Complications of treatment with local field external beam radiotherapy for localized prostate cancer

We performed this analysis to document the rate and severity of complications both during and after local field irradiation for localized prostate cancer and to assess the influence of three-dimensional conformal radiation therapy (3DCRT) on these complications. Bowel, urinary and cutaneous toxicities were noted in all patients treated with primary radiotherapy (RT) for prostate cancer using Radiation Therapy Oncology Group/European Organization for Research on Treatment of Cancer scores. Evaluations were performed weekly during RT, 6 weeks after RT and 3 monthly thereafter. Data on 111 were analysed. We also compared the complications of conventional and 3DCRT. The serious complication rates identified in this study compare favourably with those reported in the literature. Only 3.6%, 0.8% and 0% had acute grade 3 or 4 urinary, bowel or skin reactions respectively. Only two patients had chronic grade 3 or 4 urinary complications. Thus far no patients have developed chronic bowel or skin complications greater than grade 2. Despite dose escalation from 66 Gy to 70 Gy (with 3DCRT), there was a trend towards reduced toxicity when 3DCRT was compared with conventional radiation. RT is a well-tolerated treatment for early stage carcinoma of the prostate and our complication rates are compatible with international experiences. Further follow-up is required to determine the efficacy of treatment, the incidence of impotence and the final number of late complications.     

Toxicity profile with a large prostate volume after external beam radiotherapy for localized prostate cancer

PURPOSE: To assess the impact of prostate volume on health-related quality of life (HRQOL) before and at different intervals after radiotherapy for prostate cancer. METHODS AND MATERIALS: A group of 204 patients was surveyed prospectively before (Time A), at the last day (Time B), 2 months after (Time C), and 16 months (median) after (Time D) radiotherapy, with a validated questionnaire (Expanded Prostate Cancer Index Composite). The group was divided into subgroups with a small (11-43 cm(3)) and a large (44-151 cm(3)) prostate volume. RESULTS: Patients with large prostates presented with lower urinary bother scores (median 79 vs. 89; p = 0.01) before treatment. Urinary function/bother scores for patients with large prostates decreased significantly compared to patients with small prostates due to irritative/obstructive symptoms only at Time B (pain with urination more than once daily in 48% vs. 18%; p < 0.01). Health-related quality of life did not differ significantly between both patient groups at Times C and D. In contrast to a large prostate, a small initial bladder volume (with associated higher dose-volume load) was predictive for lower urinary bother scores both in the acute and late phase; at Time B it predisposed for pollakiuria but not for pain. Patients with neoadjuvant hormonal therapy reached significantly lower HRQOL scores in several domains (affecting only incontinence in the urinary domain), despite a smaller prostate volume (34 cm(3) vs. 47 cm(3); p < 0.01). CONCLUSIONS: Patients with a large prostate volume have a great risk of irritative/obstructive symptoms (particularly dysuria) in the acute radiotherapy phase. These symptoms recover rapidly and do not influence long-term HRQOL.     

前列腺癌的外照射放疗进展

外照射放疗作为前列腺癌的主要治疗手段之一,随着放疗技术的进步、靶区认识的统一,已进入精确放疗时代.高剂量放疗的准确实施,使前列腺癌的疗效显著提高.而影像引导的放射治疗、质子放疗和低分割放疗则是疗效进一步提高的研究方向.     

Impact of image guidance on outcomes after external beam radiotherapy for localized prostate cancer

