Open Access
Original Article
Published 07/18/2013 DOI: 10.7759/cureus.128 Copyright
? 2013 Smith et al. Distributed under
Creative Commons CC-BY 3.0Comparative Review of Consensus-Based Clinical T arget Volume
De?nitions for Prostate Radiotherapy
Graham Smith, George Rodrigues
Corresponding author: George Rodrigues
1. Department of Epidemiology and Biostatistics, W estern University, London ON, Canada, N6A 5C1
2. Department of Oncology, London Health Sciences Centre; Schulich School of Medicine & Dentistry, W estern University, London, Ontario, CA Categories: Radiation Oncology, Epidemiology & Public Health, Urology
Keywords: clinical target volume, prostate cancer, contouring, guidelines, radiation therapy, consensus guidelines
How to cite this article
Smith G, Rodrigues G (2013-07-18 10:50:36 UTC) Comparative Review of Consensus-Based Clinical T arget V olume De?nitions for Prostate Radiotherapy. Cureus 5(7): e128. doi:10.7759/cureus.128
Abstract
Background: A major obstacle in the delivery of postoperative
radiation therapy (RT) for prostate cancer is accurate delineation of the tumor targets and organs at risk. Although postoperative prostate cancer contouring atlases are quite common, there is still no widely accepted contouring guideline. The purpose of this study is to critically review the various postoperative prostate RT treatment planning consensus guidelines or atlases currently available.
Methods: A literature search was conducted using various electronic databases with the key terms: prostate, contour, planning tumour volume, clinical target volume, delineation or de?nition, guidelines or atlas, and radiation oncology. The search was limited to English publications from the years 1985 to 2011.
Results: A total of seven publications relating to contouring guidelines
for postoperative prostate radiotherapy were identi?ed. There are four distinct consensus guidelines developed by major institutions: Princess Margaret Hospital, the Australian and New Zealand Radiation
Oncology Genito-Urinary Group, the European Organization for Research and Treatment of Cancer, and the Radiation Therapy
Oncology Group.
Conclusions: After reviewing the consensus contouring guidelines for postoperative prostate cancer radiation therapy that were available in
the literature, it is clear that there disagreement with regards to what anatomical borders should be used for delineating an appropriate
prostate bed CTV. Additional studies comparing the reproducibility of
the various guidelines as well as the performance of these guidelines on
clinically important outcomes are needed. Introduction
Postoperative radiation therapy (RT) is indicated in the treatment of post-prostatectomy patients with high-risk of local recurrence [1]. Recent studies have shown RT to be bene?cial following radical prostatectomy in both the adjuvant setting, for patients with high-risk pathological features, such as positive surgical margins and seminal vesicle invasion [2-8], or as salvage for biochemical disease recurrence [9-10]. Two randomised controlled trials suggest adjuvant RT directly following surgery provides improved progression-free survival, biochemical relapse-free survival, and local control over watchful waiting protocols [3, 11]. Although a long-term follow-up of one of these trials also suggests that adjuvant RT also improves metastasis-free survival and overall survival compared with observation alone [2], there is insu?cient long-term follow-up data available to adequately assess the e?ect on these treatment outcomes.
A major obstacle in the delivery of postoperative radiation therapy
for prostate cancer is accurate delineation of the tumor targets and Organs at Risk (OARs). Inter-observer variability between oncologist drawn contours in prostate radiation therapy is well documented [12-15] and has been identi?ed as a highly signi?cant contributing factor to uncertainty in radiation therapy treatment planning [16]. Contouring consensus guidelines or atlases for postoperative prostate RT have been created to aid oncologists in the delineation
of tumor targets and OARs with the hope of reducing this variability.
Although postoperative prostate cancer contouring atlases are quite common, there is still no widely accepted contouring guideline. The purpose of this study is to critically review the various postoperative prostate RT treatment planning consensus guidelines or atlases currently available with emphases on the methodology and validity of each atlas.
Materials And Methods
A literature search was conducted using the electronic databases Pubmed, MEDLINE (OVID), EMBASE, Cochrane Library, and Google Scholar with the key terms: prostate, contour, planning tumour
Scholar with the key terms: prostate, contour, planning tumour volume, clinical target volume, delineation or de?nition, guidelines or atlas, and radiation oncology. The search was limited to English publications from the years 1985 to 2011. Relevant studies found on references lists of identi?ed articles were included as well as any articles found on national cooperative group websites, including the Radiation Therapy Oncology Group (RTOG) and European Organization for Research and Treatment of Cancer (EORTC). Only studies related to medicine or physics (including radiation oncology, imaging, oncology or cancer) were included. The methodology used in these articles including how each consensus was reached and study validity was reviewed, and any similarities and di?erences found in the contouring guidelines were detailed.
Results
Literature Search
A total of seven publications relating to contouring guidelines for postoperative prostate radiotherapy were identi?ed [17-23]. There are four distinct consensus guidelines developed by major institutions: Princess Margaret Hospital (PMH) [17], the Australian and New Zealand Radiation Oncology Genito-Urinary Group (FROGG) [19], the European Organization for Research and Treatment of Cancer (EORTC) [21], and the Radiation Therapy Oncology Group (RTOG) [22]. A ?fth consensus statement was identi?ed from the Radiotherapy and Androgen Deprivation In Combination After Local Surgery (RADICALS) group in their validation study [18], in which they used a modi?ed version of the PMH consensus guideline. No publication outlining the contents of this version was found. There were ?ve studies discussing the methodology used in the creation of the various consensus statements [17, 19, 21-23]. The information from the EORTC consensus was published in two separate articles [21, 23]. There were two validation publications, one from the RADICALS [18] and the other from EORTC [20]. The study by PMH [17] contains both a description of how their consensus was reached as well as a validation component. Although the article from Boehmer, et al. [23] was on guidelines for radiotherapy for intact prostate, it was referred to in the EORTC consensus for postoperative prostate radiotherapy by Poortman, et al. [21] and was included in this review. The studies were published between 2006 and 2011 and represent a large number of medical institutions from a wide range of countries (Table 1).
Primary Oncology Number of Consensus
Primary Author Group/Institution
Responsible for
Consensus
Countries Involved
Date
Published
Medical
Institutions
Involved
[C] and/or
Validation
[V] Study
K. Wiltshire PMH
Australia, Canada,
Switzerland
20074C, V
D. MitchellRADICALS United Kingdom20092V
M. Sidhom FROGG-RANZCR Australia,
Singapore, New
Zealand
20087C
P. Ost EORTC Belgium20111V
P. Poortmans EORTC
Belgium, France,
Germany,
Netherlands,
Switzerland, United
Kingdom
200713C
J.
Michalski
RTOG Canada, USA201013C
D. Boehmer*EORTC
Belgium, France,
Germany,
Netherlands,
Switzerland, United
Kingdom
200610
C
T able 1: Post-operative prostate radiation therapy contouring consensus guideline publications
Abbreviations: PMH = Princess Margaret Hospital; RADICALS = Radiotherapy and
Androgen Deprivation In Combination After Local Surgery; EORTC = European Organization for Research and T reatment of Cancer; RTOG = Radiation Therapy Oncology Group;
FROGG-RANZCR = The Faculty of Radiation Oncology Genito-Urinary Group part of the
Royal Australian and New Zealand College of Radiologists. * European Organization for Research and T reatment of Cancer consensus guidelines for intact prostate
Discussion
Consensus Methodology
The methodology for creating the consensus atlases by the RTOG, FROGG and PMH began with delineation of preliminary contours by a small group of clinicians, involving at least one oncologist or urologist experienced with postoperative prostate radiotherapy or prostatectomy [17, 19, 22]. In these studies, the clinicians responsible for delineating the initial contours were given patients with speci?c clinical scenarios and were asked to delineate an appropriate clinical target volume (CTV) based on their expert knowledge of anatomy, tumor physiology and patterns of spread [17,
19, 22]. Consensus guidelines from the RTOG, FROGG and PMH were ?nalized following a presentation and discussion of their preliminary contours at a conference or consensus workshop [17, 19, 22]. Inter-professional collaboration between diverse multi-disciplinary groups of health care professionals, speci?cally individuals with expertise in the treatment of prostate cancer, was utilized in the creation of the consensus atlases [17, 19, 21-23]. The study by PMH focused on postoperative prostate patients with or without seminal vesicle invasion [17], while the RTOG study focused on the clinical scenarios of seminal vesicle invasion and positive apex margins [22]. A review of relevant literature was present in the development of each of the consensus guidelines [17, 19, 21-23].
The initial contours generated by PMH were presented at the Australian Faculty of Radiation Oncology Genito-Urinary Oncology Group Consensus Workshop on Post-Prostatectomy Radiotherapy in June 2006 [17, 19]. The consensus guidelines created at this conference were further modi?ed by the FROGG and were used in the creation of their own consensus atlas [19].
The RTOG used an imputation method of the expected maximum (EM) algorithms for simultaneous truth and performance level estimation (STAPLE) [24] to create their preliminary contours. The STAPLE algorithm has been previously identi?ed as a useful tool in analyzing expert radiation oncologist consensus contours [25]. The RTOG STAPLE contours were presented at a RTOG conference where they were discussed and a consensus was ?nalized following a teleconference [22].
There was no information given by the EORTC regarding the exact process in which their consensus guideline was reached. Instead, the EORTC presents detailed manuscripts reviewing published works relevant to prostate cancer, speci?cally studies on surgery, anatomy and local recurrence [21, 23].
A detailed description of the methods involved in the creation of the four contouring guidelines is shown in Table 2.
Consensus How Consensus was Reached
Three urologists experienced with open or laparoscopic prostatectomy
independently delineated the anatomical borders of the prostate bed at
risk of microscopic cancer seeding on axial MRI scans of 2 patients
(with and without seminal vesicles, selected randomly from the patient
population) and presented these contours to a multi-disciplinary Genito-
Wiltshire et al (PMH)Urinary (GU) tumor board. An Interdisciplinary discussion between all members of the GU board including radiation oncologists, medical oncologists, urologists, uroradiologists and uropathologists occurred and a review of the literature (patterns of failure, surgical practice, radiologic anatomy) was completed. Final consensus CTV was de?ned by 1 uroradiologist and 2 radiation oncologists and was approved by a GU board containing 10 rad oncologists, 4 urologists and 1 uroradiologist. Consensus was modi?ed further following presentations of consensus at Australian Faculty of Radiation Oncology Genito-Urinary Oncology Group Consensus Workshop on Post Prostatectomy Radiotherapy June 2006 and Genito-Urinary Radiation Oncologists of Canada Meeting January 2007.
