Curative external beam radiotherapy for prostate carcinoma: results in 231 patients treated in Lyon.

BACKGROUND: Radical prostatectomy and external beam radiation therapy (EBRT) are the mainstays of treatment of prostate cancer with curative intent. The possible development of radiation proctitis and rectal bleeding are major concerns when using EBRT. Recently, conformal radiotherapy has been introduced in an attempt to improve the results of EBRT. This paper presents an overview of the Lyon experience using standard EBRT with doses of 68 Gy, and reports the preliminary results of a study of conformal radiotherapy with dose escalation. METHODS: From 1981 to 1995, EBRT was used to treat 231 patients with localized adenocarcinomas of the prostate. The dose of EBRT was 68 Gy/34 fractions/7 weeks using a four-field box technique with 18-MeV photons. A feasibility study of conformal radiotherapy was commenced in 1996. To date, 145 patients have been treated with doses escalating from 68 to 80 Gy. RESULTS: In the EBRT group of 231 patients, the 5-year overall survival was 80.3%. Anorectal function was scored as excellent in 90% of patients. Rectal bleeding was seen in 14.3% of patients and required local treatment in only seven. In the group treated with conformal radiotherapy, the preliminary results indicate good early tolerance. CONCLUSION: The curative treatment of patients with prostate cancer using EBRT gives good long-term survival with low rectal toxicity. Conformal radiotherapy appears to be an interesting approach to improve local control and perhaps survival.     

CURATIVE EXTERNAL BEAM RADIOTHERAPY FOR PROSTATE CARCINOMA: RESULTS IN 231 PATIENTS TREATED IN LYON

Background : Radical prostatectomy and external beam radiation therapy (EBRT) are the mainstays of treatment of prostate cancer with curative intent. The possible development of radiation proctitis and rectal bleeding are major concerns when using EBRT. Recently, conformal radiotherapy has been introduced in an attempt to improve the results of EBRT. This paper presents an overview of the Lyon experience using standard EBRT with doses of 68 Gy, and reports the preliminary results of a study of conformal radiotherapy with dose escalation. Methods : From 1981 to 1995, EBRT was used to treat 231 patients with localized adenocarcinomas of the prostate. The dose of EBRT was 68 Gy/34 fractions/7 weeks using a four-field box technique with 18-MeV photons. A feasibility study of conformal radiotherapy was commenced in 1996. To date, 145 patients have been treated with doses escalating from 68 to 80 Gy. Results : In the EBRT group of 231 patients, the 5-year overall survival was 80.3%. Anorectal function was scored as excellent in 90% of patients. Rectal bleeding was seen in 14.3% of patients and required local treatment in only seven. In the group treated with conformal radiotherapy, the preliminary results indicate good early tolerance. Conclusion : The curative treatment of patients with prostate cancer using EBRT gives good long-term survival with low rectal toxicity. Conformal radiotherapy appears to be an interesting approach to improve local control and perhaps survival.     

Current status of intensity‐modulated radiation therapy for prostate cancer: History,clinical results and future directions

External beam radiotherapy has changed dramatically over several decades with the improvement of computer hardware and software, and machinery developments. Intensity‐modulated radiation therapy is the most sophisticated technique for all cancer treatment with radiation therapy, and is widely disseminated and available for daily use in many countries. Several retrospective and prospective studies have shown that intensity‐modulated radiation therapy reduces the radiation dose in the organs at risk with diminished rates of acute and late toxicity, even with higher doses (>74 Gy). An important technique for the clinical use of intensity‐modulated radiation therapy is image‐guided radiation therapy. The clinical benefit for prostate image‐guided radiation therapy has been assessed by comparing the outcomes of patients with either the image‐guided radiation therapy or non‐image‐guided radiation therapy technique. These studies have shown that image‐guided radiation therapy significantly decreases acute and late rectal and bladder toxicities. Randomized trials and meta‐analysis have shown that higher doses result in better biochemical control. More recently, hypofractionated radiation therapy comparing hypofractionated radiation therapy versus conventional fractionated radiation therapy have shown that hypofractionated radiation therapy produces biochemical control and toxicity rated similar to those produced by conventional fractionated radiation therapy. The clinical use of ultrahypofractionated radiation therapy and simultaneous integrated boost technique is necessary to evaluate its further safety and benefits. Intensity‐modulated radiation therapy is also widely accepted in the field of salvage therapy and for the patients with distant oligometastases. The purpose of the present review is to summarize the history of intensity‐modulated radiation therapy, new techniques for intensity‐modulated radiation therapy, hypofractionation and future directions for prostate cancer.     

