Benefit of adjuvant radiation therapy for localized prostate cancer with a positive surgical margin

PURPOSE: Positive surgical margins are common after radical prostatectomy, and the role of adjuvant therapy in such cases is controversial. We determined the benefit of postoperative external beam radiation therapy in patients with margin positive prostate cancer with respect to biochemical progression or cancer recurrence. To decrease confounding factors that may affect the likelihood of biochemical progression our study was limited to men with organ confined cancer and a single positive margin. MATERIALS AND METHODS: We retrospectively evaluated the records of a nested matched cohort of 76 patients with pathological stage T2N0 prostate cancer and a single positive margin who underwent adjuvant radiation therapy within 3 months of radical prostatectomy. There was a positive margin at the prostatic apex in 35 cases, prostatic base in 18, posterior prostate in 11, urethra in 7, and prostatic apex and urethra in 5. These patients were matched 1:1 with 76 controls who did not receive adjuvant radiation therapy. Neither group received androgen deprivation therapy. Patients and controls were matched exactly for the margin positive site, age at surgery, preoperative serum prostate specific antigen, Gleason score and DNA ploidy. Biochemical relapse was defined as posttreatment PSA greater than 0.2 ng./ml. RESULTS: Overall there was significant estimated improvement plus or minus standard error in 5-year clinical and biochemical progression-free survival in 88%+/-5% versus 59%+/-11% of patients treated with adjuvant radiation therapy versus no radiation therapy (p = 0.005). No patient who received radiation therapy had local or distant recurrence, while 16% of controls had recurrence (p = 0.015). When stratified by site of margin positivity, the 5-year estimated clinical and biochemical progression-free rate in 18 cases and controls with a positive base margin was 95%+/-15% and 65%+/-13%, respectively (p = 0.02). The rate in 35 cases and cases with a positive apex margin was 95%+/-5% and 64%+/-15%, respectively (p = 0.07). Limited sample size precluded analysis of the other sites. CONCLUSIONS: Patients with localized prostate cancer and a singe positive surgical margin appear to have a lower rate of biochemical relapse at 5 years when adjuvant radiation therapy is administered. Definitive evidence of the beneficial effect of adjuvant radiation therapy for patients with involved surgical margins awaits conclusion of randomized clinical trials.     

Use of neoadjuvant and adjuvant therapy to prevent or delay recurrence of prostate cancer in patients undergoing radiation treatment for prostate cancer

Multiple oncologic treatment modalities are often integrated into the curative treatment approach for the patient with a newly established diagnosis of cancer. The combination of neoadjuvant and adjuvant therapies with radiotherapy for the care of the patient with prostate cancer is no exception. There is clear evidence that neoadjuvant androgen suppression reduces the volume of tumor in preparation for radiotherapy, and it is an effective addition to conventional-dose external radiotherapy in patients with large-volume primary prostatic tumors. Adjuvant androgen suppression improves local and systemic tumor control and improves survival duration compared with radiotherapy alone for patients with locally advanced or node-positive prostate cancer, particularly in those with high-grade disease. The role of neoadjuvant and adjuvant therapies is under intense scrutiny as several randomized clinical trials seek to optimize the combination of androgen suppression, chemotherapy, and radiotherapy. The historical precedent for combining androgen suppression with radiotherapy is described, as are the results of prior definitive trials and ongoing studies in this setting.     

Primary radiation therapy for localized prostate cancer

Prostate cancer in men is similar to breast cancer in women; both cancers rank first, respectively, in incidence and are normally responsive to radiation therapy. In addition, advances in mammography help detect earlier breast cancers, and the development and refinement of prostatic specific antigen (PSA) has resulted in early detection of low-stage localized prostate cancers. This has generated debate over the proper management of localized prostate cancer. While there have not been any controlled, prospective, randomized trials of sufficient power to compare the various local therapies, based on the current available data, the three commonly used local modalities, surgery, and external beam radiation therapy and brachytherapy (radioactive seed implant), have similar efficacy controlling the disease up to 10 years in many patients. Technological advances in treatment delivery and planning have improved the treatment of prostate cancer with external-beam radiotherapy using three-dimensional conformal radiotherapy (3DCRT), ultrasound-guided transperineal implant, or intensity-modulated radiotherapy (IMRT), as well as proton or neutron beam based therapies.     

