Tumor control probability (TCP) in prostate cancer: role of radiobiological parameters and radiation dose escalation.

The objective of this work was to assess the relative impact of radiobiological parameters and radiation dose escalation on Tumor Control Probability for prostate cancer patients treated with radiation. Radiobiological parameters included alpha/beta ratios, cell surviving fraction at 2 Gy (SF(2) and clonogenic cell density (CCD). Using the Niemierko method, TCP was calculated in ten prostate cancer patients as a function of increasing radiation doses (70-140 Gy), alpha/beta ratios (1.5-20), SF(2) (0.3-0.7) and CCD (10-20 million cells/cm(3). At 70 Gy and CCD of 10 million/cm(3), TCP was above 99% for SF(2) of 0.3 or 0.4, 97.4%-98.6% for SF(2) of 0.5 and less than 2% for SF(2) of 0.6 or 0.7. With dose escalation, TCP values above 99% were demonstrated at 80 Gy for SF(2) of 0.5 and 100 Gy for SF(2) of 0.6. For SF(2) of 0.7, TCP above 99% was demonstrated with 100 Gy and CCD of 10(4)cells/cm(3) or 140 Gy and CCD of 10(7) cells/cm(3). TCP decreased with lower alpha/beta of 1.5, but at a much smaller scale compared to SF(2) changes. TCP modeling predicts that SF(2) and CCD are dominant predictors of radioresistance in prostate cancer. Radiation doses of 100 Gy or greater may be required for tumors with SF(2) of 0.6 or above. Relating clinical tumor prognostic indicators such as Gleason score and PSA to radiobiological parameters will allow us to identify subsets of patients in need of higher radiation doses and adjuvant therapy to maximize treatment outcomes.