Improved biochemical disease-free survival of men younger than 60 years with prostate cancer treated with high dose conformal external beam radiotherapy

PURPOSE: We report the long-term prostate specific antigen relapse-free survival rates and predictors of biochemical outcome for patients 60 years or younger with prostate cancer treated with high dose conformal external beam radiotherapy. MATERIALS AND METHODS: We retrospectively reviewed the records of 740 patients with prostate cancer treated with 3-dimensional conformal radiotherapy or intensity modulated external beam radiotherapy. Patients who also received androgen deprivation therapy were excluded from this analysis. Median radiation dose was 75.6 Gy and median followup was 88 months with a minimum followup of 24 months. Median followup for patients 60 years or younger in this report was 54 months (range 24 to 132). Biochemical failure was defined according to the criteria recommended by the American Society for Therapeutic Radiology and Oncology Consensus Panel. RESULTS: Biochemical failure developed in 20 (21%) of the 96 men 60 years or younger, which was similar to the 22% failure rate observed in 644 patients older than 60. The 5 and 7-year biochemical disease-free survival rates were 82% and 79% in younger men, and 79% and 78% in older men, respectively (p = 0.48). For younger patients who received 81 Gy or greater, the 7-year prostate specific antigen relapse-free survival rates for favorable, intermediate and unfavorable risk patients were 96%, 87% and 50%, respectively. Multivariate analysis revealed that among patients 60 years or younger the most important predictor of biochemical relapse was radiation doses less than 75.6 Gy followed by Gleason score greater than 7. CONCLUSIONS: Men with prostate cancer 60 years or younger treated with high dose radiotherapy have an excellent biochemical outcome and fare as well as older patients. The use of conventional dose levels in patients 60 years or younger was associated with an 8-fold increase in the biochemical relapse rate and these doses should not be considered appropriate for the treatment of localized prostate cancer.     

Impact on rectal dose from the use of a prostate immobilization and rectal localization device for patients receiving dose escalated 3D conformal radiation therapy

PURPOSE: When >25% of the rectum is irradiated to > or = 70 Gy, the risk of developing Grade 2 or higher rectal complications is significantly increased. This study evaluates the impact on dose to the rectum from the use of an intrarectal (IR) balloon device, previously shown to immobilize the prostate gland and localize the rectum, in patients receiving dose escalated 3-dimentional (3D) conformal radiation therapy. MATERIALS AND METHODS: From July 2001 through February 2003, 28 consecutive patients with prostate cancer underwent computerized tomography-based simulation with and without the IR balloon in place. Treatment planning was performed for three clinical paradigms in which the IR balloon was not used at all (0 Gy), used during the cone-down for 15 treatments (28.35 Gy), or used for the entire course of 40 treatments (75.6 Gy). The three plans were compared for differences in the percent of rectum receiving >70 Gy. RESULTS: Dose volume histogram (DVH) analysis revealed that the median(range) of percent rectal volume exceeding 70 Gy was 25% (12.7-41.5%), 7.5% (0.9-19.5%), and 3.6% (0-8.7%) for patients in whom the IR balloon was used for 0, 15, and 40 treatments, respectively. The percent of rectum exceeding 70 Gy was significantly different for all treatment plan comparisons (P < 0.0001). CONCLUSIONS: Grade 2 or higher rectal toxicity may be minimized during dose escalated 3D conformal radiation therapy through the use of an IR balloon during the 3-week cone down portion of an 8-week treatment course.     

