A 60 year old gentleman was screened for PSA. His PSA was found to be elevated at 5.2 ng/ml. A digital rectal exam did not demonstrate any abnormality and he was without palpable lesions. Next Step?
The generally accepted next step is to repeat the PSA or alternatively compare his PSA history. If his PSA history indicates this is a significant change from prior PSA values, a trans rectal ultrasound guided biopsy should be performed. If there is no PSA history, it would not be unreasonable to re-sample his PSA in a month to insure this is not an artifactually elevated PSA. If the PSA remains elevated, he should proceed to biopsy.
A transrectal ultrasound guided biopsy revealed a Gleason score 6 (3+3) adenocarcinoma. Should there be further workup?
As long as the patient is asymptomatic, it is unlikely that this disease has developed boney metastastases. Bone scan would likely be low yield in this patient.
What is his stage? T1c (biochemical detection.)
What are his treatment options?
This is a young patient with a life expectancy measured in decades, based on the information given. His PSA is low, and his risk is low. Although active surveillance may be an option, it is likely based on a Swedish study, that he will fare worse with active surveillance than with active treatment. Likewise, early androgen deprivation may decrease his PSA, but this therapy is not without side effects and morbidity, and is probably not needed at this point. Hot flashes, loss of libido, proximal motor weakness and metabolic changes may all be related to hormonal therapy. In favorable risk prostate cancers, studies have shown no advantage to adding hormones.
Pelvic nodes are at low risk for spread in low risk prostate cancer. Using either the Parton tables or the Roach formula, the risk of pelvic lymph involvement is 2/3 PSA + 10(GS-6) = 3%. Since the risk is less than 15% most institutions will not treat the lymphatics, which adds to the toxicity of treatment.
EBRT + brachytherapy is likely not needed. Brachytherapy alone in low risk cancers are reasonable and effective.
EBRT dose and fractionation has become an increasing topic of discussion. Kupellian tested mildly hypofractionated radiation at 2.5 Gy to 70 Gy showing reasonable results. UWisconsin likewise has shown no significant adverse impact either toxicity or disease control with mildy hypofractionated series. Forman (Wayne State) used neutron boosts at 1 NGy (~ 3 photon Gy equiv) x 10 fractions as a boost without significant toxicity and good local control. Some have suggested the α/β ratio for prostate cancer is lower than 1.5, however work done at the Fox Chase Cancer Center has questioned this. The ACR rates this as "May be appropriate" and NCCN rates this as an appropriate use of radiation dose/fractionation stating: "Moderately hypofractionated image-guided IMRT regimens at 2.4 - 4 Gy/fraction over 4-6 weeks have been tested in randomized trails reporting similar efficacy and toxicity to conventionally fractionated IMRT. They can be considered as an alternative to conventionally fractgionated regimens when clinically indicated." Both the NCCN and the ACR suggest that significant hypofractionation should be reserved for a clinical trial situation, but may be appropriate.
IMRT is unique in its ability to provide convex and concave isodose distributions to permit full organ coverage while sparing adjacent normal structures which allows dose escalation. Protons have similar benefits and about 10 times the cost. The ACR ranks these both as usually appropriate with scores of 8 and 7 respectively. 3DCRT is rated as may be appropriate, based on achievable dosimetry and 2D planning permits no clear sparing and is thus considered not usually appropriate.
No role has been demonstrated for chemotherapy in early prostate cancer.
For an early stage, low risk prostate cancer, the outcomes, in retrospective review, between radiation therapy alone and surgical management are identical. Prostate brachytherapy as a sole modality treatment is cost effective, efficient, and respectful of patient's time. It does carry with it the risk of surgery, and increased early dysuria and urinary symptoms. Radical prostatectomy also carries the risk of surgery and is a significant and lengthy surgery with increased risk of incontinence although that risk is considerably lower in more recent experience. External beam radiation requires no surgical intervention but does require 7 weeks of daily treatments which can be a disadvantage.
For this patient, it is reasonable to offer permanent implant brachytherapy, external beam radiation therapy or radical prostatectomy.
This case is a 69 year old healthy man with a screening PSA of 15.2. A biopsy revealed a Gleason Score 7 (4+3) adenocarcinoma, 3/6 cores positive on the right, and 1/6 cores positive on the left. Digital rectal exam reveals a lump on the right involving less than 1/2 the lobe. Staging, risk and treatment options?
The stage is cT2a. He has intermediate risk and of the intermediate risk, it is higher based on PSA > 10 ng/ml. His treatment options are:
The ACR appropriateness criteria include as usually appropriate external beam radiation alone or with brachytherapy boost score 7 and 8. External beam with 4-6 months androgen deprivation therapy (neoadjuvant, concommitant and adjuvan) is reasonable and is scored 9. Long term ADT may not be necessary and is ranked as may be appropriate. The patient above has a risk of pelvic node involvement (based on Roach) of around 20%. Some centers do treat this, others do not. There is an increased amount of Gleason grade 4 disease present, and the PSA is 15 which makes this a solid intermediate to higher intermediate risk prostate cancer. There is no demonstrated role for chemotherapy in early prostate cancer.