PURPOSE: To verify whether rectal distention at the time of planning impacts outcomes in patients with localized prostate cancer treated with daily image guidance. METHODS AND MATERIALS: Between 1998 and 2002, a total of 488 prostate cancer patients were treated with intensity-modulated radiotherapy. The radiation dose was 70 Gy delivered at 2.5 Gy per fraction in all cases. All cases were treated with a 4-mm margin posteriorly. In all cases the total rectal volume documented on the CT scan was used for treatment planning. No special bowel preparation instructions were given, either for the simulation or the daily treatments. Before each daily treatment, alignment of the prostate was performed with the B-mode acquisition and targeting (BAT) transabdominal ultrasound system. The median follow-up for all 488 patients was 60 months (range, 24-96 months). RESULTS: For all patients the biochemical relapse-free survival (bRFS) rate at 5 years was 86%. The 5-year bRFS rate for the rectal distention<50 cm3, 50 to <100 cm3, and >or=100 cm3 groups was 90%, 83%, and 85%, respectively (p=0.18). To adjust for other potential variables affecting bRFS rates, a multivariate time-to-failure analysis using the Cox proportional hazards model was performed. Rectal distention was not an independent predictor of biochemical failure on multivariate analysis (p=0.80). Rectal distention was not a predictor of rectal or urinary toxicity. CONCLUSION: The use of daily image guidance eliminates errors such as rectal distention at the initial planning stage that can affect outcomes after radiotherapy for localized prostate cancer.     

A randomized trial of external beam radiotherapy versus cryoablation in patients with localized prostate cancer

BACKGROUND:

A recent randomized trial to compare external beam radiation therapy (EBRT) to cryoablation for localized disease showed cryoablation to be noninferior to external beam EBRT in disease progression and overall and disease‐specific survival. We report on the quality of life (QOL) outcomes for this trial.

METHODS:

From December 1997 through February 2003, 244 men with newly diagnosed localized prostate cancer were randomly assigned to cryoablation or EBRT (median dose 68 Gy). All patients received neoadjuvant antiandrogen therapy. Patients completed the EORTC QLQ C30 and the Prostate Cancer Index (PCI) before treatment and at 1.5, 3, 6, 12, 18, 24, and 36 months post‐treatment.

RESULTS:

Regardless of treatment arm, participants reported high levels of QOL with few exceptions. cryoablation was associated with more acute urinary dysfunction (mean PCI urinary function cryoablation = 69.4; mean EBRT = 90.7; P < .001), which resolved over time. No late arising QOL issues were observed. Both EBRT and cryoablation participants reported decreases in sexual function at 3 months with the cryoablation patients reporting poorer functioning (mean cryoablation = 7.2: mean EBRT = 32.9; P < .001). Mean sexual function score was 15 points lower at 3 years for the cryoablation group and 13% more of the cryoablation men said that sexuality was a moderate or big problem.

CONCLUSIONS:

In this randomized trial, no long‐term QOL advantage for either treatment was apparent with the exception of poorer sexual function reported by those treated with cryoablation. Men who wish to increase their odds of retaining sexual function might be counseled to choose EBRT over cryoablation. Cancer 2009. © 2009 American Cancer Society.     

A randomized trial of external beam radiotherapy versus cryoablation in patients with localized prostate cancer

BACKGROUND:

Localized prostate cancer can be treated several different ways, but head‐to‐head comparisons of treatments are infrequent. The authors of this report conducted a randomized, unblinded, noninferiority trial to compare cryoablation with external beam radiotherapy in these patients.

METHODS:

From December 1997 through February 2003, 244 men with newly diagnosed localized prostate cancer were assigned randomly to receive either cryoablation or radiotherapy (122 men in each arm). All received neoadjuvant antiandrogen therapy. The primary endpoint was disease progression at 36 months based on a trifecta definition: 1) radiologic evidence of metastatic disease, or 2) initiation of further antineoplastic therapy, or 3) biochemical failure. Two definitions of biochemical failure were used: 1) 2 consecutive rises in prostate‐specific antigen (PSA) with a final value >1.0 ng/mL, and 2) a rise above PSA nadir + 2 ng/mL. Secondary endpoints included overall survival, disease‐specific survival, and prostate biopsy at 36 months.

RESULTS:

The median follow‐up was 100 months. Disease progression at 36 months was observed in 23.9% (PSA nadir + 2 ng/mL, 17.1%) of men in the cryoablation arm and in 23.7% (PSA nadir + 2 ng/mL, 13.2%) of men in the radiotherapy arm. No difference in overall or disease‐specific survival were observed. At 36 months, more patients in the radiotherapy arm had a cancer‐positive biopsy (28.9%) compared with patients in the cryoablation arm (7.7%).

