Three randomized trials have demonstrated that post-radical prostatectomy (RP) radiotherapy decreases biochemical relapse for those with adverse pathology. Our purpose was to describe the incidence of pathologic risk factors for recurrence in a contemporary series of patients treated with RP and to describe the use of post-RP radiotherapy.
All incident prostate cancers diagnosed between January 2005 and December 2007 were identified from the tumour registry. Cases were then linked to radiotherapy records which included dose and modality (external beam radiotherapy and brachytherapy). The pathology reports in the tumour registry were reviewed for pathologic stage, grade and margin status.
We identified 9223 patients with prostate cancer. Overall, 36.3% of patients treated with RP had positive margins, and may have benefited from adjuvant radiotherapy. After RP, 332 (15%) patients had radiotherapy to the prostate bed; of these, only 25 (1.1%) received truly adjuvant radiotherapy (delivered within 6 months with a prostate-specific antigen of <0.2 ng/mL). Of the 2181 patients treated with RP, 270 (12%) were seen by a radiation oncologist within 6 months of RP. Of the 1015 patients (47%) with adverse RP pathology (positive margins, extracapsular extension or seminal vesicle invasion), 230 (23%) were seen by a radiation oncologist within 6 months of RP.
Not all patients with adverse prostatectomy pathology were seen by a radiation oncologist post-prostatectomy, and very few received adjuvant radiotherapy despite almost half of them having risk factors for relapse.
Radical prostatectomy and external beam radiation therapy are the established and definitive interventions for clinically localized prostate cancer. These treatment modalities are yet subject to failure observed first by biochemical recurrence, defined by increases in the serum PSA level. We investigated the significance of biochemical recurrence after definitive therapy and the available salvage therapy options for cancer recurrence.
A literature search was performed in PubMed, and applicable studies addressing biochemical recurrence and salvage options after radical prostatectomy or external beam radiation therapy were reviewed.
After radical prostatectomy, a detectable serum PSA level indicates biochemical recurrence. Whether to administer salvage therapy locally or systemically depends largely on prognostic factors including PSA doubling time, Gleason’s score, pathologic stage, and the time interval between radical prostatectomy and biochemical recurrence. Early initiation of salvage therapy has been shown to significantly impact on cancer outcomes.
After external beam radiation therapy, no single PSA level can define biochemical recurrence. Instead, it has been defined by increases in the PSA level above the nadir. Following radiation therapy, PSA doubling time and Gleason score play important roles in determining the need for local versus systemic salvage therapy.
After the diagnosis of biochemical recurrence, it is critical to perform a timely clinical assessment using the prognostic factors mentioned above. Prompt initiation of salvage therapy may prevent subsequent clinical progression and prostate cancer-specific mortality.
Prostate cancer; Radical prostatectomy; Radiation therapy; Biochemical recurrence; PSA recurrence; Salvage
Prostate cancer has a high prevalence and a rising incidence in many parts of the world. Although many screen-detected prostate cancers may be indolent, prostate cancer remains a major contributor to mortality in men. Therefore, the appropriate diagnosis and treatment of localized prostate cancer with lethal potential are of great importance. High-risk, localized prostate cancer has multiple definitions. Treatment options that should be individualized to each patient include observation, radical prostatectomy, external beam radiotherapy, brachytherapy, androgen deprivation, and combined modality treatment. Specific outcomes of radical prostatectomy and combined modality treatment for high-risk prostate cancer are reviewed. The rationale for extended pelvic lymphadenectomy at the time of surgery is discussed, as is the role for surgery in the setting of node-positive, high-risk disease. There is not yet a biomarker that accurately identifies lethal prostate cancer, but rigorous clinical studies have identified methods of optimizing oncologic outcomes in high-risk men.