Radiation dose is generally in the 78-81 Gy range. The NCCN has recently amended its guidance to allow mild hypofractionation at 2.4 Gy /fraction. Generally the ACR grants a score of 8 to the 78 - 81 Gy range, and 4 to > 81 Gy (permitting over 81 Gy only if OAR dose constraints can be met. Generally the best dose is 78 - 81 Gy. Using mildly hypofractionated radiation (as per J. Forman) treating the prostate and seminal vesicles to 45-46 Gy at 1.8 Gy - 2.0 Gy/fraction followed by a boost to the prostate and proximal seminal vesicles of 32.5 Gy at 2.5 Gy/fraction yields an EQD2 dose (α/β=1.5) of 79.5 Gy compared with an EQD2 dose of 78.0 Gy. Both of these are within the ACR criteria.
An appropriate treatment for this patient is either External Beam radiation therapy alone ± lymphatics (to 45 Gy) with 2 months neoadjuvant, concomitant and adjuvant androgen deprivation therapy to a total dose to the prostate of 78.5 Gy. Alternatively, a dose of 45 Gy with external beam radiotherapy followed by a 100 Gy 103Pd brachytherapy boost implant is reasonable with good probability of cure.
This patient is a 69 year old gentleman with a long history of coronary artery disease, and diabetes with a myocardial infarct trated with PCTA/stent with stable cardiac disease. He had a screening PSA of 15.2 ng/ml. His DRE revealed a nodule on less than 1/2 of the right lobe and biopsy demonstrated 4/12 cores positive, 3 on the right and 1 on the left. His Gleason Score is 7 (4+3) What is is stage and treatment recommendations?
Since his prostate cancer is biochemically detected, his stage is cT1c. His pathologic stage is pT2c (both lobes). Treatment recommendations depend on this life expectancy. The US Social Security life expectancy tables rate his life expectancy of around 12 years subtracting about 10% for his current cardiac condition. This would be reasonable to treat as he has a reasonable change of progression in that time with significant potential morbidity and local control at 10 years is around 85%. The ACR appropriateness criteria are similar for this case as in case 2 above. We note that the ACR in both cases uses a score of 5 for hypofractionated radiation at 2.5 Gy/day to 70 Gy, as possibly appropriate. The ACR does not score observation/active surveillance or watchful waiting in any of its case studies. In this case, his life expectancy is sufficiently long that treatment is warranted. The addition of short term ADT is probably reasonable given a survival advantage and short term ADT is not likely to affect cardiac morbidity. Long term ADT (18 months per ASCO J Clin Oncol 31, 2013 (suppl 6; abstr 3)) may increase cardiac morbidity in patients that have a history of myocardial infarct, but not in those who have non-MI histories.
This case is a 70 year old man who had a 3 year history of moderate dysuria, urinary frequency and nocturia. A DRE showed a large prostate at around 60 cm3. His PSA is 36 ng/ml and a 12 core TRUS biopsy demonstrated bilateral GS 8 (4+4) adenocarcinoma in 7/12 cores. A bone scan was negative. His stage is T2c. What are his treatment options?
Note for this patient, the ACR always recommends neoadjuvant/concomitant/adjuvant androgen deprivation therapy, generally long term, per the Bolla EORTC trial. Bolla used 3 years, but UBC and North American practices generally use 2 years. With ADT, the treatment options are: EBRT + brachytherapy (Score 8), EBRT (Score 8). IMRT is strongly recommended, while surprisingly, proton beam radiotherapy is scored 6 with a notation of "perform this treatment only if the seminal vesicles can be covered and the OAR constraints can be met."
62 year old man presents with an elevated PSA of 8, is biopsied and has a Gleason Score 6 adenocarcinoma. What are his options and outcomes?
He has a low risk prostate cancer. A Gleason Score 6 and a PSA < 10 is favorable prostate cancer. He does not need a bone scan as that is low yield, absent clear evidence of metastatic disease such as boney pain of a progressive nature. A DRE should be performed and the prostate volume from the biopsy ultrasound should be obtained. At 62, I would expect, absent other information his life expectancy is at least 20 years. Therefore it is reasonable to offer treatment.
What is his stage and prognosis?
He has PSA detected prostate cancer. Assuming his DRE was normal, that is without palpable nodules or firmness, the stage is biochemical detection: T1cN0M0, Stage II. The prognosis for low risk prostate cancer, untreated is generally one of progression which cannot be directly predicted, I would expect progression in 8-10 years. Treated, he has at least a 80% probability of being disease free in 10-15 years.
What are his treatment options?
