Visual Abstract
Abstract
The aim of this retrospective analysis was to determine prostate-specific antigen (PSA) response, PSA progression-free survival (PFS), and overall survival (OS) in a large cohort of patients with metastatic castration-resistant prostate cancer (mCRPC) treated with 177Lu-PSMA-I&T and to identify clinical and scintigraphic prognostic factors for outcome. Methods: In total, 301 consecutive mCRPC patients were included in this analysis. Prognostic factors included clinical parameters, routine laboratory parameters, and findings on posttreatment scintigraphy. Scintigraphic tumor uptake of 177Lu-PSMA-I&T was compared with salivary gland uptake and classified as high or low. The longest extent of skeletal metastatic disease was measured, and its changes during therapy were used to define scintigraphic progression, response, and stable disease. A PSA response of at least 50%, PSA PFS, and OS were calculated. Results: In total, 1,138 cycles (median, 3 cycles per patient) of 177Lu-PSMA-I&T using a standard activity of 7.4 GBq were applied intravenously every 4–10 wk (median, 6 wk). Overall, 34% (95% CI, 28%–38%) of patients showed a PSA response of at least 50%, and the median PSA PFS and OS of the total patient cohort were 16.0 wk (95% CI, 12.1–19.9) and 13.8 mo (95% CI, 12.4–15.5), respectively. Patients with high scintigraphic tumor uptake showed a higher PSA response rate of at least 50% (45.7% vs. 10.4%; P < 0.0001) and a significantly reduced risk of PSA progression (median event time, 24.9 vs. 9.0 wk; hazard ratio, 0.3; 95% CI, 0.2–0.5; P < 0.0001). In our data, risk of death was not significantly different between patients with high scintigraphic uptake and those with low scintigraphic uptake (median, 14.4 vs. 12.4 mo; hazard ratio, 0.9; 95% CI, 0.6–1.3; P = 0.6). In a multivariable analysis, the following pretherapeutic prognostic factors for OS were identified: alkaline phosphatase, lactate dehydrogenase, and PSA levels; prior chemotherapy; and the presence of visceral metastases. Scintigraphic response was a strong prognostic factor for PSA response, PSA PFS, and OS after 1 treatment cycle. Conclusion: This retrospective analysis of a large group of consecutive patients corroborates previous clinical experience for 177Lu-PSMA-I&T in mCRPC and establishes previously proposed prognostic factors. The skeletal tumor extent and its changes were identified as new potential biomarkers to predict the outcome of therapy after the first treatment cycle.
- 177Lu-PSMA-I&T
- metastatic castration-resistant prostate cancer (mCRPC)
- prognostic factors
- scintigraphic biomarkers
- clinical biomarkers
Prostate-specific membrane antigen (PSMA)–targeted radioligand therapy (RLT) has increasingly emerged for therapy of patients with metastatic castration-resistant prostate cancer (mCRPC) who exhausted approved treatment regimens (1,2). For the PSMA ligand 177Lu-PSMA-617, efficacy and low toxicity have been shown in several retrospective analyses and in 2 phase II prospective trials (1,3,4). Recently, prolonged overall survival (OS) and progression-free survival (PFS) were proven in a randomized phase III clinical trial just recently resulting in Food and Drug Administration approval (5). Further, clinical parameters such as prior chemotherapy, the presence of visceral metastases, and increased levels of serum lactate dehydrogenase (LDH) have been found to be negatively correlated with patient outcome (6).
Another PSMA ligand that has shown promise for therapy of mCRCP is 177Lu-PSMA-I&T, although clinical experience is more limited (7). 177Lu-PSMA-I&T is currently being explored in a multicenter, randomized prospective phase III trial in mCRPC prior chemotherapy (SPLASH, NCT04647526) after second-line hormonal treatment, with the first results expected in 2023.
Previously, results on 100 patients who underwent 177Lu-PSMA-I&T RLT showed mild toxicity and good antitumor activity in late-stage mCRPC (2). A prostate-specific antigen (PSA) decline of at least 50% within 12 wk was associated with longer clinical PFS and OS. A subgroup analysis identified an association of visceral metastasis at baseline and increased LDH with worse outcome.