CONCLUSIONS:

The observed difference in disease progression at 36 months was small, 0.2%; however, because of the wide confidence interval, from ?10.8% to 11.2%, it was not possible to rule out inferiority (defined a priori as a 10% difference). With longer term follow‐up, the trend favors cryoablation. Significantly fewer positive biopsies were documented after cryoablation than after radiotherapy. Cancer 2010. © 2010 American Cancer Society.     

Variation in adherence to external beam radiotherapy quality measures among elderly men with localized prostate cancer

PURPOSE: To characterize the variation in adherence to quality measures of external beam radiotherapy (EBRT) for localized prostate cancer and its relation to patient and provider characteristics in a population-based, representative sample of U.S. men. METHODS AND MATERIALS: We evaluated EBRT quality measures proposed by a RAND expert panel of physicians among men aged >or=65 years diagnosed between 2000 and 2002 with localized prostate cancer and treated with primary EBRT using data from the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare program. We assessed the adherence to five EBRT quality measures that were amenable to analysis using SEER-Medicare data: (1) use of conformal RT planning; (2) use of high-energy (>10-MV) photons; (3) use of custom immobilization; (4) completion of two follow-up visits with a radiation oncologist in the year after therapy; and (5) radiation oncologist board certification. RESULTS: Of the 11,674 patients, 85% had received conformal RT planning, 75% had received high-energy photons, and 97% had received custom immobilization. One-third of patients had completed two follow-up visits with a radiation oncologist, although 91% had at least one visit with a urologist or radiation oncologist. Most patients (85%) had been treated by a board-certified radiation oncologist. CONCLUSIONS: The overall high adherence to EBRT quality measures masked substantial variation in geography, socioeconomic status in the area of residence, and teaching affiliation of the RT facility. Future research should examine the reasons for the variations in these measures and whether the variation is associated with important clinical outcomes.     

Focal salvage therapy for localized prostate cancer recurrence after external beam radiotherapy: A pilot study

BACKGROUND:

The objective of this study was to evaluate the safety, feasibility, side‐effect profile, and proof of concept for focal salvage therapy using high‐intensity focused ultrasound (HIFU).

METHODS:

A registry‐based analysis was conducted between 2004 and 2009 of 430 patients who underwent HIFU. Thirty‐nine patients received focal salvage therapy for localized recurrence after external beam radiotherapy. Multiparametric magnetic resonance imaging studies combined with transperineal template prostate mapping biopsies or transrectal biopsies were used to localize disease. Validated questionnaires were used to assess functional outcomes. Biochemical failure was defined by using both Phoenix criteria (prostate‐specific antigen [PSA] nadir plus 2 ng/mL) and Stuttgart criteria (PSA nadir plus 1.2 ng/mL).

RESULTS:

The mean pre‐HIFU PSA level was 4.6 ng/mL. The median follow‐up was 17 months (interquartile range, 10‐29 months). International Index of Erectile Function‐5 scores decreased from a median ± standard deviation (SD) of 18 ± 16 to 13 ± 21 at 6 months, demonstrating worsening function. Scores on the University of California Los Angeles‐Expanded Prostate Cancer Index Composite Urinary domain indicate that pad‐free, leak‐free continence status was 64%, and the pad‐free rate was 87.2% at last follow‐up. One rectourethral fistula occurred and spontaneously resolved with urinary and bowel diversion. The actuarial progression‐free survival rate (including PSA nonresponders) was 69% at 1 year and 49% at 2 years according to Phoenix criteria. Excluding PSA nonresponders, these rates were 74% and 58%, respectively (Phoenix criteria).

CONCLUSIONS:

The results from this study indicated that focal salvage therapy is a potential strategy for localized recurrence after radiotherapy that may reduce the harms resulting from whole‐gland salvage therapies. Cancer 2012. © 2011 American Cancer Society.     