FROGG-RANZCR Consensus was reached following a 2-day consensus workshop. Prior to workshop extensive literature review was performed which led FROGG executives to generate a draft of post-prostatectomy guidelines.
Guidelines from PMH were presented at the conference, discussed and re?ned. Expert speakers from radiation oncology, urology and radiology presented data on topics relevant to post-prostatectomy radiotherapy at 2-day workshop. 63 delegates from Radiation Oncology, Radiology, Urology, Medical Physics, and Radiation Therapy attended. Unresolved issues handled by workshop parties for ?nal revision
RTOG 11 oncologist observers contoured 2 post-op prostate patients with 2 separate clinical scenario cases: 1) positive apex margin or 2) invasion of seminal vesicles and evaluated the inter-observer variability between oncologists (each oncologist was to use their own institution's contouring policy). From these contours they used an imputation method of the expected maximum (EM) algorithms for simultaneous truth and performance level estimation (STAPLE), to create a consensus contour derived from the collection of observer contours. The STAPLE contour represents the 'true' contour for each patient. The RTOG held a conference where they presented a review of patterns of failure, anatomy and surgical ?ndings related to radical prostatectomy. Each STAPLE contour (for each patient case) was used as a starting point for discussion and creation of consensus guidelines. The RTOG reviewed and modi?ed the consensus contours at a conference and ?nalized them via teleconference.
EORTC Presented a manuscript reviewing published work on local recurrence sites in post-op prostate cancer, surgery and anatomy. It is unclear as to how their consensus was reached.
T able 2: Description of consensus guideline methodology
Abbreviations: PMH = Princess Margaret Hospital; RADICALS = Radiotherapy and Androgen Deprivation In Combination After Local Surgery; EORTC = European Organization for Research and T reatment of Cancer; RTOG = Radiation Therapy Oncology Group;
FROGG-RANZCR = The Faculty of Radiation Oncology Genito-Urinary Group part of the Royal Australian and New Zealand College of Radiologists.
Validation Studies
There were three publications validating consensus guidelines for postoperative prostate radiotherapy found in the literature [17-18, 20]. Consensus statements from the EORTC, PMH as well as a
modi?ed version of the PMH consensus (RADICALS) were evaluated in these studies [17-18, 20]. There were no validation studies found from the RTOG or the FROGG. A summary of the validation studies is presented in Table 3.
Author (Country)Consensus
Validated
Study
Population
(#
Patients)
Health Care
Professionals
Involved (#)
Description Results
Wiltshire
et al (Canada)PMH
Study 1)
25
Study 2)
16
Study 3)
20
Study 1) 3
oncologist
observers.
Study 2) 2
oncologist
observers.
Study 3) No
information
given.
Study 1)
Assessing
consensus CTV
coverage using
prostate bed
surgical clips.
Study 2) Intra-
and inter-
observer
variability study
to determine
reproducibility of
consensus.
Study 3)
Retrospective
study to
determine the
impact of the
consensus
guidelines on
clinical practice
using dose
volume
histograms.
Study 1) Surgical clips
well distributed, with a
lower clip density
appreciated at anterior-
superior and posterior-
most extent of CTV.
Surgical Clips were
contained (338 out of
339 clips) within
consensus CTV.
Study 2) Small
systematic inter-observer
errors were observed in
the AP dimension. Most
uncertainty was
observed in
superior/posterior/lateral
aspect of CTV. Intra- and
inter-observer variability
was described as
random and not
systemic.
Study 3) CTV volume
and ?eld size increased
with consensus. Less
that 50% of patients
received prescribed
microscopic dose (V100
>95%)
Mitchell
et al (United Kingdom) *RADICALS3
6 site
specialized
observers.
Compared CTV
sizes before and
after contouring
guideline use.
Inter-observer
variability study
to compare
observer
contours using
the coe?cient of
variation
statistical
method. A
comparison using
Maximum
Volume Ratio
(MVR) to
determine the
greatest extent of
di?erence
between the
volumes before
and after the use
of guidelines was
made.
CTV increased in size
with reduced inter-
observer variability in
treatment plan contours
Ost et al (Belgium)EORTC10
1 radiologist
and 5
radiation
oncologist
observers.
Inter-observer
variability study.
Volumes were
compared using
an open-source
Matlab-based
radiation therapy
planning analysis
statistical tool for
agreement
(apparent volume
of overlap
corrected using
kappa statistics)
to determine if
EORTC
guidelines
Guidelines show
moderate inter-observer
agreement (mean kappa,
0.49) and re?nement of
EORTC guidelines were
recommended.
reduced variation
in contours.
T able 3: Consensus Guideline Validation Studies
Abbreviations: PMH = Princess Margaret Hospital; RADICALS = Radiotherapy and
Androgen Deprivation In Combination After Local Surgery; EORTC = European Organization for Research and T reatment of Cancer; CTV = Clinical T arget Volume. * Modi?ed Princess Margaret Hospital consensus guidelines.
The publication from PMH validates their consensus in three separate studies [17].
The ?rst validation study assessed the coverage of the consensus Clinical Target Volume (CTV) relative to prostate bed surgical clips placed during routine clinical practice at their institution. There were 25 postoperative prostate patients with a total of 339 surgical clips in the entire patient cohort. A single observer was responsible for delineating an appropriate CTV for each patient using the PMH consensus guidelines, while a second observer was responsible for identifying the surgical clip co-ordinates on CT scans for each patient [17]. To visualize how well the surgical clips were contained within the consensus contours deformable registration and a ?nite element modeling (FEM) method, (Mofeus), [26] was used to generate a single CTV representing the entire cohort to evaluate its coverage of the surgical clips [17]. Results showed all surgical clips were contained within the consensus CTV, minus one outlier, and the distribution throughout the CTV was uniformly observed, with a lower clip density appreciated at the anterior-superior and posterior-most aspects [17].
The second validation looked at the intra- and inter-observer reproducibility of the consensus contours. Two observers individually contoured 16 patients on MRI and CT scans and repeated this at least one week later [17]. The reproducibility of the contours was assessed using the ?nite element modeling (FEM) method, Morfeus, statistical tool used previously in their ?rst validation study [26]. The variation in observer contours were said to be “mainly random” with small systematic inter-observer errors observed in the Anterior-Posterior (AP) dimension [17].
The third PMH validation study involved a retrospective analysis of the e?ects of the consensus guidelines on clinical practice. Twenty patients previously treated with various techniques of postoperative radiotherapy (including one or two phase four-?eld box or Intensity
Modulated Radiation Therapy) were re-planned using the PMH consensus guidelines. The newly created plans were compared both volumetrically and dosimetrically to the original plans used for treatment. An increase in both the contour volumes and ?eld sizes was observed in the consensus plans and only 50% of the patients would have received the prescribed microscopic dose (V100 >95%) to the CTV in these plans [17].
The validation study by Ost, et al. assessed whether adopting the EORTC consensus guidelines would reduce inter-observer contouring variability at their institution. Ost, et al. compared the contours of 10 patients, delineated by six observers (?ve radiation oncologists and one radiologist) using the EORTC guidelines [20]. The variability was assessed using an open-source Matlab-based radiation therapy planning analysis statistical tool [27] for agreement (volume of overlap corrected using kappa statistics) [28]. The speci?city and sensitivity of the observer contours with and without the contouring guidelines was evaluated using the STAPLE method [24]. Variation in dimensions of observer contours in the superior, inferior, anterior, posterior, and lateral margins were assed by comparing the distances of the outer margins of each CTV to a pre-determined centre point [20]. The inferior margin variability was assed by comparing the inferior border distance to the penile bulb delineated on MRI. Ost, et al. described the overall inter-observer agreement for the CTVs using the EORTC guidelines as moderate (mean kappa,
0.49), and recommended a re?nement of the EORTC consensus atlas [20].
The modi?ed PMH consensus guidelines assessed by Mitchell, et al. on behalf of the RADICALS were not de?ned in their study or found
in the literature. Mitchell, et al. found that using the RADICALS consensus guidelines led to an increase in the volume of the CTV and there was a reduction in inter-observer variability [18].
T arget Volume De?nitions
The consensus information regarding the margins adopted by each institution is displayed in Table 4. Consensus statements from PMH, FROGG and the RTOG focused on border landmarks in their consensus [17, 19, 22], while the EORTC included areas at greatest risk for relapse in their CTV guidelines [21, 23].
ConsensusSuperior Margin Inferior Margin Lateral Margin Anterior
Margin
Posterior
Margin
Wiltshire et al (PMH) Superior
surgical clips (if
present) or 5
mm above the
inferior border
of the vas
deferens.
Include seminal
vesicles when
pathologically
involved.
8mm below
VUA or top of
Penile Bulb (PB)
(whichever is
most superior).
Medial boarder of
levator ani and
obturator internus
(caudal);
Sacrorectogenitopubic
fascia, lateral to the
neurovascular
structures (cranial).
Posterior
edge of
symphysis
pubis to top
of
symphysis
pubis
(caudal);
Posterior
1.5cm of
bladder
wall
(cranial).
Anterior
rectal wall
and
levator ani
(caudal);
Mesorectal
fascia
(cranial).
FROGG-RANZCR Encompass all
of the seminal
vesicle bed as
de?ned by non-
vascular clips
and should
include the
distal portion of
the vas deferens.
Include seminal
vesicles if
pathologically
involved.
5–6 mm below
the
vesicourethral
anastomosis
(extended lower
to include all
surgical clips).
When VUA is
poorly de?ned
INF border will
be the slice
above the penile
bulb.
The medial border of
the levator ani or
obturator internus.
Posterior
edge of
symphysis
pubis
(caudal);
Posterior
1.5 cm of
the bladder
(cranial).
Anterior
rectal wall
and
levator ani
(caudal);
Anterior
mesorectal
fascia
(cranial).
EORTC Bladder neck
and up to base
of seminal
vesicles Include
seminal vesicles
if pathologically
involved.
15 mm cranially
from the penile
bulb or at the
apex.