The first preliminary retrospective analyses indicate that intensity on posttherapeutic 177Lu-PSMA scintigraphy could be predictive for PSA response, suggesting it as a simple, fast, and widely available imaging biomarker for therapy response (8). However, data are sparse, and impact on OS has not been evaluated. Our clinical experience indicates that the extent of disease and, specifically, infiltration of the appendicular skeleton on posttherapeutic scans and its change during 177Lu-PSMA RLT also hold promise to serve as a new and potentially prognostic imaging biomarker.
Thus, the aim of our retrospective analysis was to update our clinical experience with 177Lu-PSMA-I&T; to evaluate, especially, the prognostic value of clinical and laboratory parameters; and to investigate the use of posttreatment whole-body scintigraphy to predict patient outcome.
MATERIALS AND METHODS
Patients and 177Lu-PSMA-I&T RLT
This retrospective analysis included 301 consecutive mCRPC patients receiving at least 2 cycles of 177Lu-PSMA-I&T between December 2014 and July 2020. All patients had previously received second-line hormonal therapy with abiraterone or enzalutamide and chemotherapy or were unfit for chemotherapy. Patient characteristics are shown in Table 1. Before treatment, sufficient PSMA expression was confirmed by PSMA ligand PET imaging (68Ga-PSMA-11, 18F-PSMA-1007, 18F-rhPSMA-7, or 18F-rhPSMA-7.3). Only patients with PSMA ligand uptake in tumor lesions at least as high as liver background uptake were treated. This patient population includes the 100 patients reported by Heck et al. but adds new patients and extended follow-up for the first 100 patients (2).
Baseline Patient Characteristics
177Lu-PSMA-I&T was prepared according to good manufacturing practice and the German Medicinal Products Act (arzneimittelgesetz §13 2b). The institutional ethics committee approved this retrospective analysis under reference number 115/18S, and all subjects gave written informed consent. Patients were treated under the conditions of the Declaration of Helsinki, article 37, “Unproven Interventions in Clinical Practice.”
Whole-Body Scintigraphy and Image Analysis
Posttherapeutic whole-body scintigraphy (planar anterior and posterior views) was performed approximately 24 h after injection at every cycle using a Symbia T series camera (Siemens) with a medium-energy parallel-hole collimator, a scan speed of 20 cm/min, and 113 keV ± 20% and 208 keV ± 12% photopeak windows. All images were evaluated by one nuclear medicine physician in training under the supervision of one board-certified nuclear medicine physician with more than 7 y of experience in PSMA-targeted imaging and therapy.
The whole-body scans were analyzed for scintigraphic tumor uptake and the extent of skeletal metastatic disease. Tumor uptake of 177Lu-PSMA-I&T on the first posttreatment scan was visually classified as high when most metastatic lesions exceeded the physiologic uptake of the salivary glands. If most lesions equaled or were lower than uptake in the salivary glands, the tumor uptake was classified as low. The extent of skeletal metastatic disease was assessed by a simple quantitative index, as follows. On the first posttherapy scintigram, the longest extent of metastatic disease in a single bone (e.g., femur) contributing to the appendicular skeleton (including clavicle, scapula, humerus, radius, ulna, and the pelvic bones, except the sacrum, femur, tibia, and fibula) was identified and its absolute extent was measured with a ruler. If metastatic bone infiltration was discontinuous in a particular bone, the extents of each site of metastatic disease were measured and summed. On the second posttherapy scintigram, the extent of the same metastatic site was reassessed. The absolute change between the first and second posttherapeutic scans was calculated and defined as change in infiltration length. Scintigraphic progression, response, and stable disease were defined as more than a 0.5-cm increase, more than a 0.5-cm decrease, and a ±0.5-cm change in infiltration length between the first and second cycles, respectively.