Prostate-specific antigen; Prostatectomy; Prostatic neoplasms; Radiotherapy
External beam radiotherapy is a potential salvage or adjuvant therapy after radical prostatectomy (RP). The purpose of this study was to investigate the treatment outcome of salvage radiotherapy (RT) following RP for clinically localized prostate cancer and to identify factors that may predict the outcome of salvage RT. Between 2000 and 2006, 41 patients received salvage RT because of increasing prostate-specific antigen (PSA) levels following an RP for clinically localized prostate cancer. All the patients received conformal radiotherapy to the prostate bed. The prescribed radiation dose was 60–70 Gy in 26–35 fractions. The overall 5-year biochemical disease-free survival rate was 38%. A multivariate analysis showed that the following pathological findings of the surgical specimen were significantly associated with biochemical failure following salvage RT: a high Gleason score, a negative surgical margin, seminal vesicle invasion, lymphatic vessel invasion and negative vascular invasion. Among these factors, lymphatic vessel invasion was the strongest predictor. In conclusion, the pathological features affected the outcome of salvage RT following RP. Lymphatic vessel invasion was strongly associated with the risk of biochemical failure despite salvage RT. Meanwhile, vascular invasion was not a significant hazardous factor.
prostatectomy; salvage radiotherapy; prostate cancer; prostate-specific antigen; pathological findings
Prostate brachytherapy can be used as a monotherapy for low- and intermediate-risk patients or in combination with external beam radiation therapy (EBRT) as a form of dose escalation for selected intermediate- and high-risk patients. Prostate brachytherapy with either permanent implants (low dose rate [LDR]) or temporary implants (high dose rate [HDR]) is emerging as the most effective radiation treatment for prostate cancer. Several large Canadian brachytherapy programs were established in the mid- to late-1990s. Prostate brachytherapy is offered in British Columbia, Alberta, Manitoba, Ontario, Quebec and New Brunswick. We anticipate the need for brachytherapy services in Canada will significantly increase in the near future. In this review, we summarize brachytherapy programs across Canada, contemporary eligibility criteria for the procedure, toxicity and prostate-specific antigen recurrence free survival (PRFS), as published from Canadian institutions for both LDR and HDR brachytherapy.
Adjuvant treatment of patients with endometrial cancer is tailored to clinical-pathological prognostic factors. Pelvic radiation therapy for stage I endometrial cancer (EC) provides a highly significant improvement of local control, but without survival advantage. Low-risk EC patients have a very favorable prognosis, and should be observed after surgery. Use of adjuvant radiotherapy (RT) is limited to patients with high-intermediate or high-risk factors. For those with high-intermediate risk features, vaginal brachytherapy alone provides excellent vaginal control with less morbidity and better quality of life than pelvic external beam RT (EBRT). For patients with stage I–III EC with high-risk features, the use of adjuvant chemotherapy alone has not shown survival benefit as compared to pelvic EBRT. A first trial comparing pelvic EBRT with or without adjuvant chemotherapy has shown better progression-free survival with combined therapy. Current ongoing trials are exploring the role of combined RT and chemotherapy, compared to chemotherapy or RT alone.
Endometrial cancer; Adjuvant therapy; Radiation therapy; Prognostic factors; Side effects; Quality of life
To clarify the significant clinicopathological and postdosimetric parameters to predict PSA bounce in patients who underwent low-dose-rate brachytherapy (LDR-brachytherapy) for prostate cancer.
We studied 200 consecutive patients who received LDR-brachytherapy between July 2004 and November 2008. Of them, 137 patients did not receive neoadjuvant or adjuvant androgen deprivation therapy. One hundred and forty-two patients were treated with LDR-brachytherapy alone, and 58 were treated with LDR-brachytherapy in combination with external beam radiation therapy. The cut-off value of PSA bounce was 0.1 ng/mL. The incidence, time, height, and duration of PSA bounce were investigated. Clinicopathological and postdosimetric parameters were evaluated to elucidate independent factors to predict PSA bounce in hormone-naïve patients who underwent LDR-brachytherapy alone.
Fifty patients (25%) showed PSA bounce and 10 patients (5%) showed PSA failure. The median time, height, and duration of PSA bounce were 17 months, 0.29 ng/mL, and 7.0 months, respectively. In 103 hormone-naïve patients treated with LDR-brachytherapy alone, and univariate Cox proportional regression hazard model indicated that age and minimal percentage of the dose received by 30% and 90% of the urethra were independent predictors of PSA bounce. With a multivariate Cox proportional regression hazard model, minimal percentage of the dose received by 90% of the urethra was the most significant parameter of PSA bounce.