Include up to the
neurovascular bundles
(if removed up to the
ilio-obturatic muscles).
Include
anastomosis
and the
urethral
axis.
Up to but
not
including
the outer
rectal wall
(caudal);
Most
posterior
part of the
bladder
(cranial).
Level of cut end
of vas deferens
or 3–4 cm above
top of symphysis
(Vas may retract
8–12 mm below
vesicourethral
anastomosis
(May include
more if concern
for apical
Levator ani and
obturator internus
(caudal);
Sacrorectogenitopubic
Posterior
edge of
pubic bone
(caudal);
Anterior
rectal wall
(caudal) -
May need
to be
concave
RTOG (Vas may retract
postoperatively).
Include seminal
vesicle if
pathologically
involved.
margin). Can
extend to slice
above penile
bulb if
vesicourethral
anastomosis not
well visualized.
fascia (cranial). If
concern about
extraprostatic disease
at base may extend to
obturator internus.
(caudal);
Post 1-2 cm
of bladder
wall
(cranial).
concave
around
lateral
aspects;
Mesorectal
fascia
(cranial).
T able 4: CTV margin recommendations from consensus guideline atlases Abbreviations: PMH = Princess Margaret Hospital; EORTC = European Organization for Research and T reatment of Cancer; RTOG = Radiation Therapy Oncology Group; FROGG-RANZCR = The Faculty of Radiation Oncology Genito-Urinary Group part of the Royal Australian and New Zealand College of Radiologists.
Superior Margin:
The anatomical landmarks used as the superior boundary in the consensus statements were the level of the cut end of the vas deferens [17, 19, 22] or the bladder neck up to the base of the seminal vesicles [21]. The superiorly located prostate bed surgical clips were included in the superior margin by PMH and FROGG [17, 19]. PMH recommends a 5mm margin above the vas deferens as an alternative superior margin in the absence of surgical clips or when the vas deferens is poorly visualized [17]. If the vas deferens retracts posteriorly, the RTOG suggests using a superior margin 3-4 cm above the top of the pubic symphysis [22]. The EORTC recommends the bladder neck up to the base of the seminal vesicles be included in
the prostate bed CTV [21].
Inferior Margin:
There were two methods used to delineate the inferior border in the consensus guidelines, involving either a designated distance below the vesicourethral anastomosis (VUA) [17, 19, 22], or slightly above the penile bulb or at the apex [21]. The measurements chosen for the distance below the VUA ranged from 5-6 mm [19] to 8-12mm [22]. The penile bulb was chosen as an alternative landmark for de?ning the inferior border by PMH, FROGG and the RTOG in the event that the VUA is poorly visualized [17, 19, 22].
Lateral Margin:
The lateral margin chosen by PMH, FROGG and the RTOG was the levator ani and obturator muscles (caudally), and the Sacrorectogenitopubic fascia (cranially) [17, 19, 22]. The EORTC
chose the neurovascular bundles as their lateral border [21].
Anterior Margin:
The anterior margin chosen by PMH, FROGG and the RTOG was the posterior edge of the pubic symphysis (caudally) and the posterior bladder wall (cranially) [17, 19, 22]. The anterior margin from the EORTC includes the anastomosis and the urethral axis [21].
Posterior Margin:
All four institutions chose the anterior rectal wall for the posterior, caudal border [17, 19, 21-22]. The mesorectal fascia was chosen by PMH, FROGG and the RTOG for the posterior cranial border [17, 19, 22], while the EORTC chose the posterior bladder [21]. Additional Consensus Information
Information regarding the imaging technology, patient positioning, vesicourethral anastomosis (VUA) visualization method, organs at risk (OARs), and additional target volume recommendations from the consensus guidelines are displayed in Table 5.
Consensus Imaging
Technology
Patient
Positioning
and Organ
Prep
VUA
Visualization
Method
OARs
Additional CTV and
PTV
recommendations
Wiltshire et al (PMH)Axial, pelvic,
helical CT (2mm
thickness with no
contrast) and
MRI used in
creation of
consensus; Use
of multi-slice CT
scanning with
MRI
recommended.
Patient
positioned
supine with
custom
Vac-Lok
device;
Bladder
comfortably
full; Empty
rectum (w
Milk of
magnesia.
Sagittal CT
Not
Discussed
CTV: Extended to
include 1 cm
beyond the gross
recurrent disease,
and visible surgical
clips located
outside
boundaries,
excluding high
lymphadenectomy
vessel clips.
PTV: Around
superior (cranial)
CTV: 15 mm
superior-inferior
[SI] and anterior-
posterior [AP] and
12 mm right–left
[RL]; Around inferior (caudal) CTV: 11 mm SI and AP and 8mmRL.
FROGG-RANZCR Imaging used to
create consensus
not discussed;
Use of multi-
slice CT (2.5-
3mm thickness -
intravenous
contrast with
delayed
scanning) and/or
MRI fusion
recommended
(If available).
Bladder
comfortably
full; Empty
rectum;
Patient
positioning
not
discussed.
Contrast
enhanced
CT or MRI
Rectum;
Bladder
CTV: Ensure a
minimum 2 cm
margin from
posterior extent of
the CTV to
posterior rectal
wall.
PTV: A 10 mm
margin around the
CTV or 5mm
margin on post
boarder (if rectal
dose is high).
EORTC Imaging used in
creating
consensus not
discussed. Use of
multi-slice CT
recommended.
Bladder
comfortably
full or
empty;
Empty
rectum;
Patient
positioning
not
discussed.
VUA
visualization
not
discussed;
Used penile
bulb as
inferior
border
reference.
Rectum;
Bladder
CTV: 5 mm in all
directions (except
the rectal wall) to
account for
microscopic
extension.
Supplementary 5
mm in posterior
and lateral
directions in
presence of
incompletely
resected
extracapsular
tumor extension,
excluding rectal
wall.
Supplementary 5
mm in direction of
microscopically
involved tumor
margins as
reported by
pathologist (except
rectal wall).
PTV: A minimum
of 5mm in all directions to account for organ motion.
RTOG CT (3mm
thickens - no
contrast) used in
creation of
consensus.
Patient
positioned
supine;
Bladder
comfortably
full; Empty
rectum.
Sagittal CT;
MRI can
improve
visualization
if available.
Not
discussed
Not discussed
T able 5: Additional Consensus Guideline Information
Abbreviations: PMH = Princess Margaret Hospital; EORTC = European Organization for Research and T reatment of Cancer; RTOG = Radiation Therapy Oncology Group; FROGG-RANZCR = The Faculty of Radiation Oncology Genito-Urinary Group part of the Royal Australian and New Zealand College of Radiologists; CT = Computed T omography; MRI = Magnetic Resonance Imaging; VUA = Vesicourethral Anastomosis; CTV = Clinical T arget Volume; PTV = Planning T arget Volume.
Multi-slice CT scans were used in the creation of the consensus guidelines by PMH and the RTOG [17, 22]. The use of MRI with or without Positron Emission Tomography (PET) fusion was recommended by PMH and FROGG for delineating treatment plan contours [17, 19]. The importance of e?ectively de?ning the vesicourethral anastomosis was identi?ed as an important step in the delineation of postoperative prostate radiotherapy contours in the publications from PMH, RTOG and FROGG [17, 19, 22]. The FROGG and EORTC consensus statements contained recommendations regarding contouring of the OARs [21, 23]. There were additional CTV and Planning Target Volume (PTV) recommendations from PMH, FROGG and the EORTC [17, 19, 21, 23].
Conclusions
After reviewing the consensus contouring guidelines for postoperative prostate cancer radiation therapy that were available in the literature, it is clear that there is some disagreement with regards to what anatomical borders should be used for delineating an appropriate prostate bed CTV. There were many similarities in
the methodology used in the creation of the atlases, although some atlases were more detailed than others. The validation studies performed using the consensus atlases were done on a small number of patients and tended to focus on inter-observer reproducibility of the newly adopted guidelines relative to a previous standard. The
results of these studies seemed inconclusive as to whether or not the consensus guidelines improved inter-observer reproducibility in the creation of target volumes or any other clinically important outcomes. Additional studies comparing the reproducibility of the various guidelines as well as the performance of these guidelines on clinically important outcomes when used in a variety of clinical sites are needed so that physicians can better decide which atlas, or part of an atlas, to adopt into their practice.
Additional Information
Disclosures
No disclosures were declared
References
1. Do LV, Do TM, Smith R, Parker RG: Postoperative radiotherapy for
carcinoma of the prostate: impact on both local control and distant disease-free survival. Am J Clin Oncol 2002, 25:1-8.
2. Thompson IM, Tangen CM, Paradelo J, et al.: Adjuvant radiotherapy
for pathological T3N0M0 prostate cancer signi?cantly reduces risk of metastases and improves survival: Long-term followup of a
randomized clinical trial. J Urol 2009, 181:956-62.
3. Bolla M, van Poppel H, Collette L, et al: Postoperative radiotherapy
after radical prostatectomy: a randomised controlled trial (EORTC trial 22911). Lancet 2005, 366:572-78.
4. Collette L, van Poppel H, Bolla M, et al: Patients at high risk of
progression after radical prostatectomy: do they all bene?t from immediate post-operative irradiation? (EORTC trial 22911). Eur J Cancer 2005, 41:2662-72.
5. Wiegel T, Bottke D, Willich N, et al: Phase III results of adjuvant
radiotherapy (RT) versus ‘‘wait and see’’ in patients with pT3
prostate cancer following radical prostatectomy (RP) (ARO 96-
02/AUO AP 09/95). J Clin Oncol 2005, 23:4513.
6. Choo R, Hruby G, Hong J, et al: Positive resection margin and or
pathologic T3 adenocarcinoma of prostate with undetectable
postoperative prostate-speci?c antigen after radical
prostatectomy: to irradiate or not?. Int J Radiat Oncol Biol Phys
2002, 52:674-80.
7. Leibovich BC, Engen DE, Patterson DE, et al: Bene?t of adjuvant
radiation therapy for localized prostate cancer with a positive
surgical margin. J Urol 2000, 163:1178-82.
8. Vicini FA, Ziaja EL, Kestin LL, et al: Treatment outcome with
adjuvant and salvage irradiation after radical prostatectomy for
prostate cancer. Urology 1999, 54:111-17.