Treating intermediate-risk prostate cancer with hypofractionated external beam radiotherapy alone

Purpose

Intermediate-risk prostate cancer has been treated in many ways; the most effective treatment is uncertain. Hypofractionated external beam radiotherapy (HyRT) is a short and convenient alternative treatment. We report our results of HyRT in intermediate-risk patients.

Material and methods

Eighty two patients with intermediate-risk prostate cancer were treated with 3-dimensional conformal HyRT plans to the dose of 66 Gy/22 fractions prescribed at the isocenter without hormones. Intermediate-risk was defined as clinical stage T2b-T2c, or pre-treatment PSA between 10 and 20 ng/mL, or Gleason Score equal 7. The planning target volume consisted of the prostate plus a uniform 7 mm margin. Toxicity was prospectively graded by the Common Terminology Criteria version3. Biochemical relapse was defined as post-radiotherapy nadir PSA + 2 ng/mL.

Results

With a median follow-up of 51 months, 5-year actuarial biochemical recurrence free survival is 95.4%. At the last follow-up visit, grade ?2 late gastro-intestinal and genito-urinary toxicity rates were 2% and 7%, respectively. No patient ever developed grade 4 or 5 toxicity.

Conclusion

HyRT to a dose of 66 Gy in 22 fractions as a single treatment modality is convenient for patients and for the health care system and appears to provide similar results to other treatment choices.     

Ultrasound image fusion for external beam radiotherapy for prostate cancer

: To determine whether real-time ultrasound imaging and targeting system for the treatment of prostate cancer was feasible. The initial phase of this project included a study to develop and determined (a) software for the fusion of ultrasound images to standard x-rays obtained during simulation, and (b) the potential reduction in field size with real time imaging.

: During 13 patient simulations a transrectal ultrasound image was obtained. Orthogonal x-ray films were acquired with the rectal probe in place. Both the x-ray and ultrasound images were digitized and a fusion image was created of the prostate position in relation to the probe, bladder, and rectum. The two-dimensional area of the rectum, bladder, and prostate was determined in the lateral projection. Potential conformal blocks were designed for the lateral portals in a four-field treatment technique.

: The transrectal ultrasound probe enabled real-time prostrate imaging. The lateral field size can be reduced to 6.08 × 5.68 cm² ± 0.62 × 0.48 cm² from the standard 8 × 8 cm² field. The posterior rectal wall was physically displaced out of the lateral field. The area of the rectum included in the lateral field in 1.75 cm² ± 0.85 cm².

: The prostate position can be determined with certainty on a regular basis with transrectal ultrasonography. The amount of normal tissue in the high dose volume can be reduced. This approach may reduce acute and chronic morbidity and allow further dose escalation.     

Association of percent positive prostate biopsies and perineural invasion with biochemical outcome after external beam radiotherapy for localized prostate cancer

