Radiotherapy For High-risk Prostate Cancer Research Articles

25 - Survival associated with radical prostatectomy versus radiotherapy for high-risk prostate cancer: A contemporary, nationwide observational analysis

25 - Survival associated with radical prostatectomy versus radiotherapy for high-risk prostate cancer: A contemporary, nationwide observational analysis

Stereotactic body radiotherapy for high-risk prostate cancer (5 treatment days): Toxicity results of a phase II trial.

46 Background: Stereotactic body radiotherapy (SBRT) for high-risk prostate cancer (CaP) remains investigational not only due to undetermined efficacy but also due to concerns for the potential toxicity when the treatment volumes extend beyond the prostate gland itself. Methods: Men with high-risk CaP, as defined by Gleason score > = 8, clinical stage T3-T4, or initial PSA > = 20 ng/mL, were enrolled on a multicenter phase II trial and were treated with 40 Gy to prostate and 25 Gy to pelvic nodes in 5 fractions and 9 months neoadjuvant and concurrent ADT. Treatment with ADT and pelvic nodal radiation was at the discretion of the treating physician. Follow-up assessment was with CTCAE v4 and Expanded Prostate Composite Index (EPIC). Results: A total of 61 patients were treated, with a median follow-up of 12 months. Forty (64.4%) received ADT and 23 (37.1%) received nodal radiation. The median initial PSA was 8.1 ng/mL and 8% of patients had clinical T3-T4 disease; 45.9% and 39.3% had Gleason score 8 and 9-10 disease, respectively. No grade 3 or higher toxicities were seen. Rates of acute and late grade 2 genitourinary toxicities were 13.1% and 6.7%, respectively; rates of acute and late grade 2 gastrointestinal toxicities were 6.6% and 8.2%, respectively. Mean changes in EPIC urinary incontinence, urinary obstructive, and bowel domain scores at 4 months were -0.35, +1.44, and -2.38, respectively. For the 32 patients with evaluable EPIC scores at 12 months, mean changes on EPIC urinary incontinence, urinary obstructive, and bowel domain scores at 4 months were -1.04, -2.70, and -6.76, respectively. The percentages of patients with minimum clinically important change in EPIC urinary incontinence, urinary obstructive, and bowel domain scores at 4 months were 11.9%, 21.4%, and 26.2%, respectively. At 12 months, these figures were 13.9%, 30.6% and 27.8%. The receipt of ADT and/or nodal radiation had no significant effect on either physician- or patient-reported toxicity profiles (p > 0.1, Fisher’s exact test). Conclusions: SBRT regimens can be safely utilized to deliver the entire course in 5 treatment days in patients with high-risk localized CaP. Clinical trial information: NCT02296229.

Clinical outcomes and late toxicity of hypofractionated intensity-modulated radiotherapy for high-risk prostate cancer.

56 Background: Since prostate cancer has intrinsic high radiation-fraction sensitivity, hypofractionated radiotherapy (HFRT) could offer treatment advantages. However, dose-escalated HFRT may increase risks of late genitourinary (GU) and gastrointestinal (GI) toxicity. Intensity-modulated radiotherapy (IMRT) can potentially deliver dose-escalated HFRT without increasing late toxicities. This study’s acute toxicity data was previously published. We now present five-year efficacy results and late toxicity data for prostate cancer patients treated with HFRT using IMRT. Methods: From 2005-2012, our Phase II prospective study enrolled one hundred patients with either high risk disease (one or more of: Stage ≥ T3, Gleason ≥ 8, or PSA ≥ 20 ng/mL) or high tier intermediate risk disease (Gleason 7 and PSA ≥ 15 ng/mL). All patients received HFRT using IMRT in 25 daily fractions. Sixty patients received 68 Gy to the prostate and proximal seminal vesicles, with simultaneous integrated boost (SIB) of 45 Gy to pelvic lymph nodes and distal seminal vesicles. Forty patients received 68 Gy to the prostate, and a SIB of 50 Gy to pelvic lymph nodes and seminal vesicles. Adjuvant hormonal therapy was given for two to three years. Biochemical failure was determined by the Phoenix definition. Late toxicity scores were recorded every 6 months after completing RT. Results: Median age of patients was 67 years. 33% had Stage ≥ T3, 52% had Gleason ≥ 8, and 44% had PSA ≥ 20 ng/mL. After a median follow-up of 5.4 years, median PSA at last follow-up was 0.10 ng/mL. Five-year biochemical control rate (BCR) was 91.8%, five-year progression-free survival (PFS) was 92.8%, and five-year overall survival (OS) was 88.7%. Five-year cumulative incidence of Grade ≥ 3 GU and GI toxicity were 13.0% and 16.7% respectively. At the five-year efficacy endpoint, ongoing Grade ≥ 3 GU and GI toxicity were 1.9% and 0% respectively. Conclusions: Dose-escalated HFRT using IMRT results in favourable five-year BCR, PFS, and OS for patients with localized high-risk prostate cancer, and is well-tolerated with acceptable late GU and GI toxicity. These findings support ongoing Phase III trials that are assessing the clinical use of IMRT-based HFRT. Clinical trial information: NCT00126802.