Three-dimensional conformal radiation therapy for prostate cancer in Hamamatsu Medical Center

We retrospectively evaluated acute and late radiation morbidity and short-term PSA relapse-free survival of 53 patients with localized prostate cancer who received three dimensional radiation therapy (3D-CRT) that targeted prostate and seminal vesicles in Hamamatsu Medical Center from 1999.10 to 2005.4. The total dose was increased from 70 to 74 Gy in increments of 2.0 Gy. We divided these patients into two groups who received 70-72 Gy or 74 Gy. Then we analyzed whether there were differences between those two groups in acute radiation morbidity. We also analyzed late radiation morbidity in the 70(-)-72 Gy group. Acute radiation morbidity and late morbidity were described according to the RTOG acute radiation morbidity scoring criteria 1995 and RTOG/EORTC late radiation morbidity scoring scheme 1995, respectively. No acute grade 3 or 4 toxicity and no late grade 4 toxicity was observed. Late grade 3 rectal bleeding was observed in only one patient who received 70 Gy. Acute toxicity was well tolerated and did not correlate with total dose.     

Percutaneous radiotherapy for low-risk prostate cancer: options for 2007

Technical developments of radiotherapy (RT) over the recent years yielded in better conformation to the target volume thus increasing the therapeutic ratio and decreasing side effects. This paper discusses these options for low-risk prostate cancer. There has been evidence from randomized trials, that for low-risk PCA doses >70 Gy are significant better in case of biochemical disease-free survival (bNED). Image-guided radiotherapy (IGRT) has been proven in several studies for reduced safety margins around the prostate target volume. Intensity-modulated radiotherapy (IMRT) allow treatment with higher doses and 5-year results are reported from several studies. Data from several randomized trials about adjuvant RT after radical prostatectomy (RP) have been reported. In two phase-III trials a significant advantage of 20% bNED was demonstrated for doses between 76 and 79 Gy compared with 70 Gy. Using IGRT, the safety margin around the prostate can be reduced for about 30–50%. Doses of >80 Gy can be given safely to the prostate with IMRT and <5% grade-III/IV late side effects. Adjuvant RT for positive margins after RP has been of proven advantage. Three phase-III trials achieved a significant better bNED of 20% for 5 years. The effect of doses >70 Gy have been proven for low-risk PCA. IGRT resulted in reduced safety margins and a decrease of acute and late side effects. The addition of IMRT allowed higher doses to the prostate. Adjuvant RT after RP for positive margins achieved a significant better bNED.     

High dose radiation delivered by intensity modulated conformal radiotherapy improves the outcome of localized prostate cancer

PURPOSE: We present the long-term outcome and tolerance of 3-dimensional (D) conformal and intensity modulated radiation therapy for localized prostate cancer. MATERIALS AND METHODS: Between October 1988 and December 1998, 1,100 patients with clinical stages T1c-T3 prostate cancer were treated with 3-D conformal or intensity modulated radiation therapy. Patients were categorized into prognostic risk groups based on pretreatment prostate specific antigen (PSA), Gleason score and clinical stage. Sextant biopsies were performed 2.5 years or greater after treatment to assess local control. PSA relapse was defined according to the consensus guidelines of the American Society for Therapeutic Radiation Oncology. Late toxicity was classified according to the Radiation Therapy Oncology Group morbidity grading scale. Median followup was 60 months. RESULTS: At 5 years the PSA relapse-free survival rate in patients at favorable, intermediate and unfavorable risk was 85% (95% confidence interval [CI] +/- 4), 58% (95% CI +/- 6) and 38% (95% CI +/- 6), respectively (p <0.001). Radiation dose was the most powerful variable impacting PSA relapse-free survival in each prognostic risk group. The 5-year actuarial PSA relapse-free survival rate for patients at favorable risk who received 64.8 to 70.2 Gy. was 77% (95% CI +/- 8) compared to 90% (95% CI +/- 8) for those treated with 75.6 to 86.4 Gy. (p = 0.04) [corrected]. The corresponding rates were 50% (95% CI +/- 8) versus 70% (95% CI +/- 6) in intermediate risk cases (p = 0.001), and 21% (95% CI +/- 8) versus 47% (95% CI +/- 6) in unfavorable risk cases (p = 0.008) [corrected]. Only 4 of 41 patients (10%) who received 81 Gy. had a positive biopsy 2.5 years or greater after treatment compared with 27 of 119 (23%) after 75.6, 23 of 68 (34%) after 70.2 and 13 of 24 (54%) after 64.8 Gy. The incidence of toxicity after 3-D conformal radiation therapy was dose dependent. The 5-year actuarial rate of grade 2 rectal toxicity in patients who received 75.6 Gy. or greater was 14% (95% CI +/- 2) compared with 5% (95% CI +/- 2) in those treated at lower dose levels (p <0.001). Treatment with intensity modulated radiation therapy significantly decreased the incidence of late grade 2 rectal toxicity since the 3-year actuarial incidence in 189 cases managed by 81 Gy. was 2% (95% CI +/- 2) compared with 14% (95% CI +/- 2) in 61 managed by the same dose of 3-D conformal radiation therapy (p = 0.005). The 5-year actuarial rate of grade 2 urinary toxicity in patients who received 75.6 Gy. or greater 3-D conformal radiation therapy was 13% compared with 4% in those treated up to lower doses (p <0.001). Intensity modulated radiation therapy did not affect the incidence of urinary toxicity. CONCLUSIONS: Sophisticated conformal radiotherapy techniques with high dose 3-D conformal and intensity modulated radiation therapy improve the biochemical outcome in patients with favorable, intermediate and unfavorable risk prostate cancer. Intensity modulated radiation therapy is associated with minimal rectal and bladder toxicity, and, hence, represents the treatment delivery approach with the most favorable risk-to-benefit ratio.     

