: Three randomised trials have demonstrated the benefit of adjuvant post-prostatectomy radiotherapy (PPRT) for high risk patients. Data also documents the effectiveness of salvage radiotherapy following a biochemical relapse post-prostatectomy. The Radiation Oncology Genito-Urinary Group recognised the need to develop consensus guidelines on to whom, when and how to deliver PPRT. MATERIALS AND METHODS: Draft guidelines were developed and refined at a consensus conference in June 2006 attended by 63 delegates where urological, radiotherapy and diagnostic imaging experts spoke on aspects of PPRT. Unresolved issues were further developed by working parties and redistributed until consensus was reached. RESULTS: Central to the recommendations is that patients with positive surgical margins, seminal vesicle invasion and/or extracapsular extension have a high risk of residual local disease and should be informed of the options of either immediate adjuvant radiotherapy or active surveillance with early salvage in the event of biochemical recurrence. Salvage radiotherapy should be instituted at the earliest confirmation of biochemical recurrence. Detailed contouring guidelines have been developed, defining the regions at risk of residual microscopic disease which should be included in the clinical target volume. The recommended doses are 60-64Gy for adjuvant, and 60-66Gy for salvage radiotherapy. The role of hormone therapy in conjunction with PPRT is yet to be defined. CONCLUSIONS: These consensus guidelines have been developed to give clinical and technical guidance to radiation oncologists and urologists in the management of high risk post-prostatectomy patients.     

Patterns of Care Related to Post-Operative Radiotherapy for Patients with Prostate Cancer among Canadian Radiation Oncologists and Urologists

The American Society for Radiation Oncology (ASTRO) and American Urological Association (AUA) developed post-prostatectomy radiotherapy (RT) guidelines to aid patient counseling on adjuvant (ART) and salvage radiotherapy (SRT). Our study compared how aware and compliant Canadian radiation oncologists and urologists are to these guidelines. Our online survey was distributed through the Canadian Association of Radiation Oncology (CARO) and Canadian Urology Association (CUA) to radiation oncologists and urologists that treat prostate cancer. We used Wilcoxon rank-sum test and Chi-square test to compare radiation oncologists and urologists. P values for significant findings are reported. A total of 128 participants responded the survey, 52 radiation oncologists, and 76 urologists. The majority (82%) of radiation oncologists had read these guidelines, compared to only 49% of urologists (p < 0.001). Radiation oncologists were more likely to recommend ART >50% for adverse pathological findings post-radical prostatectomy compared to urologists (76 vs. 51%, p = 0.011). Urologists were more likely to monitor their patient’s PSA level post-prostatectomy compared to radiation oncologists (93 vs. 77%, p = 0.016). Post-thematic analysis of open-ended questions revealed that urologists rarely refer patients to radiation oncologists for ART, with radiation oncologists confirming that they rarely receive referrals. This study demonstrates the low compliance to ASTRO/AUA guidelines. While radiation oncologists were more aware and compliant to guidelines, urologists were significantly more likely to monitor their patient’s PSA. This study highlighted the need for better communication between urologists and radiation oncologists, especially in referrals for ART, to facilitate treatment delivery that is concordant with ASTRO/AUA guidelines.     

Variation in Radiotherapy Referral and Treatment for High-risk Pathological Features after Radical Prostatectomy: Results from a Population-based Study

Aims

Guidelines recommend the discussion of adjuvant radiotherapy post-prostatectomy for prostate cancer patients with high-risk pathology to consider all of their treatment options. We determine whether patterns of radiotherapy referral and treatment post-prostatectomy reflect guideline-based use in a contemporary prostatectomy cohort.

Biochemical disease-free survival following adjuvant and salvage irradiation after radical prostatectomy