9. Trock BJ, Han M, Freedland SJ, et al: Prostate cancer-speci?c
survival following salvage radiotherapy vs observation in men with biochemical recurrence after radical prostatectomy. JAMA 2008, 299:2760-69.
10. Stephenson AJ, Shariat SF, Zelefsky MJ, et al: Salvage radiotherapy
for recurrent prostate cancer after radical prostatectomy. JAMA 2004, 291:1325e-1332.
11. Thompson IM Jr., Tangen CM, Paradelo J, et al: Adjuvant
radiotherapy for pathologically advanced prostate cancer: A
randomized clinical trial. JAMA 2006, 296:2329-35.
12. Mitchell DM, Perry L, Smith S, Elliott T, Wylie JP, Cowan RA, Livsey
JE, Logue JP: Assessing the e?ect of a contouring protocol on
postprostatectomy radiotherapy clinical target volumes and
interphysician variation. Int J Radiat Oncol Biol Phys 2009, 75:990-
98.
13. Lawton CA, Michalski J, El-Naqa I, Kuban D, Lee WR, Rosenthal SA,
Zietman A, Sandler H, Shipley W, Ritter M, et al: Variation in the
de?nition of clinical target volumes for pelvic nodal conformal
radiation therapy for prostate cancer. Int J Radiat Oncol Biol Phys 2009, 74:377-82.
14. Lawton CA, Michalski J, El-Naqa I, Buyyounouski MK, Lee WR,
Menard C,O’Meara E, Rosenthal SA, Ritter M, Seider M: RTOG GU Radiation oncologyspecialists reach consensus on pelvic lymph
node volumes for high-risk prostate cancer. Int J Radiat Oncol Biol Phys 2009, 74:383-87.
15. Livsey JE, Wylie JP, Swindell R, Khoo VS, Cowan RA, Logue JP: Do
di?erences in target volume de?nition in prostate cancer lead to clinically relevant di?erences in normal tissue toxicity?. Int J
Radiat Oncol Biol Phys 2004, 60:1076-81.
16. Jameson MG, Holloway LC, Vial PJ, Vinod SK, Metcalfe PE: A review
of methods of analysis in contouring studies for radiation
oncology. J Med Imaging Radiat Oncol 2010, 54:401-10.
17. Wiltshire KM, Brock KK, Haider MA, Zwahlen D, Kong V, Chan E,
Moseley J, Bayley A, Catton C, Chung P, Gospodarowicz M,
Milosevic M, Kneebone A, Warde P, and Menard C: Anatomic
boundaries of the clinical target volume (prostate bed) after
radical prostatectomy. Int J Radiat Oncol Biol Phys 2007, 69:1090-
99.
18. Mitchell DM, Perry L, Smith S, Elliott T, Wylie JP, Cowan RA, Livsey
JE, and Logue JP: Assessing the e?ect of a contouring protocol on
postprostatectomy radiotherapy clinical target volumes and
interphysician variation. Int J Radiat Oncol Biol Phys 2009, 75:990-
93.
19. Sidhom MA, Kneebone AB, Lehman M, Wiltshire KL, Millar J,
Mukherjee RK, Shakespeare TP, and Tai KH: Post-prostatectomy
radiation therapy: Consensus guidelines of the Australian and
New Zealand Radiation Oncology Genito-Urinary Group. Radiation and Oncology 2008, 88:10-19.
20. Ost P, De Meerleer G, Vercauteren T, De Gersem W, Veldeman L,
Vandecasteele K, Fonteyne V, and Villeirs G: Delineation of the
postprostatectomy prostate bed using computed tomography:
Interobserver variability following the EORTC delineation
guidelines. Int J Radiat Oncol Biol Phys 2011, 81:e143-e149.
21. Poortmans P, Bossi A, Vandeputte K, Bosset M, Miralbell R,
Maingon P, Boehmer D, Budiharto T, Symon Z, van den Bergh ACM, Scarse C, Van Poppel H, and Bolla M: Guidelines for target volume de?nition in post-operative radiotherapy for prostate cancer, on behalf of the EORTC radiation oncology group. Radiotherapy and Oncology 2007, 84:121-27.
22. Michalski JM, Lawton C, El Naqa I, Ritter M, O’Meara E, Seider MJ,
Lee WR, Rosenthal SA, Pisansky T, Catton C, Valicenti RK, Zietman AL, Bosch WR, Sandler H, Buyyounouski MK, and Ménard C:
Development of RTOG consensus guidelines for the de?nition of the clinical target volume for postoperative conformal radiation
therapy for prostate cancer. Int J Radiat Oncol Biol Phys 2010,
76:361-68.
23. Boehmer D, Maingon P, Poortmans P, Baron MH, Miralbell R,
Remouchamps V, Scrase C, Bossi A, and Bolla M: Guidelines for
primary radiotherapy of patients with prostate cancer.
Radiotherapy and Oncology 2006, 79:259-69.
24. War?eld SK, Zou KH, Wells WM: Simultaneous truth and per-
formance level estimation (STAPLE): An algorithm for the
validation of image segmentation. IEEE Trans Med Imaging 2004, 23:903-21.
25. Allozi R, Li X, White J, Apte A, Tai A, Michalski J, Bosch W, and El
Naqa I: Tools for consensus analysis of experts’ contours for
radiotherapy structure de?nitions. Radiotherapy and Oncology
2010, 97:572-78.
26. Brock KK, Dawson LA, Sharpe MB, et al: Application of a novel
deformable image registration technique to facilitate
classi?cation, tracking and targeting of tumor and normal tissue.
2004, 60:S227.
27. Deasy JO, Blanco AI, Clark VH. : CERR: A computational
environment for radiotherapy research. Med Phys 2003, 30:979-85.