Permanent implant brachytherapy is an efficient and cost effective method of treating this prostate cancer. There is no need in low risk disease to add either hormones or external beam radiation. His risk of ECE is around 40%, SVI 8% and nodes 5%. Hormones have been advocated to shrink the prostate if it were too large to be well covered due to anatomic constraints with brachytherapy. SBRT is unproven, Hypofractionation is now gradually becoming accepted. Standard treatments are in the range of 77-80 Gy with external beam alone and 125 Gy with Pd-103 or 145 Gy with I-125 implants.
My recommendation for this patient is treat with brachytherapy, Pd-103, using pre-planned volume study or alternatively external beam radiation therapy alone to 78.5 - 79.2 Gy, treating the prostate alone. Treatment planning should use CT based planning with IV contrast to help identify the prostate and bladder interface, if external beam is to be used. His bladder should be full, and the rectum empty. Daily cone-beam CT should be used to determine the prostate position, and if necessary treatment delayed for bladder filling/rectal emptying.
The probability of success (bDFS at 10 years) is around 90-95%, regardless of the treatment modality.
A 66 year old healthy and active gentleman visited his family doctor for an annual physical examination. His PSA was 5.2 ng/ml. What would you recommend next?
At this point, we have only an elevated PSA once. Complete the physical examination and obtain a GU history including stream characteristics, flow, frequency, nocturia, interuptions, incontinence, dysuria, hematuria, erectile function and a bowel history. Redraw the PSA and do a DRE after the PSA has been drawn. If the PSA remains elevated or there is a palpable abnormality on DRE, biopsy the prostate.
His DRE is negative and his repeat PSA is 4.7 ng/ml.
Proceed to biopsy.
The biopsy returns a Gleason score 6 prostate cancer involving 2 of 12 cores on the right.
He is a stage cT1c Gleason 6 adenocarcinoma of the prostate, with a relatively low volume of disease, making this a low risk prostate cancer in a patient with a life expectancy > 10 years. His options include: active surveillance (not recommended, due to the likelihood his disease will progress after 10 years), radical prostatectomy, either robotic or retropubic, external beam radiation alone, or brachytherapy permanent implant.
What do you recommend and why?
While surgery or radiation are likely to cure this desease, there are no head to head trials saying one is better. Radiation, either external beam or brachytherapy are relatively easy to tolerate, have few side effects, and avoid surgical intervention. Although brachytherapy is a surgical procedure, it is not a lengthy procedure, and patients generally do quite well. The significant side effects include a relatively short course of dysuria, frequency, and hematuria, results are excellent and acute side effects are self-limited. Continence is preserved and erectile function is frequently, but now always preserved. This may be aided by supplemental ED drugs post implant. Alternatively external beam radiation therapy has an advantage of no invasive procedure, other than skin tattoos, relatively few and short lived side effects, which would be similar to brachytherapy but less severe and more quickly resolved.
What are the techniques and parameters of permanent implant?
A permanent implant begins with a determination of an IPSS/AUA score. I like to see a score of less than 15, as brachytherapy will at least temporarily increase the urinary symptoms and the risk of longer term urinary symptoms increases above AUA 15. A volume study will come next. This is best performed in the implant position in the dorsal lithotomy position with legs approximating the implant position to insure pubic arch clearance. The bladder should be drained prior to the procedure. The ultrasound transducer is placed into the rectum after being well coated with transducer medium and the probe is manipulated to obtain clear images of the prostate in both transverse and sagital planes. Once the prostate is well visualized the probe is advanced to the base. This is the reference plane. Using the probe stepper system, images are captured and a slice volume is drawn. The probe is advanced at 5 mm spacing toward the apex with image capture and volume identification on each slice until the apex is identified. The bladder catheter should have ultrasound contrast to help identify the urethra, or alternatively, a T2 weighted MRI can be obtained and compared with the ultrasound volume study. Once the volume study is complete, the patient is discharged. Volume study images are then used for treatment planning and determination of needle locations on perineal implant template, depth and number of seeds. Generally, around 15 - 18 needles containing between 2 and 5 - 6 seeds are each are required. For Pd-103, the seed strength is around 2 U/seed. The length of the prostate should be determined to identify the active length of the longest needles (e.g. a 5 seed needle will have an active length of 5 cm). This should be compared to the treatment plan to make sure the plan is consistent with the volume study and the generated isodose volume. If pubic arch interference is a potential concern, the transverse ultrasound volume study should be examined to determine the highest aspect of the prostate on the template. A non-penetrating (blunt) probe can be inserted into the appropriate template position and the arch palpated to insure clearance to insert the loaded needle at the time of implant.
What are the dosimetry goals?
D90 = 90% prostate volume. For Pd-103 this is 125 Gy x 0.9 = 112.5 Gy. The planning target volume is the visualized prostate plus a 3-5 mm margin to cover potential ECE.
