Treatment of Advanced Prostate Cancer: Options and Outcomes in Late Stage with Surgery Vs Radiation
Radical prostatectomy (RP) continues to be a treatment option for clinically localized prostate cancer (PC) with a life expectancy of > 10 years. However, nearly 20-25% of cases present as locally advanced disease.
Locally advanced prostate cancer (T3-T4, N0, M0) is considered as “high-risk” since there is an increased risk of prostate specific antigen (PSA) failure, metastatic progression and cancer specific death.
The European Association of Urology guidelines recommend RP to be an appropriate option for selected patients with small low volume T3 tumor, prostate specific antigen (PSA) <20 ng/ml, Gleason score < 8 and life expectancy of > 10 years.
The advantages of RP in locally advanced PC include reduction in tumor burden, providing accurate pathological staging, and symptomatic relief.
Precise staging helps in guiding further treatment, prevents overtreatment with adjuvant hormonal therapy (AHT), and importantly, eliminates the PC ‘source’ to prevent cancer ‘seeding’ that promotes metastasis. Furthermore, RP also causes a rapid decrease in PSA after surgery that allows for quicker detection of persistent or recurrent PC and the potential of adjuvant therapy than other treatment modalities.
RP may be carried out as open radical retro pubic prostatectomy (RRP) and robot-assisted laparoscopic prostatectomy (RALP). While RALP has become increasingly popular, there is much debate as to whether it has improved oncologic outcomes compared with traditional RRP. There is no consensus if one type has superior functional outcomes or complication rates when surgeon experience is considered.
Radiotherapy (RT) in advanced prostate cancer is also an alternate option to RP. Choosing one over the other is still debated.
The landmark ProtecT (Prostate Testing for Cancer and Treatment) trial is the only randomized controlled trial showing no difference between surgery and radiotherapy at 10-year follow up. But the trial is not applicable to “high-risk” patients.
Men with high-risk PC are more likely to undergo RT plus Androgen deprivation Therapy than to undergo RP. Clinical trials have shown that higher RT dosages (78-80 Gy) have superior clinical and biochemical outcomes compared to lower RT dosages (66-70 Gy).
3D-external beam radiotherapy (EBRT) and intensity modulated radiotherapy (IMRT) can provide for higher RT dosages without excessive risk of side effects to the organs surrounding the prostate. For high-risk advanced PC, a combination of EBRT/IMRT and brachytherapy was found to be superior to EBRT alone, IMRT alone, or brachytherapy alone, although the exact radiation dosages varied among the studies though all RT options were in the ‘high-dosage’ range.
Combined EBRT and brachytherapy had improved PSA-free progression results compared to single-modality RT in high-risk PC, although brachytherapy was found to be superior to other RT modes in low-risk PC and combined therapy had similar outcomes to brachytherapy only in intermediate-risk PC.
Both RT and RP can be used in conjunction with each other or with other treatment modalities if one therapy is not satisfactory. Post-RP RT is an option if RP alone is insufficient for cancer control, as adjuvant RT and salvage RT. While adjuvant RT has been shown to lower biochemical recurrence, improve local control, decrease metastases, and improve overall survival compared with no post-RP treatment.
Current research has yet to determine the best treatment for “high-risk” PC. In general, for most cases of locally advanced prostate cancers, the chance of “cure” is equal whether RP or RT is chosen. It is dependent on evaluating the risk for unwanted effects and parameters for quality of life in individual patients. However patients with locally advanced disease with positive margins and /or positive lymph nodes post radical prostatectomy are at a high risk for local and/or distant metastases.
Two land mark trials in the early 21st century have shown radiation to be effective post operatively in such cases either immediately after surgery as an adjuvant or as salvage when there is a recurrence.
The patient should have re gained complete continence after surgery before radiation is planned.