PURPOSE: Few studies have evaluated the significance of the percentage of positive biopsies (PPB) and perineural invasion (PNI) for patients treated with external beam radiotherapy (EBRT) for localized prostate cancer. Our goal was to investigate the value of these factors in predicting biochemical control (bNED) after EBRT. METHODS AND MATERIALS: The study cohort consisted of 331 patients who received EBRT between 1993 and 1999 for clinically localized prostate cancer. The median follow-up was 4.4 years (range, 3 months to 9.6 years). The distribution by clinical T stage was as follows: T1 in 55 (17%), T2a in 94 (28%), T2b in 76 (23%), T2c in 74 (22%), T3a in 27 (8%), and T3b in 5 (2%). The pretreatment prostate-specific antigen (iPSA) level was < or =10 ng/mL in 224 patients, 10.1-20 ng/mL in 72 patients, and >20 ng/mL in 35 patients. The biopsy Gleason score was < or =6 in 216 patients and > or =7 in 115 patients. On the basis of the pathology report, the PPB was calculated for 239 patients and was < or =33% in 109, 34-66% in 72, and > or =67% in 58 patients. PNI was present in 30 patients. The median dose of EBRT was 68.4 Gy (range, 64-71 Gy). Patients were categorized into three risk groups: 142 patients were low risk (T1-T2, iPSA < or =10 ng/mL, and Gleason score < or =6), 137 were intermediate risk (increase in the value of one of the risk factors); and 52 patients were high risk (increase in value of two or more of the risk factors). Biochemical failure was defined as three consecutive rises in the PSA level. RESULTS: The 5-year bNED rate for the entire cohort was 62%. The 5-year bNED rate for the low-, intermediate, and high-risk group was 79%, 51%, and 47%, respectively (p <0.0001). On univariate analysis (log-rank test), clinical stage (p = 0.0073), grade (p <0.0001), iPSA (p = 0.0043), risk group (p <0.0001), PPB (p = 0.0193), and presence of PNI (p = 0.0137) correlated with bNED. For T1-T2a, T2b-T2c, and T3 patients, the 5-year bNED rate was 71%, 59%, and 40%, respectively. The 5-year bNED rate was 68% for those with an iPSA level of < or =10 ng/mL and 49% for those with an iPSA level of >10 ng/mL. For patients with PPB < or =33%, 34-66%, and > or =67%, the 5-year bNED rate was 75%, 67%, and 51%, respectively. Within the intermediate-risk group, the PPB was significantly associated with the bNED rate: 67%, 52%, and 30% for those with PPB < or =33%, 34-66%, and > or =67%, respectively (p = 0.0046). This association was not seen in the low- or high-risk group. The 5-year bNED rate was 64% for patients without PNI and 48% for those with PNI. On multivariate analysis (Cox proportional hazards model), the statistically significant predictive factors for bNED were risk group (p = 0.0032) and PPB (p = 0.044). Using the chi-square test, statistically significant associations between T stage, PSA level, Gleason score, and risk group with PPB were found; PNI was significantly associated with T stage and PSA level only. CONCLUSION: Our results showed that PPB and PNI have a statistically significant impact on the bNED rate in patients treated with conventional dose of EBRT (< or =71 Gy). Within the intermediate-risk group, the PPB was predictive of bNED, suggesting that patients with < or =33% PPB had a statistically significant better treatment outcome compared with those with a greater PPB. PNI was not significant for bNED in multivariate analysis. The effects of these two prognostic factors in patients who have been treated with higher doses of RT (> or =75.6 Gy) should be studied.     

The role of external beam radiotherapy in the treatment of small-cell lung cancer

External beam radiotherapy plays a significant role in the treatment of small cell lung cancer. In patients with limited stage disease (LD), thoracic irradiation improves locoregional tumor control, increases the percentage of patients achieving a complete response (CR), and produces significant increases in survival. As a result, combined modality therapy (chemotherapy/radiotherapy) is considered the treatment of choice in patients with LD. Radiotherapy plays a less significant role in extensive diseased patients, but nonetheless increases CR in the chest and has palliative benefit. Elective cranial irradiation decreases the development of central nervous system failure, thereby improving the quality of life of many patients. Its use, however, should be restricted to patients achieving CR to therapy and doses should be modest. Both whole-body and hemi-body irradiation have significant activity against the disease but should be considered strictly investigational.     

Salvage therapy for locally recurrent prostate cancer after external beam radiotherapy