Clinical Parameters, PSA Response, and PSA Progression
The following pretherapeutic parameters were collected: age, alkaline phosphatase (AP), LDH, hemoglobin, and PSA, as well as their relative changes between the first and second cycles. PSA response was defined as a PSA decline of at least 50% from baseline according to the criteria of Prostate Cancer Clinical Trials Working group 3 (9). PSA progression was defined either as a PSA increase of at least 25% and at least 2 ng/mL above the nadir after an initial PSA decline or a PSA increase of at least 25% and at least 2 ng/mL from baseline in cases with no PSA decline (9).
Prior systemic therapies (including abiraterone, enzalutamide, first- and second-line chemotherapy, and 223Ra) and metastatic patterns (N+/M1a, lymph node only disease; M1b, presence of bone metastases without visceral metastases; and M1c, presence of visceral metastases) derived from PSMA PET imaging were collected.
Statistical Analysis
Primary outcome measures were PSA response, OS, and PSA PFS. The Kaplan–Meier method was used to estimate event time distributions, and log-rank tests were used for group comparisons. To correct for log-rank test α-error accumulation, significance was assumed when P values were less than 0.016 (Bonferroni adjustment for impact of infiltration length on OS and PSA PFS). Frequencies of PSA response were compared between groups using χ2 tests.
Univariable and multivariable Cox regression analyses were performed to determine the association of pretherapeutic parameters, relative changes in laboratory parameters, and information from posttherapeutic scintigraphy (scintigraphic tumor uptake and change in infiltration length) with PSA PFS and OS. A subgroup analysis in patients without visceral metastases was performed given the known strong negative association of visceral metastases with outcome. The corresponding hazard ratios (HRs) and 95% CIs are presented. A P value of less than 0.05 was considered statistically significant.
For tumor uptake, as well as classification of scintigraphic response, stable disease, and progression, the Cohen κ-coefficient was calculated for intrarater reliability. Strength of agreement for κ values was interpreted according to the Landis and Koch benchmark scale (10).
χ2 tests, Kaplan–Meier estimation, log-rank tests, and calculation of the Cohen κ-coefficient were performed using Prism (version 8.4.3; GraphPad Software) for Mac (Apple). Uni- and multivariable Cox regression analysis was performed using SPSS Statistics (version 25.0; IBM Corp.) for Windows (Microsoft).
RESULTS
In total, 301 patients were analyzed, and 1,138 cycles of PSMA RLT with a median of 3 cycles per patient (range, 2–20) were applied. The patients received an intravenous treatment using a standard activity of 7.4 GBq of 177Lu-PSMA-I&T every 4–10 wk (median, 6 wk), which could be slightly adapted on the basis of, for example, lab test results and tumor burden. The median time on treatment was 3 mo. Posttherapeutic scintigraphy and complete laboratory results were not available for 2 and 4 patients, respectively. At baseline, pelvic lymph nodes, extrapelvic lymph nodes, bone metastases, and visceral metastases were present in 159 (52.8%), 192 (63.8%), 274 (91.0%), and 64 (21.3%) patients, respectively. The median follow-up was 9 mo (range, 1–63 mo). One hundred one (34%; 95% CI, 28%–38%) patients achieved a PSA response after PSMA-targeted RLT. In the total patient cohort, median OS was 13.8 mo (95% CI, 12.4–15.5 mo) and median PSA PFS was 16.0 wk (95% CI, 12.1–19.9 wk). At the time of analysis, 226 patients had shown PSA progression and 182 patients had died.
Impact of Scintigraphic Tumor Uptake on PSA Response, PSA PFS, and OS
High (>salivary gland level) and low (≤salivary gland level) scintigraphic tumor uptake was observed in 202 (67.6%) and 97 (32.4%) patients, respectively. The classification as high or low uptake achieved substantial agreement for intrarater reliability (κ = 0.796). PSA response was achieved in 91 (45.7%) patients with high uptake versus 10 (10.4%) patients with low uptake (P < 0.0001; Fig. 1). Examples of patients with high and low uptake are presented in Figure 2.
Waterfall plot showing response to treatment as measured by serum PSA. Best PSA response is defined as smallest increase or greatest decrease in PSA from baseline compared with color-coded 177Lu-PSMA ligand uptake in posttherapeutic whole-body scintigraphy. First 21 columns represent patients with increase of >100% as best PSA response. Red = patients with low scintigraphic uptake on posttherapeutic scintigraphy; green = patients with high scintigraphic uptake on posttherapeutic scintigraphy.
