prostate cancer ( pc ) is one of the most common cancers at present in the male population .
the number of diagnosed cases has risen predominantly due to the development of health care and the improvement of prevention and diagnostic methods , and , furthermore , presents an increasing tendency in poland .
the number of registered cases in the silesian voivodeship in 2011 ( with a decreasing population  9000 inhabitants fewer in 2012 compared to 2011 ) was 1260 ( 14.1% of cancers registered among men ) . in 2012 , these numbers were 1482 and 15.7% respectively . these patients can be treated radically with surgery or radiotherapy ( rt ) , i.e. external beam radiation therapy ( ebrt ) and brachytherapy ( bt ) .
brachytherapy is a relatively short treatment , but ebrt is time - consuming  in the vast majority of cases the overall treatment time ( ott ) is approximately 8 weeks ( the most common ebrt schedule is based on conventional irradiation 
specifically the delivery of a fraction dose ( fd ) of 1.82.0 gy to a total dose  varying usually from 76 to 81 gy ) . taking this into account , along with the increasing incidence of pc , the rationale for the numerous attempts at ott reduction is clear .
the choice of such a treatment modality is also supported by some radiobiological data suggesting a low value of pc alfa / beta coefficient  1.5 [ 4 , 5 ] . on the other hand , this fractionation schedule is clearly correlated with a higher risk of late adverse effects in healthy vital organs ( rectum , bladder ) .
the key to resolving this issue involves high precision beam delivery and limited , narrow margins around the prostate .
this condition can be accomplished using modern rt units such as the cyberknife ( ck ) .
the aim of the study was an evaluation of the effectiveness and tolerance of cyberknife - based radioablation in low and intermediate risk prostate cancer patients .
the analyzed material comprised 200 prostate cancer patients aged 53 to 83 ( mean age 69 ) treated between 2011 - 2014 with cyberknife - based radioablation .
there were 94 low ( lr ) and 106 intermediate risk ( ir ) patients . according to our protocol of ck - based pc radioablation , we treated patients from lr and ir ( except gleason 4 + 3 ) groups with a maximal prostate dimension smaller or equal to 50 mm .
all patients are referred to radiotherapy by urologists ( vast majority ) , or a patient may come directly to our institution ( we do not have a urology ward ) .
each patient and case is analysed and consulted on by our urologists or is sent to a local urologist to discuss the possibility of an operation . in total
we have two subgroups of patients treated with ck : patients who can not be operated on due to medical reasons and patients who refuse surgery .
3 patients had gleason 2 , 1 gleason 3 , 19 gleason 4 , 66 gleason 5 , 95 gleason 6 and 16 a gleason score of 7 . at our center prostate biopsies
one core is placed in one container whereas the next is put separately into paraffin .
six slices are obtained from one core and examined . as of the beginning of 2013 , the minimal gleason score diagnosed on the basis of core biopsy is 3 + 2 . in doubtful cases ( i.e. as in all cases with a gleason score less than six ) immunohistochemical examinations ( amcr and p63 ) are performed .
prostate cancer is diagnosed only if the amcr expression is positive and the p63 expression is negative .
as we are an oncology center and do not have a urology ward , the vast majority of biopsies are done at other ( sometimes remote ) centers . in the group of patients analyzed , 38 out of 89 cases with a gleason score less than 6 were diagnosed prior to 2013 .
of the remaining 51 cases , only three were diagnosed at our institution ( in all three cases gleason score 3 + 2 ) .
the maximum psa concentration varied from 1.05 to 19.53 ng / ml ( mean 8.28 , median 7.68 ) .
97 patients presented with t1c , 45 with t2a , 40 with t2b and 18 with t2c stage respectively .
the mean prostate dimensions were 42.5 x 37.6 x 40.4 mm in the x , y and z axes respectively .
123 patients suffered from hypertension and/or coronary disease , 25 from diabetes , 12 from asthma or obstructive pulmonary disease , 2 from anemia and 1 from polycythemia , rheumatoid arthritis and hyperthyroidism .
104 had nycturia , 67 polyuria , 41 urination difficulties , 10 dysuria , 3 erectile dysfunction , 2 hematuria , 2 anal bleeding and 1 case diarrhea .
on the first day of radiotherapy the initial psa concentration varied from 0.008 to 15.24 ng / ml ( mean 4.05 , median 3.61 ) . directly before the start of rt , 52.5% of patients were using adt ( androgen deprivation therapy ) ( 81 a combination of lhrh analogs and flutamide , 16 lhrh analogs alone , 7 flutamide alone and 1 bicalutamide ) . the duration of adt varied from 1 to 24 months ( mean 5.4 ) .
according to our standards , there is no justification for adt in the lr group .