If the patient refuses brachytherapy and surgery, what are the options?
External beam radiation therapy. EBRT is administered once daily to the prostate with a 1 cm inferior/superior margin, a 5 mm posterior margin and a 7 mm radial margin. Generally, the proximal 1 - 1.5 cm of seminal vesicles can be easily included but his risk of SVI is low, and the nodes are likewise low risk. Therefore the prostate only is adequate. The generally recommended dose is around 78 Gy. 79.2 Gy is often used.
What are the dosimetric constraints and treatment techniques used in EBRT in this case?
IMRT is generally the best modality to permit concave isodose volumes to spare rectum and bladder. Daily cone beam CT imaging guidance permits smaller volumes and margins by allowing compensation for variable bladder filling and rectal filling, or if necessary correction of bladder underfilling or rectal over-filling prior to treatment. 3D conformal potentially has the same coverage, but image guidance is requisite.
Normal tissue limits are generally:
This gentleman is a 73 year old man who presents with an initial PSA of 60 ng/ml. He is referred for biopsy with a positive DRE and a firm prostate on examination. His biopsy returns a Gleason Score 9 (5+4). What is his prognosis?
At this point what we know is this gentleman has a high risk prostate cancer. We do not know his medical comorbidities nor his stage. A full history and staging work up is necessary. That history should include a pain assessment, particularly boney pain, lower extremety edema which could identify pelvic lymphadenopathy, a comprehensive assessment of his urinary signs and symptoms, including IPSS and bowel habits and how they have changed over time. In addtion, a bone scan would be useful to identify potential bone metastases as well as an abdominal and pelvic CT. A CT is indicated because by the Roach formula, his probability of lymphatic involvement is 2/3 (60) + 10(9-6) = 70%. His prognosis also depends on his prior medical history and comorbidities, but absent significant comorbidities, prostate cancer is a significant concern. His risk at 5 years is at least 40%.
A further history and physical identifies no boney involvement, lymphatics are not enlarged by CT criteria, his AUA score is 7 and has been stable for years. A bone scan is performed and is negative. What are your recommendations?
This is now a high risk, localized prostate cancer, stage T1c. I recommend treating this with neoadjuvant, concomitant and long term androgen deprivation therapy and external beam radiation therapy. Although there is some debate on the length of neoadjuvant treatment with hormone therapy, most agree that between 2 and 4 months is reasonable. I start with a 2 month total androgen blockade, consisting of bicalutamide 50 mg/day for 2 weeks and leuprolide 22.5 mg/im 2 months prior to initiation of radiation. His ADT should continue for a minimum of 18 months, EORTC/Bolla used 3 years, and recent data published by ASCO in 2013 demonstrated equivalence of 18 and 36 months, but many are using 24 months. I recommend in this situation treatment of the prostate, seminal vesicles (risk of involvement is 60 + 10(9-6)=90% (Roach)), and pelvic lymphatics, even if they are not clinically involved. This is somewhat controversial, but in older treatment techniques, a common theme was to treat the pelvis to 45 Gy using a 4 to 6 field technique and then reduce to the prostate using 3d-Conformal methods for a final boost above 45 Gy. Therefore in these high risk cases, I think it is very reasonable to treat the nodes and with IMRT is its possible to treat them reasonably safely and minimize the bowel doses. If protecting the bowel is not possible, the bowel tolerance limits should be respected as these patients have a longer life expectancy, despite the prostate cancer. The EBRT dose to the prostate and at least the proximal seminal vesicles is 81 Gy.
What will his follow up be?
An initial PSA drawn about 3 months post treatment, then every 6 months thereafter with DRE.
His PSA drops post treatment at 6 months to 3 ng/ml. Does this change your recommendations?
No.
He returns for follow up at 3 years, has done well and is off hormones for about a year. His PSA is stable at 3 ng/ml for the past year. He has no bone pain or other complaints. Any management changes?
No.
He returns a year later with a complaint of low back pain he noticed while chopping wood. His PSA was redrawn and found to be 3.2 ng/ml. Any managment changes?
His back pain could come from completely non-prostate or mechanical causes. His PSA does not meet criteria for biochemical failure at this point, he is off ADT, but I think the etiology needs to be determined. First I do a DRE and second, either a bone scan or a CT of the spine. An MRI would be reasonable also, if readily available but a CT is more economical and usually can be done quicker. The physical exam and history would pay close attention to any focal neurological deficits, including bowel/blader habit changes, numbness, tingling or weakness. I would also assess for other cancer risk factors including tobacco, alcohol and do a comprehensive physical examination to seek other sources of metastases.
His DRE demonstrates a palpable nodule on the left. The bone scan shows multiple osseous metastases and the CT of the spine demonstrates a osteoblastic lesion in L1 vertebral body. He has no other pain despite uptake throughout the skeleton, his bowel and bladder functions are normal and unchanged. He hasn't noticed any neurologic changes and his neurological exam is normal. What next?