A 69-y-old patient with bone metastases presenting with high scintigraphic uptake (A) and a 76-y-old patient with bone and lymph node metastases presenting with low scintigraphic uptake (B) on posttherapeutic whole-body scintigraphy at first cycle of 177Lu-PSMA-I&T. PSA PFS and OS were 58 wk and 24 mo, respectively, in patient A and 17 wk and 10 mo, respectively, in patient B.
PSA PFS in patients with high uptake was significantly longer than in those with low uptake (median, 24.9 vs. 9.0 wk; HR, 0.3; 95% CI, 0.2–0.5; P < 0.0001; Fig. 3A). OS did not significantly differ between patients with high uptake and those with low uptake (median, 14.4 vs. 12.4 mo; HR, 0.9; 95% CI, 0.6–1.3; P = 0.6; Fig. 3B). In the subgroup of patients without visceral metastases, higher rates of PSA response (50.3% vs. 12.5%) were achieved, and PSA PFS and OS were significantly longer in patients with high uptake (median, 26.7 vs. 9.0 wk; HR, 0.3; 95% CI, 0.2–0.4; P < 0.0001) than in those with low uptake (15.5 vs. 11.4 mo; HR, 0.6; 95% CI, 0.4–1.0; P = 0.03) (Figs. 3C and 3D).
Kaplan–Meier survival curves for PSA PFS and OS stratified by high and low uptake on posttherapeutic scintigraphy: PSA PFS (A) and OS (B) in total patient cohort, and PSA PFS (C) and OS (D) in patients without visceral metastases.
Impact of Infiltration Length on PSA Response, PSA PFS, and OS
The median extent of metastases on the first and second posttreatment scans was 9.8 cm (range, 1.2–76.9 cm) and 10.3 cm (range, 0.0–78.4 cm), respectively. In 4 patients, the extents of metastatic disease in the femur and the tibia/fibula were summed because of a lack of delimitation of the infiltration path. No significant correlation between quartiles of the extent of disease and PSA PFS (P = 0.4) or OS (P = 0.2) was observed (Supplemental Fig. 1; supplemental materials are available at http://jnm.snmjournals.org).
Overall, 46 (24.7%), 65 (34.9%), and 75 (40.3%) patients showed scintigraphic response, stable disease, and progression, respectively. The classification of scintigraphic response, stable disease, and progression achieved substantial agreement for intrarater reliability (weighted κ = 0.711). A PSA response was achieved in 64.4% (n = 29) of patients with a scintigraphic response, whereas only 29.7% (n = 19) with scintigraphically stable disease and 8.1% (n = 6) with scintigraphic progression achieved a PSA response (P < 0.0001; Fig. 4). An example of a patient who showed a scintigraphic response is presented in Figure 5.
Waterfall plot showing response to treatment as measured by serum PSA. Best PSA response is compared with color-coded change in infiltration length on posttherapeutic scintigraphy. First 16 columns represent patients with increase of >100% as best PSA response. Green = patients with response (>0.5 cm decrease in infiltration length between first and second cycles); yellow = stable disease (±0.5-cm change in infiltration length); red = progression (>0.5 cm increase).
(A) An 81-y-old patient with bone, lymph node, and liver metastases presenting with metastatic disease in right femur with extent of 10.8 cm on posttherapeutic whole-body scintigraphy at first cycle of 177Lu-PSMA-I&T. (B) Same patient with decrease in infiltration length to 3.0 cm at second cycle of 177Lu-PSMA-I&T. Change in infiltration length was −7.8 cm, and classification was therefore scintigraphic response. PSA PFS and OS were 24 wk and 22 mo, respectively.
The distribution of PSA PFS and OS in patients with a scintigraphic response, stable disease, and progression significantly differed (median, 33.1 vs. 16.0 vs. 9.0 wk [P < 0.0001] and 16.5 vs. 11.6 vs. 7.4 mo [P < 0.0001], respectively; Figs. 6A and 6B).