Bladder cancer risk following primary and adjuvant external beam radiation for prostate cancer

PURPOSE: Increased rates of secondary bladder malignancies have been reported after external beam radiation therapy (EBRT) for gynecological malignancies with relative risks of 2 to 4. This study was designed to determine if there was an increase in bladder cancer after EBRT for prostate cancer. MATERIALS AND METHODS: We retrospectively reviewed the Mayo Clinic Cancer Registry for patients who received EBRT for prostate cancer (1980 to 1998). Patients diagnosed with bladder cancer were identified. Comparative incidence rates were obtained from the national Surveillance, Epidemiology and End Results database. Subset analysis included patients treated with adjuvant radiation and those residing locally. Medical histories of patients with bladder cancer were reviewed. RESULTS: A total of 1,743 patients received EBRT for prostate cancer at our institution. In more than 12,353 man-years of followup no increase in bladder cancer risk was encountered. Subset analysis of men who received adjuvant radiation demonstrated that the relative risk of bladder cancer was increased but was not statistically significant. When the analysis was restricted to patients residing in the local area, the number of patients in whom subsequent bladder cancer developed was similar to Surveillance, Epidemiology and End Results rates. However, in the adjuvant radiation subset there was a statistically significant increase in subsequent bladder cancer. Patients in whom bladder cancer develops after EBRT often present with low grade disease but many have recurrence and progression. CONCLUSIONS: This retrospective review suggests there is not evidence of increased risk of bladder cancer after radiation therapy, assuming unbiased followup and complete ascertainment of cases. The natural history of bladder cancer in this population does not seem to be altered by a history of radiation.     

Transrectal ultrasound-guided interstitial radiation therapy for localized prostate cancer.

The use of interstitial implants for the treatment of low-stage prostate cancer using transrectal ultrasound guidance is evaluated in 80 patients. This outpatient procedure involves the placement of needles through a template and into the prostate. Ultrasound guidance is used to place the needles into a preselected location. The needles are loaded with a radioactive source. In this study Palladium-103 was utilized. This technique allows accurate and complete seeding of the prostate. There was a 50 percent or greater decrease in prostate size in all of the patients who were implanted. Prostate-specific antigen (PSA) levels became normal or decreased by more than 50 percent in 97 percent of the patients. Most patients experienced urethral irritative symptoms which lasted up to five months, but none of the patients experienced rectal symptoms lasting longer than a month. The mean follow-up is 11.8 months which is too brief to ascertain the effectiveness of this therapy. The method appears to be safe and may represent an alternative to external beam irradiation.     

Salvage therapy for prostate cancer recurrence after radiation therapy

Radiotherapy has been successful in treating localized prostate cancer; however, a subset of patients will experience disease recurrence. Determination of the recurrence location must be made using pretreatment and posttreatment clinical variables, imaging, and postradiotherapy biopsy. Patients presumed to have local-only recurrence, optimal clinical risk factors, and an extended life expectancy may be considered for salvage local treatment. Current options include salvage surgery, cryoablation, and brachytherapy. Although they are associated with higher morbidity than primary therapy, salvage treatments can be effective and can still provide patients with a good oncologic and functional outcome. As these modalities continue to improve and patient selection is optimized, better results will evolve.     

辅助内分泌配合放射性粒子组织间植入治疗局限性前列腺癌

目的探讨辅助内分泌配合放射性粒子组织间植入治疗局限性前列腺癌的安全性和有效性。方法22例T1-T24前列腺癌患者在采用直肠超声引导经会阴穿刺放射性^125I粒子组织间植入治疗前后，给予辅助内分泌治疗4—7（平均5．7）个月。术前2—4（平均3．2）个月，术后1—4（平均2．1）个月。结果22例手术均顺利完成，手术时间60-120（平均90）min，植入^125I粒子数40-75（平均56）枚，术后随访12—48个月，血PSA≤1ng／mL15例，1ng／mL≤PSA≤2ng／mL2例，PSA≥2ng／mL5例。结论辅助内分泌配合放射性粒子组织间植入治疗局限性前列腺癌安全有效。     

High-dose intensity modulated radiation therapy for prostate cancer

The trend in prostate cancer radiation over the past several years has been to increase the dose to the gland while minimizing the dose to normal tissues. Intensity modulated radiation therapy is a computer-driven treatment planning and delivery system that has shown promise in improving disease-free outcome while decreasing the associated gastrointestinal and urinary complication rates. This technique continues to evolve, working toward image-guided radiation therapy, which is adjusted daily for positional and architectural changes of the gland.     