PURPOSE: To present the biochemical cure rates (biochemically no evidence of disease) after external irradiation (RT) in patients with high-risk prostate cancer after radical prostatectomy. METHODS AND MATERIALS: Seventy-six patients who underwent radical prostatectomy and subsequent RT were included in this analysis. No patient received hormonal therapy. Adjuvant RT was administered in 35 patients (46%), and 41 patients (54%) underwent salvage RT. After prostatectomy, the Gleason score was <7 in 87%, and 24% had seminal vesicle invasion. The median RT dose in the adjuvant RT and salvage RT groups was 60 Gy and 65 Gy, respectively. The biochemical cure rate was defined as a serum prostate-specific antigen of < or =0.2 ng/mL. RESULTS: The overall 5-year Kaplan-Meier biochemical control rate from the end of RT was 70%. The 5-year biochemical cure rate for adjuvant RT was significantly superior to that after salvage RT (86% vs. 57%). The significant predictors of biochemical failure were seminal vesicle invasion in the adjuvant RT group and the presence of Gleason grade 4 or 5 in the salvage RT group. The clinical local control rate in the prostate bed was 100%. CONCLUSION: This report demonstrates the efficacy of RT in achieving high biochemical cure rates after radical prostatectomy. Additional clinical studies are required to determine the optimal treatment of patients at high risk of biochemical failure after postprostatectomy RT.     

Radiation therapy in prostate cancer: a risk-adapted strategy

External-beam radiotherapy and brachytherapy, widely utilized as curative treatment modalities for prostate cancer, have undergone significant clinical and technological advances in recent decades. Contemporary radiotherapy treatment algorithms use pretreatment prognostic factors to stratify patients into low-, intermediate-, and high-risk groups that correlate with both pathologic stage of disease and risk of recurrence after treatment. The use of risk groups and additional prognostic factors guide selection of the optimal treatment modalities for individual patients. Here, the roles of external-beam radiotherapy, brachytherapy, and neoadjuvant or adjuvant androgen deprivation therapy are discussed in that context. Additional prognostic factors for recurrence in the post-prostatectomy setting and the role of adjuvant and salvage radiation therapy are also reviewed. The risk-adaptive approach in radiotherapy for prostate cancer aims to optimize cancer control outcomes while minimizing the morbidity of treatment.     

Radiation therapy after radical prostatectomy: a review of the issues and options

The role of postoperative radiation therapy after radical prostatectomy is controversial. Radiation can be delivered as an adjuvant therapy in the immediate postoperative period for high-risk patients or as salvage therapy in the setting of a rising prostate-specific antigen. There are important issues that must be addressed when considering radiation therapy after prior prostatectomy. One issue is the determination of whether a patient has local disease amenable to salvage pelvic radiation or whether the patient has occult metastatic disease. In addition, the radiation oncologist must decide if an acceptable dose of radiation therapy can be administered safely to the prostate bed. There are no published randomized clinical trials on the topic of postprostatectomy radiation therapy, although several have completed accrual or are in progress. Based on the available literature, postoperative radiation is a safe option in the patient at high risk for local recurrence based on adverse pathology or clinical features (eg, extensive extracapsular disease, positive margins, high volume Gleason score >7, and so on). Administration of an adequate dose of prostate bed radiation (ie, >64 Gy) in men with these adverse prognostic features appears to effectively reduce prostate-specific antigen (PSA) recurrence rates. The protracted natural history of prostate cancer requires longer follow-up to determine if survival will be ultimately affected by adjuvant or salvage radiation therapy. Some urologists have advised a "wait and watch policy" for high-risk postprostatectomy patients. Administration of radiation therapy is done only if and when the PSA rises. However, data suggest this approach may have limited durability in high-risk prostate cancer and could reduce the likelihood of prolonged progression-free survival. This review summarizes published retrospective and prospective data to guide decision making in selecting appropriate candidates for postprostatectomy radiation therapy.     

Expression of HER/erbB family of receptor tyrosine kinases and induction of differentiation by glial growth factor 2 in human rhabdomyosarcoma cells

Because of the uncertainties regarding the efficacy of postoperative radiation therapy for early prostate cancer, treatment strategies following radical prostatectomy include: (1) observation alone in high-risk patients, (2) adjuvant radiation therapy (PSA undetectable) in high-risk patients, or (3) salvage radiation therapy for biochemical and clinical recurrence. Fifty-two patients treated with postoperative radiation therapy in either an adjuvant setting (13) or for salvage (39) were retrospectively reviewed. The actuarial biochemical disease-free survival (bNED) rates following radiation therapy were calculated using the life-table method. Univariate and multi variate analyses were used to define the clinical factors that predict biochemical failure following postoperative radiation therapy. In addition, the bNED survival rate for 36 high-risk surgery patients who were simply observed following prostatectomy was determined. The 3-year bNED survival rate for the adjuvant radiation group was 85% compared with 27% for salvage radiation and 43% for the observation group. These results are statistically significant. Factors that predict biochemical failure following postoperative radiation therapy include preoperative PSA level, pre-radiation therapy PSA level, and seminal vesicle involvement. At our institutions, adjuvant radiation therapy was a superior strategy compared with either observation alone or salvage radiation therapy for high-risk postoperative prostate cancer patients. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 29-36 (2000).     

