External beam radiation for prostate cancer

Prostate cancer radiation improved by high-precision image guided markers placed in the prostate gland which is integrated into the treatment machine with delivery of the intended dose within 2 mm of specified location.

Older patients with localized prostate cancer and life expectancy of more than 10 years without significant risk factors for radiation toxicity most likely to benefit from radiation therapy.

Intensity modulated radiotherapy has further enhanced treatment allowing modulation of the intensity of the dose in each of many pixels within each beam allowing for steep gradients of intensity within the prostate and between the prostate and adjacent organs.

May be combined with brachytherapy and follow a radical prostatectomy in men with high risk pathology and persistent or recurrent PSA as adjuvant or salvage therapy.

A minimum dose of 70 Gy is dose recommended for patients with lowest-risk tumors and at least 75-80 Gy for other patients.

Freedom from failure rates of 69% and 79% at 5 years for 70 Gy and 72 Gy, respectively (Pollack).

Freedom from failure rates 53% and 55% at 8 years for patients treated with 60 -70 Gy vs greater than 70 Gy, respectively (Kuban).

With the use of high dose treatment vs. conventional dose therapy patients more likely to be free of increasing PSA levels and less likely to have locally persistent disease at 5 years.

In the RTOG 0126 study of high-dose radiotherapy (79.2-Gy) versus standard dose of 70.2 Gy in patients with stage II localized prostate cancer found at high dose radiotherapy improve rates of local tumor control and distant metastases, but did not improve overall survival at 7 years.

In the above study 5-year-overall survival rates were 88% and 89% in the high dose and standard radiotherapy arms, respectively, and 10 year overall survival rates was 67% and 66% in the high dose and standard arms, respectively (Michalski JM et al).

The entire prostate is the target for prostate radiation for cancer is the lesion is often multifocal and not always fully identified.

Median time to resolution of spectroscopic abnormalities as assessed by endorectal magnetic resonance imaging and spectroscopy is 32.2 months, compared to 24.8 months with permanent prostate seed implantation (Pickett).

Adjuvant radiation following prostatectomy is associated with risks as likely sites of residual disease such as the bladder neck, retrovesical space and vesicourethral anastomosis all require treatment: this will result in temporary urinary frequency, urgency bowel irritability and incontinence.

The rate of sexual potency after adjuvant radiation is lower than after surgey alone.

The most severe acute effects are an increase in bowel problems.

Associated with erectile dysfunction in 2-34% of cases in patients treated wirh radiation for prostate cancer.

When the estimated risk for microscopic spread to seminal vesicles, pelvic lymph nodes, or both exceeds an estimated 15% these sites are included in the radiation field.

Risk of adverse affects of radiation related to proximity of prostate to bladder and rectum as well associated variations in the patient’s position during treatment and movement of the prostate between sessions.

With use of conformal radiation techniques dose escalations to more than 79 Gy can be safely achieved with small increases in rectal toxicity without increase in genitourinary morbidity.

In a National Cancer Institute Surveillance, Epidemiology and End Results (SEER) program reviewing 104,577 patients with nonmetastatic prostate cancer between 1973 and 1990, representing about of 14% of U.S. population of such patients, had a 34% reduction in deaths when treated by external beam radiation compared to patients not treated, and a 43% reduction in deaths from prostate cancer.

The addition of 6 months of androgen suppression therapy to external radiation therapy increases overall survival in localized but unfavorable risk prostate cancer.

For patients with intermediate or risk local disease concurrent androgen deprivation therapy improves overall survival compared to radiation alone.

Among patients with locally advanced disease phase 3 trials showed that when androgen deprivation treatment added to radiotherapy long-term treatment, of two years or greater, improved overall survival but also increases erectile dysfunction and the rate of myocardial infarction.

Short-term androgen deprivation therapy (phase 3 clinical trials) for four months before and during radiation significantly improves local control and disease free survival among patients with bulky stage to T2c-T4 tumors.

In the SPCG-7 study 875 patients with locally advanced prostate cancer were randomized to total androgen blockade followed by radiotherapy and continuous anti-androgen therapy or hormone treatment alone: At 7.6 years of follow-up there was a 12% reduction in prostate cancer specific mortality in the radiotherapy arm versus the control group, with the combination therapy more than doubling the 10 year survival rate.

RTOG 94-08 study 1,979 patients woth T1b, to T2B prostate ca and aPSA level of 20 ng or lowere randomized to hormonal therapy two months prior to and two months during radiation , or radiation alone: 51% of patients with hormonal therapy plus RT and 46% of patients with RT alone were alive at 12 years-indicating that patients with intermediate risk prostate cancer should receive adjuvant hormonal therapy (Jones CU)

In the above study short-term hormonal therapy given prior to and during RT increased chance of living compared to RT alone from 57% to 62% and increased the 10 year disease specific survival rate from 92% to 96% (Jones CU).

At two years following treatment 843 men underwent repeat prostate biopsy in the above study and those treated with hormonal therapy and RT showed no cancer in 78% of biopsies while the RT group alone only 60% were cancer free (Jones CU).

In the above study men with low-risk prostate cancer, hormonal therapy did not provide benefit.

For 635 patients who underwent radical prostatectomies for T1 and T2 disease with PSA relapse, only, were randomized to local salvage radiation alone or in combination with hormonal therapy-397 men did not receive salvage radiation , 160 received salvage radiation alone and 78 received salvage radiation plus hormonal therapy: salvage radiotherapy for biochemical relapse at a median follow-up of 6 years resulted in a threefold lesser risk for prostate associated deaths, hormonal therapy did not lead to significantly longer prostate cancer specific survival associated with salvage radiotherapy, survival benefit with salvage radiation benefit was limited to men with PSA doubling time of less than 6 months and if salvage radiotherapy was initiated more than 2 years after recurrence was not associated with survival prostate cancer specific survival, and finally if PSA did not become undetectable after salvage radiotherapy there was no benefit (Dreicer).

