Surgery and Adjuvant RT Show Superiority in Locally Advanced Prostate Cancer

Grace Lu-Yao, PhD

Higher survival rates were observed with radical prostatectomy (RP) and adjuvant radiotherapy (RT) compared with radiotherapy and androgen deprivation therapy (ADT) in men with locally advanced prostate cancer, according to a comparative analysis published in Cancer.^1,2

Results showed that 10 years after treatment, 89% of men who received radical prostatectomy and RT were still alive, compared with 74% of those who received RT and ADT, demonstrating a 15% survival benefit in the prostatectomy arm. The coprimary endpoints were prostate cancer—specific survival and overall survival (OS), both of which were improved in the prostatectomy/RT arm, regardless of tumor stage or Gleason score.

“There is a lot of debate about whether to remove the whole prostate and follow up with radiation therapy,” senior author Grace Lu-Yao, PhD, associate director of Population Science at the Sidney Kimmel Cancer Center, said in a statement. “Or, as a second option, to spare the prostate and treat it using radiation therapy plus hormone-blocking therapy. Our study suggests that removing the prostate followed by adjuvant radiotherapy is associated with greater overall survival in men with prostate cancer.”

The analysis compiled data from the SEER database from 1992 to 2009 of men older than 65 years old who were diagnosed with locally or regionally advanced prostate cancer and had received either radical prostatectomy/RT or RT/ADT. Additional exclusion criteria included a history of previous malignancy; stage T1/T2, in situ, or M1 disease; distant lymph node involvement; Health Maintenance Organization coverage during the 6 months following diagnosis; no Part A or B Medicare coverage during the 6 months after diagnosis; indiscernible treatment; and primary chemotherapy.

Men who had received surgery that was not considered curative were excluded from the prostatectomy/RT group. This included cryotherapy, subtotal prostatectomy, and transurethral resection of the prostate. The study defined adjuvant RT as RT received within 6 months after RP. RT/ADT was defined as ADT given 2 months prior to receiving RT until anytime 3 years after RT.

Among men who received prostatectomy/RT, >55.7% were aged 65 to 69, 9.6% were aged 75 to 79, and <1.3% were aged 80 or older, whereas >26.7% of men who received RT/ADT were aged 65 to 69, 26.1% were 75 to 79, and 13.5% were aged 80 or older (P < .0001).

Of the 13,856 men eligible for evaluation, 6.1% (n = 848) received prostatectomy/RT versus 23.6% (n = 3272) who received RT/ADT. Among men who received RT after prostatectomy, 29.8% (n = 253) also received concurrent ADT.

Comorbidity index scores of 0 (90.1% and 79.2%), 1 (7.8% and 13.7%), and ≥2 (2.1% and 7.1%) were attributed to patients who received prostatectomy/RT as opposed to RT/ADT (P < .0001).

Patients were staged according to the American Joint Committee on Cancer criteria, and comparison groups were matched by age, race, and comorbidity. Propensity score methods were used to account for differences between treatment arms. The 10-year survival analyses were conducted with the Kaplan-Meier method and Cox proportional hazards models. Prostate-specific antigen data were excluded from all analyses.

The adjusted 10-year survival advantage seemed to favor those without lymph node metastasis, though men with high-risk disease that was not localized still seemed to derive benefit from prostatectomy/RT (T3a/bN0M0, 88.9%; T3a/bN1M0, 75.7%; T4N0M0, 72%) over RT/ADT (T3a/bN0M0, 74.2%; T3a/bN1M0, 58.6%%; T4N0M0, 60.5%).

The prevalence of treatment-associated adverse events served as a secondary endpoint of the study. Higher rates of erectile dysfunction (28.3% vs 20.4%; P = .0212) and urinary incontinence (49.1% vs 19.4%; P < .001) were seen with prostatectomy/RT versus RT/ADT, respectively. Additionally, men on the prostatectomy arm were more likely to undergo procedures to address urinary incontinence (12.4% vs 1.6%; P = .0007) and erectile dysfunction (8.4% vs 3.7%; P = .0186). Higher rates of bladder neck contractures (37.6% vs 18.3%; P < .0001) and corrective procedures (34.3% vs 12.8%; P < .0001 were also observed in men who received prostatectomy/RT compared with RT/ADT.

Rates of acute myocardial infarction, sudden cardiac death, coronary artery disease, thromboembolic events, skeletal fractures, and osteoporosis were similar between groups.

“Prostatectomy is an unpopular treatment,” said Lu-Yao. “Our study showed that only 6% of men with high-risk cancer were treated with it. It’s not just the risk of side effects. For some men, especially those who are not fit enough for the surgery, prostatectomy is not an option. However, this may be an option for some patients to reconsider.”

Moving forward, the authors noted there should be a surgical arm in future clinical trials for men with high-risk prostate cancer in addition to prospective trial data to confirm these findings.

References

1. Jefferson University Hospitals (2018). Combination therapy of prostatectomy plus radiotherapy may improve survival in patients with locally advanced prostate cancer. Published September 25, 2018. https://bit.ly/2P1Doxt. Accessed 4 Oct. 2018.
2. Jang TL, Patel N, Faiena I, et al. Comparative effectiveness of radical prostatectomy with adjuvant radiotherapy versus radiotherapy plus androgen deprivation therapy for men with advanced prostate cancer [published online September 25, 2018]. Cancer. doi: 10.1002/cncr.31726.