Durable efficacy of adjuvant radiation therapy for prostate cancer: will the benefit last?

Radical prostatectomy can be an effective therapy for men with organ-confined disease. However, extension beyond the confines of the prostate (pT3) can be found in many men, and this is often associated with longterm prostate-specific antigen (PSA) failure. Not all patients will progress with pT3 disease. The identification of additional adverse prognostic features (high Gleason score, PSA greater than 10 ng/mL, and seminal vesical invasion) can help identify those men at highest risk of progression following definitive surgery. The role of postoperative therapy in patients with high-risk features is often controversial. The lack of long-term survival benefit, toxicity, and cost are often cited. We reviewed our experience with a unified approach to this patient population and performed matched-pair analysis of patients with similar adverse prognostic features treated with and without postoperative radiation therapy. For our series, the results indicate that the addition of adjuvant radiation therapy is associated with a significantly reduced risk of PSA recurrence. The 5-year bNED rate after adjuvant radiation therapy was 89% (95% CI: 76% to 100%) compared with 55% (95% CI: 34% to 79%) after surgery alone (P = .002). This benefit also appears to hold true for men with pathological involvement of their seminal vesicles. A dose-response curve was observed with improved disease control above a level of 61.2 Gy. Appropriate patient selection and delivery of an adequate dose of radiation can improve the PSA recurrence of most patients with pT3 disease.     

Adjuvant and salvage radiotherapy after radical prostatectomy

BACKGROUND: Following radical prostatectomy, between 15 and 60% of all patients with pT3 prostate cancer experience persistence or increasing levels of prostate-specific antigen (PSA) as a sign of tumor persistence or progression within 5 years. Retrospective studies have shown a rate of 35-55% of positive biopsies from the vesicourethral anastomosis in this situation. Best treatment for these disease conditions is under debate, current strategies include adjuvant radiotherapy (RT), 'wait-and-see' and salvage RT or hormone therapy for increasing PSA. RESULTS: A number of retrospective studies have shown an increased rate of local control and 'freedom from treatment failure' following adjuvant RT with doses in the range of 50-60 Gy. However, no survival benefit could be demonstrated by now. Results of three major phase III studies are pending. In case of persisting or increasing PSA levels following radical prostatectomy, 30-70% of these patients will reach an undetectable PSA level after conformal RT with total doses of 60-70 Gy, which will stay undetectable or at least stable within the next 2-5 years in about 50% and therefore offering a chance of cure. When starting RT, PSA should be as low as possible (<2 ng/ml). With higher PSA levels the chance of achieving an undetectable PSA again decreases below 35%. High Gleason scores of 8-10, seminal vesicle involvement and a short PSA doubling time are adverse prognostic factors. Severe late side effects of conformal RT are infrequent (<3%). In contrast, hormonal treatment is of palliative nature in the long run, with a median time to development of metastases of 4-7 years, and can be offered to patients with progressive disease after RT. CONCLUSIONS: Adjuvant RT following radical prostatectomy for pT3 prostate cancer offers higher local control rates and an increase in 'freedom from treatment failure', but no prolongation of survival has yet been shown. In the situation of increasing PSA levels after radical prostatectomy, salvage RT seems to offer a chance of cure in selected patients, although it is difficult to draw firm conclusions because of generally too short follow-up times.     

Multiparametric MRI for prostate cancer: a national survey of patterns of practice among radiation oncologists in Spain

Purpose

To investigate patterns of practice among Spanish radiation oncologists in the use of multiparametric magnetic resonance imaging (mpMRI) for the treatment of prostate cancer (PCa). We evaluated (1) access to mpMRI, (2) current clinical practices, and (3) physician expectations of mpMRI.

Methods

Cross-sectional survey of 118 radiation oncologists at 75 Radiation Oncology (RO) departments in Spain.

