Thursday, January 22, 2015

Prostate Cancer salvage therapy - radiation - where, when and how much - role of ADT or imuno

Cancer is Back -What to do?

Best strategy depends on your numbers. The MSK tool provides some guidance:

Prostate Cancer: Salvage Radiation Therapy | Memorial Sloan Kettering Cancer Center
Our salvage radiation therapy nomogram predicts whether a recurrence of prostate cancer after radical prostatectomy can be treated successfully with salvage radiation therapy (external-beam radiation given after the prostate cancer returns). It calculates the probability that the cancer will be controlled and PSA level undetectable six years after salvage therapy. You can use this nomogram for applicable results if your post-radical prostatectomy serum PSA level was at first undetectable (less than 0.05 ng/mL) and then rose steadily, indicating a recurrence. more…
Results produced by this tool are based on studies conducted at large research institutions with physicians who perform a high volume of prostate cancer procedures. All results must be understood in the context of each patient’s specific treatment plan. Patients and caregivers using this tool should discuss the result with the patient’s physician.
Predicting the Outcome of Salvage Radiation Therapy for Recurrent Prostate Cancer After Radical Prostatectomy

Prostate Cancer Treatment (PDQ®) - National Cancer Institute

Where is it? Where to fire radiation? 

After primary treatment for Prostate Cancer, rising PSA tells you it's come back, but in order to kill the cancer cells with minimal collateral damage, it would be good to know where they are instead of firing blind.

DCE-MRI

Example of a patient classified as true positive.
A contrast enhancing lesion was detected on pre-RT DCE-MRI
(a) (arrowhead), with completely morphologic
response on the post-RT DCE-MRI (b).
Radiation Oncology | Full text | Detection of local recurrent prostate cancer after radical prostatectomy in terms of salvage radiotherapy using dynamic contrast enhanced-MRI without endorectal coil

DCE-MRI without endorectal coil may detect local recurrent PC at low PSA levels with acceptable accuracy. All false negative DCE-MRI scans were detected using a PSA cut-off of ≥0.54 ng/mL. This image modality may therefore be considered in radiation oncology as a tool to more accurately define the gross tumor volume to increase the efficacy of salvage radiation treatment and to decrease radiation side effects.

C11-Acetate/Choline PET/CT

 PET Imaging of Prostate Cancer Using 11C-Acetate
Biochemical evidence of prostate cancer recurrence after radical prostatectomy or radiation treatment, frequently defined as a serum PSA level of 0.2 ng/ml, precedes the clinical manifestations of recurrent disease. Once metastatic disease develops the prognosis is poor with an overall patient survival of 5 years 35. In patients with locally recurrent disease salvage radiation therapy can improve patient survival 6. The main diagnostic challenge is therefore to detect and localize early cancer recurrence. Several studies evaluated the relationship between serum PSA levels and detection of prostate cancer recurrence with 11C-acetate PET. In one study of 25 patients, the degree of 11C-acetate uptake (SUV) correlated with serum PSA levels 36.
In an early trial 37 of patients with suspected recurrence (based on serum PSA measurements) trans-rectal ultrasound followed by biopsy served as gold standard for 11C-acetate imaging findings. PET was true positive for disease recurrence in 15/18 patients with biopsy proven recurrence and true negative in all 13 patients without recurrent disease (sensitivity and specificity of 83 and 100%, respectively). In this study PET was positive in 4 of 5 patients with biopsy proven cancers and serum PSA levels of <2 ml.="" ng="" p="">

In summary recurrent prostate cancer can be detected with 11C-acetate but since detectability appears to be correlated with serum PSA levels, detectability is limited in patients with serum PSA levels below 3 ng/ml.

The Utility of C-11 Choline PET/CT for Prostate Cancer: Improving Detection of Locoregional and Metastatic Disease | Genitourinary Cancers Symposium
The potential utility of C-11 choline PET/CT for localizing prostate cancer has been demonstrated in multiple studies. Currently there is no other FDA-approved imaging option with comparable sensitivity and specificity, but future studies will help to further define its main applications and refine patient selection.



 

How Much and How Long? 

Ok, you know where it is. How many Grays of Radiation over how many treatment times is needed to be effective with limited damage. Can you tie imagery into the radiation plan to stay on target.

Radiation Oncology |Full text | Dose-escalated salvage radiotherapy after radical prostatectomy in high risk prostate cancer patients without hormone therapy: outcome, prognostic factors and late toxicity
Dose-escalated SRT achieves high biochemical control. The data strongly support the application of at least 70 Gy rather than 66 Gy. They do not prove positive effects of doses >70 Gy but do not disprove them as these doses were only applied to an unfavorable patients selection.

Can salvage radiation therapy be safely and effectively completed in less time? | THE "NEW" PROSTATE CANCER INFOLINK
Salvage or adjuvant external beam radiation therapy for prostate cancer is usually a protracted affair, more so since we learned that a total dose of about 64 Gy to 70 Gy was needed to be effective in the salvage setting. At the typical rate of 1.8 Gy to 2.0 Gy per treatment, it takes approximately 35 treatments over the course of 7 weeks to complete. This is very costly and extremely time consuming. Can it be accomplished in less time without adding side effects or rendering it less effective?
Using fewer treatments for radiation therapy is called hypofractionation. Stereotactic body radiation therapy or SBRT is on the fastest end of the hypofractionation spectrum. It is accomplished in a blazingly fast five treatments. With its pinpoint accuracy, many radiation oncologists are using it for primary treatment at doses up to 8 Gy per treatment. But that is also its drawback for salvage therapy – it may be too accurate. Because we don’t know exactly where in the prostate bed the cancer may be hiding, IMRT or 3D-CRT – radiation technologies with less abruptly ending margins – have been traditionally preferred. There has also been some concern that blasting the anastomosis (the place where the urethra has been cut and re-attached, and where most recurrences occur) with high intensity X-rays may be too much for the fragile tissue.

How do cancer cells that only absorb a sub-lethal dose of radiation get destroyed by the immune system? | THE "NEW" PROSTATE CANCER INFOLINK
A recent commentary on combined radiation and immune therapy included the following statement without further explanation: “Radiation-modified cancer cells that escaped direct annihilation become more immune-susceptible too.” This effect is known as “immune modulation” and has previously been observed in test tube and mouse studies in castrate-resistant prostate cancer cells. A new study by Gameiro et al. of NCI/NIH extends the observation to the kind of cells responsible for hormone-sensitive bone metastases, and provides a biochemical mechanism for the observed effect. Because radiation alone only results in weak immune modulation, it is hoped that by understanding the precise mechanism responsible for radiation-induced killing of cancer cells by cytotoxic T cells, called “immunogenic cell death”, we can tailor therapies given along with radiation to enhance and sustain the immune modulation effect.





ADT

Cancer Cells usually grow from testosterone hormone. Do you need hormone therapy to supplement radiation, and what kind of combined side effects can you expect.




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