Minimal percentage of the dose received by 90% of the urethra was the most significant predictor of PSA bounce in hormone-naïve patients treated with LDR-brachytherapy alone.
Prostate cancer; Brachytherapy; PSA bounce; Post-dosimetry; UD90 (%)
Biochemical control from series in which radical prostatectomy is performed for patients with unfavorable prostate cancer and/or low dose external beam radiation therapy are given remains suboptimal.
The treatment regimen of HDR brachytherapy and external beam radiotherapy is a safe and very effective treatment for patients with high risk localized prostate cancer with excellent biochemical control and low toxicity.
Clinically localized prostate cancer is typically managed by well established therapies like radical prostatectomy, brachytherapy, and external beam radiation therapy. While many patients can be cured with definitive local therapy, some will have biochemical recurrence (BCR) of disease detected by a rising serum prostate-specific antigen (PSA). Management of these patients is nuanced and controversial. The natural history indicates that a majority of patients with BCR will not die from prostate cancer but from other causes. Despite this, a vast majority of patients with BCR are empirically treated with non-curable systemic androgen deprivation therapy (ADT), with its myriad of real and potential side effects. In this review article, we examined the very definition of BCR after definitive local therapy, the current status of imaging studies in its evaluation, the need for additional therapies, and the factors involved in the decision making in the choice of additional therapies. This review aims to help clinicians with the management of patients with BCR. The assessment of prognostic factors including absolute PSA level, time to recurrence, PSA kinetics, multivariable nomograms, imaging, and biopsy of the prostatic bed may help stratify the patients into localized or systemic recurrence. Patients with low-risk of systemic disease may be cured by a salvage local therapy, while those with higher risk of systemic disease may be offered the option of ADT or a clinical trial. An algorithm incorporating these factors is presented.
prostate cancer; radical prostatectomy; radiation therapy; biochemical recurrence; PSA recurrence; salvage
Radical radiotherapy is one of the options for the management of prostate cancer. In external beam therapy, 3D conformal radiotherapy (3DCRT) and intensity modulated radiotherapy (IMRT) are the options for delivery of increased radiation dose, as vital organs are very close to the prostate and a higher dose to these structures leads to an increased toxicity. In brachytherapy, low dose rate brachytherapy with permanent implant of radioactive seeds and high dose rate brachytherapy (HDR) with remote after loaders are available. A dosimetric analysis has been made on IMRT and HDR brachytherapy plans. Ten cases from each IMRT and HDR brachytherapy have been taken for the study. The analysis includes comparison of conformity and homogeneity indices, D100, D95, D90, D80, D50, D10 and D5 of the target. For the organs at risk (OAR), namely rectum and bladder, V100, V90 and V50 are compared. In HDR brachytherapy, the doses to 1 cc and 0.1 cc of urethra have also been studied. Since a very high dose surrounds the source, the 300% dose volumes in the target and within the catheters are also studied in two plans, to estimate the actual volume of target receiving dose over 300%. This study shows that the prescribed dose covers 93 and 92% of the target volume in IMRT and HDR brachytherapy respectively. HDR brachytherapy delivers a much lesser dose to OAR, compared to the IMRT. For rectum, the V50 in IMRT is 34.0cc whilst it is 7.5cc in HDR brachytherapy. With the graphic optimization tool in HDR brachytherapy planning, the dose to urethra could be kept within 120% of the target dose. Hence it is concluded that HDR brachytherapy may be the choice of treatment for cancer of prostate in the early stage.