Results

A total of 55 radiation oncologists from 52 RO departments (52/75; 69%) completed the survey. Prostate mpMRI is performed at 94.5% of the centres that provided data. The most common indications for mpMRI in routine clinical practice were: (1) detection/localization of the tumour prior to second biopsy (82.7%), (2) cancer staging (80.8%), and (3) detection of recurrence after definitive treatment (80.8%). Most respondents (72.7%) reported modifying the primary radiotherapy treatment when mpMRI findings indicate a more advanced T stage with a resultant change in the risk group. Most respondents (90.5%) treat macroscopic local recurrence after prostatectomy with high doses, ranging from 71 to 83 Gy; in 37.7% of cases, the full dose is delivered to the entire prostate bed. In pelvic nodal recurrence, more than half (59.3%) of the respondents reported performing elective pelvic radiotherapy, including the prostate bed, with a boost to the involved nodes.

Conclusions

This survey shows that prostate mpMRI is routinely used by radiation oncologists in Spain in a wide range of clinical scenarios. The findings reported here underscore the need to standardize treatment protocols for definitive and salvage radiotherapy in patients evaluated with mpMRI.

     

Attitudes of Canadian Radiation Oncologists towards Post-lumpectomy Radiotherapy for Elderly Women with Stage I Hormone-responsive Breast Cancer

AimsPost-lumpectomy breast radiation is the standard of care for all patient subgroups. However, elderly women with stage I breast cancer on adjuvant tamoxifen therapy have a 4% risk of local recurrence after lumpectomy without adjuvant breast radiation. The purpose of this study was to explore the attitudes of Canadian radiation oncologists who treat breast cancer with respect to their use of adjuvant post-lumpectomy radiotherapy, and their willingness to implement a decision aid for this patient population.Materials and methodsThe questionnaire was mailed to 141 Canadian radiation oncologists who treat breast cancer. The respondents were asked to complete an online survey consisting of four parts: (1) demographic information; (2) factors determining post-lumpectomy radiation treatment decisions; (3) hypothetical case scenarios; (4) interest in using a decision aid in their practice.ResultsAmong the 61 (43%) physicians who completed the survey, there was substantial response variation. After contraindications to radiotherapy, patient overall health and patient preference had the greatest influence on their decision to offer radiotherapy to this patient subgroup. Margin status and use of hormonal therapy were given less importance. For each of the case scenarios, 60–83% of physicians (depending on the case scenario) would offer the patient a choice; far fewer (12–57%) would be comfortable not irradiating. Sixty-four per cent of respondents welcomed the concept of a decision aid for this population.ConclusionsAlthough there is significant variation in practice patterns and attitudes among radiation oncologists regarding post-lumpectomy radiotherapy for elderly, low-risk breast cancer patients, the vast majority value patient choice and would be willing to use a decision aid designed for this population in their practice.     

Palliation of bone metastases: a survey of patterns of practice among Canadian radiation oncologists.

BACKGROUND: Palliative radiotherapy constitutes nearly 50% of the workload in radiotherapy. Surveys on the patterns of practice in radiotherapy have been published from North America and Europe. Our objective was to determine the current pattern of practice of radiation oncologists in Canada for the palliation of bone metastases. METHOD: A survey was sent to 300 practicing radiation oncologists in Canada. Five case scenarios were presented. The first three were patients with a single symptomatic site: breast cancer patient with pelvic metastasis, lung cancer male with metastasis to L3 and L1, respectively. The last two were breast and prostate cancer patients with multiple symptomatic bone metastases. RESULTS: A total of 172 questionnaires were returned (57%) for a total of 860 responses. For the three cases with a single painful bone metastasis, over 98% would prescribe radiotherapy. The doses ranged from a single 8 to 30 Gy in ten fractions. Of the 172 respondents, 117 (68%) would use the same dose fractionation for all three cases, suggesting that they had a standard dose fractionation for palliative radiotherapy. The most common dose fractionation was 20 Gy in five fractions used by 84/117 (72%), and 8 Gy in one fraction by 19/117 (16%). In all five case scenarios, 81% would use a short course of radiotherapy (single 8 Gy, 17%; 20 Gy in five fractions, 64%), while 10% would prescribe 30 Gy in ten fractions. For the two cases with diffuse symptomatic bone metastases, half body irradiation (HBI) and radionuclides were recommended more frequently in prostate cancer than in breast cancer (46/172 vs. 4/172, P<0. 0001; and 93/172 vs. 10/172, P<0.0001, respectively). Strontium was the most commonly recommended radionuclide (98/103=95%). Since systemic radionuclides are not readily available in our health care system, 41/98 (42%) of radiation oncologists who would recommend strontium were not familiar with the dose. Bisphosphonates were recommended more frequently in breast cancer than in prostate cancer 13/172 (8%) vs. 1/172 (0.6%), P=0.001. CONCLUSION: Local field external radiotherapy remains the mainstay of therapy, and the most common fractionation for bone metastases in Canada is 20 Gy in five fractions compared with 30 Gy in ten fractions in the US. Despite randomized trials showing similar results for single compared with fractionated radiotherapy, the majority of us still advocate five fractions. The frequency of employing a single fractionation has not changed since the last national survey in 1992. Nearly 70% use a standard dose fractionation to palliate localized painful metastasis by radiotherapy, independent of the site of involvement or tumor type. The pattern of practice of palliative radiotherapy for bone metastases in Canada is different to that reported previously from the US. The reasons why the results of randomized studies on bone metastases have no impact on the patterns of practice are worth exploring.     