Opinion statement The greatest obstacle in the cure of patients with locally recurrent prostate cancer after radiation therapy is the lack of early detection markers. The majority of patients who are candidates for local salvage therapy have locally advanced disease, precluding successful salvage therapy. A low pretreatment prostate specific antigen (PSA) has shown to be a favorable prognostic variable for disease progression, regardless of the specific local salvage therapy used. Of all the local salvage treatment options for these patients, we believe that salvage radical prostatectomy (RP) offers patients the great-est likelihood of a cure. The salvage RP results approach those achieved with standard RP for patients of similar pathologic stage. When patients are treated early in the course of recurrent disease (preoperative PSA < 10 ng/mL), an estimated two-thirds of patients will be disease-free 5 years after salvage RP alone. With better patient selec-tion and continued technical modifications, the morbidity associated with salvage RP has substantially improved. Perioperative complications approach those observed with standard RP and approximately two-thirds of patients will recover urinary continence. Select patients may also recover functional erections when nerve-sparing techniques are used. Salvage cryotherapy and brachytherapy are minimally invasive alternatives to salvage RP. The cancer control results of these procedures appear to be inferior to results achieved with salvage RP. Each of these procedures is associated with signifi-cant morbidity and do not appear to provide a clear advantage over salvage RP in terms of posttreatment complications, urinary continence, and erectile function. A long-term cure is possible for patients with locally recurrent prostate cancer after radiation therapy. Local salvage therapy must be instituted early to be successful in the course of progressive disease.     

Urinary incontinence in prostate cancer patients treated with external beam radiotherapy.

BACKGROUND AND PURPOSE: To describe the incidence of urinary incontinence among prostate cancer patients treated with external beam radiotherapy (RT) and to investigate associated risk factors. PATIENTS AND METHODS: One thousand and hundred ninety-two patients with >or=24 months follow-up were the subjects of this series. All patients received between 50 and 72 Gy in 20-37 fractions (median 66 Gy/33#). Post-RT urinary incontinence was scored by direct patient interviewing according to the modified RTOG/SOMA scale: Grade 1--occasional use of incontinence pads, Grade 2--intermittent use of incontinence pads, Grade 3--persistent use of incontinence pads, and Grade 4--permanent catheter. Risk-factors investigated were: age, diabetes, TURP prior to RT, elapsed time from TURP to RT, clinical stage, RT dose and presence of Grade >or=2 acute GU and GI toxicity. Non-parametric, actuarial univariated (Kaplan-Meier) and multivariated tests (MVA, Cox regression) were performed. RESULTS: Median follow-up for the group is 52 months (24-109). Thirty-four patients (2.9%) had incontinence prior to RT, which was more common in TURP patients (7.8% vs 1.6% P<0.001). These are excluded from further analysis. Fifty-seven patients (4.9%) developed Grade 1 incontinence, 7 (0.6%) Grade 2, and 7 (0.6%) Grade 3. There was no Grade 4 incontinence. Actuarial rates for Grade >or=1 and >or=2 incontinence at 5 years are 7 and 1.7%, respectively. Risk factors on MVA associated with the development of Grade 1 or worse incontinence are pre-RT TURP (5-year rates 10% vs 6%, P=0.026), presence of Grade >or=2 acute GU toxicity (5-year rates 11% vs 5%, P=0.002). Age, diabetes, clinical stage, elapsed time from TURP to RT, RT dose or fraction size, acute GI toxicity were not significant. Patients who underwent post-RT TURP or dilatation for obstructive symptoms (4.3%), were more likely to develop Grade 2-3 incontinence (5-year rate 8 vs 1.5%, P=0.0015). CONCLUSIONS: Grade 2 or greater urinary incontinence is rare among patients who have been treated with external beam radiotherapy. Associated risk factors are pre-RT TURP and the presence of increased acute GU toxicity. Post-radiaton TURP increases the risk of incontinence five-fold.     

The role of external beam radiation therapy after prostatectomy for prostate cancer

The role of radiation therapy as an adjuvant to prostatectomy is evaluated in 21 patients. Eleven were treated prior to clinical recurrence with 100% local control, no serious complications, and 86% long-term survival. Ten were treated after local recurrence with 80% local control, no serious complications, and 71% long-term survival. These data and the available literature indicate that the patient found to have capsular penetration, seminal vesicle involvement, or positive surgical margins at prostatectomy can be salvaged by postsurgical radiation therapy. When this is done after recovery from surgery, rather than waiting for clinical recurrence, a lower radiation dose can be used (6000 rad vs. 7000 rad), improved local control is obtained (94% vs. 79%), and fewer serious complications are observed.