High biologically effective dose radiation therapy using brachytherapy in combination with external beam radiotherapy for high-risk prostate cancer.

PurposeTo evaluate the outcomes of high-risk prostate cancer patients treated with biologically effective dose (BED) ≥ 220 Gy of high-dose radiotherapy, using low-dose-rate (LDR) brachytherapy in combination with external beam radiotherapy (EBRT) and short-term androgen deprivation therapy (ADT).Material and methodsFrom 2005 to 2013, a total of 143 patients with high-risk prostate cancer were treated by radiotherapy of BED ≥ 220 Gy with a combination of LDR brachytherapy, EBRT, and androgen deprivation therapy (ADT). The high-risk patients in the present study included both high-risk and very high-risk prostate cancer. The number of high-risk features were: 60 patients with 1 high-risk factor (42%), 61 patients with 2 high-risk factors (43%), and 22 patients with 3 high-risk factors (15%) including five N1 disease. External beam radiotherapy fields included prostate and seminal vesicles only or whole pelvis depending on the extension of the disease. Biochemical failure was defined by the Phoenix definition.ResultsSix patients developed biochemical failure, thus providing a 5-year actual biochemical failure-free survival (BFFS) rate of 95.2%. Biochemical failure was observed exclusively in cases with distant metastasis in the present study. All six patients with biochemical relapse had clinical failure due to bone metastasis, thus yielding a 5-year freedom from clinical failure (FFCF) rate of 93.0%. None of the cases with N1 disease experienced biochemical failure. We observed four deaths, including one death from prostate cancer, therefore yielding a cause-specific survival (CSS) rate of 97.2%, and an overall survival (OS) rate of 95.5%.ConclusionsHigh-dose (BED ≥ 220 Gy) radiotherapy by LDR in combination with EBRT has shown an excellent outcome on BFFS in high-risk and very high-risk cancer, although causal relationship between BED and BFFS remain to be explained further.

EP-2011: High-dose-rate brachytherapy combined with external beam radiotherapy for high-risk prostate cancer

EP-2011: High-dose-rate brachytherapy combined with external beam radiotherapy for high-risk prostate cancer

Evolving Paradigm of Radiotherapy for High-Risk Prostate Cancer: Current Consensus and Continuing Controversies.

High-risk prostate cancer is an aggressive form of the disease with an increased risk of distant metastasis and subsequent mortality. Multiple randomized trials have established that the combination of radiation therapy and long-term androgen deprivation therapy improves overall survival compared to either treatment alone. Standard of care for men with high-risk prostate cancer in the modern setting is dose-escalated radiotherapy along with 2-3 years of androgen deprivation therapy (ADT). There are research efforts directed towards assessing the efficacy of shorter ADT duration. Current research has been focused on assessing hypofractionated and stereotactic body radiation therapy (SBRT) techniques. Ongoing randomized trials will help assess the utility of pelvic lymph node irradiation. Research is also focused on multimodality therapy with addition of a brachytherapy boost to external beam radiation to help improve outcomes in men with high-risk prostate cancer.