Despite his low PSA he has clear evidence of metastatic disease. It would not be unreasonable to get a biopsy at this point, or alternatively a PET/CT to identify other potential malignancies. If these are negative and the biopsy is consistent with prostate cancer, or unattainable, I would recommend palliative treatment to the bone met, 30 Gy in 10 fractions, and refer for bisphosphonate therapy, with dental evaluation prior to initiation of therapy. He is not, yet, a candidate for Ra-223, although it is likely he will be sooner than later. He is a candidate for permanent androgen suppression and I would restart him on total androgen blockade, followed by either surgical castration or leuprolide, as is his pleasure, castration being the most cost effective, but least emotionally desirable course.
When would he be a candidate for Ra-223?
At present, the indications are hormone refractory disease, multiple symptomatic bone metastases. Ra-223 is given at 50 kBq/kg once per month for 6 months. His platelets should initially be > 100 and white count > 1.5, Hb ≥ 10. I prefer not to let the platelets drop below 100 and the subsequent white counts drop below 1.0. There is a demonstrated survival advantage for Ra-223.
An 87 year old gentleman presented to his family doctor with a complaint of increasing urinary obstructive symptoms. A DRE was performed and a firm nodule covering the right half of the prostate was palpated. He otherwise has no complaints and states longevity is in his family, his mother died at 102 and his father at 101. He states his grandfather died young at 96 after a farm accident. His grandmother died in childbirth at age 36. His PSA was drawn and found to be 12 ng/ml. What do you want to do next?
At this point, he is likely to have prostate cancer and a life expectancy by social security tables of about 6 years. Given his family history, his appraent absence of medical comorbidities, and symptoms, it would would be reasonable to pursue further intervention. A TURP would likely reveal a prostate cancer and solve his urinary symptoms, but would potentially preclude a brachytherapy implant, if needed and desirable. ADT would likely cover him and control his prostate cancer, once a tissue diagnosis is confirmed for as long as needed, but with a risk of the development of metastatic disease. It would also be reasonable to pursue biopsy to confirm disease which I think is likely and treatment to a.) control his prostate symptoms and b.) treat his prostate cancer. I recommend consideration of TRUS biopsy.
His biopsy confirms 8/12 cores Gleason 8 prostate cancer (4+4) on the right. What do you recommend now?
Given his excellent health and family history and his histopathologic high risk prostate cancer, there are two recommendations available. Repeat the PSA and obtain a testosterone level in a month to see its doubling time/velocity or alternatively proceed to treatment. Radiation alone has a reasonable probability of controlling both symptoms and disease for 4-5 years. Alternatively, ADT alone can also control both. Ultimately, this treatment will depend more on patient preferences and willingness to tolerate treatment than anything. If he wishes treatment, it is reasonable to offer radiation alone, or with ADT of about 18-24 months or long term ADT alone. The advantage to treating now is that it is likely to delay development of bone metastases in the future.
This is a 66 year old with a biopsy confirmed prostate cancer, Gleason Score 6 PSA 9.2 cT2a disease. What additional workup do you recommend?
History and physical with focus on urinary signs and symptoms, IPSS score and any boney pain complaints.
Would you get a bone scan?
Not without a good reason, such as a specific bone complaint unlikely to be arthritic and certainly not without a comprehensive assessment of possible old trauma. His risk of bone mets is low at this point and the concern would be old trauma being mistaken for a metastases.
What are his treatment options?
What are his medical comorbidities?
None.
He is young, a life expectancy greater than 10 years and no significant morbidities. I would recommend treatment in this situation. His prostate cancer is low risk. With treatment he has about a 90+ probability of no further problems with treatment of curative intent. In this situation, he has several options, surgery either retropubic or robotic prostatectomy or radiation therapy, either brachytherapy or external beam radiation therapy.
He elects radiaiton therapy. What do you recommend?
He is a good candidate for either external beam radiation or brachytherapy, assuming his IPSS score is ≤ 15. The advantages of EBRT are no invasive procedures, the advantages of brachytherapy are: one day treatment at the cost of significantly greater, but transient and treatable obstructive urinary symptoms.
He elects external beam treatment. Please describe your procedure.