however , nearly 100% of our prostate cancer patients are referred for radiotherapy by urologists from other centers ( in the analyzed group 47 lr patients started adt before irradiation ) . in a substantial percentage of cases ,
we endeavour to discuss this with leading urologists and , in a number of cases , have convinced them to withdraw adt .
all patients were irradiated using cyberknife  a linear accelerator generating a 6 mv photon beam , installed on a 6-degrees - of - freedom robotic arm , integrated with a 6-degrees - of - freedom robotic couch . for prostate cancer patients ,
one of the options of the multiplan treatment planning system , the prostate template path , specifically designed for these clinical situations , was used .
the tracking of implanted fiducials , ensuring the highest treatment precision , was continuously used during the treatment session .
all patients underwent implantation with 3 fiducials  20 mm in length , 0.3 mm in diameter , incised each 2 mm golden wires , forming a stable , compressed form ( gold anchors ) during implantation ( figure 1 ) . compressed form of marker ( gold anchor ) .
the implantation was performed transrectally , using an ultrasound head with a specially - designed guide and a 203 mm long needle ( diameter 0.71 mm ) ( figured 2 and 3 ) .
markers were implanted in a triangular - like configuration to ensure the possibility of potential prostate movement as well as its rotation , evaluation , and , furthermore , its correction ( tracking ) .
as one ck fraction delivery takes quite a long time ( 40 - 65 min . ) , the prostate can change its position in the pelvis as a result of bladder and rectum filling .
for this reason , the prostate position has to be checked periodically and additionally , the position of the patient and the beam inlet geometry should be corrected .
this procedure is fully automatic and can be done every 5 to 150 seconds . at the beginning of the fractional dose delivery ,
the prostate position is checked frequently ; if it is stable / unaltered the frequency of checking may be decreased .
patients were irradiated every other day ( overall treatment time [ ott ] 9 days ) using a fraction dose ( fd ) of 7.25 gy to the total dose ( td ) of 36.25 gy .
td was delivered to the planning target volume ( ptv ) , comprised of the clinical target volume ( ctv  prostate with proximal 1 cm of seminal vesicles ) and an additional margin ( 3 mm in the posterior and 5 mm in the other directions respectively ) .
the maximal accepted dose in the target ( ptv ) was 120% of the planned ( 36,25 gy ) dose .
the constraints for healthy tissues respected / observed during treatment planning are presented in table 1 .
constraints for organ at risk for femoral heads , 25 gy was accepted for 45% of their volume .
radiotherapy planning ( inverse ) was performed on the basis of the ct and mri fusion using the multiplan system .
patients were controlled at the radiotherapy end , and subsequently at 1 , 4 , 8 , 14 , 20 and 26 months , after treatment completion .
the gastrointestinal ( gi ) and genitourinary ( gu ) acute adverse effects according to the eortc / rtog scale   were monitored at the end of treatment and , moreover , 1 and 4 months thereafter .
next , the late gi and gu reactions in the eortc / rtog scale   were evaluated . during follow - up ( fu )
the percentage of evaluated patients without adt , gi and gu adverse effects , and their psa concentrations during fu gi  gastrointestinal adverse effect ( grade ) ,
androgen deprivation therapy , rt  radiotherapy graphical illustrations of psa concentration decrease and the course of acute and late gi and gu adverse effects during follow - up are presented in figures 6 , 7 and 8 .
the course of acute gi ( gastrointestinal ) and gu ( genitourinary ) adverse effects during follow - up .
the course of late gi ( gastrointestinal ) and gu ( genitourinary ) adverse effects during follow - up . during fu one patient had a confirmed relapse ( 18 months after rt )  ( positive phoenix criterion + biopsy ) and was treated with salvage brachytherapy .
four patients , during follow - up , developed a second malignancy : one bladder cancer , one squamous cell lung cancer , one colon cancer and one papillary cancer of the thyroid gland .
one of the largest patient groups ( 1100 ) is presented in a metaanalysis by king et al . .
all patients were treated with a fd of 7.25 gy to a td of 36.25 gy ( median fu 36 months ) .
the 5-year biochemical failure - free survival rate ( bffs ) was 93% for the whole group , 95% for low risk ( lr ) , 83% for intermediate risk ( ir ) and 78% for high risk ( hr ) cancer patients .