Standard vs conformal radiation therapy for adenocarcinoma of the prostate: no difference

Objective: To compare results of treatment of adenocardinoma of the prostate using Standard (2D) vs Conformal (3D) treatment planning. Methods: The records of all patients with adenocarcinoma of the prostate treated curatively with radiation therapy alone from July 1991 to June 1994 were reviewed. Acute and late complications were scored by the RTOG criteria. Biochemical failure was defined as a rising PSA of at least 10% on two measurements separated >/=1 month or either a PSA nadir >4 ng/ml or >1 ng/ml. Disease free survival (DFS) was defined as no evidence of local, distant, or biochemical failure. 2D planning included standard simulation with target volume drawn from the treatment planning or diagnostic CT. 3D planning included a CT in the treatment position with computer simulation using beam's-eye-view for field design. Results: Two-hundred and seventeen 2D and 45 3D patients had similar median age and pre-treatment PSA, T-stage, and dose to the prostate. The median follow-up periods for the 2D and 3D groups were 32.0 and 21.5 months, respectively. The two-year actuarial survival, local or biochemical control, and DFS were not different. The 3D group had a significantly higher incidence of acute bladder side effects of all grades and acute grade 1/2 rectal complications. There were no differences in the incidence of late bladder or rectal complications. Conclusions: Careful 2D planning for the treatment of localized adenocarcinoma of the prostate is an acceptable means of treatment. Within the dose range of 64-70 Gy, this preliminary analysis demonstrated no reduction in complications nor improvement in local or biochemical control, or DFS was seen with the the use of 3D treatment planning.     

Salvage radiotherapy for pT3 prostate cancer with PSA failure after radical prostatectomy

We assessed the effectiveness of salvage radiotherapy in 13 patients at pathologic stage T3 (pT3) with prostate specific antigen (PSA) failure after radical prostatectomy: 9 patients at pT3a and 4 patients at pT3b. Three-dimensional dynamic conformal radiotherapy was used for all patients in this study, and the median radiation dose was 57.7 Gy (range, 44-70 Gy) in daily amounts of 2 Gy. The median follow-up after salvage radiotherapy was 643 days (range, 193-1562 days). In 12 of the 13 patients, PSA levels decreased after salvage radiotherapy, but in 1 patient, the PSA level increased and hence the treatment was discontinued at 44 Gy. However, 10 patients exhibited a lasting PSA response. The 3-year biochemical progression-free rate was 74%, and no serious acute or late toxicity was observed during the follow-up. Salvage radiotherapy is likely to become one of the effective treatments for the patients at pT3 with PSA failure following radical prostatectomy.     