Effect of adjuvant radiation therapy on prostate specific antigen following radical prostatectomy.

A total of 21 patients received adjuvant radiation therapy after radical prostatectomy for a persistently detectable prostate specific antigen value (more than 0.6 ng. per ml.) postoperatively. Adjuvant radiation therapy decreased serum prostate specific antigen values to the undetectable range in 6 of 21 patients (29%) all of whom have remained free of tumor recurrence with a mean followup of 12.6 months (range 6 to 30). Three patients initially showed a decrease in serum prostate specific antigen to undetectable levels but they subsequently demonstrated an increasing level within 12 months after adjuvant radiation therapy. Additionally, 7 of 13 patients whose prostate specific antigen values remained in the detectable range despite adjuvant radiation therapy have had clinical evidence of tumor recurrence. Further followup will be required to determine what ultimate impact adjuvant radiation therapy will have on survival free of tumor.     

Underutilization of local salvage therapy after radiation therapy for prostate cancer

ObjectiveTo evaluate the rates at which patients are offered and receive local salvage therapy (LST) after failure of primary radiotherapy for localized prostate cancer, as it is the only potentially curative treatment for localized recurrence but appears to be underutilized when compared with androgen-deprivation therapy (ADT) or observation.Materials and methodsPatients with localized prostate cancer who received primary radiotherapy with curative intent between 1999 and 2000 were identified in the British Columbia Tumour Registry. Exclusion criteria included patient age >72 years, prostate-specific antigen>40 ng/ml, and clinical stage T4 at diagnosis. Data on clinicopathologic features, primary therapy, prostate-specific antigen kinetics, and salvage therapy were collected retrospectively. Radiation failure was defined as biochemical recurrence according to the Phoenix criteria or by initiation of salvage therapy.ResultsOf 1,782 patients treated in the study period, 1,067 met inclusion criteria. Of these, 257 failed radiation therapy. Radiation therapy failure was managed with observation (>12 mo) in 126 patients and ADT in 119. Of the observed patients, 66 subsequently received ADT. Five patients (1.8%) received LST (3 radical prostatectomy and 2 brachytherapy).ConclusionsOnly 2% of patients relapsing after radiation therapy for localized prostate cancer received LST. Although the benefits of LST are unproven, these findings reveal a possible underutilization of LST and indicate a need for enhanced collaboration between specialties to optimize care of this challenging cohort.     

Limited operation for lung cancer in combination with postoperative radiation therapy.

PURPOSE: Combination therapy of lung wedge resection and postoperative radiation was performed to confirm the procedure's feasibility as a curative therapeutic modality. PATIENTS AND METHODS: Among the patients with clinical stage I lung cancer, who could not undergo a standard lobectomy due to their poor pulmonary function, six cases were studied, who agreed with the experimental trial after the informed consent. One patient of clinical N0 with chest wall invasion (T3) was also included in combination with intraoperative chest wall radiation therapy. At first, a wedge lung resection was performed using an auto-suture technique or manual suturing. Two weeks after the surgery, concomitant radiation therapy of the area including the remnant lung around the cancer and the hilum was initiated. Total dose was 40-50 Gy. All of the patients were followed up for more than five years. RESULTS: All cases tolerated the procedure and survived more than five years. Six were cancer-free. Cancer recurred in only one case. Its manifestation was pleuritis carcinomatosa. Pleural dissemination, which was undetectable at the time of operation, was presumed to be the cause of the recurrence. CONCLUSION: This procedure was tolerated and feasible, preventing local recurrence following the limited surgery.     

