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Comparison of Outcome Endpoints in Intermediate- and High-Risk Prostate Cancer After Combined-Modality Radiotherapy - Beyond the Abstract

The aim of our study was to compare the surgical standard definition for a biochemical recurrence (BR) with the radiotherapeutic standard definition after combined-modality radiation therapy (CRT) for prostate cancer. Here, we provide additional data from our database on 425 patients with intermediate- and high-risk prostate cancer according to the National Cancer Comprehensive Network (NCCN) classification system. All patients received androgen deprivation therapy for one year and CRT consisting of external-beam radiotherapy (59.4 Gy, 33 fractions) and 125J seed-brachytherapy (100 Gy)1.

The definition
  • for radio-oncological biochemical recurrence (rBR) was prostate-specific antigen (PSA) nadir + 2 ng/ml (so-called Phoenix definition)2 and
  • for surgical biochemical recurrence (sBR) a PSA ≥0.2 ng/ml3.

In addition, we defined a PSA-bounce (PSA-B) as a transient PSA increase of at least 0.2 ng/ml above the PSA nadir followed by a decrease to or below the initial PSA nadir. As a PSA-B could be mistaken as a BR, we analyzed all patients with sBR (n=124) for the occurrence of PSA-B.

Using the sBR definition in intermediate-risk patients (n=258) we saw a significant reduction of the 5- and 10-year biochemical recurrence-free survival (BRFS) (5 years: 72% and 10 years: 68%) compared to the rBR definition (5 years: 97% and 10 years: 91%, p< 0.005).

If a biochemical recurrence was seen according to sBR definition the probability of developing metastases after 10 years was only 15%, whereas according to rBR definition the chance after 9 years was 89% (Fig. 1 A, B). Corresponding values for cancer-specific death were 6% and 34%, respectively.

We analyzed the same parameters in the high-risk group (n=167). Here we saw a difference using the sBR or rBR definition only after 5 years follow up (sBR: 63%, rBR: 86%, p<0.005). After 10 years both calculated values were about 60%. If a biochemical recurrence was seen according to sBR definition the probability of developing metastases after 10 years was 53%, whereas according to rBR definition the chance was 88% (Fig. 1 C, D). Corresponding values for cancer-specific death were 43% and 41%, respectively.

In more than half of all patients showing a recurrence according to the sBR definition the PSA increase was transient and therefore classified as PSA bounce. Interestingly such bounces were significantly more often seen in the intermediate-risk group (53 of 71 patients, 75%) compared to only 16 of 53 (30%) in the high-risk group (p< 0.05).
We concluded that for the intermediate-risk group after CRT the sBR definition is not a reliable predictor for metastases and cancer-specific death and therefore cannot be recommended. As one reason for this deficiency, we identified an increased occurrence of a PSA bounce, which leads to a higher number of false-positive findings. The bounce effect occurs in up to 30% of the patients after seed brachytherapy4,5. Intriguingly, it is more likely if the cancer was pre-therapeutically assessed as low or intermediate risk6. In our high-risk group, only a small proportion of patients showed a PSA bounce and a similar 10-year BRFS was found for both the rBR and the sBR definition. Due to the lower threshold of the sBR definition, recurrences and thus therapy failures might be detected earlier. This is why in our opinion sBR definition could be used for patients with high-risk prostate cancer whereas in intermediate-risk the use should be restricted.

figure 1 Metastases free survival MFS of intermediate risk group

Fig. 1: Metastases-free survival (MFS) of intermediate-risk group (A: MFS after surgical biochemical recurrence (sBR)), B: MFS after radio-oncological biochemical recurrence (rBR)) vs. high-risk group (C: MFS after sBR, D: MFS after rBR)

Written by: Katharina Katic, MD, Department of Urology, University of Lübeck, Germany; Inke R. König, PhD, MD, Institute for Medical Biometry and Statistics, University of Lübeck, Germany; Irina Robrahn-Nitschke, MD, CURAVID Radiology and Radiotherapy, Liübeck, Germany; Bernd Brandenburg, CURAVID Radiology and Radiotherapy, Liübeck, Germany; Andreas Böhle, PhD, MD, Department of Urology, University of Lübeck, Germany and HELIOS Agnes-Karll Hospital Bad Schwartau, Germany.

References:

  1. Boehle, A., K. Katic, I. R. König, I. Robrahn-Nitschke, P. Renner, and B. Brandenburg. "Combined-modality 125 J-seed-brachytherapy, external beam radiation and androgen deprivation therapy of unfavorable-risk prostate cancer: report of outcomes and side-effects." World journal of urology 37, no. 11 (2019): 2355-2363.
  2. Abramowitz, Matthew C., Tiaynu Li, Mark K. Buyyounouski, Eric Ross, Robert G. Uzzo, Alan Pollack, and Eric M. Horwitz. "The Phoenix definition of biochemical failure predicts for overall survival in patients with prostate cancer." Cancer: Interdisciplinary International Journal of the American Cancer Society 112, no. 1 (2008): 55-60.
  3. Mottet, Nicolas, Joaquim Bellmunt, Michel Bolla, Erik Briers, Marcus G. Cumberbatch, Maria De Santis, Nicola Fossati et al. "EAU-ESTRO-SIOG guidelines on prostate cancer. Part 1: screening, diagnosis, and local treatment with curative intent." European urology 71, no. 4 (2017): 618-629.
  4. Caloglu, Murat, Jay P. Ciezki, Chandana A. Reddy, Kenneth Angermeier, James Ulchaker, Nabil Chehade, Andrew Altman, Christina Magi-Galuzzi, and Eric A. Klein. "PSA bounce and biochemical failure after brachytherapy for prostate cancer: a study of 820 patients with a minimum of 3 years of follow-up." International Journal of Radiation Oncology* Biology* Physics 80, no. 3 (2011): 735-741.
  5. Lee, Byron H., Adam S. Kibel, Jay P. Ciezki, Eric A. Klein, Chandana A. Reddy, Changhong Yu, Michael W. Kattan, and Andrew J. Stephenson. "Are biochemical recurrence outcomes similar after radical prostatectomy and radiation therapy? analysis of prostate cancer–specific mortality by nomogram-predicted risks of biochemical recurrence." European urology 67, no. 2 (2015): 204-209.
  6. Åström, Lennart, Fredrik Sandin, and Lars Holmberg. "Good prognosis following a PSA bounce after high dose rate brachytherapy and external radiotherapy in prostate cancer." Radiotherapy and Oncology 129, no. 3 (2018): 561-566.
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