We use IMRT with image guided radiotherapy using cone beam ct daily. We treat with bladder full and rectum empty. We do not do any special bowel preparation but do try to schedule the simulation CT at about the same time of day as the planned treatment to try to minimize rectal variability. A vac-lock immobilization is constructed with the patient in the supine position, arms on chest to immobilize the pelvis and legs in the treatment position. The patient is positioned in a large bore CT scanner and a scout film is obtained to verify straightness of setup, evenness of the pelvis and any rotation in axial, coronal or sagital planes are corrected as best acheivable. Then a CT is obtained with IV contrast if possible using 1.25 to 2.5 mm cuts covering the prostate and adequate tissue above and below to permit good dosimetry, generally sacrum to below the obturators. Once this is done, an isocenter is identified, marks are placed on the patient using in-room lasers and the images are sent to the treatment planning system. The prostate and at least the proximal seminal vesicles are contoured, along with the bladder, rectum and the bowel bag and femoral heads. The femoral heads are contoured to include the femoral neck. Once this is complete inverse planning is used to generate the desired dosimetry. The prostate is treated to 78 Gy. Nodes are not treated as he is low risk and the risk of nodes by the Roach formula is 2/3(9)+0 or about 6% which is below a cutoff of about 15%. Organs at risk include femoral heads (limited to 45 Gy), Rectum, limited as follows: 75 Gy to ≤ 15%, 70 Gy to ≤ 25%, 65 Gy to ≤ 35%, 60 Gy to ≤ 50%, Bladder 80 Gy to ≤ 15%, 75 Gy to ≤ 25%, 70 Gy to ≤ 35% and 65 Gy yo ≤ 50%.
How do you define your prostate volume?
The prostate is the visualized prostate generally starting at mid prostate and drawing to the prostate bladder junction, superiorly, then proceding inferiorly to the prostate apex at the urogenital diaphragm. 3D orthogonal views are essential to proper drawing of the prostate, to allow determination of the penile bulb, UG diaphragm, and prostating apex. An MRI T2 image may be helpful, provided the MRI goemetry is fusable. This constructs the GTV/CTV. The PTV is an expansion on this of 7 mm radially, except at the rectal boundary where 5 mm is used, and between 7 mm and 1 cm inferiorly and superiorly. If possible the penile bulb should be kept less than 52 Gy.
A 65 year old man with a biopsy confirmed prostate cancer, Gleason Score 6, PSA 9.1 presents as above requesting permanent implant brachytherapy, staged T1c.
Obtain a history of medical comorbidities, and specific urinary symptoms, including IPSS. Assuming his IPSS is less than 15 and he has no bone pain history he may be a good candidate. He should proceed to an ultrasound volume study. Assuming his volume is such that he can receive an implant, without pubic arch interference, this is an excellent and cost effective treatment for low risk prostate cancer.
What dose and treatment technique will you use?
A volume study should be obtained in the dorsal lithotomy position. If his prostate is unusually large, an assessment should be made to determine whether there will be pubic arch interference with a transperineal implant. If so, an adjustment to an extended dorsal lithotomy position may be required. If the implant cannot be achieved, then he should proceed to external beam therapy or prostatectomy. However, in most situations, an implant can be acheived, or alternatively, hormones can be given to shrink the prostate and a repeat volume study performed. Once the volume study has been obtained, treatment planning should take place and an implant scheduled.
The prostate volume is planned with a peripheral loaded technique to reduce the dose to the urethra, covering the prostate plus a 3-5 mm margin in all dimensions except posteriorly (rectal wall interface). Generally 15-18 needles containing between 3 and 5 seeds is adequate. The activity of Pd-103 is around 2 U/seed and we use linked seeds to minimize the cranial-caudal displacement. The active length of the needles is a function of the cranial-caudal length of the prostate, with a typical 4 seed needle having an active length of 8 cm. Once the implant is planned, and the the patient is ready, the implant is performed.
The patient is brought to the OR, identified, and spinal anesthesia is placed. He is prepped and draped, and placed in boots in the dorsal lithotomy position to replicate as much as practical, the volume study position and a foley catheter is placed in the bladder and the bladder drained. The scrotum is moved away from the peritoneum and the ultrasound probe which has been prepped with transducer medium is placed in the rectum. The prostate is identified and the stepper system is moved into place. The stepper system is then adjusted to provide good geometry and the prostate base and apex are identified and compared with the preplanned study. Assuming good conformality, the stepper is then zeroed at the base and the implant proceeds. If there is not good conformality, then the plan and the obtained prostate studies are examined to determine if modification of source loadings can be achieved to obtain a good implant. If so, the implant proceeds, otherwise it must be abandoned and replanned. Finally, stablization needles are placed in unused locations on the template and the implant proceeds. I generally implant longest active length needles placed at the base first, starting top and proceeding symmetrically laterally. With stabilization needles in place, this minimizes initial torque displacement and with linked strands provides additional stability. The needles should be slowly withdrawn to prevent hydraulic force from displacing the seeds distally. Then working medial to laterally and top to bottom I complete the longest needles at the base. I then proceed to the next shorter needles, if any at the base until all base needles are implanted. Depth is checked with each drop using either sagital ultrasound or flouroscopy. Additionally, I recheck the base and apex at each move of the ultrasound to insure that the prostae has not shifted. I then proceed to the next preplanned step back, in similar fashion. Once the implant is complete, it is surveyed with ultrasound and flouroscopy to detect any obvious gaps in coverage. Generally one or two spare needles containing seeds are ordered in case there is a need to fill a gap in coverage.