Brachytherapy; conformity; intensity modulated radiotherapy; prostate
Radical prostatectomy, external beam radiotherapy and permanent brachytherapy are the most common treatment options for nonmetastatic localised adenocarcinoma of the prostate (PCa). Accurate pretherapeutic clinical staging is difficult, the number of positive cores after biopsy does not imperatively represent the extension of the cancer. Furthermore postoperative upgrading in Gleason score is frequently observed. Even in a localised setting a certain amount of patients with organ-confined PCa will develop biochemical progression. In case of a rise in PSA level after radiation the majority of patients will receive androgen deprivation therapy what must be considered as palliative. If local or systemic progressive disease is associated with evolving neuroendocrine differentiation hormonal manipulation is increasingly ineffective; radiotherapy and systemic chemotherapy with a platinum agent and etoposide are recommended. In case of local progression complications such as pelvic pain, gross haematuria, infravesical obstruction and rectal invasion with obstruction and consecutive ileus can possibly occur. In this situation palliative radical surgery is a therapy option especially in the absence of distant metastases. A case with local and later systemic progression after permanent brachytherapy is presented here.
High-dose-rate (HDR) brachytherapy as monotherapy is a comparatively new brachytherapy procedure for prostate cancer. In addition to the intrinsic advantages of brachytherapy, including radiation dose concentration to the tumor and rapid dose fall-off at the surrounding normal tissue, HDR brachytherapy can yield a more homogeneous and conformal dose distribution through image-based decisions for source dwell positions and by optimization of individual source dwell times. Indication can be extended even to T3a/b or a part of T4 tumors because the applicators can be positioned at the extracapsular lesion, into the seminal vesicles, and/or into the bladder, without any risk of source migration or dropping out. Unlike external beam radiotherapy, with HDR brachytherapy inter-/intra-fraction organ motion is not problematic. However, HDR monotherapy requires patients to stay in bed for 1–4 days during hospitalization, even though the actual overall treatment time is short. Recent findings that the α/β value for prostate cancer is less than that for the surrounding late-responding normal tissue has made hypofractionation attractive, and HDR monotherapy can maximize this advantage of hypofractionation. Research on HDR monotherapy is accelerating, with a growing number of publications reporting excellent preliminary clinical results due to the high ‘biologically effective dose (BED)’ of >200 Gy. Moreover, the findings obtained for HDR monotherapy as an early model of extreme hypofractionation tend to be applied to other radiotherapy techniques such as stereotactic radiotherapy. All these developments point to the emerging role of HDR brachytherapy as monotherapy for prostate cancer.
prostate cancer; high-dose-rate (HDR); brachytherapy; monotherapy; hypofractionation
To describe the sexual consequences of prostate cancer and its treatments
(prostatectomy, external beam radiation, brachytherapy, androgen deprivation
therapy) and to suggest treatments for sexual side effects of these
QUALITY OF EVIDENCE
Most studies of the sexual consequences of prostate cancer treatments and
studies of therapy for these side effects provide level II evidence.
Diagnosis of prostate cancer in itself can cause sexual dysfunction. All
forms of treatment for this cancer cause serious sexual problems for men.
Treatments for the erectile dysfunction that results have varying success
rates. Prostatectomy has been shown to cause erectile dysfunction in 30% to
98% of men, depending on whether both, one, or neither nerve bundles was
spared. Radiation therapy results in erectile dysfunction in more than 70%
of those treated; brachytherapy produces the least amount of sexual deficit.
Hormone ablation therapy has serious consequences: more than 80% of men
report loss of erections at 1 year after therapy in addition to profound
loss of libido.
Family physicians are ideally placed to provide anticipatory guidance to men
with prostate cancer on the sexual consequences of both the cancer and its
treatments. Family physicians can also assist men and their partners in
managing these sexual side effects.
External-beam radiation therapy with intracavitary high-dose-rate brachytherapy is the standard treatment modality for advanced cervical cancer; however, late gastrointestinal complications are a major concern after radiotherapy. While radiation proctitis is a well-known side effect and radiation oncologists make an effort to reduce it, the sigmoid colon is often neglected as an organ at risk. Herein, we report two cases of radiation sigmoiditis mimicking sigmoid colon cancer after external-beam radiation therapy with intracavitary high-dose-rate brachytherapy for uterine cervical cancer with dosimetric consideration.