Competing events and costs of clinical trials: Analysis of a randomized trial in prostate cancer

BackgroundClinical trial costs may be reduced by identifying enriched subpopulations of patients with favorable risk profiles for the events of interest. However, increased selectivity affects accrual rates, with uncertain impact on clinical trial cost. MethodsWe conducted a secondary analysis of Southwest Oncology Group (SWOG) 8794 randomized trial of adjuvant radiotherapy for high-risk prostate cancer. The primary endpoint was metastasis-free survival (MFS), defined as time to metastasis or death from any cause (competing mortality). We used competing risks regression models to identify an enriched subgroup at high risk for metastasis and low risk for competing mortality. We applied a cost model to estimate the impact of enrichment on trial cost and duration. ResultsThe treatment effect on metastasis was similar in the enriched subgroup (HR, 0.42; 95% CI, 0.23–0.76) compared to the whole cohort (HR, 0.50; 95% CI, 0.30–0.81) while the effect on competing mortality was not significant in the subgroup or the whole cohort (HR 0.70; 95% CI 0.39–1.23, vs. HR 0.94; 95% CI, 0.68–1.31). Due to the higher incidence of metastasis relative to competing mortality in the enriched subgroup, the treatment effect on MFS was greater in the subgroup compared to the whole cohort (HR 0.55; 95% CI 0.36–0.82, vs. HR 0.77; 95% CI, 0.58–1.01). Trial cost was 75% less in the subgroup compared to the whole cohort ($1.7million vs. $6.8million), and the trial duration was 30% shorter (8.4 vs. 12.0years). ConclusionCompeting event enrichment can reduce clinical trial cost and duration, without sacrificing generalizability.

EP-1227: Hypo-fractionated biological optimized dose-painting radiotherapy for high-risk prostate cancer

EP-1227: Hypo-fractionated biological optimized dose-painting radiotherapy for high-risk prostate cancer

Outcome of hypofractionated biological optimized dose-painting radiotherapy for high-risk prostate cancer.

107 Background: Prostate dose-painting radiotherapy and hypo-fractionation both can improve biochemical contol in localised disease. We report toxicity and outcome for a cohort of high risk patients. Methods: We selected 28 patients with high-risk localised prostate cancer and 2 or 3 risk factors. Functional MRI’s were used to define boost volumes with a margin of 5 mm PTV. Neo-adjuvant hormone therapy was given for 3 months. Dose volume constraints, TCP and NTCP parameters were used for optimization of rotational IMRT treatment plans. We used fiducial markers, bowel and bladder preparation and daily IGRT. Results: Mean age was 66 years, mean PSA was 17.4 ng/ml (range 4.6-59.1), 20 patients had T3a and 10 had Gleason score ≥ 8. The mean dose to the prostate excluding the boost volume was 61.4 Gy (range 60.6-62.3) and the boost PTV 66.1 Gy (range 60.9-72.5). Mean NTCP for rectal bleeding was 4.7% (range 3.4-5.8), for faecal incontinence 3.5% (range 2.3-5) and mean TCP 75% (range 71-79) assuming a 71% biochemical control at 5 years for a standard plan. All patients completed radiotherapy, 16/28 patients had acute bladder toxicity grade 2 (RTOG score), but no grade 3 toxicity was observed. Worst acute bowel toxicity was grade 1 (4/28). Mean follow up was 15 months (range 8-25). For the 20 patients who had neo-adjuvant hormone therapy beyond 6months, the mean PSA was 0.33 ng/ml (range 0.2-0.8), 2 patients had relapsed at 12 month, 6 patients are still on hormone therapy. 4 patients had Grade 2 urinary late toxicities (CTCv4). Two patients developed grade 1 diarrhoea. Patient reported outcomes >6 month after completion of radiotherapy (EPIC QOL questionnaire) demonstrated similar scores to controls without prostate cancer for the bowel domains; reduction in the urinary domains was similar to other cohorts treated with external beam radiotherapy and hormone therapy. Conclusions: In this high risk group, dose escalation with hypo-fractionated dose painting radiotherapy achieved good biochemical control and urinary and bowel toxicity similar to standard dose radiotherapy during follow up.

Early radiation response between GnRH agonist versus antagonist combined with radiotherapy in high-risk prostate cancer.