Once the final needle is implanted, the ultrasound is removed, the urologist then performs cystoscopy to search for seeds in the bladder or urethra. Any such seeds are removed with a grasper, and twisted 90 degrees without pulling on the strand. Generally the seed detaches easily and is removed from the bladder. The patient is discharged home with flomax, cipro x 3 days and Viagara as soon as he is able to urinate.
We do a post implant CT volume study at 1 month or so after implant to determine the quality of implant. Our goal is D90 (dose greater than 90% or about 112.5 Gy) to 90% or greater of the prostate. We try to keep the rectum dose of 2 ml < 100%, the urethra < 150% (187.5 Gy).
This patient is a healthy mid 70s gentleman with a Gleason Score 6 prostate cancer, T1c, excellent health, no pain with a PSA of 17 ng/ml. What are the treatment options and risk factors?
He has an intermediate risk prostate cancer due to PSA 10 - 20 ng/ml. His risk for ECE is 3/2 PSA + 10(GS-3) = 55%, SVI is PSA + 10(GS-6) = 17% and LN is 2/3 PSA + 10(GS-6)= 12%. His treatment options are surgery with a risk of requiring post-op radiation, external beam radiation therapy. My recommendation would be radiation therapy for intermediate risk prostate cancer, with neoadjuvant, concomitant and short term adjuvant hormonal therapy.
What specifically would you treat and to what dose?
Since is risk of lymphatic involvement is less than 15%, treatment of the nodes is controversial and not without toxicity, even with IMRT. I would treat the prostate and at least the proximal 1.5 - 2 cm of seminal vesicles to full dose of 78.5 - 79.2 Gy with 2 months of neoadjuvant hormone therapy, concomitant and 2 months of adjuvant hormone therapy. The more distal seminal vesicles are usually included to a lower dose, if the rectum, bladder constraints can be well met, which usually they can be. Rectal constraints are: 75 Gy to ≤ 15%, 70 Gy to ≤ 25%, 65 Gy to ≤ 35%, 60 Gy to ≤ 50%. Bladder constraints are 80 Gy to ≤ 15%, 75 Gy to ≤ 25%, 70 Gy to ≤ 35% and 65 Gy to ≤ 50%. Simulation is performed in the supine position with a vac-lock to immobilize the legs and lower pelvis, markers are placed on the skin, the patient is simulated and treated bladder full and with rectum as empty as reasonable, simmed at the same time as is proposed treatment start time, assuming he has regular bowel movements to attempt to have a stable rectum during treatment. CBCT is used to correct prostate position changes prior to each daily treatment.
What is his prognosis?
His prognosis is reasonably good. 8-10 year BCF free survival is around 80-85%. BCF is defined for intact prostates as nadir + 2.0 ng/ml. Urologists object to this definition as a double standard since the definition of post-prostatectomy BCF is two consecutive rises or failure to drop to undetectable levels.
This is a 59 year old in excellent health who had a PSA of 25, Gleason Score 8 with known extraprostatic extension, stage T3a. What is his risk? And additional workup?
He has high risk prostate cancer by PSA, Gleason Score and stage. Further workup would include a detailed H & P with focus on bone pain and urinary symptoms (IPSS). A bone scan is indicated as well as a CT of the abdomen and pelvis. His lymph node risk (Roach) is 2/3 (25) + 10(8-6)=36%
How would you recommend treating this?
External beam radiation therapy with neoadjuvant, concomitant and adjuvant androgen deprivation therapy for a minimum of 18 months. I would start by 2 months neoadjuvant androgen deprivation with a combination of Leuprolide 22.5 mg injection together with bicalutamide 50 mg/day PO. At six weeks, I would have him return for simulation at a time close to his preferred treatment time, bladder full and rectum as empty as practical. Simulation would be performed in the supine position arms on chest, vac lock to immobilize the legs and lower torso, radio-opaque markers on the skin near the proposed anatomic isocenter. CT scout films would be taken with IV constrast (delayed to enhance the bladder) to insure the setup is corrected for any rotation, tilt or roll. Then CT images of the pelvis from about L4/L5 to below the penile bulb would be obtained at 2.0 mm cuts. The isocenter markers would be inspected for appropriateness and if necessary shifted before the patient's skin is marked, and the patient rescanned.