Progressing prostate carcinoma

In the Karnell Cancer Center Grand Rounds, we present a patient who underwent radical prostatectomy with bilateral pelvic lymphadenectomy, but had positive margins and subsequently developed local recurrence and then systemic disease. Pathologic and radiologic aspects of his disease are discussed. Therapeutic options at different stages of the disease are examined from the point of view of the urologist, radiation oncologist, and medical oncologist. The surgical portion of the discussion focuses on the selection of initial therapy. Both the selection of surgical candidates and choice of pre- or post-operative therapy in patients can be aided by prognostic tools looking at several variables, including prostate-specific antigen (PSA) level, Gleason score of the tumor, seminal vesicle invasion, extracapsular invasion, and lymph node involvement. Low-risk patients can be treated with monotherapy, such as radical prostatectomy, external beam radiation therapy, prostate brachytherapy, or cryosurgical ablation of the prostate. Higher risk patients may require adjuvant and possibly neoadjuvant therapy in addition. The radiation portion of the discussion focuses on the use of radiation therapy as salvage for relapsing disease. Of particular importance is the point that treating high-risk patients whose PSA levels have started to rise but are less than 1 ng/ml results in a long-term PSA control rate as high as 75%, but that limiting the use of salvage radiation therapy to patients with high PSA levels or biopsy confirmation of local recurrence in the face of a negative bone scan results in biochemical long-term control of less than 40%. In the medical oncology part of the discussion, the major focus is on the use of chemotherapy to treat patients whose disease has become resistant to hormonal therapy. Mitoxantrone plus a corticosteroid has been found to offer significant palliation for such patients. Combination therapy with estramustine plus taxanes, other microtubule inhibitors, or other agents such as topoisomerase II inhibitors, has been found to cause shrinkage of measurable soft tissue disease and diminution of serum PSA levels. The development of effective hormonal and chemotherapeutic drugs for treatment of metastatic disease has led to new interest in adjuvant and neoadjuvant therapy of high-risk patients.     

Treatment results of adjuvant radiotherapy and salvage radiotherapy after radical prostatectomy for prostate cancer

Background The indications for and the efficacy of radiation therapy after radical operation for patients with prostate cancer are not clear. We analyzed the treatment results of adjuvant radiotherapy and salvage radiotherapy after radical prostatectomy. Methods Between September 1997 and November 2004, 57 patients received adjuvant radiotherapy or salvage radiotherapy after radical prostatectomy. Fifteen patients received radiation therapy because of positive margins and/or extracapsular invasion in surgical specimens (adjuvant group). Forty-two patients received radiation therapy because of rising prostate-specific antigen (PSA) during follow-up (salvage group). Radiation therapy was delivered to the fossa of the prostate ± seminal vesicles by a three-dimensional (3-D) conformal technique to a total dose of 60–66 Gy (median, 60 Gy). Biochemical control was defined as the maintenance of a PSA level of less than 0.2 ng/ml. Results The median follow-up period after radiation therapy was 33 months (range, 12–98 months). Three-year biochemical control rates were 87% for the adjuvant group and 61% for the salvage group. For patients in the salvage group treated without hormone therapy, the preradiation PSA value was the most significant factor for the biochemical control rate. The 3-year biochemical control rate was 93% in patients whose preradiation PSA was 0.5 ng/ml or less and 29% in patients whose preradiation PSA was more than 0.5 ng/ml. No severe adverse effects (equal to or more than grade 3) were seen in treated patients. Conclusion Radiation therapy after radical prostatectomy seemed to be effective for adjuvant therapy and for salvage therapy in patients with a preradiation PSA of 0.5 ng/ml or less. Also, radiation to the fossa of the prostate ± seminal vesicles, to a total dose of 60–66 Gy, using a three-dimensional (3-D) conformal technique, seemed to be safe.     