Radiation complication; Radiation therapy; Sigmoiditis; Uterine cervical carcinoma
The face of prostate cancer has been dramatically changed since the late 1980s when PSA was introduced as a clinical screening tool. More men are diagnosed with small foci of cancers instead of the advanced disease evident prior to PSA screening. Treatment options for these smaller tumors consist of expectant management, radiation therapy (brachytherapy and external beam radiotherapy) and surgery (cryosurgical ablation and radical prostatectomy). In the highly select patient, cancer specific survival employing any of these treatment options is excellent, however morbidity from these interventions are significant. Thus, the idea of treating only the cancer within the prostate and sparing the non-cancerous tissue in the prostate is quite appealing, yet controversial. Moving forward if we are to embrace the focal treatment of prostate cancer we must: be able to accurately identify index lesions within the prostate, image cancers within the prostate and methodically study the litany of focal therapeutic options available.
Population-based patterns of care studies are important for monitoring cancer care but conducting them is expensive and resource-intensive. Linkage of routinely collected administrative health data may provide an efficient alternative. Our aim was to determine the accuracy of linked routinely collected administrative data for monitoring prostate cancer care in New South Wales (NSW), Australia.
The NSW Prostate Cancer Care and Outcomes Study (PCOS), a population-based survey of patterns of care for men aged less than 70 years diagnosed with prostate cancer in NSW, was linked to the NSW Cancer Registry, electronic hospital discharge records and Medicare and Pharmaceutical claims data from Medicare Australia. The main outcome measures were treatment with radical prostatectomy, any radiotherapy, external beam radiotherapy, brachytherapy or androgen deprivation therapy, and cancer staging. PCOS data were considered to represent the true treatment status. The sensitivity and specificity of the administrative data were estimated and relevant patient characteristics were compared using chi-squared tests.
The validation data set comprised 1857 PCOS patients with treatment information linked to Cancer Registry records. Hospital and Medicare claims data combined described treatment more accurately than either one alone. The combined data accurately recorded radical prostatectomy (96% sensitivity) and brachytherapy (93% sensitivity), but not androgen deprivation therapy (76% sensitivity). External beam radiotherapy was rarely captured (5% sensitivity), but this was improved by including Medicare claims for radiation field setting or dosimetry (86% sensitivity). False positive rates were near 0%. Disease stage comparisons were limited by one-third of cases having unknown stage in the Cancer Registry. Administrative data recorded treatment more accurately for cases in urban areas.
Cancer Registry and hospital inpatient data accurately captured radical prostatectomy and brachytherapy treatment, but not external beam radiotherapy or disease stage. Medicare claims data substantially improved the accuracy with which all major treatments were recorded. These administrative data combined are valid for population-based studies of some aspects of prostate cancer care.
To report urethroplasty outcomes in men who developed urethral stricture after undergoing radiation therapy for prostate cancer.
Our urethroplasty database was reviewed for cases of urethral stricture after radiation therapy for prostate cancer between June 2004 and May 2010. Patient demographics, prostate cancer therapy type, stricture length and location, and type of urethroplasty were obtained. All patients received clinical evaluation, including imaging studies post procedure. Treatment success was defined as no need for repeat surgical intervention.
Twenty-nine patients underwent urethroplasty for radiation-induced stricture. Previous radiation therapy included external beam radiotherapy (EBRT), radical prostatectomy (RP)/EBRT, EBRT/brachytherapy (BT) and BT alone in 11 (38%), 7 (24%), 7 (24%), and 4 (14%) patients, respectively. Mean age was 69 (±6.9) years. Mean stricture length was 2.6 (±1.6) cm. Anastomotic urethroplasty was performed in 76% patients, buccal mucosal graft in 17%, and perineal flap repair in 7%. Stricture was localized to bulbar urethra in 12 (41%), membranous in 12 (41%), vesicourethra in 3 (10%), and pan-urethral in 2 (7%) patients. Overall success rate was 90%. Median follow-up was 40 months (range 12-83). Time to recurrence ranged from 6-16 months.
Multiple forms of urethroplasty appear to be viable options in treating radiation-induced urethral stricture. Future studies are needed to examine the durability of repairs.