515 pc patients treated to a td of 35 - 36.25 gy are reported ( median fu 72 months ) .
the bffs for lr , ir and hr were 95.8% , 89.3% and 68.5% respectively .
concerning the group of 477 lr and ir patients ( td of 35 - 36.25 gy ) reported by katz , psa decreased from 5.3 to 0.11 ng / ml . in the aforementioned study ,
late g2 gu and gi reactions were reported in 9.1% and 4% of patients respectively . in another study ( a 6-year report )
, katz also describes late g3 adverse effects  2% and 6% for gu and gi respectively .
a rather substantial percentage of gu late adverse effects is also described by chen et al . on the basis of 204 patients ( td of 35 - 36.25 gy )  three years after treatment , 5.7% reported leaking more frequently than once a day , 6.4% required pad usage and 10.8% indicated frequent dribbling .
another large review of 1472 patients shows a very low percentage of severe acute effects after ck - based treatment of pc patients ( g2  542% gu and 027% gi ; g3  0.5% gu and 0% gi ) .
the same authors report 0 - 29% of gu g2 and 1.3% of gu g3 late effects .
report 11.5% of moderate and 8.5% of severe acute gi reactions ( diarrhea ) and only 1.5% of late gi events ( 2 years after treatment ) in the group of 269 patients irradiated to a td of 35.036.25 gy .
describe 14.5% of gu late effects in a group of 228 patients with a minimum fu of 24 months . in the group of 100 patients
describe 12% of g2 gu , 18% gi acute and 3% of g2 and 1% g3 gu late reactions .
similarly , as in metaanalyses and in the aforementioned large single center patients group , the authors also report very good results in the smaller single center series .
bernetich et al . , in a group of 142 patients irradiated to a td of 35 - 36.25 gy in 5 fractions , present a 5-year 100% success rate bffs for very low risk ( vlr ) , 91.7% for lr , 90% for ir and 86.7% for hr patients .
report a decrease in psa median from 5.4 before treatment ( 4 x 9.5 gy ) to 0.05 ng / ml 5 years later ( bffs 96.2% ) in the group of 79 lr and ir patients . in spite of a very aggressive radioablation schedule , acceptable percentages of g2 acute and g3 late gu adverse events were observed ( 10% and 6% respectively ) . a survey published by oliai et al .
( 70 patients ) showed , during a 3-year - long observation , 100% , 95% and 77.1% of bffs for lr , ir and hr patients respectively irradiated to a td of 3536.25 gy delivered in five fractions . in the
, concerning the irradiation of 57 patients ( lr , ir , hr [ 9 patients ] ) with a large prostate ( > 50 ccm ) to 3536.25 gy ( 5 fractions ) , a 2-year observation revealed a decrease in psa median from 6.5 to 0.4 ng / ml and a relatively high percentage of late gu g2 ( 49.1% ) adverse effects .
it is very difficult to compare our results ( longest observation period 26 months ) to those mentioned above  with a substantially longer fu .
moreover , considering the analysis of percentages of late ( lack of g3 , the maximum observed percentage of g2  0.7% for gi and 3.4% for gu ) and acute ( the maximum observed percentage of g3  0.6% for gi and 1% for gu ;
2.1% gi and 8.5% gu of g2 ) adverse effects observed in the analyzed group , these are even lower than those reported by other publications .
we conclude from the above results and discussion that cyberknife - based radioablation in low and intermediate risk prostate cancer patients is an effective and safe radiation modality , enabling the achievement of a very low percentage of biochemical failures ( 0.5% ) and adverse effects during a 26-month - long follow - up .
 introductionprostrate cancer ( pc ) is one of the most common malignancies and is frequently treated with an 8-week course of radiotherapy . 
 cyberknife ( ck ) based radioablation enables completion of therapy within 5 - 9 days . 
 the aim of this study is an evaluation of the effectiveness and tolerance of cyberknife - based radioablation in prostate cancer patients.material and methods200 pc patients ( 94 low risk [ lr ] , 106 intermediate risk [ ir ] ) underwent ck irradiation every other day ( fraction dose [ fd ] 7.25 gy , total dose [ td ] 36.25 gy , time 9 days ) . 
 psa varied from 1.1 to 19.5 ( median 7.7 ) and t stage from t1c to t2c . 
 the percentage of patients with androgen deprivation therapy ( adt ) , gi ( gastrointestinal ) and gu ( genitourinary ) toxicity ( eortc / rtog scale ) , and psa were checked at 1 , 4 and 8 months , and thereafter every 6 months  up to a total of 26 months  
 post-treatment.resultsthe percentage of patients without adt increased from 47.5% to 94.1% after 26 months . 
 the maximum percentage of acute g3 adverse effects was 0.6% for gi , 1% for gu and g2  
 2.1% for gi and 8.5% for gu . 
 no late g3 toxicity was observed . 
 the maximum percentage of late g2 toxicity was 0.7% for gi and 3.4% for gu . 
 median psa decreased from 7.7 to 0.1 ng / ml during fu . 
 one patient relapsed and was treated with salvage brachytherapy.conclusionswe conclude that ck - based radioablation in low and intermediate risk pc patients is an effective treatment modality enabling ott reduction and presents a very low percentage of adverse effects . 
INTRODUCTION
MATERIAL AND METHODS
RESULTS
DISCUSSION
CONCLUSIONS
CONFLICTS OF INTEREST