28. Fleiss JL, Levin BA, Paik MC: Statistical methods for rates and
proportions. 3rd ed.. Edited by Hoboken. N.J.: Wiley; 2003:
前列腺癌根治性放疗规范 目前在前列腺癌根治性放疗靶区勾画上欧美国家已基本形成共识，参照美国放疗肿瘤学研究组（RTOG）关于前列腺癌的放疗靶区勾画建议、美国国立综合癌症网络（NCCN）和欧洲泌尿协会制定的前列腺癌诊治指南，并结合我们的临床实践，对局限期前列腺癌根治性放疗的靶区勾画提出规范化建议。 1、体位固定及CT定位：定位前4小时可口服4% 1000 ml稀释的肠道对比剂，定位前排空直肠，憋尿充盈膀胱。CT定位采取仰卧位，体模固定，层厚3 mm扫描，扫描范围从腰4椎体下缘至坐骨结节下3 cm。 2、前列腺及精囊腺靶区勾画 （1）局限低危前列腺癌放疗靶区只包括前列腺；局限中危前列腺癌或盆腔淋巴结转移几率 ≤15%的局限高危前列腺癌放疗靶区包括前列腺和精囊腺。 （2）前列腺癌往往为多发灶，且CT和磁共振成像（MRI）无法检测出前列腺内的全部病灶，因此，前列腺癌难以勾画肿瘤靶区（GTV，转移淋巴结除外），只勾画临床靶区（CTV）（图1）。（3）前列腺靶区勾画自前列腺底至前列腺尖的全部前列腺组织（图1），若前列腺存在钙化，须包全全部钙化区域。 （4）前列腺尖部以尿道球部上0.5 cm或阴茎脚上缘为标志（图2）。
（5）精囊腺只需包含紧邻前列腺2～2.5 cm的范围（图3）。 （6）计划靶区（PTV）为CTV向各方向外放1 cm，但向后方向仅外放0.5—0.6 cm以减少直肠照射（图4）。 （7）前列腺及精囊腺靶区的放疗剂量为75.6-81 Gy。 3、盆腔淋巴引流区靶区勾画 （1）对于有多个高危因素、根据Roach公式或Partin表推断盆腔淋巴结转移几率＞15%的前列腺癌，建议行盆腔淋巴引流区预防照射。 盆腔淋巴结转移几率评估方法： Pisansky等: T分期与盆腔淋巴结转移关系：T2a（3.3％），T2b（10.8％），T3（25％）。Roach公式：Node(+)=[2/3PSA+(Gleason-6)]% ＞15%有较大盆腔淋巴结转移危险；＞30%有很大盆腔淋巴结转移危险。 前列腺癌盆腔淋巴结转移可能性估计（Partin表）：
常见肿瘤靶区勾画集团标准化工作小组 #Q8QGGQT-GX8G08Q8-GNQGJ8-MHHGN#
前列腺癌根治性放疗靶区建议 作者：中国医学科学院肿瘤医院放疗科刘跃平李晔雄王维虎房辉来源：中国医学论坛报日期：2012-03-30 随着人均寿命的延长，我国老年人口的不断增加，的发病率逐年上升。放疗是前列腺癌根治性治疗手段之一，从局限低、中、高危前列腺癌到盆腔淋巴结转移，甚至远处转移前列腺癌，放疗均有广泛的应用。对于局限期前列腺癌，放疗可取得与手术相当的疗效且并发症的发生较少。 近年来，随着各种放疗新技术的出现和发展，前列腺癌的放疗越来越准确，正常组织的保护则更可靠，因此，接受放疗的患者越来越多。我们参照美国放疗肿瘤学研究组（RTOG）关于前列腺癌的勾画建议、美国国立综合癌症网络（NCCN）和欧洲泌尿协会制定的前列腺癌诊治指南，并结合我们的临床实践，对局限期前列腺癌根治性放疗的靶区勾画提出参考性建议，旨在使前列腺癌放疗靶区定义规范化和合理化。 从表1得知，前列腺癌靶区勾画主要包括前列腺、精囊腺及盆腔淋巴引流区，对局限期前列腺癌根治性放疗的靶区确定，我们提出如下建议。 1CT定位及放疗 ·定位前时排空膀胱和直肠，口服1000ml稀释的肠道对比剂，然后憋尿充盈膀胱。CT定位采取仰卧位，体模固定，层厚3mm扫描，扫描范围从腰4椎体下缘至坐骨结节下3cm。 ·建议采用3D-CRT或IMRT，若放疗剂量≥78Gy，建议使用图像引导放疗（IGRT）。 2前列腺及精囊腺靶区勾画
·局限低危前列腺癌放疗靶区只包括前列腺；局限中危前列腺癌或盆腔淋巴结转移几率≤15%的局限高危前列腺癌放疗靶区包括前列腺和精囊腺。 ·前列腺癌往往为多发灶，且CT和磁共振成像（MRI）无法检测出前列腺内的全部病灶，因此，前列腺癌难以勾画大体靶区（GTV，转移淋巴结除外），我们只勾画临床靶区（CTV）（图1）。 ·前列腺靶区勾画自前列腺底至前列腺尖的全部前列腺组织（图1），若前列腺存在钙化，须包全全部钙化区域。 ·前列腺尖部以尿道球部上cm或阴茎脚上缘为标志（图2）。 ·精囊腺只需包含紧邻前列腺2～cm的范围（图3）。 ·计划靶区（PTV）为CTV向各方向外放1cm，但向后方向仅外放cm以减少直肠照射（图4）。 ·前列腺和精囊腺的放疗剂量为~81Gy。 3盆腔淋巴引流区靶区勾画 ·对于有多个高危因素、根据Roach公式或Partin表推断盆腔淋巴结转移几率＞15%的前列腺癌，建议行盆腔淋巴引流区预防照射。 ·盆腔淋巴引流区从腰5椎体与骶1椎体交界处（L5与S1交接水平）勾画至耻骨联合上缘水平。
《NCCN前列腺癌临床实践指南》解读 作者：北京大学第一医院泌尿外科北京大学泌尿外科研究所张骞周利群来源：中国医学论坛报日期： 2010-05-13 2010版《NCCN前列腺癌临床实践指南》（以下简称《指南》）的内容与2009版相比有一定修改，在前列腺癌的诊断、治疗和预后等方面都有新的推荐意见。本文将按照原文的结构就修订内容进行叙述总结，希望能对临床医师有所帮助。 诊断、分级和复发危险分层（PROS-1） 在2009版《指南》中，对于影像学检查提示可能存在淋巴结转移的前列腺癌患者，可采用细针抽吸细胞学检查（FNA）得到淋巴结组织，以求证是否存在肿瘤转移，而2010版《指南》则推荐以活组织切片检查替代FNA，从而提高诊断的敏感性，避免细针抽吸时取不到肿瘤细胞的情况。 新版《指南》扩充了一项前列腺癌的复发危险等级，即极低危前列腺癌（见表）。极低危是从2009版低危前列腺癌中划分出来的，这使得复发危险等级的划分更加细化。 初始治疗及辅助治疗 极低危和低危前列腺癌的初始治疗（PROS-2） 在2010版《指南》中，极低危前列腺癌患者的预期寿命一般＜20年。对此类患者，初始治疗推荐仅定期积极监测（2B类），目的是早期发现病变的进展。积极监测包括每半年1次血清PSA检测及每年1次直肠指检（DRE）。 对于预期寿命≥10年的低危前列腺癌患者的初始治疗，2010版《指南》主要有两项修订。
一项是对定期积极监测方法的调整。对于接受定期积极监测的患者，检测方法在原有血清PSA和DRE的基础上增加了每年1次的前列腺活组织切片检查，这可早期发现前2种检查方法无法发现的病变，从而改善患者预后。 另一项是对行“根治性前列腺癌切除术”时行盆腔淋巴结清扫的指征进行了调整。行“根治性前列腺癌切除术”时，盆腔淋巴结的清扫取决于淋巴结转移的预测可能性。依据这个标准，2010版《指南》推荐行盆腔淋巴结清扫的门槛有所降低，由原来预测可能性的7%降至2%。另外，《指南》还增加了“异常病理特点”这一概念，其定义从根治性前列腺癌切除术后的单纯切缘阳性扩展到精囊受累、腺体外蔓延或腺体外组织可检测到PSA等，对此类患者的治疗，可选择放疗或继续观察。 中危前列腺癌的初始治疗（PROS-3） 对于接受放疗的中危前列腺癌患者，2009版《指南》明确了可采用的各种高精度放射治疗方法，包括三维适形放射治疗（3D-CRT）或逆向调强放射治疗（IMRT）联合应用影像引导放射治疗（IGRT），但并未强调IGRT应用的时间。 2010版《指南》重点强调了IGRT需配合3D-CRT或IMRT每天应用，无论患者预期寿命的长短，都须照此方案执行。 局部晚期极高危前列腺癌的初始治疗和辅助治疗（PROS-4） 对于接受放疗+雄激素剥夺疗法（ADT）的局部晚期极高危前列腺癌患者，2010版《指南》推荐ADT的治疗时间由相对较短的4~6个月延长至2~3年，虽然时间有所延长，但仍按照原方案与放疗联合应用。 补救检查方法（PROS-7） 对于放疗后PSA水平继续上升或DRE阳性的患者，除了2009版《指南》提到的进行活组织穿刺、腹部CT等检查外，2010版《指南》又新增了直肠内磁共振成像（MRI）及PSA倍增时间（PSADT）的检查指标，这些方法的增加有助于对病变的监测，相互弥补不足之处。 对于此类患者，如活组织穿刺结果为阴性且无转移，新版《指南》取消了低温手术治疗和近距离放射治疗；如检查结果示有转移，新版《指南》取消了单纯观察和ADT两种方式；如考虑患者为局部复发，新版《指南》推荐采用有创性检查方法，如活组织病理切片、直肠内MRI等进行检查。 系统治疗及系统补救治疗
前列腺癌诊治指南 疾病简介： 前列腺癌(Prostate cancer)就是发生于男性前列腺组织中的恶性肿瘤，是前列腺腺泡细胞异常无序生长的结果。前列腺癌的发病率具有明显的地理和种族差异。在欧美等发达国家和地区，它是男性最常见的恶性肿瘤，其死亡率居各种癌症的第二位;在亚洲，其发病率低于西方国家，但近年来呈迅速上升趋势。 疾病分类 95%以上的前列腺癌是发生于前列腺腺体组织的腺癌，其发展通常遵循一定的顺序：局限于前列腺内—>侵犯前列腺包膜—>突破前列腺包膜— >侵犯精囊腺—>转移至邻近区域淋巴结—>转移至骨骼和其他脏器。另一种重要的前列腺癌类型是神经内分泌癌或称为小细胞未分化癌，可能起源于神经内分泌细胞而非前列腺腺体。这种类型前列腺癌一般较早出现转移和播散，但并不分泌前列腺特异抗原(psa)，且常规的前列腺癌治疗方法对其作用不明显，反而对化疗较为敏感。此外，前列腺还可发生一些较少见的恶性肿瘤，如横纹肌肉瘤、平滑肌肉瘤、恶性神经鞘(膜)瘤、恶性间质瘤，以及其他器官的恶性肿瘤转移至前列腺。这些少见肿瘤患者的血清psa值一般无明显增高，肿瘤体积一般较大，往往产生局部邻近脏器受压迫，大多数患者以排尿和(或)排便困难就诊。 发病原因 前列腺癌的确切病因至今尚未明确，可能与基因的改变相关。如雄激素受体相关基因的改变会导致前列腺癌的患病风险增高;具有brca1基因的男性患前列腺癌的危险性是无brca1基因男性的3倍;而p53基因的异常与高级别、高侵袭性的前列腺癌密切相关。基因的改变也可能与饮食等环境因素相关。基因改变越多，患前列腺癌的危险越大。在少数情况下，前列腺癌可能具有遗传性。 目前总结出与前列腺癌发生相关的危险因素有： 1.绝对危险因素： (1) 年龄：年龄是前列腺癌主要的危险因素。前列腺癌在小于45岁的男性中非常少见，但随着年龄的增大，前列腺癌的发病率急剧升高，绝大多数前列腺癌患者的年龄大于65 岁。基本上，在40岁以后年龄每增加10岁，前列腺癌的发病率就几乎加倍，50~59岁男性患前列腺癌的危险性为10%，而80~89岁男性患前列腺癌的危险性陡增至70%。
复旦大学肿瘤医院前列腺癌诊疗指南（更新版）