Conformal radiotherapy of prostate cancer

A number of retrospective and prospective studies have demonstrated that radiotherapy of prostate cancer must be actually conformal. Three-dimensional (3D) treatment planning consists in an as accurate as possible definition of target-volume, usually by CT-scan, and design of radiation fields shaped to this target-volume. Several steps are required, each step being important for the overall quality of the treatment. Conformal radiotherapy is better tolerated than conventional irradiation, with significantly less rectal toxicity. It allows dose-escalation up to 80 Gy. It is now possible to go beyond this dose with intensity-modulated radiotherapy. The benefit of these high doses was demonstrated by some large retrospective studies and some prospective dose-escalation trials. Several randomized trials are in progress, preliminary results of two of them have been published, both showing an improvement in disease control with the higher doses. The advantage of higher doses is clearly evident for patients in the intermediate prognostic group, but is still discussed for patients with a low risk tumour or treated in combination with hormone therapy. Late proctitis is the main toxicity of these high doses. Some volume constraints have been defined during the last years and will allow a decrease of the rate of rectal toxicity. Because of these technological improvements, results of radiation therapy are now similar to those of surgery: no direct comparison with a randomized trial is available, but large comparative studies show that long-term disease control are identical with both techniques. Radiation therapy must be proposed to all patients with a prostate carcinoma as an alternative to surgery.     

Secondary Cancer After Radiotherapy for Prostate Cancer: Should We Be More Aware of the Risk?

OBJECTIVES: As the number of prostate cancer survivors is increasing, the long-term health of prostate cancer patients has become a significant health issue. Radiation is known to induce malignant transformation, and prostate cancer radiotherapy is suggested to induce secondary malignancies. This report reviews the available data regarding the risk of secondary cancer after radiation for prostate cancer. METHODS: Epidemiological studies of the secondary cancer risk in patients with a history of prostate cancer radiation and the literature regarding radiation-induced carcinogenesis were reviewed. RESULTS: Prostate cancer is not associated with an increased number of additional malignancies. The data suggests a modest increase in secondary cancers associated with radiation for prostate cancer, as approximately one in 70 patients undergoing radiation and surviving more than 10 yr will develop secondary cancer. The most common sites for secondary cancers are bladder and rectum. In addition to the cancers adjacent to the radiation field, there is also an increase of cancers in distant sites, such as lung. The increased risk for secondary cancers is reported after external radiation, not after brachytherapy. The available data originated from studies of patients undergoing conventional radiotherapy. New treatment methods, such as intensity-modulated radiotherapy, may be associated with a higher risk of secondary cancers. CONCLUSION: Although the incidence of secondary cancers after prostate cancer radiotherapy is not dramatically different from the overall population, patients should be informed about this risk. Other treatment modalities should be considered for patients with long life expectancy and for patients with additional risk factors.     

Three-dimensional conformal radiotherapy for localized prostate cancer in kidney transplant recipients

BACKGROUND: This is the first report of graft function and prostate cancer control in renal transplant recipients subjected to modern conformal radiotherapy. METHODS: Eight kidney transplant recipients were treated with three-dimensional conformal radiotherapy. All patients but one were subjected to transitory hormonal deprivation. A three-dimensional radiotherapy-planning system (Pinnacle, Philips Medical System, Bothell, WA) was used to delineate anatomic contours on pretreatment computed tomography and for dose computation. The clinical target volume encompassed the prostate and was expanded with a 10-mm wide margin in all directions to obtain the planning target volume. The irradiation technique consisted of a nine-field arrangement delivering 70 Gy in 2-Gy fractions, with 18-MV photon beams. Biochemical recurrence was defined as two consecutive increases in prostate-specific antigen (>1.5 ng/mL). Graft function was monitored by creatinine clearance. Excretory profiles were assessed by furosemide-stimulated diethylenetriaminepentaacetic acid renography. All patients were subjected to hip magnetic resonance imaging to assess for avascular hip necrosis. RESULTS: After a mean follow-up of 28 months, two patients showed isolated biochemical recurrence and six patients remained free of recurrence. In seven patients with functional allografts, the creatinine clearance was unimpaired by treatment. However, significant obstruction of the terminal ureter was revealed in two patients by furosemide-stimulated diethylenetriaminepentaacetic acid renograms. The doses delivered to the uretero-neocystostomy were calculated to range from less than 20 Gy to more than 45 Gy depending on bladder repletion. CONCLUSIONS: Adequate cancer control was achieved at the expense of infraclinical ureteral obstruction. The doses delivered to the uretero-neocystostomy may be reduced by having a full bladder at the time of irradiation. No avascular hip necrosis was observed.     