Kaplan–Meier survival curves stratified by scintigraphic response (>0.5-cm decrease in infiltration length between first and second cycles), scintigraphically stable disease (±0.5-cm change in infiltration length), and scintigraphic progression (>0.5-cm increase) for PSA PFS (A) and OS (B).
Uni- and Multivariable Analysis of Prognostic Factors for Outcome
Univariable Cox regression analysis revealed that rising levels of AP, LDH, PSA, as well as prior chemotherapy and the presence of visceral metastases at baseline, were potential negative prognostic factors for OS, whereas the presence of lymph node–only metastases was a significant positive prognostic factor for OS (Table 2). In multivariable analysis, only rising levels of AP, LDH, and PSA and the presence of visceral metastases were identified as significant prognosticators (Table 2).
Uni- and Multivariable Analysis for Association of Baseline Variables with OS
High tumor uptake was not associated with OS (P = 0.3) but was associated with longer PSA PFS in both the univariable and the multivariable analyses (P < 0.0001 for each) (Supplemental Table 1). Furthermore, scintigraphic progression was negatively associated with OS on both univariable and multivariable analyses (P < 0.0001 for each) (Table 3).
Uni- and Multivariable Analysis for Association of Changes in Various Parameters with OS
DISCUSSION
177Lu-PSMA-I&T is the second most commonly used PSMA-targeted radiopharmaceutical for palliative treatment of mCRPC; however, significantly fewer data have been published for 177Lu-PSMA-I&T than for 177Lu-PSMA-617 so far (11). Our retrospective analysis of 301 patients treated with 177Lu-PSMA-I&T substantially expands clinical knowledge about it, underlines its effectiveness, and establishes previously proposed prognostic parameters until the results from the multicenter, randomized prospective phase III trial are published. One important prospective study to which its results might be compared is the SPLASH study (NCT04647526), despite the slight difference in inclusion criteria between that study and ours. Most of our patients also received chemotherapy in addition to second-line hormonal therapy (abiraterone or enzalutamide), contrary to those in SPLASH, who previously received only a single novel androgen receptor axis–targeted therapy but no chemotherapy.
In addition, our analysis underlines the value of PSMA ligand uptake as a noninvasive prognostic imaging biomarker. Specifically, we observed high scintigraphic tumor uptake resulting in a significantly higher PSA response rate and a lower risk of PSA progression. Further, scintigraphic response (defined as a decrease in skeletal infiltration length between 2 cycles) significantly prognosticated a better outcome, with longer PSA PFS and OS.
The number of patients with a 50% PSA decline in our analysis (34%) is well in line with data reported in the literature and, especially, our previous report for 177Lu-PSMA-I&T. A large variation in PSA response rates has been found in the literature, ranging from 20% to 60%, with an estimated PSA response rate of 46% of patients in a recent metaanalysis (11). The lower number of PSA responders in our cohort is most likely explained by differences in the patient population. More than two thirds of the patients in our analysis had received chemotherapy before RLT. In univariable analysis, previous exposure to chemotherapy resulted in a 1.5-fold increased risk of death when compared with patients who had not previously received chemotherapy. In the recent metaanalysis by Sadaghiani et al. (11), the rate of pretreatment with chemotherapy varied between 0% and 80%. Our data compare well with a retrospective analysis using 177Lu-PSMA-617 RLT in 104 mCRCP posttaxane patients and reporting PSA response in 33% of patients and a median OS of 14 mo (95% CI, 12.6–15.4 mo) (12).
Recently, the VISION trial, an international, open-labeled, phase 3 trial evaluating 177Lu-PSMA-617 in patients presenting with mCRPC, was published (5). OS was significantly prolonged in patients receiving 177Lu-PSMA-617 as compared with standard care alone (median, 15.3 vs. 11.3 mo; P < 0.001). Median OS in our patient cohort receiving 177Lu-PSMA-I&T was slightly shorter, at 13.8 mo (95% CI, 12.4–15.5 mo). However, a substantial number of patients (253/551) in the VISION trial undergoing 177Lu-PSMA-617 RLT had also received androgen-receptor–pathway inhibitors with enzalutamide, abiraterone, or apalutamide as part of the standard of care, which might have some additive effect. In our clinical practice, 177Lu-PSMA-I&T was applied in addition to standard application of gonadotropin-releasing hormone analog but without a combination with other active agents.