目录 一、前列腺癌流行病学和中国发病趋势 3 二、前列腺癌的诊断8 （一）、前列腺癌症状8 （二）、前列腺癌诊断8 （三）、前列腺癌分期14三、前列腺癌治疗18（一）、观察等待治疗18 （二）、前列腺癌根治性手术治疗 19 （三）、前列腺癌外放射治疗 22 （四）、前列腺癌近距离治疗 26 （五）、试验性前列腺癌局部治疗 30 （六）、前列腺癌内分泌治疗 33 四、前列腺癌的随访 40 （一）、前列腺癌治愈性治疗后的随访40（二）、前列腺癌内分泌治疗后的随访43 五、前列腺癌治愈性治疗后复发的诊治45（一）、根治术后复发的诊治46 （二）、前列腺癌放射治疗后复发的诊治 49 六、激素非依赖性前列腺癌治疗 53 （一）、激素非依赖前列腺癌的概念 53 （二）、疗效评估方法53 （三）、激素非依赖前列腺癌的治疗 54 七、前列腺癌骨转移的治疗 56 （一）、骨转移的诊断 56 （二）、前列腺癌骨转移的临床表现 57 （三）、前列腺癌骨转移的治疗 57 （四）、前列腺癌骨转移治疗后的随访 58
一、前列腺癌的流行病学和中国的发病趋势 2002年全球有679,000例前列腺癌新发病例，占所有肿瘤新发病例的11.7％，位列常见肿瘤的第5位和男性肿瘤的第2位。但是前列腺癌发病率的地区分布并不均衡，在发达国家前列腺癌占肿瘤新发病例的19％，而在发展中国家仅占5.3％[1]。中国是前列腺癌发病率较低的国家，2002年的标化发病率为1.6/10万，远低于美国的124.8/10万[2]。然而近年来国内部分发达地区的前列腺癌发病率迅速升高，上海1997－1999年的发病率较1985－1987年增加了3.5倍[3]。 1 前列腺癌的流行病学 1.1 发病率和死亡率 前列腺癌发病率最高的地区是北美和斯堪的纳维亚半岛，大部分亚洲国家都是低发病率地区。1993－1997年美国黑人的标化发病率达到了185.7/10万，是同期上海市民的60倍[4]（见图1）。虽然绝对数差别很大，但是近30年来前列腺癌发病率在大部分国家都有明显的升高。1978年至1997年美国黑人的前列腺癌发病率上升了92.8％，同期新加坡华人的发病率增加了88.4％[4]。美国前列腺癌发病率的增高明显受到了PSA筛查的影响：1986年随着PSA检查技术的广泛使用，发现了许多无症状的前列腺癌患者，使得前列腺癌发病率迅速上升，并在1992年达到高峰，随后由于早期筛查的缘故发病率出现下降，1995年以来保持缓慢增长[5]。同期上海、台湾和新加坡三个亚洲发达地区的肿瘤发病率资料显示：近20年时间，三个地区前列腺癌的发病率分别增加了3.3倍、8.5倍和4.8倍[3, 6, 7]（见图2）。目前新加坡和台湾的前列腺癌发病率都在15/10万以上，位列男性常见肿瘤的前６位。 虽然美国和中国的前列腺癌发病率差异显著（高达78倍），但是前列腺癌死亡率的差别要小得多（16倍）。由于PSA筛查和治疗手段的进步，1998－2002年美国的前列腺癌死亡率为30.3/10万，并且仍处在下降趋势中。而亚洲地区的死亡率变化趋势和发病率变化相接近，1978年至1997年新加坡华人的前列腺癌死亡率增加了173.7％。死亡率和发病率的比值是反映肿瘤致死性的指标，虽然美国前列腺癌的发病率和死亡率都位居前列，但死亡率和发病率的比值低于亚洲国家且逐渐降低。 1.2 临床特点 由于PSA筛查的广泛使用以及公众对前列腺癌认知度高，美国75％的前列腺癌患者仅有PSA的异常，91％的患者病变局限。90年代以来美国前列腺癌患者的5年生存率在90％以上。而国内大部分患者是以尿路症状或骨痛而就诊，一项多中心研究显示：仅6.2％的患者是由于PSA升高而被发现，就诊患者的PSA中位数为46.1ng/ml[8]。由于大部份患者病变已为晚期，长期预后不佳，1988－1995年上海前列腺癌患者的5年生存率仅为36.5％[9]。 2 前列腺癌的危险因素 2.1 年龄和种族 前列腺癌的发病情况与年龄密切相关，美国70％以上的前列腺癌患者年龄大于65岁[10]。据美国癌症协会统计：39岁以下的男性发生前列腺癌的几率为0.01％，40－59岁的几率为 2.58％（1/39），60－79岁的几率达14.76％（1/7）[10]。国内也呈现高年龄组发病率高的分布，1997－1999年上海75岁以上前列腺癌患者占总数的51.2％[11]。 除了年龄，不同种族的前列腺癌发病率的差异也很大。美国黑人前列腺癌的发病率最高，达到
百度文库 【前列腺癌放疗】 一、适应症及治疗原则 放射治疗是局限期和局部晚期前列腺癌的根治性治疗手段。早期患者（T1-2N0M0）行根治性放射治疗，其局部控制率和10年无病生存率与前列腺癌根治术相似。局部晚期前列腺癌（T3-4N0M0）治疗原则以放疗和内分泌治疗为主。转移性癌可行姑息性放疗，以减轻症状、改善生活质量。 近年来，三维适形放疗和调强适形放疗成为前列腺癌的主要治疗方式，在此基础上，CT 引导的螺旋断层放疗不但克服了摆位误差，而且减少了正常组织的受照剂量，从而提高可以治疗剂量，达到更好的疗效，逐渐被广泛地应用于临床。可以说，如TOMO精确放疗的先进放疗技术已使早、中、晚期前列腺癌全部摆脱了无可奈何的境地。 二、放射治疗 （一）前列腺癌根治性放疗 1、定位 患者在定位1小时前饮1000ml水+泛影葡胺20ml，定位前排空直肠。仰卧于腹部平架上，双手上举抱肘置额前，用热塑成型体膜固定下腹部。利用激光灯标记定位中心，在体膜上描记3个“十”字，然后用把3个不透光铅点贴在3个“十”字的中心。 进行模拟CT扫描，扫描范围为真骨盆上下5cm，层间距5mm。 激光灯对准腹部平架上刻度为15的位置，保持患者不动，拿下体膜。在患者体表用皮肤墨水描记激光灯所示的体侧的两个“十”字和体表的前正中线。 将定位CT图像传输到计划系统工作站，登记确认。 2、治疗计划设计 （1）靶区勾画 A、CTV：CTV包括整个前列腺及其包膜。中危或高危患者，CTV还需包括精囊。对于淋
巴结转移可能性＞15%，或者T2c-T4期并且Gleason评分≥6的局限期前列腺癌患者，CTV可以考虑包括盆腔淋巴引流区 B、PTV：前列腺和精囊：CTV外放，后方为5mm，其他方向为10mm。盆腔淋巴引流区：CTV外放，头脚方向为10mm，前后左右为7—10mm。 （2）剂量学要求 A、常规剂量 传统的放射治疗根据分期不同，将照射剂量定位T1a期64Gy，T1b-c期66—70Gy，T2-3期70—72Gy。目前认为，无论对于任何分期患者，根治性放疗剂量至少未66—70Gy。 如盆腔淋巴结需行预防性照射，则盆腔野照射45—50Gy，然后缩野至前列腺区（前列腺±精囊腺），补量20—25Gy，总剂量仍为65—70Gy。 但实践证明，常规剂量照射疗效并不理想。 B、高剂量照射 由于前列腺精确放疗技术的不断革新，目前的适形放疗、调强放疗以及螺旋断层放疗（TOMO放射治疗系统）已经可以在减少正常组织的受照剂量同时，最大限度地提高照射剂量。 MD Anderson癌症中心研究了1127例T1-4N0M0患者采取不同剂量放疗的结果，得出中危性肿瘤的照射剂量和生化控制的关系，发现在65—77Gy剂量范围，肿瘤的生化控制与剂量成直线关系。其前瞻性随机试验得出结论，治疗前PSA＞10的患者照射78Gy后局控率高于70Gy组。同时，利用超分割5次*33.5Gy治疗前列腺癌的Ⅰ期临床实验研究结果，通过周密的治疗计划，每日对靶区进行校对，超分割治疗前列腺癌是可行的，且急性期及晚期泌尿道和胃肠道副反应可以接受，通过增大剂量达到提高生化控制率并降低复发率有可能实现。 总体而言，前列腺的放疗根治量至少为70Gy；低于此剂量，效果明显下降。对于中危肿瘤，照射剂量升高（至少在80Gy水平）具有显著的生化治疗效果。 3、计划评价，确认及报告签字 医师审核剂量分布和DVH图，确保计划达到临床剂量学要求，并予确认。 4、模拟机校位 把扫描的CT图像与计划打印的治疗中心层CT图像进行比较，保证两者是在同一解剖层面。然后测量治疗中心与体表的距离，与治疗计划所得数据比较，保证误差在1mm以内。 5、治疗（加速器）验证 第一次治疗时根据治疗中心摆位，拍摄0°和90°的治疗中心验证片，与治疗计划打印
Open Access Original Article Published 07/18/2013 DOI: 10.7759/cureus.128 Copyright ? 2013 Smith et al. Distributed under Creative Commons CC-BY 3.0Comparative Review of Consensus-Based Clinical T arget Volume De?nitions for Prostate Radiotherapy Graham Smith, George Rodrigues Corresponding author: George Rodrigues 1. Department of Epidemiology and Biostatistics, W estern University, London ON, Canada, N6A 5C1 2. Department of Oncology, London Health Sciences Centre; Schulich School of Medicine & Dentistry, W estern University, London, Ontario, CA Categories: Radiation Oncology, Epidemiology & Public Health, Urology Keywords: clinical target volume, prostate cancer, contouring, guidelines, radiation therapy, consensus guidelines How to cite this article Smith G, Rodrigues G (2013-07-18 10:50:36 UTC) Comparative Review of Consensus-Based Clinical T arget V olume De?nitions for Prostate Radiotherapy. Cureus 5(7): e128. doi:10.7759/cureus.128 Abstract Background: A major obstacle in the delivery of postoperative radiation therapy (RT) for prostate cancer is accurate delineation of the tumor targets and organs at risk. Although postoperative prostate cancer contouring atlases are quite common, there is still no widely accepted contouring guideline. The purpose of this study is to critically review the various postoperative