Preoperative radiotherapy for rectal cancer: hypofractionation with multiple fractions (15-25 Gy)

Preoperative radiotherapy lowers local recurrence rates after rectal cancer surgery, as seen in several randomised trials. Postoperative radiotherapy is also effective, although a higher radiation dose is required. In addition, preoperative, but not postoperative (unless combined with chemotherapy) radiotherapy also improves survival slightly. Since the toxicity profile also favours preoperative therapy, this is a more attractive approach. The trials have also shown that a sufficiently high biological dose is required to achieve any influence on local failure rates. If the dose at each radiation fraction is higher (e.g. 5 Gy), the radiation can be given much faster (during one week) than if a 'conventional' fraction size of about 2 Gy is used (4-5 weeks). Surgery can also safely be performed immediately after the end of the short radiation course, but not until several weeks later after conventional radiotherapy. This adds to the practicability of the short schedules. An inappropriate radiation technique was used particularly in one trial using multiple 5 Gy fractions. This resulted in unacceptable acute and late toxicity. However, several other trials have shown that the treatment is safe. Preoperative 5 x 5 Gy is one of the most extensively investigated oncological treatments with proven efficacy. Since the total dose is comparably low (25 Gy), the decreased therapeutic ratio of using fraction sizes above 2 Gy appears to have no clinical relevance. The experience indicates, however, that every therapeutic modality should be used in an optimal way.     

Hydrogelapplikation als Spacer in den „Denovier-Raum“

Background

Radiotherapy is an appropriate primary therapy for localized prostate cancer in accordance with urological guidelines. Especially in tumors of higher grade malignancy, dose escalation up to 80,0 Gy seems to be an advantage; however rectum toxicity can be a problem. By injecting a synthetic hydrogel (SpaceOAR®) as a spacer between the prostate and rectum, rectal toxicity can be reduced. We report on our experiences with 47 patients and an average follow-up of 241 days.

Methods

From February 2012 to November 2012, 47 patients were included in the study series. Before external radiotherapy the hydrogel was injected between prostate and rectum in the so-called Denovier space. This interdisciplinary procedure was carried out with the patient under general anesthesia using transrectal ultrasound guidance and video documentation. The patients were hospitalized for 1 day. The exact position of the gel was assessed by means of magnetic resonance imaging (MRI). Radiotherapy was initiated 7-14 days after gel application in a dose escalation manner by means of intensity modulated radiation therapy (IMRT) up to a dose of 80,0 Gy. Average follow-up was 241 (100–386, SD 91) days.

Results

No early side effects specific for the application were observed. The achieved distance between rectum and the mid-plane of the prostate gland was on average 13.8 (6–24, SD=3.8) mm. Calculated V70 (rectal volume irradiated with 70.0 Gy or more) could be reduced to an average of 1.5 (0–8, SD=1.7) %. One patient showed an asymptomatic lesion of the rectal mucosa after irradiation with 38,0 Gy. This lesion was closely controlled and gel penetration was found. As a result radiotherapy was discontinued. Without further treatment the necrosis had completely healed 3 months later.

Conclusions

Hydrogel application between prostate and rectum allows dose escalation up to 80,0 Gy and seems to reduce morbidity in patients with localized prostate cancer receiving radiotherapy. However, before final judgement of the new technique further studies must follow.     

Transurethral intracavitary irradiation for carcinoma of the prostate

This paper describes a new technique and preliminary clinical results of remote after-loading transurethral irradiation for cancer of the prostate. As of January 1986, twelve patients with adenocarcinoma of the prostate have been treated by our radiotherapy technique. Clinically, 3 patients were in stage B2, 3 in stage C, 3 in stage D1 and 3 in stage D2. These patients have been followed up for 13 to 33 months with a median follow-up period of 20.6 months. The dose of transurethral irradiation was 9-10 Gy. to the prostatic capsule and about 2 Gy. to the rectum in one procedure. We repeated this radiotherapy 3 to 4 times within an about 1-month period. Three patients in stage D1 and one patient in stage C received an additional external beam radiation (40 Gy.) to the entire pelvis. A needle biopsy was also performed every 4-6 months after irradiation. Local tumor response proved rapid and satisfactory as verified by a rectal examination and ultrasonography. The biopsies revealed a 70% negative rate within one year. The most common side effect was transient frequency observed in 7 patients. Severe complications such as incontinence, urethral stricture, or proctitis were not evident. This study suggests that intracavitary irradiation of cancer of the prostate is effective and safe. This method may have wider application.     