In addition, discrepancies between treatment outcome in compassionate-use programs and prospective trials might be further explained by an inconsistency in the applied inclusion criteria. The recently published multicenter, randomized prospective phase II trial TheraP reported a significantly higher treatment response in patients receiving 177Lu-PSMA-617 than in patients receiving cabazitaxel (4). However, on the basis of the strict selection criteria, only patients with high 68Ga-PSMA-11 tumor uptake and the absence of 18F-FDG–positive/PSMA ligand–negative lesions were treated. These criteria led to exclusion of 28% of the initially screened patients, with visceral metastases being present in only 7% of the included patient cohort (as compared with 21% of patients in our analysis). The PSA response rate was 66%, compared with 34% in our study.
Our analysis of potential prognostic factors indicated a significant relationship between baseline laboratory parameters (LDH, AP, and PSA) and PSA PFS, and OS, as is in line with previous smaller studies (13). However, these findings still remain controversial, and a variety of other reports lack clear associations in multivariable analyses (14).
Finally, prior therapy with 223Ra was not associated with a worse outcome of 177Lu-PSMA-I&T therapy. One could assume that β-emitting 177Lu-PSMA-I&T is less effective in tumors that have already progressed after α-emitter treatment, with a much higher linear energy transfer than for 177Lu. However, 223Ra may affect predominantly the tumor stroma because it accumulates in the bone matrix surrounding the cancer cells (15). Conversely, 177Lu-PSMA-I&T accumulates directly in prostate cancer cells.
Our data also demonstrate a potential prognostic value of routine posttreatment scintigraphy, as patients with high scintigraphic tumor uptake more frequently achieved PSA response and presented with a reduced risk of PSA progression (PSA PFS, 24.9 vs. 9.0 wk; HR, 0.3; 95%CI, 0.2–0.5; P < 0.0001). This finding corroborates a recent retrospective analysis of 50 mCRPC patients showing that high scintigraphic uptake on posttherapeutic scintigraphy was a significant predictor of PSA decline of at least 50% from baseline (OR, 11.77; P = 0.003) and PSA PFS (OR, 0.2029; P = 0.0111) (16). Similarly, Rathke et al. described intense scintigraphic tumor uptake (>salivary gland level) as a significant predictor of partial remission in univariable analysis (OR, 18.0; 95% CI, 2.230–145.3119; P = 0.0067) and multivariable analysis (OR, 60.265; 95% CI, 5.038–720.922; P = 0.001) (8). Tumor response in this analysis was defined by a visual decrease in uptake by metastatic lesions during later treatment cycles, and no correlation with independent clinical outcome parameters (e.g., PSA PFS, and OS) was available. Our analysis adds further data on the potential of scintigraphic tumor uptake to predict OS: no significant reduction in risk of death for patients with high scintigraphic tumor uptake was observed (14.4 vs. 12.4 mo; HR, 0.9; 95% CI, 0.6–1.3; P = 0.6). Similar results have recently been published by Hotta et al. (17) demonstrating significantly shorter PSA PFS in patients who did not fulfill the VISION criteria but still underwent 177Lu-PSMA-RLT than in those who did fulfill the VISION criteria (2.1 vs. 4.1 mo; HR, 1.6; P = 0.0025). Median OS was shorter (9.6 vs. 14.2 mo; HR, 1.4; P = 0.16) but not to a statistically significant extent. One potential confounder could be the presence of visceral metastases, which are one of the strongest predictors for OS (18). When excluding patients with visceral metastases from our analysis, median OS was significantly longer for high tumor uptake than for low tumor uptake (15.5 vs. 11.4 mo; HR, 0.6; 95% CI, 0.4–1.0; P = 0.03).