Obesity as a predictor of biochemical recurrence and survival after radiation therapy for prostate cancer

OBJECTIVE: Obesity has been demonstrated to predict biochemical progression in men undergoing radical prostatectomy for prostate adenocarcinoma, and is associated with a higher risk of biochemical and clinical relapse after radiation therapy (RT). We evaluated if obesity, determined by body mass index (BMI), is associated with adverse disease characteristics, pre-treatment serum testosterone, biochemical disease free survival (bDFS), disease-specific survival (DSS), or overall survival (OS) in patients undergoing radical external beam radiation therapy for prostate cancer. PATIENTS AND METHODS: A cohort of 706 patients with localized prostate adenocarcinoma treated with RT between 1993 and 2001 were categorized as obese (BMI > or = 30 kg/m(2)), overweight (BMI 25-29.9 kg/m(2)) or normal (BMI < 25 kg/m(2)). The association between BMI, disease characteristics, and progression were evaluated by Chi-square and ANOVA tests, Kaplan-Meier survival analysis, and Cox regression analysis. RESULTS: 195 patients (27.6%) were normal weight, 358 (50.7%) were overweight and 153 (21.7%) were obese. Obese men had lower serum testosterone levels than overweight and normal-weight men (means 12.8, 14.1, and 15.7 nmol/L, respectively; p < 0.001). The BMI groups did not differ in Gleason score, pretreatment PSA, or stage. On multivariate analysis, BMI group was predictive of reduced bDFS (p = 0.02) and DSS (p = 0.008), with a trend toward reduced OS (p = 0.062). CONCLUSION: Obesity was associated with lower serum testosterone levels but not with adverse pretreatment pathological features. Obese men have a higher risk of biochemical recurrence and prostate-cancer specific death after RT.     

Carbon‐ion radiation therapy for prostate cancer

In 1994, carbon‐ion radiotherapy was started at the National Institute of Radiological Sciences using the Heavy‐Ion Medical Accelerator in Chiba. Between June 1995 and March 2000, two phase I/II dose escalation studies (protocols 9402 and 9703) of hypofractionated carbon‐ion radiotherapy for both early‐ and advance‐stage prostate cancer patients had been carried out to establish radiotherapy technique and to determine the optimal radiation dose. To validate the feasibility and efficacy of hypofractionated carbon‐ion radiotherapy, a phase II study (9904) was initiated in April 2000 using the shrinking field technique and the recommended dose fractionation (66 gray equivalents in 20 fractions over 5 weeks) obtained from the phase I/II studies, and was successfully completed in October 2003. The data from 175 patients in the phase II study showed the importance of an appropriate use of androgen deprivation therapy according to tumor risk group. Since November 2003, carbon‐ion radiotherapy for prostate cancer was approved as “Highly Advanced Medical Technology” from the Ministry of Health, Labor, and Welfare, and since then approximately 1100 patients have received carbon‐ion radiotherapy as of July 2011. In this review, we introduce our steps thorough three clinical trials carried out at National Institute of Radiological Sciences, and show the updated data of carbon‐ion radiotherapy obtained from approximately 1000 prostate cancer patients. In addition, our recent challenge and future direction will be also described.     

Late gastrointestinal toxicities following radiation therapy for prostate cancer

Background

Radiation therapy is commonly used to treat localized prostate cancer; however, representative data regarding treatment-related toxicities compared with conservative management are sparse.

Objective

To evaluate gastrointestinal (GI) toxicities in men treated with either primary radiation or conservative management for T1-T2 prostate cancer.

Design, setting, and participants

We performed a population-based cohort study, using Medicare claims data linked to the Surveillance Epidemiology and End Results data. Competing risk models were used to evaluate the risks.

Measurements

GI toxicities requiring interventional procedures occurring at least 6 mo after cancer diagnosis.

Results and limitations

Among 41 737 patients in this study, 28 088 patients received radiation therapy. The most common GI toxicity was GI bleeding or ulceration. GI toxicity rates were 9.3 per 1000 person-years after three-dimensional conformal radiotherapy, 8.9 per 1000 person-years after intensity-modulated radiotherapy, 5.3 per 1000 person-years after brachytherapy alone, 20.1 per 1000 person-years after proton therapy, and 2.1 per 1000 person-years for conservative management patients. Radiation therapy is the most significant factor associated with an increased risk of GI toxicities (hazard ratio [HR]: 4.74; 95% confidence interval [CI], 3.97-5.66). Even after 5 yr, the radiation group continued to experience significantly higher rates of new GI toxicities than the conservative management group (HR: 3.01; 95% CI, 2.06-4.39). Because our cohort of patients were between 66 and 85 yr of age, these results may not be applicable to younger patients.

Conclusions

Patients treated with radiation therapy are more likely to have procedural interventions for GI toxicities than patients with conservative management, and the elevated risk persists beyond 5 yr.