97 Background: Degarelix, a GnRH antagonist, provides a very rapid and sustained testosterone suppression alongside with the VEGF pathway inhibition through the FSH receptors. This raises the question as to whether high risk localized prostate cancer (HRPCa) could respond differently to radiotherapy (RT) + Degarelix when compared with RT + GnRH agonist. Methods: 30 HRPCa patients were treated with exclusive RT combined with a GnRH agonist (n= 19) or Degarelix (n= 11). MRSI was performed before the start of hormones and 3 months after the end of RT. Choline (tumor metabolism) and citrate (healthy prostate metabolism) were quantified with MR spectroscopy and the slopes of gadolinium wash-in (SWI) and wash-out (SWO) were assessed in the peripheral zone (PZ), the central gland (CG) and the tumor with DCE-MRI. Results: At baseline, 14 patients had a T3 (46.7%) and 9 patients (30%) had a GS≥8. The median PSA values were 12.7 ng/mL [3.0-153.7] for agonists and 14.0 ng/mL [6.8-23.6] for Degarelix (p=ns). The mean prostate volumes (Pvol) were 32.0±15.5 mL for agonist and 33.0±10.0 mL for Degarelix (p=ns). The median dose of RT was 78Gy in each group, [72.0-80.0] with agonist and [70.2-80.0] with Degarelix. There were no significant differences in choline, citrate, SWI and SWO in the PZ, the CG and the tumor. At 3 months, Pvol were 20.8±8.0 mL for agonist and 21.4±6.2 mL for Degarelix (p=0.71) and the mean and median PSA values for agonist vs Degarelix were 0.5±0.8 ng/mL vs 0.1±0.1 ng/mL and 0.1 ng/mL [0.02-2.8] vs 0.1 ng/mL [0.005-0.3], respectively. Citrate was significantly decreased with Degarelix in the PZ (4.3±4.4 vs 1.1±0.8, p=0.0142), in the CG (4.0±4.0 vs 1.1±1.0, p=0.009) but not in the tumor (2.5±2.6 vs 1.7±1.9, p=0.23). Choline concentrations were similar between both groups in the PZ, the CG and the tumor. There was a trend towards a lower contrast uptake in the tumor with Degarelix (mean SWI and SWO: 134.6±56.2 s-1 vs 104.1±36.3 s-1, p=0.13 and 259.6±103.1 s-1 vs 306.1±70.4 s-1, p=0.15). Conclusions: Degarelix combined with RT offers a significant early, more profound metabolic atrophy in the prostate, but not in the tumor. There is a trend towards a lower tumor vascularization with Degarelix compared with GnRH agonists.

Radiotherapy for high-risk prostate cancer.

The combination of radiation treatment and long-term androgen deprivation therapy (ADT) has been shown in multiple clinical trials to prolong overall survival in men with high-risk prostate cancer compared with either treatment alone. New radiation technologies enable the safe delivery of high radiation doses that improve cancer control compared with lower radiation doses. Based on the results of multiple randomized trials, clinical practice guidelines for high-risk prostate cancer recommend total radiation doses of at least 75.6 Gy, with long-term (2-3 years) ADT. Ongoing research into hypofractionated radiation treatment, whole-pelvic radiation, and combinations of radiation with novel hormonal agents could further improve cancer control and survival outcomes for patients with high-risk prostate cancer.

Diffusion-weighted MRI in early assessment of tumour response to radiotherapy in high-risk prostate cancer.

The objective of this study was to assess the efficacy of diffusion-weighted MRI (DWI) in monitoring response to radiotherapy in high-risk prostate cancer (PC). This retrospective study included 78 patients with high-risk PC undergoing 3.0-T MRI (supplemented by DWI) before and after intensity-modulated radiotherapy (IMRT). Based on follow-up clinical examinations, patients were divided into two groups: the recurrence group (patients who suffered biochemical/clinical recurrence within 3 years, n = 13) and the non-recurrence group (patients who were recurrence free for over 3 years, n = 65). The apparent diffusion coefficient (ADC) values before and after IMRT were compared between these two groups. The receiver-operating characteristics (ROC) analysis was carried out to investigate the discriminatory capability for pre- and post-IMRT ADC values. The overall ADC values were 1.04 ± 0.18 × 10(-3) mm(2) s(-1) for PCs before IMRT and 1.45 ± 0.15 × 10(-3) mm(2) s(-1) after IMRT (p < 0.001). A statistically significant difference in post-IMRT ADC values was noted between patients with and without recurrence (1.27 ± 0.14 × 10(-3) mm(2) s(-1) vs 1.49 ± 0.12 × 10(-3)mm(2) s(-1); p < 0.001), although there was no statistical difference between them in pre-IMRT ADC values (1.00 ± 0.17 × 10(-3) mm(2) s(-1) vs 1.05 ± 0.18 × 10(-3) mm(2) s(-1); p = 0.31). The ROC curve analysis revealed that the post-IMRT ADC values could help identify patients suffering recurrences (area under the curve, 0.88; p < 0.001). Marked increase in ADC values was observed in PC after radiotherapy, especially in good responders. DWI is a valuable tool for monitoring the response to radiotherapy. This study examined the relationship between ADC changes and tumour response to treatment of PC.