Pretherapeutic PSMA ligand PET/CT is usually performed to assess whether the patient is eligible for PSMA RLT. Depending on the logistic workflow, there may be a potentially substantial difference in the time to the start of PSMA RLT. Posttherapeutic scintigraphy, usually performed 24 h after injection, offers an intratherapeutic assessment of the disease state and has potential for longitudinal assessment of its changes over time, with no bias due to disease progression in between. Evaluation of posttherapeutic scintigraphy is easy to apply and has the potential to yield a useful imaging biomarker for prognosticating treatment outcome.
Finally, we present the extent of disease in the appendicular skeleton on posttherapeutic scintigraphy and its change between the first and second treatment cycles as a potential simple and quickly assessable new biomarker. Patients with a scintigraphic response (defined as a decrease in skeletal infiltration length between 2 cycles) presented with a significantly higher likelihood for a PSA response (64.4%), a significantly longer median PSA PFS (33.1 wk), and a longer median OS (16.5 mo). Moreover, whereas whole-body posttreatment scans allow detection of suggestive tumor uptake from head to toe and therefore enable a potentially powerful and inexpensive way to monitor tumor response, pretherapeutic PET/CT imaging is usually performed from skull base to mid thigh (skull and extremities are not included routinely) and is not suitable for routine assessment of the extent of disease in the appendicular skeleton.
Our study had several limitations, including the retrospective nature of the analysis. Qualitative evaluation of scintigraphic uptake and quantitative measurement of skeletal involvement are prone to potential error. However, all posttherapeutic scintigrams were analyzed and measured by the same reader, providing consistency within our patient cohort. Nevertheless, future studies also analyzing interreader agreement are warranted. Finally, the proposed biomarker of scintigraphic response as defined in this analysis is applicable only to patients with metastases in the appendicular skeleton and should be expanded to other organ systems in the future.
CONCLUSION
Our retrospective analysis of a large cohort of consecutive mCRPC patients undergoing 177Lu-PSMA-I&T corroborates previous clinical data on treatment efficacy. It establishes known clinical and laboratory prognostic factors, such as the presence of visceral metastases, elevated LDH, and elevated AP. The clear association between PSA PFS and OS and posttreatment scintigraphic tumor uptake underlines the value of PSMA expression as a prognostic indicator. Finally, we propose skeletal tumor extent on posttherapeutic scintigraphy as a potential novel and simple prognostic imaging biomarker that should be explored in further prospective studies.
DISCLOSURE
Matthias Eiber reports fees from Blue Earth Diagnostics Ltd. (consultant, research funding), Novartis/AAA (consultant), Telix (consultant), Bayer (consultant, research funding), RayzeBio (consultant), Point Biopharma (consultant), Janssen Pharmaceuticals (consultant, speakers’ bureau), Parexel (image review), and Bioclinica (image review) outside the submitted work and a patent application for rhPSMA. No other potential conflict of interest relevant to this article was reported.
KEY POINTS
QUESTION: Is it possible to predict patient outcome using clinical and laboratory parameters and newly proposed posttreatment whole-body scintigraphy parameters updating our experience in a large number of consecutive mCRPC patients?
PERTINENT FINDINGS: Our retrospective analysis on a large number of mCRPC patients undergoing 177Lu-PSMA-I&T corroborated previous reports on 177Lu-PSMA-617 considering PSA response, PSA PFS, and OS. Moreover, it significantly established known prognostic factors, such as the presence of visceral metastases, elevated LDH, and elevated AP, and introduced tumor extent in the appendicular skeleton on posttherapeutic scintigraphy as a significant imaging biomarker predicting patient outcome.
IMPLICATIONS FOR PATIENT CARE: Our retrospective analysis might pave the way for widespread use and better patient selection of 177Lu-PSMA-I&T in mCRPC patients and potentially introduces a simple and inexpensive imaging tool for tumor response assessment.
Footnotes
Published online Sep. 22, 2022.
- © 2023 by the Society of Nuclear Medicine and Molecular Imaging.
REFERENCES
- Received for publication May 11, 2022.
- Revision received September 14, 2022.