Salvage radiation defined as radiation treatment for suspected recurrent malignant disease after a period of observation after prostatectomy.

This is to be distinguished from adjuvant radiation treatment directly after prostatectomy in patients potentially without residual disese and with an undetectable PSA.

Randomized studies for pT3 or pT2 disease revealed that adjuvant radiation after radical prostatectomy reduces risk of local relapse and biochemical progression by approximately 20% at 5 years (Bolla,M, Thompson IM).

Adjuvant radiotherapy after radical prostatectomy in patients with pT3mN0 tumors randomly assigned to wait and see therapy or radiation revealed higher biochemical progression free survival after 5 years with undetectable PSA (Wiegel T).

Adjuvant radiation for prostate cancer shows an advantage in freedom from biochemical failure for immediate postoperative radiation rather than for salvage radiation in the above study, and in a second study with longer follow-up indicated a reduction in clinical failure (Bolla M et al), and a third study with more than 15 years of follow-up showed improvement in survival rates ( Thompson IM et al).

Adjuvant radiation for prostate cancer for patients with stage pT3 disease, to prevent one death at 10 years, 12 patients will needed to be treated.

Randomized trials have shown adjuvant radiation therapy provides benefit, whereas salvage radiation therapy evidence is lacking (Parker C).

Palliative radiotherapy is used to improve symptoms of advanced metastatic prostate cancer.

Palliative radiotherapy will prostate cancer may be required for dramatic metastatic disease to lymph nodes, bones or less commonly for local symptoms such as mechanical obstruction of the bladder, rectum, or for hematuria and pain.

Meta-analyses demonstrate no difference in clinical response with a single dose of 8-Gy compared with more fractionated radiation schedules such as 20 Gy in 5 fractions, 24 Gy in 6 fractions or 30 Gy in 10 fractions.

For patient to need a second course of radiation for osseous pain, another single dose or 5 doses, are associated with equivalent and meaningful pain responses.

For metastatic spinal cord compression from prostate cancer, steroids and surgery followed by radiation would be standard therapy.

In patients with metastatic spinal cord compression who are not surgical candidates 30 Gy in 10 fractions is standard therapy.

The prognosis for patients with metastatic spinal cord disease is grouped based on 5 factors: Ambulatory or not status, performance status, other bone metastases, visceral metastasis, and interval from cancer diagnosis radiotherapy.

Persistent prostate cancer following radiation therapy results in cancer-related death in at least 27% of patients within 5 years of exhibiting a rising serum prostate-specific antigen (PSA) level.

Approximately 90% of patients who achieve a PSA nadir below 0.5 ng/mL within 2 years of external beam radiation remain free of recurrent disease.

Disease progression following salvage radical prostatectomy is lowest when the disease is treated at a serum PSA below 10 ng/mL.

Severe radiation effects with both nuclear and cytoplasmic alterations are seen in many prostatic biopsies and may confound the diagnosis of residual cancer.

67% of patients with adenocarcinoma on a biopsy at 12 months following radiation will convert to negative histology by 16–29 months.

Incidence of positive biopsy results after primary radiation therapy appears to be higher for external beam radiation than for brachytherapy.

Salvage radical prostatectomy is capable of eradicating the local lesion and providing long-term disease-specific survival, but it is complicated by the tissue effects of radiation and is associated with significant side effects, such as universal erectile dysfunction.

Prostatic cryoablation, and salvage brachytherapy may successfully control local disease within the prostate in some patients.

Studies suggest a significant association between reduced risk of death and treatment of node positive prostate cancer patients using both external beam radiation treatment of the prostate and pelvic lymph nodes and androgen deprivation therapy compared with androgen deprivation therapy alone.

Stereotactic body radiation therapy (SBRT) has been found to be a safe and effective option for patients with low- and intermediate-risk prostate cancer.

Conventional radiation therapy requires treatment daily, for an average duration of 9 weeks.

With SBRT patients can reduce their treatment course to approximately 4 or 5 days.

Conventional radiation therapy requires treatment daily, for an average duration of 9 weeks.

With SBRT patients can reduce their treatment course to approximately 4 or 5 days.

Using stereotactic body radiotherapy, which has a higher dose of radiation, can safely and effectively be done in a much shorter time frame without the additional toxicity or compromising any chance of a cure.

Results showed that the 7-year cumulative biochemical recurrence rate for men with low-risk disease was 4.5%, 8.6% for favorable intermediate-risk disease, and 14.9% for those with unfavorable intermediate-risk disease.

The biochemical recurrence rate for all patients with intermediate-risk disease was 10.2%.

Using stereotactic body radiotherapy, which has a higher dose of radiation, can safely and effectively be done in a much shorter time frame without the additional toxicity or compromising any chance of a cure.

When comparing CT guidance to MRI guided SBRT, there was a significant reduction in toxic effects and decrements in patient reporting quality of life.

Hypofractionated radiotherapy is noninferior to conventional radiotherapy in men with low-risk prostate cancer, yielding no differences in prostate cancer–specific and general quality of life, as well as in anxiety and depression.

Treatment with hypofractionated radiotherapy is noninferior to conventional radiotherapy in men with low-risk prostate cancer in terms of disease-free survival and, in prostate cancer-specific and general QOL, as well as in anxiety and depression.

A large population based cohort study, found that IMRT for prostate cancer was not associated with an increased risk of second primary cancers, either solid or hematologic (Pithadia K).

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