Treatment simulations with a statistical deformable motion model to evaluate margins for multiple targets in radiotherapy for high-risk prostate cancer

Background and purposeDeformation and correlated target motion remain challenges for margin recipes in radiotherapy (RT). This study presents a statistical deformable motion model for multiple targets and applies it to margin evaluations for locally advanced prostate cancer i.e. RT of the prostate (CTV-p), seminal vesicles (CTV-sv) and pelvic lymph nodes (CTV-ln). Material and methodsThe 19 patients included in this study, all had 7–10 repeat CT-scans available that were rigidly aligned with the planning CT-scan using intra-prostatic implanted markers, followed by deformable registrations. The displacement vectors from the deformable registrations were used to create patient-specific statistical motion models. The models were applied in treatment simulations to determine probabilities for adequate target coverage, e.g. by establishing distributions of the accumulated dose to 99% of the target volumes (D99) for various CTV–PTV expansions in the planning-CTs. ResultsThe method allowed for estimation of the expected accumulated dose and its variance of different DVH parameters for each patient. Simulations of inter-fractional motion resulted in 7, 10, and 18 patients with an average D99 >95% of the prescribed dose for CTV-p expansions of 3mm, 4mm and 5mm, respectively. For CTV-sv and CTV-ln, expansions of 3mm, 5mm and 7mm resulted in 1, 11 and 15 vs. 8, 18 and 18 patients respectively with an average D99 >95% of the prescription. ConclusionsTreatment simulations of target motion revealed large individual differences in accumulated dose mainly for CTV-sv, demanding the largest margins whereas those required for CTV-p and CTV-ln were comparable.

Dosimetric Advantages and Superior Treatment Delivery Efficiency of RapidArc over Conventional Intensity-modulated Radiotherapy in High-risk Prostate Cancer Involving Seminal Vesicles and Pelvic Nodes

AimsTo compare the dosimetry and treatment delivery efficiency of RapidArc with conventional intensity-modulated radiotherapy (IMRT) in the treatment of high-risk prostate cancer. Materials and methodsFifteen patients with high-risk localised prostate cancer were studied. Sequential treatment was used. The initial planning target volume (PTV-L) included the prostate, seminal vesicles and pelvic lymphatics, whereas the prostate boost PTV (PTV-P) included the prostate and seminal vesicles only. The total prescription dose was 76 Gy (44 Gy to PTV-L, 32 Gy to PTV-P; 2 Gy/fraction). Two separate planning techniques were generated for each patient: seven static-field IMRT versus two-arc RapidArc. Dose–volume parameters for the organs at risk, conformity index and homogeneity index for the PTVs, the calculated monitor units and treatment delivery time for both techniques were compared. ResultsRapidArc gave more conformal plans than IMRT for both PTVs. RapidArc gave a higher homogeneity index to the PTV-P and a similar homogeneity index to the PTV-L. The two techniques gave similar dosimetric results for the rectum, bladder and femoral heads. The mean dose (Dmean) and the maximum dose (Dmax) of the bowel space were reduced by 3.06 and 2.83%, respectively, with RapidArc. The V20 Gy, V30 Gy and V40 Gy for healthy tissues were reduced by 7.77, 14.25 and 17.55%, respectively, with RapidArc. The calculated treatment delivery time and monitor units were reduced by 74.09%/60.93% and 68.32%/48.06% for the PTV-L/PTV-P, respectively, with RapidArc. ConclusionRapidArc is better than conventional IMRT in terms of dosimetry and delivery efficiency for high-risk prostate cancer.