Radiotherapy after prostatectomy: is the evidence for dose escalation out there?

PURPOSE: To study the effective doses of radiotherapy (RT) after prostatectomy in search for evidence of a dose-response. METHODS AND MATERIALS: Original and available data from published studies of adjuvant and salvage RT after prostatectomy were analyzed in the context of biochemical tumor control probability (TCP) dose-response curves. Comparisons were made with dose-escalation studies of radical RT for localized disease. Arguments based on a microscopic vs. macroscopic disease dose-response relationships were used to interpret the clinical data. RESULTS: The tumor control rates after salvage RT were consistent with the TCP dose-response curve of radical RT, suggesting the presence of macroscopic-equivalent disease among salvage patients. For radical RT, the dose to achieve 50% biochemical tumor control was 65.9 Gy (95% confidence interval [CI], 64.8-66.8) and the Slope(50) was 2.6%/Gy (95% CI, 2.3-3.0). For salvage RT, the corresponding values were 66.8 Gy (95% CI, 65.1-68.4) and 3.8%/Gy (95% CI, 2.5-7.6). For a comparable TCP, the dose for adjuvant RT was approximately 6 Gy lower, consistent with one-tenth the burden of local disease. The present doses for adjuvant or salvage RT in the range of 60-70 Gy appear to be still on the steep part of the TCP dose-response curve. CONCLUSIONS: The effective doses and dose-response relation observed with RT after prostatectomy are consistent with the presence of macroscopic-equivalent disease for salvage patients and about a tenth of the residual disease for adjuvant patients. Greater doses would potentially achieve significantly greater disease-free control rates. A randomized trial with 250 patients comparing 64 vs. 70 Gy for salvage RT or 60 vs. 66 Gy for adjuvant RT would be capable of addressing this issue.     

Opinions from the Experts: Exploring What Prostate Cancer Patients Should Know About Post-Operative Radiotherapy

The present study investigated health professionals’ opinions about important questions that should be discussed with patients who may require post-prostatectomy radiotherapy. A 74-question survey was conducted among radiation oncologists, urologists, nurses, and radiation therapists involved in the care of prostate cancer patients. Survey questions covered six domains: understanding my situation and prostate cancer diagnosis, making a decision, radiotherapy: procedures involved, potential benefits, side effects, and my support network during radiation treatment. Respondents rated the importance of addressing these questions as either essential, important, no opinion, or avoid with a hypothetical post-prostatectomy case. The majority of questions were rated as either essential or important. There was disagreement between professions on essential questions, mostly between nurses and urologists in the side-effects domain. There was agreement between all professions regarding which questions should be avoided.     

Clinical utility of indium 111-capromab pendetide immunoscintigraphy in the detection of early, recurrent prostate carcinoma after radical prostatectomy