Radical radiotherapy with salvage surgery for invasive bladder cancer: results following a reduction in radiation dose.

The management of invasive bladder cancer in Edinburgh, as in many other centres in the UK, has been by radical radiotherapy, with cystectomy reserved for local treatment failure or relapse. A review of the results of this policy in 1987 highlighted what was felt to be an unacceptably severe morbidity rate of 15%. The dose of radiation was therefore reduced from 55 Gy in 20 daily fractions to 52.5 Gy. Forty of 80 patients (50%) treated in this way have achieved a complete response at 6 months which is a similar response rate to that in previous reports. In addition, ten of 23 frail or elderly patients (43%) achieved a complete response with a lower dose of 50 Gy given as a split course over 7 weeks. Eighteen patients have had a salvage cystectomy, and 12 of 18 (67%) are alive and disease-free. Although follow-up is short, to date toxicity has been reduced, and our results support our decision to reduce the radiation dose.     

Radiotherapy of vertebral hemangiomas]

The paper presents the analysis of results of treatment with radiotherapy of 14 cases of vertebral hemangiomas. All patients were irradiated in accordance with conventional schedule fractionated doses, using 2 Gy per fraction. The total radiation dose amounted to 20 Gy (1 case), 24 Gy (4 cases) and 30 Gy (9 cases). The degree of pain relief and lesion reossification was assessed 1 months and 6 months after completion of radiotherapy. Complete pain relief 1 month post radiotherapy was noted in 5 cases (on average patients claimed that radiotherapy resulted in a 70% decrease of pain syndromes). Six months post radiotherapy complete pain relief was noted in 8 cases (on average patients reported a 90% decrease in pain). Signs of reossification were observed in cases 6 months after treatment. No correlation was noted neither between the degree of pain relief and reossification, nor between the total delivered dose and the degree of pain relief. The obtained results allow to conclude that conventionally fractionated radiotherapy (using 20-24 Gy as total dose) is a good method of analgetic treatment of vertebral hemangiomas probably based on the anti-inflammatory effect of radiation.     

Radiotherapy for High Grade Clinically Localized Adenocarcinoma of the Prostate

Purpose

We defined the efficacy of radiotherapy for the treatment of high grade (Gleason scores 8 to 10) adenocarcinoma of the prostate.

Materials and Methods

A total of 50 patients underwent radiotherapy with curative intent for clinically localized prostate cancer with Gleason scores of 8 to 10 at 1 of 4 facilities affiliated with the University of California San Francisco. Patients were considered to have biochemical failure if they had a significant increase in prostate specific antigen (PSA) of 0.5 ng./ml. per year, an increase in PSA to greater than 1.0 ng./ml. or a positive biopsy.

Results

Among the 50 patients median PSA was 22.7 ng./ml. (range 1.3 to 93.4). Tumors were clinical stage T1 or T2 in 46 percent of the cases and stage T3 or T4 in 54 percent. The overall actuarial probability of freedom from biochemical failure at 4 years was 23 percent. In a multivariate analysis including all patients pretreatment PSA was the only predictor of PSA failure, with 64 percent free of progression if the pretreatment PSA was 10 ng./ml. or less compared to only 16 percent at 3 years if PSA was more than 10 ng./ml. (p = 0.01). In a multivariate analysis restricted to patients with PSA less than 20 ng./ml. 83 percent of those treated to more than 71 Gy. were free of progression compared to 0 percent for those treated to less than 71 Gy. (p = 0.03). In a multivariate analysis PSA 10 ng./ml. or less (related risk 11.4, p = 0.02), T stage 1 or 2 (relative risk 3.8, p = 0.05) and radiation dose more than 71 Gy. (relative risk 4.0, p = 0.06) were associated with a favorable outcome.

Conclusions

At 4 years the freedom from PSA failure following radiotherapy for high grade prostate cancer was comparable to previously reported surgical series. The high failure rate among patients with PSA greater than 20 ng./ml. suggests that these patients should be considered for investigational approaches. The apparent improvement in freedom from progression with the use of higher doses provides reason for optimism.