Current role of neoadjuvant and adjuvant systemic therapy for high-risk localized prostate cancer.

Although most men are diagnosed with readily curable localized prostate cancer, those with high-risk features face a significant mortality risk. Androgen deprivation therapy (ADT) is a standard adjunct to radiotherapy for high-risk prostate cancer, but its role around prostatectomy has not been as clearly defined, and concerns over cardiovascular toxicity have led to decreasing use. The use of chemotherapy for localized disease remains experimental. We review the most recently published trials of neoadjuvant or adjuvant systemic therapy for prostate cancer. The optimal duration of ADT with higher dose modern radiation techniques is under active investigation, but current data support the use of longer duration as standard. Prostate-specific antigen (PSA) and MRI changes may be useful in future studies optimizing duration of neoadjuvant ADT. Two years of combined ADT after prostatectomy is associated with a lower risk of disease recurrence and better prostate cancer specific mortality than predicted. Persistence of intraprostatic androgens during neoadjuvant ADT may contribute to resistance. Androgen deprivation added to definitive radiation or surgery improves outcomes for high-risk prostate cancer, although the role of chemotherapy remains undefined. Molecular classification is needed to improve risk stratification.

Androgen deprivation in combination with radiotherapy in high-risk prostate cancer

Androgen deprivation in combination with radiotherapy in high-risk prostate cancer

Death from high‐risk prostate cancer versus cardiovascular mortality with hormonal therapy

Randomized trials have demonstrated improved survival when hormonal therapy (HT) is added to radiation therapy (RT) for high-risk prostate cancer. However, it is still unknown whether men who have a history of myocardial infarction (MI) or MI risk factors achieve a superior outcome from HT. A Markov decision analysis model was used to compare quality-adjusted life expectancy (QALE) in men aged 50, 60, and 70 years who received RT and no HT, 6 months of HT (short-term), or 3 years of HT (long-term) for high-risk prostate cancer stratified by cardiac risk group. In men with a history of MI, there was a decrease of 0.1 to 0.2 quality-adjusted life years and 0.5 to 0.6 quality-adjusted life years across all ages with short-term HT and long-term HT, respectively, compared with no HT. In men without MI, receipt of short-term or long-term HT was associated with a QALE benefit versus no HT in all cohorts. Among men without MI, the optimal duration of HT was a function of age and the number of MI risk factors. Long-term HT improved QALE (range, 1.4-5.4 years) for men aged 50 or 60 years except those with MI; whereas, for men aged 70 years with 4 cardiac risk factors, short-term and long-term HT yielded identical QALE. Men who received RT for high-risk prostate cancer and had a history of MI experienced net harm when they received HT. Men without MI gained a QALE benefit from HT, even if they had up to 4 cardiac risk factors. The optimal duration of HT is a function of patient age and the number of cardiac risk factors.

Whole pelvic intensity-modulated radiotherapy for high-risk prostate cancer: a preliminary report

PurposeTo assess the clinical efficacy and toxicity of whole pelvic intensity-modulated radiotherapy (WP-IMRT) for high-risk prostate cancer.Materials and MethodsPatients with high-risk prostate cancer treated between 2008 and 2013 were reviewed. The study included patients who had undergone WP-IMRT with image guidance using electronic portal imaging devices and/or cone-beam computed tomography. The endorectal balloon was used in 93% of patients. Patients received either 46 Gy to the whole pelvis plus a boost of up to 76 Gy to the prostate in 2 Gy daily fractions, or 44 Gy to the whole pelvis plus a boost of up to 72.6 Gy to the prostate in 2.2 Gy fractions.ResultsThe study cohort included 70 patients, of whom 55 (78%) had a Gleason score of 8 to 10 and 50 (71%) had a prostate-specific antigen level > 20 ng/mL. The androgen deprivation therapy was combined in 62 patients. The biochemical failure-free survival rate was 86.7% at 2 years. Acute any grade gastrointestinal (GI) and genitourinary (GU) toxicity rates were 47% and 73%, respectively. The actuarial rate of late grade 2 or worse toxicity at 2 years was 12.9% for GI, and 5.7% for GU with no late grade 4 toxicity.ConclusionWP-IMRT was well tolerated with no severe acute or late toxicities, resulting in at least similar biochemical control to that of the historic control group with a small field. The long-term efficacy and toxicity will be assessed in the future, and a prospective randomized trial is needed to verify these findings.