BACKGROUND: Despite the ability of radical prostatectomy to eradicate prostate carcinoma, biochemical evidence of recurrent prostate carcinoma may be seen in approximately 40% of patients 15 years after they undergo surgery. Localization of recurrent disease after radical prostatectomy is difficult and may greatly influence subsequent clinical management. The authors examined the utility of indium 111 ((111)In)-capromab pendetide immunoscintigraphy to detect recurrent prostate carcinoma radiographically in men with early biochemical evidence of failure (serum prostate specific antigen [PSA] < or = 4.0 ng/mL) and assessed the minimum serum PSA level necessary for imaging recurrent disease. METHODS: Between May 1987 and August 1995, 255 hormone-na?ve men with a mean (+/- standard deviation) age of 65 years +/- 7 years who underwent radical prostatectomy for clinically localized prostate carcinoma were followed without adjuvant therapy until early PSA recurrence in this multicenter study. Preoperatively, all patients had negative bone scans and pathologically negative lymph nodes, and they did not undergo hormonal ablation, chemotherapy, or radiation therapy preoperatively or postoperatively until the (111)In-capromab pendetide scan was performed. All men in this study had postoperative serum PSA levels < or = 4.0 ng/mL at the time of radionuclide imaging. All men underwent imaging with the capromab pendetide scan to localize recurrent disease, and charts were reviewed to document clinical evidence of recurrence. RESULTS: Pathologic findings included mean Gleason scores of 6.7 +/- 1.2; pathologic tumors classified as pT2a (18%), pT2b (26%), pT3a (38%), pT3b (16%), and pT4a (2%); a pathologic lymph node status of pN0 (100%); positive surgical margins (44%); and perineural invasion (42%). Capromab pendetide uptake was seen in 72% of 255 men throughout a range of patients' postoperative serum PSA levels (0.1-4.0 ng/mL), with 31% of men having local uptake (prostatic fossa) only. Of 151 men who underwent additional imaging studies, 16 of 139 men (12%) and 15 of 92 men (16%) showed evidence of recurrent disease by bone scintigraphy and computed tomography scans, respectively. Gleason score, pathologic stage, perineural invasion, and margin status were not correlated significantly with the (111)In-capromab pendetide scan. CONCLUSIONS: Capromab pendetide imaging can localize early PSA recurrence and may guide appropriate treatment after patients undergo radical prostatectomy. No minimum serum PSA value was needed to potentially detect radiographic disease after surgery. Further confirmatory studies and long-term follow-up of this cohort documenting response to salvage therapy are needed to validate these imaging findings.     

Prostate cancer update: 2006

PURPOSE OF REVIEW: This review highlights the most important developments in the diagnosis, prevention, and treatment of prostate cancer published in the medical literature over the past year. RECENT FINDINGS: Recent research has revealed a relatively high rate of prostate specific antigen screening in elderly men regardless of comorbidity status. Other findings include data that finasteride may increase the sensitivity of prostate specific antigen to detect prostate cancer. In terms of use of androgen deprivation therapy as part of primary therapy, a randomized trial has demonstrated that immediate therapy for locally advanced prostate cancer improves overall survival. There is growing literature, however, confirming the risks associated with this treatment, including an increased incidence of cardiovascular events and diabetes. New randomized trial data of adjuvant radiotherapy for high-risk disease have not demonstrated a survival benefit over observation. For patients who experience disease relapse following local therapy, definitions of biochemical failure following prostatectomy and radiation therapy are proposed. In more advanced disease, immunotherapy has preliminarily demonstrated survival benefit in a randomized trial. SUMMARY: Data reported over the last year have significant implications for those involved in the management of prostate cancer, ranging from primary care physicians to medical oncologists, urologists, and radiation oncologists.     

Radical external beam radiotherapy for prostate cancer in Japan: preliminary results of the changing trends in the Patterns of Care process survey between 1996-1998 and 1999-2001

OBJECTIVE: To report the preliminary results of a study to delineate the changing trends in radical external beam radiotherapy usage for prostate cancer between the 1996-1998 and 1999-2001 survey periods in Japan. METHODS: The 1996-1998 Patterns of Care Study (PCS) and the 1999-2001 PCS in Japan reviewed the detailed information on 694 patients with prostate cancer treated with radiotherapy. Of them, 298 patients with clinically localized prostate cancer treated with radical external beam radiotherapy in A1 and B1 institutions were selected for analysis (1996-1998 PCS, 117 patients; 1999-2001 PCS, 181 patients). RESULTS: High-risk prostate cancer (defined as T3-T4 tumors, a pretreatment prostate-specific antigen level >20 ng/ml, and/or poorly differentiated adenocarcinoma) was diagnosed in 82.1% of the patients in the 1996-1998 PCS and in significantly less (70.2%) of those in the 1999-2001 PCS (P = 0.021). Moreover, significantly earlier T stages (T1-T2: 49.7%) and more well-differentiated tumors (24.7%) were found between 1999 and 2001 than between 1996 and 1998 (T1-T2: 31.9%, well-differentiated tumors: 13.9%). Although only 6.1% of patients were treated with radiotherapy by patient's choice in 1996-1998, a larger proportion (32.2%) chose this treatment in 1999-2001. The median radiation dose was 65.0 Gy (range, 24-74 Gy) in 1996-1998 and increased to 69 Gy (range, 14-80 Gy) in 1999-2001. The percentage of radiation doses <60 Gy was 20.5% in 1996-1998 but only 2.2% in 1999-2001. Moreover, the incidence of treatment with total doses of > or =70 Gy was higher in 1999-2001 (43.9%) than in 1996-1998 (19.7%). These increased radiation doses were predominantly observed in B1 institutions. Although the usage of > or =10 MV was significantly increased in 1999-2001 (82.0%) compared with that in 1996-1998 (65.8%), conformal therapy administered to 52.1% of patients in 1996-1998 was almost the same (55.8%) in 1999-2001. The median number of full-time equivalent (FTE) radiation oncologists (2.4 in A1 institutions and only 0.6 in B1 institutions) in 1996-1998 increased slightly in 1999-2001 (2.7 in A1 institutions, 0.7 in B1 institutions), but remained low in B1 institutions. CONCLUSIONS: In Japan, there is a trend to fewer high-risk prostate cancer patients being treated with radical external beam radiotherapy. An increasing percentage of patients chose radiotherapy and also increased radiation doses, which might reflect the growing acceptance of radical external beam radiotherapy as a treatment of choice for prostate cancer in Japan. Therefore, to optimize delivery of radiotherapy, more advanced equipment and more FTE radiation oncologists are warranted.     