Introduction. Treatment of locally advanced prostate cancer is under discussion. Differences between clinical and pathological staging and risk factors such as positive surgical margins and seminal vesicle involvement challenge the individual treatment decisions. Case Presentation. Clinical tumor stage before treatment was assessed to be T2. After radical prostatectomy, pathological examination revealed the stage pT3b N0 M0 including positive surgical margin and seminal vesicle involvement. Early adjuvant androgen deprivation therapy and late adjuvant radiation therapy were added in response to the pathological risk factors. No evidence of disease was observed for 15 years after the treatment. The unexpected pathological findings were not explained by the physicians in charge. Discussion. A narrative review of the recent literature showed that multiple treatment modalities including adjuvant radiotherapy following radical prostatectomy are consistent with current recommendations. The multimodal approach has possibly cured a high-risk patient and may also work successfully in other patients. An alternative treatment option with better preservation of health-related quality of life might have also achieved a similar good overall survival.
We evaluated the post-operative pattern of prostate volume (PV) changes following prostate brachytherapy (PB) and analyzed variables which affect swelling.
Material and methods
Twenty-nine patients treated with brachytherapy (14) or combined brachytherapy and external beam radiotherapy modality (15) underwent pre- and post-implant computed tomography (CT). Prostate volume measurements were done on post-operative days 1, 9, 30, and 60. An observer performed 139 prostate volume (PV) measurements. We analyzed the influence of pre-implant PV, number of needles and insertion attempts, number and activity of seeds, Gleason score, use of hormonal therapy and external beam radiation therapy on the extent of edema. We computed a volume correction factor (CF) to account for dosimetric changes between day 1 and day 30. Using the calculated CF, the dose received by 90% (D90) of the prostate on day 30 (D90Day30) was obtained by dividing day 1 (D90Day1) by the CF.
The mean PV recorded on post-operative day 1 was 67.7 cm3, 18.8 cm3 greater than average pre-op value (SD 15.6 cm3). Swelling returned to pre-implant volume by day 30. Seed activity, treatment modality, and Gleason score were significant variables. The calculated CF was 0.76. After assessment using the CF, the mean difference between estimated and actual D90Day30 was not significant.
We observed maximum prostate size on post-operative day 1, returning to pre-implant volume by day 30. This suggests that post-implant dosimetry should be obtained on or after post-operative day 30. If necessary, day 30 dosimetry can be estimated by dividing D90Day1 by a correction factor of 0.76.
prostate brachytherapy; post-implant dosimetry; computed brachytherapy
Magnetic resonance imaging (MRI) provides superior visualization of the prostate and surrounding anatomy, making it the modality of choice for imaging the prostate gland. This pilot study was performed to determine the feasibility and dosimetric quality achieved when placing high-dose-rate prostate brachytherapy catheters under MRI guidance in a standard “closed-bore” 1.5T scanner.
Methods and Materials:
Patients with intermediate-risk and high-risk localized prostate cancer received MRI-guided high-dose-rate brachytherapy boosts before and after a course of external beam radiotherapy. Using a custom visualization and targeting program, the brachytherapy catheters were placed and adjusted under MRI guidance until satisfactory implant geometry was achieved. Inverse treatment planning was performed using high-resolution T2-weighted MRI.
Ten brachytherapy procedures were performed on 5 patients. The median percentage of volume receiving 100% of prescribed minimal peripheral dose (V100) achieved was 94% (mean, 92%; 95% confidence interval, 89–95%). The urethral V125 ranged from 0% to 18% (median, 5%), and the rectal V75 ranged from 0% to 3.1% (median, 0.3%). In all cases, lesions highly suspicious for malignancy could be visualized on the procedural MRI, and extracapsular disease was identified in 2 patients.
High-dose-rate prostate brachytherapy in a standard 1.5T MRI scanner is feasible and achieves favorable dosimetry within a reasonable period with high-quality image guidance. Although the procedure was well tolerated in the acute setting, additional follow-up is required to determine the long-term safety and efficacy of this approach.