Once images are taken the prostate would be contoured with expansions for visualized extracapsular extension. In this case, it would not be unreasonable to obtain an MRI in the treatment planning position to fuse with the CT to identify the extent of extracapsular extension. The GTV/CTV is the prostate proper and the extensions of disease seen on imaging. I contour the seminal vesicles separately. the lymphatics likewise are contoured from the iliac bifurcation through the obturators at the level of the top of the femoral heads. If there are any enlarged nodes they will receive a boost, if safe. Otherwise, the nodes, prostate and full seminal vesicles are treated to 45 Gy at 1.8 Gy/fraction. The prostate is then boosted to an additional dose of 79.2 Gy including, if safe, the proximal or imaging involved seminal vesicles whichever is greater. The prostate PTV is constructed by a margin of 0.5 cm posteriorly, 0.7 - 1.0 cm radially, except at the prostate rectal interface, 1 cm superiorly and inferiorly. If at all possible the penile bulb is kept below about 52 Gy, the rectum dose constraints are: 75 Gy to ≤ 15%, 70 Gy to ≤ 25%, 65 Gy to ≤ 35%, 60 Gy to ≤ 50%. The bladder is kept to 80 Gy ≤ 15%, 75 Gy to ≤ 25%, 70 Gy to ≤ 35%, 65 Gy to ≤ 50%. Femoral heads are kept below 45 Gy and bowel is kept below 45 Gy. Bowel is contoured using the "bowel bag" approach rather than individual loops of bowel.
What is his prognosis?
He has a 5 year 70% biochemical freedom from failure, dropping to about 65% at 10 years or so. We can generally buy another 4-5 years with permanent ADT, but eventually he will develop hormone refractory disease. His areas at highest risk for recurrence distantly are bone and lymphatics. If he develops bone disease, palliative radiation usually 3 Gy to 30 Gy provides excellent palliation. By then there will be likely other options available as well.
He is now 11 years post original diagnosis. He has a rising PSA with a 3 month doubling time, he has been treated for painful bone metastases twice in the femur and the T-spine, he has multiple bone metastases on bone scan but no extraosseous disease. He is symptomatic from his bone mets, but there is no risk of pathologic fractures. What are his options?
Abaritarone is a reasonable choice or Ra-223 or both. Ra-223 will require limited or no lymphatic disease and multiple symptomatic osseous sites, which he has. There is a survival advantage with both of these treatments. Ra-223 unlike its earlier isotope cousins has far less hematotoxicity and does have a survival advantage. I would recommend Ra-223 at 50 kBq/kg provided his Hb is ≥ 10, White Count is ≥ 1.5 and platelets above 100. The treatment interval is 1/month x 6 treatments with counts drawn prior to scheduling the next dose, preferably after nadir time of about 3 weeks. After that, then chemotherapy.
This is a 63 year man who had a Gleason Score 7 (4+3) adenocarcinoma of the prostate. His pre-treatment PSA was 19.7, and his biopsy showed 9/12 cores positive involving between 25% and 100% of the core lengths. He had a bone scan which was negative. His original DRE was not reported. His PSA in the immediate post-prostatectomy period dropped to undetectable levels at 1 month, but by 6 months had risen to 0.18 ng/ml and by 9 months to 0.22 ng/ml. What would you like to do?
Here an H & P is essential. Does he have any new onset symptoms indicative of metastatic disease? Is the bed of the prostate free of nodularity? Next, a review of the pathology including margins and areas of disease. His original stage was not disclosed except he had a biopsy stage of pT2c. No mention of nodes sampled was made, nor was there any mention of pelvic imaging or pre-prostatectomy bone scan. An additional item of interest is the prostate volume.
His prostate volume was 35 cm3. He had positive margins at both the apex and bladder neck. There was seminal vesicle invasion and perineural invasion. His surgery was nerve sparing. Disease was predominantly on the right, involving more than 1/2 the prostate on that side but did extend to nearly all the left side as well. 3 LN were negative. A CT did not disclose any frank disease or pathologically enlarged lymph nodes and the bone scan was negative. The DRE however did demonstrate a palpable nodule in the lower prostatic fossa about 5 mm in diameter.
At this point, we have no evidence of distant recurrence or skeletal metastases. I would recommend biopsy of the nodule and I think it is likely to be tumor for two reasons: 1. his post prostatectomy PSA dropped to undetectable levels and then began rising, and 2. it is either residual prostate tissue or neoplastic tissue. If he refuses biopsy, I would recommend treatment anyway, but if it was biopsy confirmed I would probably recommend either a small boost to that area or concomitant ADT or both. I realize the data is not yet available on ADT, but if there is residual tissue in there, I think it reasonable to infer from intact prostate data that ADT will likely be helpful.
The biopsy is positive for GS 8 adenocarcinoma of the prostate. CT of the pelvis demonstrates no pathologically enlarged nodes. How would you treat?
His original nodal risk (Roach) is 2/3(20)+10(8-6)=33%. I would use IMRT to treat the pelvic nodes to 46 Gy and boost the bed of the prostate and any residual seminal vesicles, the bladder neck and uretheral anastomosis to 66 Gy. The prostate bed and nodule itself would be treated to 68-70 Gy using sequential boosts, provided the bowel and rectum can be protected. These should be treated with IMRT using CT based treatment planning.