High-dose radiotherapy plus prolonged hormone therapy in CT2-3 prostatic carcinoma: is it useful?

AIMS AND BACKGROUND: Clinical studies published in the last decade have shown the possible improvement in prognosis of patients with prostatic carcinoma undergoing radiation therapy with dose escalation or in combination with hormone therapy. However, in studies on hormone therapy, moderate doses of radiation therapy have been used, whereas in studies with high-dose radiotherapy, hormone therapy usually was not administered. Therefore, it is not clear whether the concomitant use of high doses and prolonged hormone therapy could determine an additional beneficial effect. The aim of the present study was therefore to evaluate the relative prognostic role of different dose levels (< 70 versus > or = 70 Gy) of external beam radiotherapy and of different hormone therapies (neoadjuvant only versus neoadjuvant + adjuvant). METHODS: A total of 426 patients (median age, 71 yrs; range, 51-87 yrs) underwent external beam radiotherapy (70 Gy median dose to prostate volume +/- 45 Gy to pelvic lymph nodes) and neoadjuvant hormone therapy (bicalutamide for 30 days; goserelin, 3.6 mg every 28 days starting two months before radiotherapy and for its entire duration). Dose to the prostate was < 70 Gy in 44.8% of patients and > or = 70 Gy in 55.2%. A total of 244 patients received adjuvant hormonal therapy. The distribution according to the clinical stage was 48.1% T2 and 51.9% T3. The distribution according to the Gleason score was 14.3% grades 2-4, 66.7% grades 5-7 and 19.0% grades 8-10. The distribution according to pretreatment prostate-specific antigen levels (in ng/mL) was 7.0% for 0-4, 29.3% for 4-10, 30.3% for 10-20, and 33.3% for > 20. RESULTS: With a median follow-up of 35 months (range, 1-151), 81 patients (19.0%) showed biochemical recurrence, 17 patients (4.0%) showed local disease progression, and 12 patients (2.8%) showed distant metastases. Overall, 23 patients (5.4%) showed disease progression. Four patients (0.9%) died. At the time of this writing, no patient has died from prostatic carcinoma. At univariate analysis, the radiation dose delivered to the tumor and the administration of adjuvant hormone therapy were shown to be significantly correlated with biochemical disease-free survival. At multivariate analysis, the single parameter significantly correlated with biochemical disease-free survival was the radiation dose delivered to the tumor. In the subset of patients not treated with adjuvant hormone therapy, there was a significant correlation between radiation dose and biochemical disease-free survival at univariate and multivariate analysis. A similar correlation between adjuvant hormone therapy and biochemical disease-free survival was observed in the subset of stage cT3 patients at univariate and multivariate analysis. In patients undergoing combined treatment without adjuvant hormone therapy, a significant correlation was observed between clinical stage and biochemical disease-free survival, at univariate and at multivariate analysis. CONCLUSIONS: The results of the study confirmed the positive impact of radiotherapy doses > 70 Gy and of adjuvant hormone therapy in patients with locally advanced prostatic carcinoma. Owing to the lack of evidence of a correlation between radiation dose and biochemical outcome in patients undergoing prolonged hormone therapy, the role of further dose escalation in patients undergoing combined hormone and radiation therapy is still unclear.