Prostate cancer; Brachytherapy; MRI; Image guidance
High plasma osteopontin (OPN) has been linked to tumour hypoxia, metastasis, and poor prognosis. This study aims to assess whether plasma osteopontin was a biomarker of increasing progression within prostate cancer (PCa) prognostic groups and whether it reflected treatment response to local and systemic therapies.
Baseline OPN was determined in men with localised (n=199), locally recurrent (n=9) and castrate-resistant, metastatic PCa (CRPC-MET; n=37). Receiver-operating curves (ROC) were generated to describe the accuracy of OPN for distinguishing between localised risk groups or localised vs metastatic disease. We also measured OPN pre- and posttreatment, following radical prostatectomy, external beam radiotherapy (EBRT), androgen deprivation (AD) or taxane-based chemotherapy.
The CRPC-MET patients had increased baseline values (mean 219; 56–513 ng ml−1; P<0.0001) compared with the localised, non-metastatic group (mean 72; 12–438 ng ml−1). The area under the ROC to differentiate localised vs metastatic disease was improved when OPN was added to prostate-specific antigen (PSA) (0.943–0.969). Osteopontin neither distinguished high-risk PCa from other localised PCa nor correlated with serum PSA at baseline. Osteopontin levels reduced in low-risk patients after radical prostatectomy (P=0.005) and in CRPC-MET patients after chemotherapy (P=0.027), but not after EBRT or AD.
Plasma OPN is as good as PSA at predicting treatment response in CRPC-MET patients after chemotherapy. Our data do not support the use of plasma OPN as a biomarker of increasing tumour burden within localised PCa.
osteopontin; biomarkers; radiotherapy; chemotherapy; surgery; prostate cancer
Prostate cancer is the most common noncutaneous malignancy and the second leading cause of cancer death in men. In the United States, 90% of men with prostate cancer are more than age 60 years, diagnosed by early detection with the prostate-specific antigen (PSA) blood test, and have disease believed confined to the prostate gland (clinically localized). Common treatments for clinically localized prostate cancer include watchful waiting (WW), surgery to remove the prostate gland (radical prostatectomy), external-beam radiation therapy and interstitial radiation therapy (brachytherapy), and androgen deprivation. Little is known about the relative effectiveness and harms of treatments because of the paucity of randomized controlled trials. The Department of Veterans Affairs/National Cancer Institute/Agency for Healthcare Research and Quality Cooperative Studies Program Study #407:Prostate Cancer Intervention Versus Observation Trial (PIVOT), initiated in 1994, is a multicenter randomized controlled trial comparing radical prostatectomy with WW in men with clinically localized prostate cancer. We describe the study rationale, design, recruitment methods, and baseline characteristics of PIVOT enrollees. We provide comparisons with eligible men declining enrollment and men participating in another recently reported randomized trial of radical prostatectomy vs WW conducted in Scandinavia. We screened 13 022 men with prostate cancer at 52 US medical centers for potential enrollment. From these, 5023 met initial age, comorbidity, and disease eligibility criteria, and a total of 731 men agreed to participate and were randomized. The mean age of enrollees was 67 years. Nearly one-third were African American. Approximately 85% reported that they were fully active. The median PSA was 7.8ng/mL (mean 10.2ng/mL). In three-fourths of men, the primary reason for biopsy leading to a diagnosis of prostate cancer was a PSA elevation or rise. Using previously developed tumor risk categorizations incorporating PSA levels, Gleason histologic grade, and tumor stage, it was found that approximately 40% had low-risk, 34% had medium-risk, and 21% had high-risk prostate cancer based on local histopathology. Comparison to our national sample of eligible men declining PIVOT participation as well as to men enrolled in the Scandinavian trial indicated that PIVOT enrollees are representative of men being diagnosed and treated in the United States and quite different from men in the Scandinavian trial. PIVOT enrolled an ethnically diverse population representative of men diagnosed with prostate cancer in the United States. Results will yield important information regarding the relative effectiveness and harms of surgery compared with WW for men with predominately PSA-detected clinically localized prostate cancer.