High-Risk Prostatic Cancer: Radiation Therapy and Concomitant Docetaxel

High risk (cT3, N1, PSA ≥20 ng/mL and/or Gleason score ≥8) prostate cancer patients (pts) have a 5-years biochemical failure rate more than 50% after surgery or radiation. Neoadjuvant, concomitant and adjuvant hormone therapy (HT) are currently the only systemic treatments with escalation dose of radiation therapy (RT). To improve the outcome with RT, weekly chemotherapy (CT) during RT in high-risk prostate cancer is being explored. Docetaxel has demonstrated significant antitumor effect and favorable impact on survival in hormone-refractory prostate cancer and a strong sensitization of tumor cells to RT injury. From 2005 to 2010, 30 high-risk pts were treated with high dose RT and concomitant Docetaxel. All pts had clinically (13/30) or pathologically (17/30) advanced disease. Clinically Advanced Tumor: median age 73 years (range, 65-81); Gleason score: 7 (4+3) in 1 pt, 8 in 4, 9 in 7 and 10 in 1 pt; median PSA at diagnosis was 9.3 (range, 5.27-71.3) and PSA prior to RT was 0.51 ng/mL (range, 0.05-3.83); RT median dose was 80 Gy (76-80). Pathologically Advanced Tumor: median age 65 years (57-80); Gleason Score: 8 in 4 pts and 9 in 13; pT2c in 2 pts, pT3a in 3, pT3b in 10 and pT4 in 2 pts; nodes were positive in 3 pts; 6 pts were R1. Median PSA at diagnosis was 18 (range, 4.25-56.3), PSA prior to RT was 0.65 ng/mL (range, 0.01-4.22); RT median dose was 70 Gy (66-76). Docetaxel was administered at a standard weekly dose (30 mg for pts with surface area <2 mq and 40 mg for pts with ≥2 mq). The median number of CT cycles was 7 (range, 2-8). All pts had HT before and during RT and continued HT for 2 years after RT. At median follow-up of 36 months (range, 8-60), 6 pts (20%) had biochemical or clinical progression of disease (median period of recurrence: 14 months). Toxicity: gastrointestinal grade I was reported in 18/30 and urological grade I in 12/30 pts. Two patients stopped CT after two cycles for systemic toxicity. During the same period at the same institution, 139 high risk pts with the same pathological characteristics were treated with standard therapy: 42 with adjuvant RT+HT and 97 with radical RT+HT. At median follow up of 34 months, 33% of these pts had a relapse. These preliminary data confirmed the feasibility and tolerability of weekly Docetaxel in combination with RT in pts at high risk of disease progression. At a median follow-up of 36 months, only 20% of pts had relapse, whereas the global relapse was 33% with the standard treatment. These encouraging results indicate that a multimodal treatment should be offered to patients with high-risk prostate cancer and pts should be encouraged to participate in multimodality trials.

Radical Radiotherapy for High-Risk Prostate Cancer in Older Men

Historical data for older men with high-risk nonmetastatic prostate cancer treated with radiotherapy alone have demonstrated a 10-year prostate-cancer-specific mortality of around 30%. The development of dose escalation, using techniques such as intensity-modulated radiotherapy, has enabled more targeted delivery of treatment with improved efficacy and a reduction in the risk of toxicity compared with conventional radiotherapy. The combination of radiotherapy and androgen-deprivation therapy (ADT) has been shown to improve overall survival compared with radiotherapy or ADT alone without a significant increase in toxicity in patients with minimal comorbidities. There is evidence that patient age has only a marginal effect on genitourinary and gastrointestinal toxicities following radiotherapy. Further research has shown that although age does have an effect on the likelihood of sexual dysfunction after radiation therapy, there is no significant difference in the proportion of men aged ≥ 75 years who feel that sexual dysfunction is a moderate or serious problem before or 24 months after diagnosis. Radical radiotherapy is effective and well tolerated in senior men with high-risk prostate cancer and should be offered in combination with long-term ADT to patients with minimal comorbidities. In case of significant comorbid conditions, shorter durations of ADT may be considered.