prostate RT treatment planning consensus guidelines or atlases currently available. Methods: A literature search was conducted using various electronic databases with the key terms: prostate, contour, planning tumour volume, clinical target volume, delineation or de?nition, guidelines or atlas, and radiation oncology. The search was limited to English publications from the years 1985 to 2011. Results: A total of seven publications relating to contouring guidelines for postoperative prostate radiotherapy were identi?ed. There are four distinct consensus guidelines developed by major institutions: Princess Margaret Hospital, the Australian and New Zealand Radiation Oncology Genito-Urinary Group, the European Organization for Research and Treatment of Cancer, and the Radiation Therapy Oncology Group. Conclusions: After reviewing the consensus contouring guidelines for postoperative prostate cancer radiation therapy that were available in the literature, it is clear that there disagreement with regards to what anatomical borders should be used for delineating an appropriate
958?主堡鲨屡之￡型苤查!!!i生!!旦筮!!鲞筮!!塑堡!也』堕丛:旦!!!些 塑!!!i:!!!:!!,堕!:!! 前列腺癌局部治疗新进展 黄红星麦智鹏 前列腺癌局部治疗作为非根治性的治疗方式,具有创伤小、并发症少等优点,通常被应用于晚期前列腺癌的姑息性治疗,如放疗后复发性前列腺癌的挽救性治疗。1引。随着 PSA筛查的广泛应用和穿刺技术的不断提高,越来越多低级别、局限性的前列腺癌被发现。避免过度治疗是目前关于此类前列腺癌在治疗上的研究热点。近年来,由于模板定位下的经会阴穿刺和多参数MRI的发展,准确定位前列腺癌灶和评估肿瘤的恶性程度成为可能。3“。另外,关于前列腺癌病理多灶性和主要肿瘤概念的提出,为前列腺特定癌灶的局部消除提供理论的可行性’6J。对于部分早期前列腺癌,不少研究初步表明了局部治疗在疗效和并发症上都有满意的结果L『”J。因此,局部治疗在前列腺癌的治疗领域有了新的定位和应用。 一、前列腺癌局部治疗的适应证及治疗范围 前列腺癌的根治性治疗手段,如根治性前列腺切除术或前列腺癌根治性放疗,是前列腺癌标准的治疗方式。然而, 这些治疗手段导致的并发症(如尿失禁、勃起功能障碍和直肠瘘等却严重影响患者的生活质量。另外,对于选择主动监测的低危前列腺癌患者,有研究发现其中很大一部分都因肿瘤的恶性程度被低估或肿瘤进展而最终选择根治性治疗方式。在这些接受根治性前列腺切除术患者的大体病理标本中,大部分都会发现有临床意义的肿瘤。1…。主动监测仅适用于部分低危前列腺癌患者。虽然前列腺癌局部治疗目前处于研究阶段,但初步结果表明局部治疗既可兼顾控瘤效果又能有效减少并发症07’9J。因此,不少学者认为局部治疗可应用于低、中危的前列腺癌患者。1“。对于其治疗适应证, 目前的专家共识是:预期寿命≥10年,PSA<,15ng/ml,临床 T分期≤T2。,穿刺Gleason评分≤3+4分且穿刺或影像学检查无肿瘤包膜外或精囊腺侵犯¨…。
欧洲泌尿学会更新前列腺癌诊疗指南 临床泌尿外科杂志 编辑部摘 欧洲泌尿学会(EAU)的首个前列腺癌(CaP)诊疗指南于2001年发表。在过去的几年里,每当出现影响CaP 临床治疗的重要变革时,EAU 都会对指南进行更新。2005年8月,EAU 再次更新了CaP 诊疗指南。从w ww.uro https://www.doczj.com/doc/5e16775311.html, 网站上可以获得新指南的完整版本。 工作小组对新数据进行文献回顾,并按循证医学(EBM )原则,插入了证据水平和推荐分级,以便读者更好地理解推荐资料的质量。 下面就指南中CaP 的危险因素、CaP 的筛查、CaP 的诊断与分期方法和CaP 的治疗原则部分分别进行介绍。 1 CaP 的危险因素 这次更新的指南指出,遗传因素在临床确定前列腺癌患病危险时是非常重要的,外在因素也可对这种危险产生重大的影响。关键问题在于是否有值得推荐的证据,改变生活方式(减少摄入动物脂肪,多食水果、谷物和蔬菜)能降低这种危险。现有一些这方面的证据,在CaP 患者的男性亲属咨询饮食影响的时候可将这些信息提供给他们(证据水平:3~4级)。 2 CaP 的筛查 普查或大规模筛查就是对无症状的危险人群进行检查,通常仅在筛查者进行试验或研究时才会开展筛查工作。但早期检查或随机筛查可以发现散发病例。通常由被筛查者(患者)或他们的医师决定是否进行这类筛查。 有两项正在进行的大型随机研究可评估CaP 筛查的效果,即在美国进行的PLCO(前列腺、肺、结肠直肠和卵巢)研究和在欧洲进行的ERSPC(欧洲CaP 随机筛查)研究。2008年将对这两项研究的主要终点--CaP 致死率差异--进行首次分析(证据水平:1级)。 因此,目前缺乏支持性的证据,或忽视了在所有特定人群中男性的CaP 早期大规模筛查。将前列腺特异抗原(PSA)和直肠指诊(DRE)联合检查对知情良好的患者进行早期诊断,是没有争议的,并已广泛应用于临床(证据水平:3级)。 3 CaP 的诊断与分期 通过进行深入的诊断和分期工作,结合考虑患者的年龄和并发症,确定患者可选择的治疗方案。要避免采用对治疗决策无作用的操作。下面列出了对CaP 诊断和分期的七条指导: DRE 结果异常或血清PSA 检测值升高可作为CaP 的指征。正常PSA 水平的精确临界值尚未确定,但通常用PSA 水平2.5~3 g/L 作为青年男性正常值标准(C 级推荐)。 CaP 的确诊依靠组织病理学(或细胞学)诊断(B 级推荐)。根据管理患者的需要做活检和进一步的分期。 对多数可疑CaP 患者,推荐使用经直肠超声引导下系统组织活检确诊。推荐穿刺活检在前列腺各方向取样至少6~10个点,对较大的前列腺要在更多点取样(B 级推荐):由于移行区活检检出率较低,不推荐在第一次活检时对此部位取样(C 级推荐)。对持续存在CaP 指征(DRE 异常,PSA 升高,或第一次组织活检病理所见提示恶性疾病)的患者要再次进行活检。总而言之,不推荐进行更多活检(三次或更多次);是否进行只能由患者决定(C 级推荐)。 给患者经直肠在前列腺周围注射局部麻醉药物,可使接受前列腺活检的患者得到有效的麻醉(A 级推荐)。 根据DRE 结果和可能有的M RI 检查结果,判断CaP 的局部分期(T 期)。前列腺活检阳性结果的数量和部位、取样点受累的百分比、肿瘤的分级和血清PSA 水平可为诊断提供更多信息(C 级推荐)。 仅当计划进行治愈性治疗时,淋巴结状态才较重要(N 期)。T 2期或者更低分期者(PSA<20 g/L,Gleason 评分<6分),淋巴结转移的可能性低于10%,可省去淋巴结评估。只有淋巴结清扫术才能确定精确的淋巴结分期(B 级推荐)。 对骨转移(M 期),最好的评价方法是骨扫描。在血清PSA 水平低于20 g /L 、肿瘤分化良好或者中度分化的无症状患者,可不进行此项评价(B 级推荐)。 4 CaP 的治疗 通常不可能将一种治疗方案描述得比另一种治疗方案更好,因为在这个领域缺乏随机对照研究。但基于可利用的有限文献资料,仍可做出一些推荐方案。对CaP 患者初步治疗总体方案列于表1中。表1中概述了根据诊断分期的详细分类的治疗方案。 399 临床泌尿外科杂志2006年5月第21卷第5期
前列腺癌的内外放射治疗 上海市东方医院 同济大学附属东方医院 放疗科 秦庆亮 前列腺癌发病率 黑人最高，(150/10万男性)，白人其次，黄种人最低(1/10万男性)。 在过去10年中，CaP在亚洲国家和地区的发病率明显提高，分别增加1.34-4.7倍。我国则增高了2.3倍。 在亚洲国家中日本最高(18.1/10万)，韩国最低(3.87/10万)，我国北京市的发病率为 4.55/10万，但亚洲国家整体发病水平仍明显低于欧美国家。 目前CaP的发病率在我国男性肿瘤中具第11位，死亡率居第16位。 治疗——密切随访观察 适用于A1期低危患者，定期复查血PSA水平及相应的影象学检查，以确定患者病变是否有进展。 治疗——手术治疗 包括根治性手术和姑息性手术。 对晚期肿瘤患者为解除其膀胱颈部梗阻可行姑息性的经尿道电切除术，目的仅在于缓解梗阻症状。 对临床分期为A2期、B期的患者可行根治性前列腺切除术。 根治手术一般限于预期寿命>10年的患者。 放射治疗的优越性 ?放疗是目前肿瘤治疗（手术,放疗,化疗)主要手段之一 ?技术方法可靠，疗效肯定 ?放射治疗可保留病人的器官生理功能 ?适用广，可治疗各部位的肿瘤 ?年龄大/体质差/多次手术者，均可接受放疗 ?治疗副作用相对少，不一定需住院 ?三维立体放射技术可最大程度杀伤肿瘤，且使肿瘤邻近正常组织的放射损伤最小化放射治疗(RADIOTHERAPY)分类: 远距离体外放射治疗(TELETHERAPY) 低能射线,如X线kv级(低LET射线); 高能X线, ?电子线, 以及60Co-γ线; 重粒子如快中子(Neutron),质子(Proton), 氦核,中微子,碳离子，α粒子(高LET射线) 近距离体内放射治疗(BRACHYTHERAPY) 组织间插植(Interstitial); 腔內照射(Intra-cavitary); 术中放射治疗(Intra-operative); 放射性粒子植入(如125-I inserted); 放射源体表敷贴模(Mould); 靶向治疗(Targeted) 体外放射治疗采用的照射技术