Combined transperineal prostate brachytherapy (TPPB) and external beam radiation (EBRT) is widely used for treatment of prostate cancer. Long-term efficacy and toxicity results of a multicenter Phase II trial assessing combination of EBRT and TPPB boost with androgen deprivation therapy (ADT) for intermediate-risk prostate cancer are presented.
Intermediate-risk patients per MSKCC/NCCN criteria received six months of ADT, 45 Gy EBRT to the prostate and seminal vesicles, followed by TPPB with I125(100 Gy) or Pd103(90 Gy). Toxicity was graded using NCI CTC version 2 and RTOG late radiation morbidity scoring systems. Disease free survival (DFS) was defined as time from enrollment to progression (biochemical, local, distant or prostate cancer death). In addition to the protocol definition of biochemical failure (3 consecutive PSA rises >1.0ng/ml after 18 months from treatment start), the 1997 ASTRO consensus and Phoenix definitions were also assessed in defining DFS. The Kaplan-Meier method was used to estimate DFS and overall survival.
61/63 enrolled patients were eligible. Median follow-up was 73 months. Late grade 2 and 3 toxicity, excluding sexual dysfunction, occurred in 20% and 3% of patients. Six year DFS applying the protocol definition, 1997 ASTRO consensus, and Phoenix definitions was 87.1%, 75.1%, and 84.9%. 6 deaths occurred, only one was attributed to prostate cancer. 6 year overall survival was 96.1%.
In a cooperative setting, combination of EBRT and TPPB boost plus ADT resulted in excellent DFS with acceptable late toxicity for patients with intermediate-risk prostate cancer.
prostate; brachytherapy; radiation; cooperative group trial; hormonal therapy
To assess the relationship between prognostic factors, post-radiation prostate-specific antigen (PSA) dynamics, and clinical failure following prostate cancer radiation therapy using contemporary statistical models.
Methods and materials
Data from 4,247 patients with 40,324 PSA measurements treated with external beam radiation monotherapy in five cohorts were analyzed. Temporal change of PSA following treatment completion was described by a specially developed linear mixed model (LMM), including standard prognostic factors. These factors, along with predicted PSA evolution, were incorporated into a Cox model to establish their predictive value for the risk of clinical recurrence over time.
Consistent relationships were found across cohorts. The initial PSA decline after radiation therapy was associated with baseline PSA and T-stage (p<0.001). The long-term PSA rise was associated with baseline PSA, T-stage and Gleason score (p<0.001). The risk of clinical recurrence increased with current level (p<0.001) and current slope of PSA (p<0.001). In a pooled analysis, higher doses of radiation were associated with a lower long-term PSA rise (p<0.001) but not with the risk of recurrence after adjusting for PSA trajectory (p=0.63). Conversely, after adjusting for other factors, increased age at diagnosis was not associated with long-term PSA rise (p=0.85) but directly associated with increased risk of recurrence (p<0.001).
LMM can be reliably used to construct typical patient PSA profiles following prostate cancer radiation therapy. Pre-treatment factors along with PSA evolution and the associated risk of recurrence provide an efficient and quantitative way to assess impact of risk factors on disease progression.
Prostate cancer; Prostate-specific Antigen; PSA velocity; Radiation therapy; Prognostic calculator
Up to now, the role of adjuvant radiation therapy and the extent of lymph node dissection for early stage endometrial cancer are controversial. In order to clarify the current position of the given adjuvant treatment options, a systematic review was performed.
Materials and methods
Both, Pubmed and ISI Web of Knowledge database were searched using the following keywords and MESH headings: "Endometrial cancer", "Endometrial Neoplasms", "Endometrial Neoplasms/radiotherapy", "External beam radiation therapy", "Brachytherapy" and adequate combinations.
Recent data from randomized trials indicate that external beam radiation therapy - particularly in combination with extended lymph node dissection - or radical lymph node dissection increases toxicity without any improvement of overall survival rates. Thus, reduced surgical aggressiveness and limitation of radiotherapy to vaginal-vault-brachytherapy only is sufficient for most cases of early stage endometrial cancer.