前列腺癌根治性放疗靶区建议 中国医科院肿瘤医院放疗科 刘跃平 李晔雄 王维虎 房辉 随着人均寿命的延长，我国老年人口不断增加，威胁着老年男性健康的前列腺癌发病率逐年上升。放射治疗是前列腺癌的重要治疗手段，放疗从局限低中高危的前列腺癌到盆腔淋巴结转移或远处转移的前列腺癌都能发挥积极作用。对于局限期前列腺癌，放射治疗可取得与手术相当的疗效但治疗并发症却比根治性前列腺切除术更低，近年来随着放射治疗技术的不断进步，三维适形放疗、调强放射治疗、立体定向放疗、以及影像引导放疗等新技术的出现和发展，使前列腺癌靶区放疗越来越准确，而正常组织的保护则更为可靠，因而接受放射治疗的病例越来越多，为了能使前列腺癌放疗靶区规范和合理，我们参照了美国放射肿瘤协会（RTOG）关于前列腺癌放疗靶区勾画建议、美国国家癌症综合治疗指南（NCCN）、欧洲泌尿协会前列腺癌诊治指南、并结合我们的临床实践，对局限期前列腺癌根治性放疗的靶区勾画提出参考性建议。依据危险因素分组的局限期前列腺癌放疗及内分泌治疗建议以及放疗靶区建议见表1。 表1：依据危险因素分组的局限期前列腺癌放疗及内分泌治疗建议以及放疗靶区建议 危险分组 低危组 中危组 高危组 危险评价指标 T1–T2a PSA <10 ng/mL GS <7 T2b–T2c PSA 10–20 ng/mL GS 7 T3–T4 PSA >20 ng/mL GS 8–10 放疗及内分泌 治疗建议 3DCRT/IMRT=75.6‐79.2Gy 3DCRT/IMRT = 76‐81 Gy +新辅助及辅助内分 泌治疗4‐6个月 3DCRT/IMRT≧81 Gy +新辅助及辅助内 分泌治疗2‐3年 放疗靶区建议 前列腺 前列腺+ 2‐2.5 cm SV 前列腺 + 2‐2.5 cm SV + 盆腔淋巴引流区 (LNM >15%) 缩写：PSA：前列腺特异性抗原；GS：（Gleason score）格里森评分；3DCRT：三维适形放疗；IMRT：调强适形放疗；Gy：戈瑞，放疗剂量单位；SV：（seminal vesicle）精囊腺；LNM：淋巴结转移。 从上表可以得知，前列腺癌靶区勾画主要包括前列腺、精囊腺、及盆腔淋巴引流区，对局限期前列腺癌根治性放疗靶区确定我们提出如下建议： 1. CT定位及放疗建议： 1.1 定位前1小时排空膀胱和直肠，口服1000ml稀释的肠道对比剂，然后憋尿充盈膀胱。
前列腺癌诊断治疗指南主编那彦群 北京大学吴阶平泌尿外科医学中心副主编孙颖浩 第二军医大学附属长海医院泌尿外科编委（按姓氏拼音排序） 曹登峰 北京大学肿瘤医院病理科 高献书 北京大学第一医院放疗科 胡志全 华中科技大学同济医学院同济医院泌尿外科 牛晓辉 北京积水潭医院骨肿瘤科 谢立平 浙江大学医学院附属第一医院泌尿外科 徐 勇 天津医科大学第二医院泌尿外科 周爱萍 中国医学科学院肿瘤医院肿瘤内科 朱 刚 北京医院泌尿外科 朱清毅 江苏省中医院泌尿外科 秘书 张 争 北京大学第一医院泌尿外科 任善成 第二军医大学附属长海医院泌尿外科
目录 一、前列腺癌流行病学 二、前列腺癌的诊断 三、前列腺癌的治疗 四、前列腺癌的随访 五、前列腺癌治愈性治疗后复发的诊治 六、去势抵抗性前列腺癌的治疗 七. 前列腺癌骨转移的诊断和治疗 八、前列腺癌诊断流程图 九、前列腺癌治疗流程图
一、前列腺癌流行病学 前列腺癌发病率有明显的地理和种族差异，澳大利亚/新西兰、加勒比海及斯堪的纳维亚地区最高，亚洲及北非地区较低[1-7]。世界范围内，前列腺癌发病率在男性所有恶性肿瘤中位居第二[1]。在美国前列腺癌的发病率已经超过肺癌，成为第一位危害男性健康的肿瘤，据美国癌症协会估计，美国2013年前列腺癌发病人数将达到238，590人，占男性中所有恶性肿瘤的28%，但死亡人数有轻微下降，从2010年的32,050人降低到2013年的29,720人[2]。在欧洲，2008 年的新发前列腺癌病例大约有382,000人，2008年造成90,000余名患者死亡[3]。 亚洲前列腺癌的发病率远远低于欧美国家，但近年来呈现上升趋势，且增长比欧美发达国家更为迅速。来自全国肿瘤防治研究办公室/全国肿瘤登记中心收集全国30个登记处的数据显示，1988～1992年的前列腺癌发生率为1.96/10万人口，1993～1997年为3.09/10万人口，1998～2002年为4.36/10万人口[5]。根据国家癌症中心的最新数据，前列腺癌自2008年起成为泌尿系统中发病率最高的肿瘤，2009年的发病率达到9.92/10万，在男性恶性肿瘤发病率排名中排第6位；死亡率达到4.19/10万，在所有男性恶性肿瘤中排第9位[6,7]。根据2012年世界范围的调查结果，也可看出前列腺癌在中国的发病率出现了显著上升，1988年-1994年期间中国每年前列腺癌发病率的增长率为2.1%，而到了 1994-2002年间，前列腺癌发病率每年增长13.4% [1]。 值得注意的是我国前列腺癌发病率在城乡之间存在较大差异，特别是大城市的发病率更高。2008年、2009年城市人口与农村人口前列腺癌发病率之比分别为3.7:1和4.4:1，而2009年北京、上海、广州的前列腺癌发病率更是分别达到19.30/10万、32.23/10万和17.57/10万[6,7]。 前列腺癌患者主要是老年男性，新诊断患者中位年龄为72岁，高峰年龄为75～79岁。在我国，小于60岁的男性前列腺癌发病率较低，超过六十岁发病率明显增长[4]。在美国，大于70%的前列腺癌患者年龄都超过65岁，50岁以下的患者很少见，但是在大于50岁的患者中，发病率和死亡率就呈指数增长。年龄小于39岁的个体，患前列腺癌的可能性为0.005%，40-59岁年龄段增至2.2%（1/45），60-79岁年龄段增至13.7%（1/7）。
前列腺癌肿瘤标志物的研究现状 【摘要】前列腺癌是西方国家的多发病，在我国亦成上升趋势，如何更早、更准确的发现和诊断前列腺癌，对该病的治疗和患者的预后显得十分重要。 【Abstract】Prostate cancer whose morbidity is uptrend in our country,is a frequently-occurring disease in western world.It’s becoming significant for patients’treatment and prognosis to diagnose the disease earlier and more precisely. 【Keywords】prostate cancer,tumor marker,PSME 前列腺癌(Prostate Cancer)是欧美男性中最常见的恶性肿瘤，其死亡率已超过肺癌，成为发达国家男性第一致死率恶性肿瘤。在我国，前列腺癌诊出率呈升高趋势。因此，前列腺癌的早期诊断显得尤为重要，现就前列腺癌肿瘤标志物研究进展叙述如下。 1 前列腺癌特异性膜抗原前列腺特异性膜抗原(prostate-specific membrane antigen，PSMA)是存在于前列腺细胞膜的一种多功能的Ⅱ型跨膜蛋白，由750个氨基酸残基组成。编码PSMA的蛋白质具有叶酸水解酶和N-乙酰基α-连接二肽酶两种活性，与其生物学性质有关。研究发现，PSMA具有较高的前列腺组织特异性，在区分前列腺癌和其他类型恶性肿瘤的敏感度和特异性分别是65.9%和94.5%，因此PSMA仍然是前列腺癌细胞上一个相当敏感的、高度特异性的抗原物质。唐庆来等[1]在进行了PSMA与PSA在不同分期前列腺癌组织中的表达差异性研究后发现，PSMA在前列腺组织良、恶性鉴别中优于PSA，且临床分期越晚，其表达越强，与肿瘤恶性程度成正相关。因此PSMA是较PSA更具特异性的前列腺癌瘤标志物，可作为前列腺癌预后评估的重要指标。 2 前列腺特异性膜抗原剪切变异体 可变剪接是通过对外显子、内含子选择性的切除和保留，使剪接后的转录体发生变化，从而改变原基因的结构和功能，进而编码不同功能的蛋白质。PSME 便是PSMA可变剪切后的一种变异体。此外，PSMA还有PSM’、PSMC、PSMD 三种变异体。目前对这四种剪切变异体的研究还停留在组织表达鉴定水平。研究发现，PSM’、PSM-C和PSM-D均位于细胞浆内，缺少蛋白质的跨膜区，属非跨膜蛋白，缺乏PSMA原有生物学功能及诊断和治疗前列腺癌时的靶细胞定位作用。而PSME为一种跨膜蛋白，是通过RT-PCR从前列腺癌组织中获得。相关研究发现，PSM-E比PSMA具有更高的前列腺组织特异性，且高表达于前列腺癌组织，并与前列腺癌恶性程度呈正相关，随癌肿Gleason评分的增高而表达增加，比PSMA具有更高的肿瘤特异性。随着对PSME生物特性认识的加深，PSME 有望成为诊断和治疗前列腺癌新的细胞靶抗原。 3 早期前列腺特异性抗原(EPCA及EPCA-2)
前列腺癌根治性放疗靶区建议 作者：中国医学科学院肿瘤医院放疗科刘跃平李晔雄王维虎房辉来源：中国医学论坛报日期： 2012-03-30 此文章来源于https://www.doczj.com/doc/5e16775311.html, 随着人均寿命的延长，我国老年人口的不断增加，前列腺癌的发病率逐年上升。放疗是前列腺癌根治性治疗手段之一，从局限低、中、高危前列腺癌到盆腔淋巴结转移，甚至远处转移前列腺癌，放疗均有广泛的应用。对于局限期前列腺癌，放疗可取得与手术相当的疗效且并发症的发生较少。 近年来，随着各种放疗新技术的出现和发展，前列腺癌的放疗越来越准确，正常组织的保护则更可靠，因此，接受放疗的患者越来越多。我们参照美国放疗肿瘤学研究组（RTOG）关于前列腺癌的放疗靶区勾画建议、美国国立综合癌症网络（NCCN）和欧洲泌尿协会制定的前列腺癌诊治指南，并结合我们的临床实践，对局限期前列腺癌根治性放疗的靶区勾画提出参考性建议，旨在使前列腺癌放疗靶区定义规范化和合理化。 从表1得知，前列腺癌靶区勾画主要包括前列腺、精囊腺及盆腔淋巴引流区，对局限期前列腺癌根治性放疗的靶区确定，我们提出如下建议。
1CT定位及放疗 ·定位前时排空膀胱和直肠，口服1000 ml稀释的肠道对比剂，然后憋尿充盈膀胱。CT定位采取仰卧位，体模固定，层厚3 mm扫描，扫描范围从腰4椎体下缘至坐骨结节下3 cm。 ·建议采用3D-CRT或IMRT，若放疗剂量≥78 Gy，建议使用图像引导放疗（IGRT）。 2前列腺及精囊腺靶区勾画 ·局限低危前列腺癌放疗靶区只包括前列腺；局限中危前列腺癌或盆腔淋巴结转移几率≤15%的局限高危前列腺癌放疗靶区包括前列腺和精囊腺。 ·前列腺癌往往为多发灶，且CT和磁共振成像（MRI）无法检测出前列腺内的全部病灶，因此，前列腺癌难以勾画大体靶区（GTV，转移淋巴结除外），我们只勾画临床靶区（CTV）（图1）。 ·前列腺靶区勾画自前列腺底至前列腺尖的全部前列腺组织（图1），若前列腺存在钙化，须包全全部钙化区域。 ·前列腺尖部以尿道球部上0.5 cm或阴茎脚上缘为标志（图2）。 ·精囊腺只需包含紧邻前列腺2～2.5 cm的范围（图3）。 ·计划靶区（PTV）为CTV向各方向外放1 cm，但向后方向仅外放0.5 cm以减少直肠照射（图4）。 ·前列腺和精囊腺的放疗剂量为75.6~81 Gy。